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Purpose: Central nervous system (CNS) metastases from lung cancers and melanoma, significantly contribute to morbidity and mortality. Despite advances in local therapies, there is a need for effective systemic treatments. Pembrolizumab, a PD-1 inhibitor, has shown promise for some patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC). This study aims to analyze the response of brain metastasis to pembrolizumab and associate characteristics like size and location with treatment outcome., Methods: This retrospective study used imaging data from a phase II trial of pembrolizumab in melanoma or NSCLC patients with untreated brain metastases. MRI evaluations were conducted at 2 month intervals, with each brain metastasis treated as a distinct tumor for response assessment, based on modified RECIST criteria (maximum 5 lesions, 5 mm target lesions)., Results: Of 130 individual target metastases (> 5 mm), in 65 patients with NSCLC (90 metastases) and Melanoma (40 metastases), 32 (24.6%) demonstrated complete resolution, 24 (18.5%) had partial resolution, 32 (24.6%) were SD and 42 (32.3%) demonstrated PD. Those smaller than 10 mm were more likely to show complete resolution (p = 0.0218), while those ≥ 10 mm were more likely to have PR. There was no significant association between size, number or location (supratentorial vs. infratentorial) and lesion progression. The median time to metastatic lesion progression in the brain was 5.7-7 weeks., Conclusion: Pembrolizumab is effective in brain metastases from NSCLC and melanoma, showing response (CR + PR) in 43% and progression (PD) in 32% of metastases. With the median time to CNS progression of 5.7-7 weeks, careful radiographic monitoring is essential to guide timely local treatment decisions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Studies have explored the connections between tobacco use, sleep and cardiovascular disease (CVD) risks in adults, but no study has examined the link between tobacco use and sleep among adults with CVDs. This study explores the association between tobacco use (cigarette only, e-cigarette only, and dual use) and poor sleep duration among adults with CVDs., Methods: A sample of 47,180 US adults with CVDs (myocardial infarction, coronary heart disease, or stroke) was drawn from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) cross-sectional survey. Poor/inadequate sleep (< 7 h/24-hour) was defined based on National Sleep Foundation recommendations. Logistic regression models assessed tobacco use status across seven categories (i.e., non-use [reference], current [past-month use] cigarette only, current e-cigarettes only, current dual use, former cigarette only, former e-cigarette only, and former dual use) with inadequate sleep, adjusting for demographics and health conditions., Results: Overall, 40% of US adults with a history of CVD reported inadequate sleep. Current cigarette, e-cigarette, and dual use were associated with a relatively higher proportion of inadequate sleep duration. Unweighted findings revealed a significant association between current cigarette use (OR = 1.35, 95%CI: 1.26-1.44), e-cigarette use (1.40 [1.19-1.63]) and dual use (1.50 [1.27-1.77]) and increased odds of reporting inadequate sleep among adults with CVDs. Weighted analysis showed only a significant link between current cigarette use and inadequate sleep (1.34 [1.17-1.54])., Conclusions: Current cigarette use is associated with poor sleep in adults with CVDs. Unweighted findings suggested a similar association for e-cigarettes. Interventions targeting smoking cessation may offer promising avenues for improving sleep health and reducing the burden on adults with CVDs., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition characterized by recurrent re-experiencing of traumatic events. Despite increasing evidence suggesting that the cerebellum is involved in PTSD pathophysiology, it remains unclear whether this involvement is related to symptoms directly resulting from previous trauma exposure, such as involuntary re-experiencing of the traumatic events, or reflects a broader cerebellar engagement in negative affective states. In this study, we investigated the specific role of the cerebellum in PTSD by employing a script reactivation paradigm with personalized traumatic and sad autobiographical memories in 28 individuals diagnosed with chronic PTSD. Functional magnetic resonance imaging (fMRI) data were collected while participants listened to their own autobiographical narratives recounted by a third person. Activation in the right cerebellar lobule VI was uniquely associated with traumatic autobiographical recall and was parametrically modulated by the severity of re-experiencing symptoms. In contrast, cerebellar Crus II showed increased activation during both traumatic and sad autobiographical recall, suggesting a broader involvement in processing negative emotions. Our findings highlight the unique contribution of the right cerebellar lobule VI in the processing of traumatic autobiographical memories, potentially through its engagement in low-level representation of sensory and emotional aspects of traumatic events., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Recurrence for high-grade gliomas is inevitable despite maximal safe resection and adjuvant chemoradiation, and current imaging techniques fall short in predicting future progression. However, we introduce a novel whole-brain magnetic resonance spectroscopy (WB-MRS) protocol that delves into the intricacies of tumor microenvironments, offering a comprehensive understanding of glioma progression to inform expectant surgical and adjuvant intervention., Methods: We investigated five locoregional tumor metabolites in a post-treatment population and applied machine learning (ML) techniques to analyze key relationships within seven regions of interest: contralateral normal-appearing white matter (NAWM), fluid-attenuated inversion recovery (FLAIR), contrast-enhancing tumor at time of WB-MRS (Tumor), areas of future recurrence (AFR), whole-brain healthy (WBH), non-progressive FLAIR (NPF), and progressive FLAIR (PF). Five supervised ML classification models and a neural network were developed, optimized, trained, tested, and validated. Lastly, a web application was developed to host our novel calculator, the Miami Glioma Prediction Map (MGPM), for open-source interaction., Results: Sixteen patients with histopathological confirmation of high-grade glioma prior to WB-MRS were included in this study, totaling 118,922 whole-brain voxels. ML models successfully differentiated normal-appearing white matter from tumor and future progression. Notably, the highest performing ML model predicted glioma progression within fluid-attenuated inversion recovery (FLAIR) signal in the post-treatment setting (mean AUC = 0.86), with Cho/Cr as the most important feature., Conclusions: This study marks a significant milestone as the first of its kind to unveil radiographic occult glioma progression in post-treatment gliomas within 8 months of discovery. These findings underscore the utility of ML-based WB-MRS growth predictions, presenting a promising avenue for the guidance of early treatment decision-making. This research represents a crucial advancement in predicting the timing and location of glioblastoma recurrence, which can inform treatment decisions to improve patient outcomes., (© 2024. The Author(s).)

Background: In the present assessment environment in undergraduate medical education at U.S. medical schools, the prevalence and implementation of Entrustable Professional Activities (EPAs) in internal medicine (IM) clerkships are not well understood., Objective: To describe the prevalence and approach to EPA use in U.S. IM clerkships., Design: Cross-sectional, nationally representative survey of core IM clerkship directors., Participants: One-hundred forty IM clerkship directors at Liaison Committee on Medical Education-accredited U.S./U.S. territory-based allopathic medical schools with membership in the Clerkship Directors in Internal Medicine (CDIM) as of December 2022., Main Measures: Use of EPAs in IM core clerkships, including use for grading, types of EPAs, use of supportive measures for assessment, and current validity frameworks., Key Results: The survey response was 80% (112/140); two additional respondents completed the section on EPA use (n = 114). Approximately half of respondents (47%) reported their IM clerkship used EPAs. Among schools accredited after 1977, a higher percentage was associated with having incorporated EPAs (p = 0.03). The Association of American Medical Colleges Core EPAs for Entering Residency (CEPAER) was the most common framework used by Clerkship Directors (CDs) for developing EPAs (55%). Most CDs (56%) used EPAs for both formative and summative assessments, and approximately half of CDs (48%) used EPAs for a portion of the final grade determination. CDs who used EPAs were no more likely to report efforts to ensure the validity of assessment, the use of faculty development, or that written assessments were a valid measure of students' performance compared to those who did not use EPAs., Conclusions: Although EPAs have experienced substantial uptake in the IM clerkship and contribute to formative and summative assessment of learners, their use does not appear to be associated with enhanced efforts to obtain validity information., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Female physicians often report lower self-confidence in their procedural and clinical competency compared to male physicians. There is limited data regarding self-reported confidence of female versus male trainees and any relation to objective competency in central venous catheter insertion., Objective: To analyze differences between male and female trainees in self-confidence and skill-based outcomes in placing central venous catheters., Design: Using data from a central venous catheter simulation training program at a large tertiary medical center, we performed linear regressions to analyze confidence difference pre- and post-training, number of restarts, and number of cannulation attempts while controlling for baseline demographic characteristics of the sample., Participants: PGY-1 physician residents in all residency specialties who insert central venous catheters in the clinical setting at a tertiary academic center with a sample size of 281 residents., Main Measures: Confidence difference pre- and post-training measured on a Likert scale 1-5, number of restarts (novel global assessment variable), and number of cannulation attempts during the competency evaluation., Key Results: Female trainees had both lower pre-program confidence (1.35 versus 1.74 out of 5, p < 0.001) and lower post-program confidence (3.77 versus 4.12 out of 5, p = 0.0021) as compared to male trainees. There was no statistically significant difference in number of restarts (95% CI - 0.073 to 0.368, p = 0.185) or cannulation attempts (95% CI - 0.039 to 0.342, p = 0.117) between sexes in linear regressions controlled for age, specialty designation, prior central venous catheter training, prior ultrasound guided vessel cannulation training, and pre-training confidence level., Conclusions: Female trainees rated their confidence significantly lower than their male counterparts both before and after the training program, despite no significant difference in skill-based outcomes. We discuss potential implications for trainees acquiring procedural skills during residency and for physician educators as they design training programs and delegate procedural opportunities., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

The credo of the generalist physician has always been the promotion of health for all, in every aspect: not just multiple vulnerable organ systems, but multiple social, cultural, and political factors that contribute to poor health and exacerbate health inequity. In recent years, the field of global health has also adopted this same mission: working across both national and clinical specialty borders to improve health for all and end health disparities worldwide. Yet within the Society for General Internal Medicine, and among American generalists, engagement in global health, both within and outside the USA, remains uncommon. We see this gap as an opportunity, because in fact generalists in America already have the skills and experience that global health badly needs. SGIM could promote generalists to global health's vanguard, with three core steps. First, we generalists must continue to integrate health for the vulnerable into our domestic work, generating care models applicable in low-resource settings around the globe. Conversely, we must also engage with and implement international ideas and solutions for universal access to primary care for vulnerable patients in the USA. And lastly, we must build platforms to connect ourselves with colleagues worldwide to exchange these learnings., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Purpose: The New England VA Hernia Registry was created in 2011 to prospectively collect relevant details of ventral hernia repairs, with the intention to assess and improve long term outcomes. The goal of this study is to assess registry compliance., Methods: All ventral hernia operations performed in five VA hospitals between 2011-2022 were obtained. We assessed compliance at the hospital and surgeon level., Results: 3,516 cases were performed. Overall compliance with registry entry was 37.5%, ranging from 10.8% to 67.2% across hospitals. At the hospital level, there was a negative correlation between average yearly hernia volume per surgeon and registry compliance (r 2  = 0.53). Surgeon compliance varied within hospitals and over time., Conclusion: Registry compliance was low and highly variable. Lack of interest, incentives, oversight, and surgeon turnover are possible factors for noncompliance. Building a registry with these factors in mind, providing timely feedback, and conducting frequent audits may improve compliance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: The prevalence of co-occurring chronic pain and posttraumatic stress disorder (PTSD) has yet to be established in a nationally representative sample of US veterans, and little is known about the individual contributing roles of these disorders to the psychiatric and functional burden of this comorbidity., Objective: To determine the prevalence of chronic pain, PTSD, and co-occurring chronic pain and PTSD, and psychiatric comorbidities and psychosocial functioning in these groups., Design: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of US veterans., Participants: Veterans (n=4069) were classified into four groups: control (i.e., no PTSD or chronic pain), chronic pain only, PTSD only, and co-occurring chronic pain and PTSD., Main Measures: A probable PTSD diagnosis was established using the PTSD Checklist for DSM-5, and a chronic pain diagnosis using a self-report item that queried health care professional diagnoses. Psychiatric and functional status were assessed using the Patient Health Questionnaire-4, Alcohol Use Disorders Identification Test, Screen of Drug Use, Suicide Behaviors Questionnaire-Revised, Short Form Health Survey-8, Brief Inventory of Psychosocial Functioning, and Medical Outcomes Study Cognitive Functioning Scale., Key Results: A total of 3.8% of veterans reported both probable PTSD and a diagnosis of chronic pain. Relative to veterans with chronic pain alone, those with co-occurring chronic pain and probable PTSD were more likely to screen positive for psychiatric disorders (odds ratios [ORs]=2.59-9.88) and scored lower on measures of psychosocial functioning (Cohen's ds=0.38-1.43). Relative to veterans with probable PTSD only, those with co-occurring chronic pain and probable PTSD were more likely to have attempted suicide (OR=4.79; 95%CI, 1.81-12.69)., Conclusions: Results underscore the importance of whole health care that considers a broad range of health and functional domains in the assessment and treatment of co-occurring chronic pain and PTSD in veterans., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Purpose: Continuous positive airway pressure (CPAP) is the primary therapy for obstructive sleep apnea (OSA); however the effectiveness of CPAP remains suboptimal. We describe the Novel PhysIologiC prEdictors of Positive Airway Pressure Effectiveness (NICEPAP) study. Its purpose is to determine whether physiological traits of OSA contribute to CPAP effectiveness., Methods: NICEPAP (NCT05067088) is a prospective, observational cohort study conducted at an academic sleep center. Adults newly diagnosed with OSA (n = 267) are assessed for OSA traits of loop gain, arousal threshold, pharyngeal collapsibility, and muscle compensation from baseline polysomnography. We perform a comprehensive assessment of covariates relevant to CPAP adherence, efficacy, and patient-centered outcomes. Participants are followed for 12 months. Primary outcomes include (1) CPAP adherence (hours/night), (2) CPAP efficacy (apneas-hypopneas/hour), and (3) quality of life at six months measured by objective CPAP data and Functional Outcomes of Sleep Questionnaire. Secondary outcomes include sleep quality, sleepiness, insomnia, and neurocognitive function., Results: Data on covariates, including demographics, sleep symptoms, medical history, medications, sleep quality, OSA and treatment self-efficacy, decisional balance, and socio-economic and social and partner support, are collected using validated instruments. The analysis for primary outcomes includes a generalized linear mixed model for an outcome (e.g., CPAP adherence) with OSA traits as exposures followed by the addition of relevant covariates., Conclusion: The findings of the NICEPAP study will inform research aimed to enhance CPAP effectiveness. Understanding the role of physiological OSA traits in CPAP effectiveness is a crucial step toward a precision medicine approach to OSA., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The proliferation of the endothelium is a highly coordinated process to ensure the emergence, expansion, and homeostasis of the vasculature. While Bone Morphogenetic Protein (BMP) signaling fine-tunes the behaviors of endothelium in health and disease, how BMP signaling influences the proliferation of endothelium and therefore, modulates angiogenesis remains largely unknown. Here, we evaluated the role of Activin A Type I Receptor (ACVR1/ALK2), a key BMP receptor in the endothelium, in modulating the proliferation of endothelial cells. We show that ACVR1/ALK2 is a key modulator for the proliferation of endothelium in the retinal vessels. Loss of endothelial ALK2 leads to a significant reduction in endothelial proliferation and results in fewer branches/endothelial cells in the retinal vessels. Interestingly, venous endothelium appears to be more susceptible to ALK2 deletion. Mechanistically, ACVR1/ALK2 inhibits the expression of CDKN1A/p21, a critical negative regulator of cell cycle progression, in a SMAD1/5-dependent manner, thereby enabling the venous endothelium to undergo active proliferation by suppressing CDKN1A/p21. Taken together, our findings show that BMP signaling mediated by ACVR1/ALK2 provides a critical yet previously underappreciated input to modulate the proliferation of venous endothelium, thereby fine-tuning the context of angiogenesis in health and disease., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy., Methods: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS., Results: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07)., Conclusions: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality., (© 2024. The Author(s).)

Although intimate partner violence (IPV) is an important risk factor for child physical abuse, most IPV-exposed children are not evaluated for abusive injuries. A Community Advisory Board (CAB) was formed to (a) optimize a program to evaluate IPV-exposed children for abusive injuries and (b) inform research methods to engage IPV victims and their children. The objectives of this study were to implement and to evaluate the family violence CAB. Following best practices on CAB formation, we recruited local stakeholders with key roles as service providers, community leaders, and knowledge experts in IPV, child abuse, and emergency care. Fourteen members met bimonthly to develop a family-centered intervention and to inform research and advocacy activities. A shared memorandum of understanding outlined goals and objectives. One year after the CAB's implementation, a research assistant interviewed CAB members to understand their experiences, perceived benefits of participation, and desired improvements. Eleven CAB members, including an IPV survivor, participated. Emerging categories included (a) motivations to join the CAB (victim advocacy), (b) benefits of participation (development of relationships among members and increased acceptability of research methods), (c) facilitators of sustainability (program adaptability and development of trust), and (d) desired improvements (case-based follow-up). The CAB was successfully implemented and facilitated the development of collaborative relationships among stakeholders with key roles in IPV and child abuse. The CAB led to community member-proposed changes in research activities and clinical care for victims of IPV., (© 2024 Springer Publishing Company.)

Attention training is an evidence-based, computerized treatment for anxiety and its disorders rooted in cognitive neuroscience. Though experimental research and clinical trials data on attention training in children span two decades, the literature has focused on attention training's anxiety reduction effects, with little guidance on its implementation in clinical practice. Guidance on implementation is needed given recent efforts to increase accessibility of attention training in clinical practice settings. In this article, we move from research to clinical implementation, providing guidelines with pragmatic clinical steps. We include guidance on psychoeducation, setting and delivery of sessions, potential challenges, and frequently asked questions regarding implementation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With annual point-in-time counts indicating a rise in unsheltered homelessness in the United States, much attention has been paid to how to best provide care to this population. Mobile medical units (MMUs) have been utilized by many programs. However, little is known regarding the evidence behind their effectiveness. A scoping review is conducted of research on MMU provision of medical services for populations experiencing homelessness in the USA to examine the extent and nature of research activity, summarize available evidence, and identify research gaps in the existing literature. Following guidelines for scoping reviews, PubMed and Google Scholar were used to identify an initial 294 papers published from January 1, 1980, to May 1, 2023, using selected keywords, which were distilled to a final set of 50 studies that met eligibility criteria. Eligible articles were defined as those that pertain to the provision of healthcare (inclusive of dental, vision, and specialty services) to populations experiencing homelessness through a MMU in the United States and have been published after peer review. Of the 50 studies in the review, the majority utilized descriptive (40%) or observational methods (36%), with 4 review and 8 controlled studies and no completed randomized controlled trials. Outcome measures utilized by studies include MMU services provided (58%), patient demographics (34%), health outcomes (16%), patient-centered measures (14%), healthcare utilization (10%) and cost analysis (6%). The studies that exist suggest MMUs can facilitate effective treatment of substance use disorders, provision of primary care, and services for severe mental illness among people experiencing homelessness. MMUs have potential to provide community-based healthcare services in settings where homeless populations reside, but the paucity of randomized controlled trials indicates further research is needed to understand if MMUs are more effective than other care delivery models tailored to populations experiencing homelessness., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Hypertension is a heritable disease that affects one-fourth of the population and accounts for about 50% of cardiovascular deaths. The genetic basis of hypertension is multifaceted, involving both monogenic and most commonly complex polygenic forms. With the advent of the human genome project, genome-wide association studies (GWAS) have identified a plethora of loci linked to hypertension by examining common genetic variations. It's notable, however, that the majority of these genetic variants do not affect the protein-coding sequences, posing a considerable obstacle in pinpointing the actual genes responsible for hypertension. Despite these challenges, precise mapping of GWAS-identified loci is emerging as a promising strategy to reveal novel genes and potential targets for the pharmacological management of blood pressure. This review provides insight into the monogenic and polygenic causes of hypertension. Special attention is given to PRDM6, among the earliest functionally characterized GWAS-identified genes. Moreover, this review delves into the roles of genes contributing to renal and vascular forms of hypertension, offering insights into their genetic and epigenetic mechanisms of action., (© 2024. The Author(s).)

Melanoma has the highest propensity among solid tumors to metastasize to the brain. Melanoma brain metastases (MBM) are a leading cause of death in melanoma and affect 40-60% of patients with late-stage disease. Therefore, uncovering the molecular mechanisms behind MBM is necessary to enhance therapeutic interventions. Vascular mimicry (VM) is a form of neovascularization linked to invasion, increased risk of metastasis, and poor prognosis in many tumor types, but its significance in MBM remains poorly understood. We found that VM density is elevated in MBM compared to paired extracranial specimens and is associated with tumor volume and CNS edema. In addition, our studies indicate a relevant role of YAP and TAZ, two transcriptional co-factors scarcely studied in melanoma, in tumor cell-vasculogenesis and in brain metastasis. We recently demonstrated activation of the Hippo tumor suppressor pathway and increased degradation of its downstream targets YAP and TAZ in a metastasis impaired cell line model. In the current study we establish the utility of anti-YAP/TAZ therapy in mouse models of metastatic melanoma whereby treatment effectively inhibits VM and prolongs survival of mice with MBM. The data presented herein suggest that VM may be an important and targetable mechanism in melanoma and that VM inhibition might be useful for treating MBM, an area of high unmet clinical need, thus having important implications for future treatment regimens for these patients., (© 2024. The Author(s).)

Background: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI., Objective: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI., Methods: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022., Results: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission., Conclusion: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity., (© 2024. The Author(s).)

Alcohol dependence is a disorder with a high recurrence rate that leads to a considerable public health burden. The risk of relapse appears to be related to a complex interplay of multiple factors. Herein, we aimed to explore the potential neural predictors of relapse in Chinese male patients with alcohol dependence. This study enrolled 58 male patients with alcohol dependence who had undergone acute detoxification. General demographic information and clinical features were collected. Magnetic resonance imaging data were used to measure cortical thickness across 34 regions of the brain. Patients were followed up at six months, and 51 patients completed the follow-up visit. These patients were divided into a relapser and an abstainer group. A binary logistic regression analysis was performed to investigate the potential risk factors of relapse. Compared to abstainers, relapsers showed higher inattention and non-planning impulsivity on the 11th version of the Barratt Impulsive Scale. The cortical thicknesses of the inferior-parietal lobules were significantly higher in abstainers compared with those in relapsers. Furthermore, binary logistic regression analysis showed that the thickness of the inferior parietal lobule predicted relapse, and lower non-planning impulse was a protective factor against relapse. Relapsers show poorer impulse control than abstainers, and structural magnetic resonance imaging revealed a decreased thickness of the inferior parietal lobule in relapsers. Our results indicate the thickness of the inferior parietal lobule as a potential relapse predictor in male patients with alcohol dependence., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Obesity is the main driving factor for comorbidities in Prader-Willi syndrome (PWS) patients due to overeating behaviors. The gut microbiota has been implicated in the etiology of obesity and associated comorbidities. The purpose of the present study was to characterize the fecal microbiota in Chinese patients with PWS and compare it to that of patients with obesity as well as healthy controls., Methods: We conducted a cross-sectional study with 35 PWS patients (PWS), 35 patients with obesity (OB), and 35 healthy controls (HC). Metagenomic sequencing was performed in stool samples., Results: The composition of the fecal microbiota in PWS patients differed from that of participants in the OB and HC groups. It was characterized by increased Akkermansia Eubacterium, Eubacterium rectale, and Roseburia intestinalis and decreased Parabacteroides and Phascolarctobacterium. Additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was lower in PWS patients than in patients with obesity. Spearman rank correlation analysis showed that Achromobacter, Acidiphilium, Xylophilus, and Frisingicoccus were significantly negatively correlated with HOMA-IR., Conclusion: The composition of the gut microbiota in Chinese PWS patients differed from that in patients with obesity, which might contribute to higher insulin sensitivity in PWS patients., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: Few data describe how general psychiatry residencies prepare trainees to care for individuals with neurocognitive disorders (NCDs), despite increasing recognition of the need for psychiatrists to provide care for the growing numbers of patients with NCD. This study aims to identify training needs and approaches, as the resident experience is one important perspective that can be added to others, such as milestones developed by expert educators., Methods: The authors conducted three focus groups of third- and fourth-year general adult psychiatry residency trainees from three different training programs in May and June of 2021. Focus groups consisted of three to eight unique participants per group. Qualitative data analysis techniques derived in grounded theory were utilized to identify themes., Results: Four main themes emerged from the focus groups: unique challenges of NCD care, intrinsic rewards of working with families, perceived gaps in educational experiences, and limited comfort in future practice., Conclusions: Participants expressed that aspects of NCD care were fundamentally different than care for other mental health conditions encountered in psychiatry residency. They found the progressive nature of the disease to be particularly challenging, and they also expressed challenges with clinical interviews and establishing rapport with individuals with NCDs. However, working with families was especially rewarding. Regardless of training program, participants expressed a need for additional longitudinal and diversified training opportunities to prepare them for future practice in this area., (© 2024. The Author(s), under exclusive licence to American Association of Chairs of Departments of Psychiatry, American Association of Directors of Psychiatric Residency Training, Association for Academic Psychiatry and Association of Directors of Medical Student Education in Psychiatry.)

Background: Lower body negative Pressure (LBNP)-induced hypovolemia is simulating acute hemorrhage by sequestrating blood into lower extremities. Bioelectrical Impedance Analysis (BIA) is based on the electrical properties of biological tissues, as electrical current flows along highly conductive body tissues (such as blood). Changes in blood volume will lead to changes in bioimpedance. This study aims to study changes in upper (UL) and lower (LL) extremities bioimpedance during LBNP-induced hypovolemia., Methods: This was a prospective observational study of healthy volunteers who underwent gradual LBNP protocol which consisted of 3-minute intervals: at baseline, -15, -30, -45, -60 mmHg, then recovery phases at -30 mmHg and baseline. The UL&LL extremities bioimpedance were measured and recorded at each phase of LBNP and the percentage changes of bioimpedance from baseline were calculated and compared using student's t-test. A P-value of < 0.05 was considered significant. Correlation between relative changes in UL&LL bioimpedance and estimated blood loss (EBL) from LBNP was calculated using Pearson correlation., Results: 26 healthy volunteers were enrolled. As LBNP-induced hypovolemia progressed, there were a significant increase in UL bioimpedance and a significant decrease in LL bioimpedance. During recovery phases (where blood was shifted from the legs to the body), there were a significant increase in LL bioimpedance and a reduction in UL bioimpedance. There were significant correlations between estimated blood loss from LBNP model with UL (R = 0.97) and LL bioimpedance (R = - 0.97)., Conclusion: During LBNP-induced hypovolemia, there were reciprocal changes in UL&LL bioimpedance. These changes reflected hemodynamic compensatory mechanisms to hypovolemia., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Frailty is associated with significant morbidity and mortality and may have clinical implications in an advanced age population with atrial fibrillation undergoing left atrial appendage occlusion (LAAO). We sought to develop a novel frailty scale to predict worse outcomes in patients undergoing LAAO., Methods: Patients in the NCDR LAAO Registry between 2016 and 2021 receiving percutaneous LAAO devices were categorized as non-frail (0 points), pre-frail (1-3 points), or frail (4-5 points) based on a 5-point scale representing multiple domains of frailty: hemoglobin <13.0 g/dL in male, <12.0 g/dL in female; creatinine ≥1.2 mg/dL; albumin <3.5 g/dL; body mass index <20 kg/m2; and increased risk of falls., Results: Of 57,728 patients, 44,360 (76.8%) were pre-frail and 7693 (13.3%) were frail. Compared to non-frail, pre-frail and frail patients were older, had a higher burden of co-morbidities, and more disability based on the Modified Rankin Scale. Compared to non-frail patients after adjustment, frail patients were at higher risk of in-hospital major complication (OR 1.29, 95% 1.02-1.62, p = 0.01), any complication (OR 1.29, 95% CI 1.09-1.52, p = 0.0005), and death (OR 5.79, 95% CI 1.75-19.17, p = 0.001), while no difference was observed in pre-frail patients. At 45-day follow-up, there was no difference in the risk of complications in frail patients as compared to non-frail, although mortality was significantly higher (OR 3.01, 95% CI 1.97-4.85, p < 0.0001)., Conclusion: A simple and practical frailty scale accurately predicts adverse events in patients undergoing LAAO. The 13% of patients considered frail were at significantly higher risk of in-hospital adverse events and 45-day mortality., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Disparities in mental health treatment have consistently been documented for clients of color as compared to White clients. Most mental health care disparities literature focuses on access to care at the point of initial engagement to treatment, resulting in a dearth of viable solutions being explored to retain clients in care once they begin. Measurement-based care (MBC) is a person-centered practice that has been shown to improve the therapeutic relationship, make treatment more personalized, and empower the client to have an active role in their care. Problems with therapeutic alliance and treatment relevance are associated with early termination for communities of color in mental health services. However, MBC has not been explored as a clinical practice to address therapeutic alliance and continual engagement for people of color seeking mental health care. This Point of View describes several MBC features that may be able to impact current sources of disparity in mental health treatment quality and provides a rationale for each. Our hope is that the field of MBC and progress feedback will more explicitly consider the potential of MBC practices to promote equity and parity in mental health services of color and will start to explore these associations empirically. We also discuss whether MBC should be culturally adapted to optimize its relevance and effectiveness for communities of color and other groups experiencing marginalization. We propose that MBC has promise to promote equitable mental health service quality and outcomes for communities of color., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Visual face recognition-the ability to encode, discriminate, and recognize the faces of others-is fundamentally supported by eye movements and is a common source of difficulty for autistic individuals. We aimed to evaluate how visual processing strategies (i.e., eye movement patterns) directly support encoding and recognition of faces in autistic and neurotypical (NT) individuals., Methods: We used a hidden Markov modeling approach to evaluate the spatiotemporal dynamics of eye movements in autistic (n = 15) and neurotypical (NT) adolescents (n = 17) during a face identity recognition task., Results: We discovered distinct eye movement patterns among all participants, which included a focused and exploratory strategy. When evaluating change in visual processing strategy across encoding and recognition phases, autistic individuals did not shift their eye movement patterns like their NT peers, who shifted to a more exploratory visual processing strategy during recognition., Conclusion: These findings suggest that autistic individuals do not modulate their visual processing strategy across encoding and recognition of faces, which may be an indicator of less efficient face processing., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The gender gap in physician compensation has persisted for decades. Little is known about how differences in use of the electronic health record (EHR) may contribute., Objective: To characterize how time on clinical activities, time on the EHR, and clinical productivity vary by physician gender and to identify factors associated with physician productivity., Design, Setting, and Participants: This longitudinal study included general internal medicine physicians employed by a large ambulatory practice network in the Northeastern United States from August 2018 to June 2021., Main Measures: Monthly data on physician work relative value units (wRVUs), physician and practice characteristics, metrics of EHR use and note content, and temporal trend variables., Key Results: The analysis included 3227 physician-months of data for 108 physicians (44% women). Compared with men physicians, women physicians generated 23.8% fewer wRVUs per month, completed 22.1% fewer visits per month, spent 4.0 more minutes/visit and 8.72 more minutes on the EHR per hour worked (all p < 0.001), and typed or dictated 36.4% more note characters per note (p = 0.006). With multivariable adjustment for physician age, practice characteristics, EHR use, and temporal trends, physician gender was no longer associated with productivity (men 4.20 vs. women 3.88 wRVUs/hour, p = 0.31). Typing/dictating fewer characters per note, relying on greater teamwork to manage orders, and spending less time on documentation were associated with higher wRVUs/hour. The 2021 E/M code change was associated with higher wRVUs/hour for all physicians: 10% higher for men physicians and 18% higher for women physicians (p < 0.001 and p = 0.009, respectively)., Conclusions: Increased team support, briefer documentation, and the 2021 E/M code change were associated with higher physician productivity. The E/M code change may have preferentially benefited women physicians by incentivizing time-intensive activities such as medical decision-making, preventive care discussion, and patient counseling that women physicians have historically spent more time performing., (© 2023. The Author(s).)

In the last decade, immunotherapy has become the cornerstone in the management of patients with melanoma, the foremost cause of skin-cancer-related death in the USA. The emergence of immune checkpoint blockade as a crucial element in current immunotherapy and combination strategies has significantly transformed the treatments of resectable and advanced (unresectable or metastatic) melanoma. This paper reviews the landmark clinical trials that formed the basis of management of melanoma in the perioperative and metastatic setting. Furthermore, we discuss the rationale for the applications of PD-1 blockade and its combination with anti-CTLA-4 and anti-LAG-3. The review also explores new experimental combinations of PD-1 blockade with other immunomodulatory agents, including targeted therapies, anti-TIGIT antibodies, TLR-9 agonists, antiangiogenic agents, and mRNA vaccines., (© 2023. Society of Surgical Oncology.)

Burnout is a syndrome characterized by mental and emotional fatigue or exhaustion, depersonalization, and a lessened sense of personal accomplishment and efficacy. Burnout leads to negative consequences for mental health clinicians and for mental health care organizations. Measurement-based care (MBC) is a clinical process in which clinicians and clients use patient-generated data, also called treatment feedback, to collaboratively monitor mental health care and to inform goal-setting and treatment planning. We propose that MBC may improve the experience of care for both clients and clinicians, and ultimately protect against each of the three components of burnout. When combined with other organizational changes, adoption of MBC may support organizational level efforts to reduce burnout in mental health services., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

There are approximately 5 million pregnancies per year in the USA, with 1 million ending in miscarriage (a loss occurring prior to 20 weeks of gestation) and over 20,000 ending in stillbirth at or beyond 20 weeks of gestation. As many as 50% of these losses are unexplained. Our objective was to evaluate the effect of expanding the placental pathology diagnostic categories to include the explicit categories of (1) dysmorphic chorionic villi and (2) small placenta in examining previously unexplained losses. Using a clinical database of 1256 previously unexplained losses at 6-43 weeks of gestation, the most prevalent abnormality associated with each loss was determined through examination of its placental pathology slides. Of 1256 cases analyzed from 922 patients, there were 878 (69.9%) miscarriages and 378 (30.1%) antepartum stillbirths. We determined the pathologic diagnoses for 1150/1256 (91.6%) of the entire series, 777/878 (88.5%) of the miscarriages (< 20 weeks' gestation), and 373/378 (98.7%) of the stillbirths (≥ 20 weeks' gestation). The most common pathologic feature observed in unexplained miscarriages was dysmorphic chorionic villi (757 cases; 86.2%), a marker associated with genetic abnormalities. The most common pathologic feature observed in unexplained stillbirths was a small placenta (128 cases; 33.9%). Our classification system reinforced the utility of placental examination for elucidating potential mechanisms behind pregnancy loss. The improved rate of diagnosis appeared to be the result of filling a gap in previous pregnancy loss classification systems via inclusion of the categories of dysmorphic chorionic villi and small placenta., (© 2023. The Author(s).)

A variety of observational studies have demonstrated that coffee, likely acting through caffeine, improves health outcomes in patients with chronic liver disease. The primary pharmacologic role of caffeine is to act as an inhibitor of adenosine receptors. Because key liver cells express adenosine receptors linked to liver injury, regeneration, and fibrosis, it is plausible that the biological effects of coffee are explained by effects of caffeine on adenosinergic signaling in the liver. This review is designed to help the reader make sense of that hypothesis, highlighting key observations in the literature that support or dispute it., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The Primary Care Exception (PCE) is a billing rule from the Centers for Medicare and Medicaid Services (CMS) that allows supervising physicians to bill for ambulatory care provided by a resident without their direct supervision. There has been increased focus on entrustment as a method to assess readiness for unsupervised practice., Objective: To understand the factors influencing attending physicians' use of the PCE in ambulatory settings and identify common themes defining what motivates faculty preceptors to use the PCE., Approach: This was a qualitative exploratory study. Participants were interviewed one-on-one using a semi-structured template informed by the entrustment literature. Analysis was conducted using a thematically framed, grounded theory-based approach to identify major themes and subthemes., Participants: Twenty-seven internal medicine teaching faculty took part in a multi-institutional study representing four residency training programs across two academic medical centers in Connecticut., Key Results: Four predominant categories of themes influencing PCE use were identified: (1) clinical environment factors, (2) attending attitudes, (3) resident characteristics, and (4) patient attributes. An attending's "internal rules" drawn from prior experiences served as a significant driver of PCE non-use regardless of the trainee, patient, or clinical context. A common conflict existed between using the PCE to promote resident autonomy versus waiving the PCE to promote safety., Conclusions: The PCE can serve as a tool to support resident autonomy, confidence, and overall clinical efficiency. Choice of PCE use by attendings involved complex internal decision-making schema balancing internal, patient, resident, and environmental-related factors. The lack of standardized processes in competency evaluation may increase susceptibility to biases, which could be mitigated by applying standardized modes of assessment that encompass shared principles., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Defining monogenic drivers of autoinflammatory syndromes elucidates mechanisms of disease in patients with these inborn errors of immunity and can facilitate targeted therapeutic interventions. Here, we describe a cohort of patients with a Behçet's- and inflammatory bowel disease (IBD)-like disorder termed "deficiency in ELF4, X-linked" (DEX) affecting males with loss-of-function variants in the ELF4 transcription factor gene located on the X chromosome. An international cohort of fourteen DEX patients was assessed to identify unifying clinical manifestations and diagnostic criteria as well as collate findings informing therapeutic responses. DEX patients exhibit a heterogeneous clinical phenotype including weight loss, oral and gastrointestinal aphthous ulcers, fevers, skin inflammation, gastrointestinal symptoms, arthritis, arthralgia, and myalgia, with findings of increased inflammatory markers, anemia, neutrophilic leukocytosis, thrombocytosis, intermittently low natural killer and class-switched memory B cells, and increased inflammatory cytokines in the serum. Patients have been predominantly treated with anti-inflammatory agents, with the majority of DEX patients treated with biologics targeting TNFα., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Involution of the mammary gland after lactation is a dramatic example of coordinated cell death. Weaning causes distension of the alveolar structures due to the accumulation of milk, which, in turn, activates STAT3 and initiates a caspase-independent but lysosome-dependent cell death (LDCD) pathway. Although the importance of STAT3 and LDCD in early mammary involution is well established, it has not been entirely clear how milk stasis activates STAT3. In this report, we demonstrate that protein levels of the PMCA2 calcium pump are significantly downregulated within 2-4 h of experimental milk stasis. Reductions in PMCA2 expression correlate with an increase in cytoplasmic calcium in vivo as measured by multiphoton intravital imaging of GCaMP6f fluorescence. These events occur concomitant with the appearance of nuclear pSTAT3 expression but prior to significant activation of LDCD or its previously implicated mediators such as LIF, IL6, and TGFβ3, all of which appear to be upregulated by increased intracellular calcium. We further demonstrate that increased intracellular calcium activates STAT3 by inducing degradation of its negative regulator, SOCS3. We also observed that milk stasis, loss of PMCA2 expression and increased intracellular calcium levels activate TFEB, an important regulator of lysosome biogenesis through a process involving inhibition of CDK4/6 and cell cycle progression. In summary, these data suggest that intracellular calcium serves as an important proximal biochemical signal linking milk stasis to STAT3 activation, increased lysosomal biogenesis, and lysosome-mediated cell death., (© 2024. The Author(s).)

Purpose: Primary osseous neoplasms of the spine, including Ewing's sarcoma, osteosarcoma, chondrosarcoma, and chordoma, are rare tumors with significant morbidity and mortality. The present study aims to identify the prevalence and impact of racial disparities on management and outcomes of patients with these malignancies., Methods: The 2000 to 2020 Surveillance, Epidemiology, and End Results (SEER) Registry, a cancer registry, was retrospectively reviewed to identify patients with Ewing's sarcoma, osteosarcoma, chondrosarcoma, or chordoma of the vertebral column or sacrum/pelvis. Study patients were divided into race-based cohorts: White, Black, Hispanic, and Other. Demographics, tumor characteristics, treatment variables, and mortality were assessed., Results: 2,415 patients were identified, of which 69.8% were White, 5.8% Black, 16.1% Hispanic, and 8.4% classified as "Other". Tumor type varied significantly between cohorts, with osteosarcoma affecting a greater proportion of Black patients compared to the others (p < 0.001). A lower proportion of Black and Other race patients received surgery compared to White and Hispanic patients (p < 0.001). Utilization of chemotherapy was highest in the Hispanic cohort (p < 0.001), though use of radiotherapy was similar across cohorts (p = 0.123). Five-year survival (p < 0.001) and median survival were greatest in White patients (p < 0.001). Compared to non-Hispanic Whites, Hispanic (p < 0.001) and "Other" patients (p < 0.001) were associated with reduced survival., Conclusion: Race may be associated with tumor characteristics at diagnosis (including subtype, size, and site), treatment utilization, and mortality, with non-White patients having lower survival compared to White patients. Further studies are necessary to identify underlying causes of these disparities and solutions for eliminating them., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: The COVID-19 pandemic resulted in rapid adoption of telemedicine in rheumatology. We described perspectives of patients with rheumatic diseases related to telemedicine use., Methods: An anonymous online survey for people with rheumatic diseases was launched in January 2021. We collected data on reasons for telemedicine use, perceived benefits, disadvantages and obstacles of telemedicine, perceived telemedicine effectiveness for different clinical tasks, level of satisfaction with telemedicine use, and future preferences for telemedicine. We summarized results with descriptive statistics and identified themes in free text responses to describe perspectives of telemedicine qualitatively., Results: We received 596 complete responses (85% female and 47% 41-60 years old). During the COVID-19 pandemic, 78% (467/596) of respondents used telemedicine, and 61% (283/467) of telemedicine users reported that telemedicine was as effective or more effective than an in-person visit. Younger participants and those in North America reported effectiveness and satisfaction with telemedicine at higher frequencies. Participants reported similar effectiveness to in-person visits for making medication changes and discussing disease symptoms or complications., Conclusion: Most respondents found telemedicine at least as effective as in-person visits. Participants found telemedicine to be effective for specific scenarios, such as making medication changes and discussion of disease activity. Telemedicine may continue to be of importance in the care of patients with rheumatic diseases post pandemic, but likely for specific subsets of patients for specific visit indications. Key Points • Most patients with rheumatic disease found telemedicine as effective as in-person visits, particularly for some indications., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

How to successfully integrate mental health and primary care remains a critically important question given the continued morbidity and early mortality of people with serious mental illness. This study investigated integration in a community mental health center (MHC) primarily treating people with SMI in a large, urban northeastern city where an on-site primary care center (PCC) was opened resulting in co-located mental health and primary care services being provided. Using focus groups and online surveys this study asked participants about their thoughts and interactions with the on-site PCC. Participants included staff from clinical, non-clinical, and leadership roles in the mental health center (MHC; PCC staff; and MHC clients who did not use the on-site PCC). MHC staff also offered their thoughts about and experiences with the on-site PCC one year and two years after the on-site PCC opened through an on-line survey. In both methods, staff reported limited awareness and expectations of the PCC in the first year. Staff indicated that successful care integration goes beyond co-location and peer health navigation can enhance integration. Finally, staff discussed desires for enhancing care integration and co-located services into a medical home that included communicating across medical records and providers at different agencies. Our results suggest that, in addition to the previously researched three C's of care integration (consultation, coordination, and collaboration), two more C's were essential to successful care integration: co-location and communication. Communication across medical records and providers at different agencies was an essential component of care integration, and co-location added increased ability to communicate across providers., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There are great and growing behavioral needs in the United States. The Department of Health and Human Services (HHS) already invests in many lines of research and services to address those needs. But there are opportunities for other federal agencies to provide investments as well. All federal agencies are now required to develop evidence-building plans, called Learning Agendas, per the Evidence-Based Policy Making Act. This commentary reviews the content of 2022-2026 Learning Agendas for priorities related to behavioral health across all U.S. federal agencies besides HHS. Across 4 other federal agencies and 2 cross-government plans, there are Learning Agenda priorities related to behavioral health. These priorities cover examining ways to expand access to mental health and substance use disorder treatment to veterans, Medicaid beneficiaries, and lesbian, gay, bisexual, transgender, and intersex individuals; and improving the social and emotional well-being of school children, veterans with disabilities, and veterans with military sexual trauma. Some important developing areas were not mentioned in any of the Learning Agendas, which are worth considering. These areas include new digital technologies and artificial intelligence for behavioral health, psychotropic agents, and the strong link between physical and mental health. To meet the behavioral health needs of the country, there are opportunities for inter-agency collaboration at the federal level to build evidence and incorporate new, important developments in behavioral health., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

We investigated the prognostic utility of visually estimated coronary artery calcification (VECAC) from low dose computed tomography attenuation correction (CTAC) scans obtained during SPECT/CT myocardial perfusion imaging (MPI), and assessed how it compares to coronary artery calcifications (CAC) quantified by calcium score on CTACs (QCAC). From the REFINE SPECT Registry 4,236 patients without prior coronary stenting with SPECT/CT performed at a single center were included (age: 64 ± 12 years, 47% female). VECAC in each coronary artery (left main, left anterior descending, circumflex, and right) were scored separately as 0 (absent), 1 (mild), 2 (moderate), or 3 (severe), yielding a possible score of 0-12 for each patient (overall VECAC grade zero:0, mild:1-2, moderate: 3-5, severe: >5). CAC scoring of CTACs was performed at the REFINE SPECT core lab with dedicated software. VECAC was correlated with categorized QCAC (zero: 0, mild: 1-99, moderate: 100-399, severe: ≥400). A high degree of correlation was observed between VECAC and QCAC, with 73% of VECACs in the same category as QCAC and 98% within one category. There was substantial agreement between VECAC and QCAC (weighted kappa: 0.78 with 95% confidence interval: 0.76-0.79, p < 0.001). During a median follow-up of 25 months, 372 patients (9%) experienced major adverse cardiovascular events (MACE). In survival analysis, both VECAC and QCAC were associated with MACE. The area under the receiver operating characteristic curve for 2-year-MACE was similar for VECAC when compared to QCAC (0.694 versus 0.691, p = 0.70). In conclusion, visual assessment of CAC on low-dose CTAC scans provides good estimation of QCAC in patients undergoing SPECT/CT MPI. Visually assessed CAC has similar prognostic value for MACE in comparison to QCAC., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Child and adolescent anxiety disorders (ADs) contribute to impairment in social functioning and peer relationships, exacerbating anxiety and related difficulties. The extent to which the AD treatment with the strongest evidence-base, cognitive-behavioral therapy (CBT), improves social functioning and peer relationships is unclear. In this article, we report results of the first systematic narrative review of this topic. Randomized clinical trials of CBT for child and/or adolescent ADs were included if they used at least one measure of social functioning or peer relationships as a treatment outcome. Sixteen studies met our inclusion criteria. From each study, we extracted the sample characteristics, treatment arms, social and/or peer outcome measures, and statistical findings. Results show that social functioning and/or peer relationships improved over time in the majority of studies, highlighting an important aspect of treatment efficacy beyond anxiety reduction. There were also several treatment-specific effects, but considerable variability across studies' samples, methods, and findings, makes it difficult to draw firm conclusions about which specific treatments improve specific outcomes. We recommend next steps for research to reconcile these findings, including improved operationalization and standardization of social and peer outcomes, and research on treatment specificity and mechanisms., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)