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San Francisco Bay (SFB), which supports large populations of the California native cordgrass Spartina foliosa, has been the recipient of introductions of S. alterniflora and S. densiflora. Hybrids have arisen between the native and these exotic species. Sterile F1 S. densiflora × foliosa hybrids have formed numerous times in a number of marshes, while introgressing S. alterniflora × foliosa hybrids are fully fertile and invaded widely in SFB, especially onto naturally-open low tidal flats by inundation-tolerant hybrids. Sarcocornia pacifica, pickleweed, dominates the mid-to-upper marsh zones where the hypersaline conditions that occur during the summer drought, characteristic of this climate, exclude S. foliosa. Here we report on two glasshouse experiments investigating the salinity tolerance of hybrid Spartina. Some hybrids of both origins grew well and flowered at high salinity levels while the parental species grew little and did not flower. Our results imply that mid-zone marshes are also vulnerable to invasion by salinity-tolerant Spartina hybrids. Herbicide control implemented over the last 10 years targeting both the exotic species and their hybrids have reduced their extent. However, efforts in monitoring and management of exotic Spartina and its hybrids must continue as vast areas of tidal marsh restoration are underway and planned in SFB; colonization by Spartina hybrids tolerant to inundation and/or salinity will greatly alter restoration trajectories. These concerns are all the more vital given projections of climate change and its effects on salinity and sea level rise in SFB salt marshes.

Seungtaek Choi, Andrew K LeeDepartment of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USAAbstract: Androgen deprivation therapy (ADT) is the most effective systemic treatment for prostate cancer. ADT has been shown to have a high rate of response and to improve overall survival in patients with metastatic prostate cancer. In addition, multiple studies have shown that adding ADT to external beam radiation therapy leads to improvement in cure rates and overall survival in prostate cancer patients. The most commonly used ADT is gonadotropin-releasing hormone (GnRH) agonist therapy. Although GnRH agonist therapy has significant benefits for patients with prostate cancer, it has also been shown to have significant side effects, including fatigue, hot flashes, decreased libido, decreased quality of life, obesity, diabetes mellitus, coronary artery disease, decreased bone mineral density, and increased risk of fractures. Therefore, it is crucial that the benefits of ADT be weighed against its potential adverse effects before its use.Keywords: androgen deprivation therapy, gonadotropin-releasing hormone agonists, prostate cancer

The Laryngeal Mask Airway Supreme (LMAS) is a new, single-use laryngeal mask airway with gastric access. We conducted a randomised controlled study comparing the LMAS with the reusable ProSeal Laryngeal Mask Airway (PLMA) in 70 patients undergoing general anaesthesia with paralysis for gynaecological laparoscopic surgery. Our primary outcome measure was the oropharynegal leak pressure. We also compared the two devices for ease of insertion, adequacy of ventilation and incidence of complications. Both devices had similar rates of successful insertion at the first attempt (LMAS 94% vs PLMA 91%). There was no difference in the time to establish an effective airway (LMAS 25 +/- 22 vs PLMA 24 +/- 9 seconds), although gastric tube insertion was faster for the LMAS (5 +/- 1 vs 7 +/- 3 seconds, P < 0.001). The mean oropharyngeal leak pressure in the LMAS was significantly lower than in the PLMA (27.9 +/- 4.7 vs 31.7 +/- 6.3 cmH2O, P = 0.007). This was consistent with a lower maximum tidal volume achieved with the LMAS (481 +/- 76 vs 515 +/- 63 ml, P = 0.044). We found that after 60 minutes the cuff pressure was significantly higher in the PLMA (110 +/- 21 vs 57 +/- 8 cmH2O, P < 0.001). There was no difference in the ability to provide adequate ventilation and oxygenation during anaesthesia. Complication rates were similar We conclude that the oropharyngeal leak pressure and the maximum achievable tidal volume are lower with the LMAS than with the PLMA. [ABSTRACT FROM AUTHOR]

Clinically insignificant prostate cancer, defined as at most microscopic foci of Gleason grade < or = 3 disease in the radical prostatectomy specimen, has been recognized in some low risk (PSA < 10, biopsy Gleason score < or = 6, clinical Tlc, 2a) patients with minimal biopsy cancer volume. The purpose of this study is to determine if the fraction of cancer in a single positive core biopsy could identify a subset of low risk prostate cancer patients with clinically insignificant disease. Of 1100 patients with Tlc,2 prostate cancer that consecutively underwent radical prostatectomy at Brigham and Women's Hospital between 1989 to 2000, 130 low risk patients whose diagnoses were made on the basis of a single positive core comprised the study cohort. The pathologic findings at radical prostatectomy were enumerated for men with < or = 5% of a single core involved with prostate cancer in order to determine the rate of clinically insignificant prostate cancer in this population. Estimates of PSA survival were calculated using the actuarial method of Kaplan and Meier. Pairwise comparisons were made using the log rank test. For patients with < or = 5% (n = 14) and > 5% (n = 116) involvement of a single positive core, the 4 year PSA failure free survivals were 100% vs. 89% (P = 0.048), respectively. Within the subset of patients with < or = 5% of a single core involved, 7% (1/14) met the criteria for clinically insignificant disease. However, of the remaining 93%, 3, 8, and 2 patients had pathologic stage T2a, T2b, and T3a, respectively. Eleven patients had prostatectomy Gleason scores < or = 3 + 3, two patients had pathologic Gleason scores of 3 + 4, and one patient had a positive surgical margin. Given that only 7% of low risk patients in this cohort with < or = 5% involvement of a single positive core had clinically insignificant disease, the involved core length alone cannot be used to identify patients with clinically insignificant disease. Further studies are needed in order to delineate which patients may not benefit from treatment. [ABSTRACT FROM AUTHOR]

The article features a paper which aims to describe the facilitators and barriers experience by advanced practice psychiatric nurses (APPN) in the early stages of implementing an intervention protocol for improving medication adherence in the human immunodeficiency virus/serious mental illness protocol. The results of this small-scale study intend to address the role of the APPN and examine the perceptions of practicing APPNs implementing a strict clinical protocol.

Introduction: Understanding conditions in which interventions succeed or fail is critical. The PRimary care Opioid Use Disorders treatment (PROUD) trial, a cluster-randomized hybrid study, tested whether implementation of office-based addiction treatment supported by a nurse increased medication of OUD. Six health systems each provided two primary care (PC) clinics that were randomly assigned to implement the intervention or usual care. This secondary, exploratory study used an innovative mixed methods approach to understand contextual factors that consistently distinguished intervention clinics that increased OUD treatment from those that did not., Methods: The study collected contextual information through field notes, health system debriefs, and nurse interviews. Rapid qualitative analysis using a template based on the Practical, Robust Implementation and Sustainability Model identified themes reflecting the external environment, recipients, and implementation infrastructure. The study used qualitative themes to create binary factors reflecting barriers and facilitators potentially critical to implementation success and assigned clinics a factor value of 1 if present and 0 if absent. Two clinic-level outcomes were defined: 1) significant increase in patient-years of OUD treatment from baseline to two-year follow-up; and 2) high rate of OUD treatment at two-year follow-up (≥20 per 10,000 patient-years). Coincidence analysis, a cross-case configurational method, identified difference-makers for both OUD outcomes across intervention clinics., Results: Qualitative analysis yielded 11 themes which were dichotomized and consolidated into 9 factors. Two factor values perfectly distinguished between intervention clinics with and without increased OUD treatment (outcome #1): (a) presence of strong support from PC staff and providers and (b) lack of OUD treatment in the community. Intervention clinics increased OUD treatment when either factor value was present; when both were absent, clinics did not increase treatment. Strong support from PC staff and providers was independently sufficient to achieve high rates of OUD treatment (outcome #2) while the absence of support explained low rates of treatment. Importantly, strong support from leadership was not sufficient for either outcome., Conclusion: Strong support from staff and providers consistently differentiated between clinics with increased OUD treatment across both outcomes in the PROUD trial from those without. OUD programs should consider increasing support across clinic roles., Competing Interests: Declaration of competing interest Outside of this study, Paige Wartko received funding from a research contract awarded to Kaiser Permanente Washington Health Research Institute from Syneos Health to conduct Food and Drug Administration-mandated post-marketing research on the risks of opioid analgesic use. Dr. Glass reports that Pear Therapeutics Inc. provided digital therapeutic prescriptions at no cost to Kaiser Permanente Washington during a quality improvement pilot study that he led. All other authors report no conflicts of interest., (Copyright © 2025. Published by Elsevier Inc.)

It is not well understood how neighborhood disadvantage is associated with specific domains of cognitive function and underlying brain health within older adults. Thus, the objective was to examine associations between neighborhood disadvantage, brain health, and cognitive performance, and examine whether associations were more pronounced among women. The study included 136 older adults who underwent cognitive testing and MRI. Neighborhood disadvantage was characterized using the Area Deprivation Index (ADI). Descriptive statistics, bivariate correlations, and multiple regressions were run. Multiple regressions, adjusted for age, sex, education, and depression, showed that higher ADI state rankings (greater disadvantage) were associated with poorer working memory performance ( p  < .01) and lower hippocampal volumes ( p  < .01), but not total, frontal, and white matter lesion volumes, nor visual and verbal memory performance. There were no significant sex interactions. Findings suggest that greater neighborhood disadvantage may play a role in working memory and underlying brain structure.

Objectives: Determination of hip instability associated with posterior wall acetabular fractures may be difficult. Thus, dynamic stress examination under anesthesia (EUA) was developed as a tool for guiding treatment. EUA uses positioning of the hip and application of force across the hip to detect instability. While aspects of the EUA technique seems consistently described in the literature and practiced by surgeons, some components are ill-defined. The goal of this study was to assess standardization of applied force during EUA among experienced acetabular surgeons., Methods: Fellowship-trained orthopaedic trauma surgeons with experience in acetabular fracture treatment performed EUA for posterior wall instability on an intact, fresh human cadaver. All surgeons used a similar method, and each expert performed EUA multiple times separated by a brief hiatus. The maximum force applied along the femur's vector in Newtons (N) was measured using a hand-held digital dynamometer., Results: The EUAs of 19 surgeons were evaluated. Five surgeons had been practicing for <5 years, six for 6 to 10 years, five for 11 to 20 years, and three for >20 years. The mean force applied during EUA was 173N, with a notable variability between surgeons (range, 77-368N). Notable variability was also observed between sequential measures of individual surgeons with six surgeons (31.6%) having a >50N range on repeat trials., Conclusion: This is the first study to report force applied during an EUA to assess for posterior wall acetabular fracture stability. Notable variability was observed among surgeons performing the examination and in repeated examinations by the same surgeon, suggesting that results of EUA may be surgeon-dependent. Further study is needed to determine what optimal applied force should be used to assess hip stability after a posterior wall acetabular fracture., Level of Evidence: Level V. An assessment of a diagnostic tool., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Importance: The Primary Care Opioid Use Disorders (PROUD) treatment trial was a 2-year implementation trial that demonstrated the Massachusetts office-based addiction treatment (OBAT) model of nurse care management for opioid use disorder (OUD) increased OUD treatment in the 2 years after implementation began (8.2 more patient-years of OUD treatment per 10 000 primary care patients). The intervention was continued for a third year, permitting evaluation of 3-year outcomes., Objective: To compare OUD medication treatment in intervention and usual care clinics over 3 years of implementation., Design, Setting, and Participants: This is a preplanned secondary analysis of a cluster randomized implementation trial, conducted in 6 health systems in 5 states (2 primary care clinics per health system) with clinic randomization stratified by system (assignment notification February 28, 2018 [August 31, 2018, in 1 system]). Data were obtained from electronic health records and insurance claims. Eligible patients were those aged 16 to 90 years visiting intervention or usual care clinics from 3 years before to 2 years after randomization. Patients new to clinics during the third year after randomization could not be included because COVID-19-era transitions to virtual care precluded assignment of patients to clinics. Data analysis occurred from November 2023 to September 2024., Intervention: Clinics were randomized to intervention or care as usual. Intervention included 3 implementation components: salary for 1 full-time OBAT nurse per intervention clinic; training and ongoing technical assistance for nurses; and 3 or more primary care buprenorphine prescribers., Main Outcome and Measures: Patient-years of OUD treatment (buprenorphine or extended-release naltrexone) per 10 000 primary care patients in the 3 years postrandomization. Mixed-effect models adjusted for baseline values of the outcome and included a health system-specific random intercept to account for correlation of clinic pairs within a system., Results: Prerandomization, a total of 290 071 primary care patients were seen, including 130 618 in intervention clinics (mean [SD] age, 48.6 [17.7] years; mean [SD] female, 59.3% [4.0%]) and 159 453 in usual care clinics (mean [SD] age, 47.2 [17.5] years; mean [SD] female, 64.0% [5.3%]). Over 3 years postrandomization, intervention clinics provided 19.7 (95% CI, 11.1-28.4) more patient-years of OUD treatment per 10 000 primary care patients compared with usual care clinics., Conclusions: In this secondary analysis of the PROUD cluster randomized trial, after an added year of the intervention, OUD treatment continued to increase in intervention clinics compared with usual care. The treatment increase over 3 years exceeded that of the first 2 years, suggesting that implementation of the Massachusetts OBAT model leads to ongoing increases in OUD treatment among primary care patients in the third year of implementation., Trial Registration: ClinicalTrials.gov Identifier: NCT03407638.

The precise organization of pre- and postsynaptic terminals is crucial for normal synaptic function in the brain. In addition to its canonical role as a neurotrophin-3 receptor tyrosine kinase, postsynaptic TrkC promotes excitatory synapse organization through interaction with presynaptic receptor-type tyrosine phosphatase PTPσ. To isolate the synaptic organizer function of TrkC from its role as a neurotrophin-3 receptor, we generated mice carrying TrkC point mutations that selectively abolish PTPσ binding. The excitatory synapses in mutant mice had abnormal synaptic vesicle clustering and postsynaptic density elongation, more silent synapses, and fewer active synapses, which additionally exhibited enhanced basal transmission with impaired release probability. Alongside these phenotypes, we observed aberrant synaptic protein phosphorylation, but no differences in the neurotrophin signaling pathway. Consistent with reports linking these aberrantly phosphorylated proteins to neuropsychiatric disorders, mutant TrkC knock-in mice displayed impaired social responses and increased avoidance behavior. Thus, through its regulation of synaptic protein phosphorylation, the TrkC-PTPσ complex is crucial for the maturation, but not formation, of excitatory synapses in vivo., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

Background: Primary care encounters are common among patients at risk for suicide., Objective: To evaluate the effectiveness of implementing population-based suicide care (SC) in primary care for suicide attempt prevention., Design: Secondary analysis of a stepped-wedge, cluster randomized implementation trial. (ClinicalTrials.gov: NCT02675777)., Setting: 19 primary care practices within a large health care system in Washington State, randomly assigned launch dates., Patients: Adult patients (aged ≥18 years) with primary care visits from January 2015 to July 2018., Intervention: Practice facilitators, electronic medical record (EMR) clinical decision support, and performance monitoring supported implementation of depression screening, suicide risk assessment, and safety planning., Measurements: Clinical practice and patient measures relied on EMR and insurance claims data to compare usual care (UC) and SC periods. Primary outcomes included documented safety planning after population-based screening and suicide risk assessment and suicide attempts or deaths (with self-harm intent) within 90 days of a visit. Mixed-effects logistic models regressed binary outcome indicators on UC versus SC, adjusted for randomization stratification and calendar time, accounting for repeated outcomes from the same site. Monthly outcome rates (percentage per 10 000 patients) were estimated by applying marginal standardization., Results: During UC, 255 789 patients made 953 402 primary care visits and 228 255 patients made 615 511 visits during the SC period. The rate of safety planning was higher in the SC group than in the UC group (38.3 vs. 32.8 per 10 000 patients; rate difference, 5.5 [95% CI, 2.3 to 8.7]). Suicide attempts within 90 days were lower in the SC group than in the UC group (4.5 vs. 6.0 per 10 000 patients; rate difference, -1.5 [CI, -2.6 to -0.4])., Limitation: Suicide care was implemented in combination with care for depression and substance use., Conclusion: Implementation of population-based SC concurrent with a substance use program resulted in a 25% reduction in the suicide attempt rate in the 90 days after primary care visits., Primary Funding Source: National Institute of Mental Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0024.

Background: Studies have shown apolipoprotein E (APOE) genotype disclosure to be safe and well-tolerated in cognitively unimpaired (CU) older adults. This study aimed to examine the effect of the disclosure process on decisions about future directives and health behaviors in community-dwelling CU older adults from the Butler Alzheimer's Prevention Registry (BAPR)., Methods: CU APOE E4 non-carriers (n = 106) and carriers (n = 80) aged 58-78 completed in-person psychological readiness screening to undergo APOE disclosure. Follow-up assessments were completed online 3 days, 6 weeks, and 6 months post-disclosure. The primary outcomes were future directives, dietary habits, and physical activity scores., Results: Disclosure was associated with decision making on future directives in E4 carriers ( t = 3.59, P = .01) at 6 months compared to baseline, but not non-carriers. Family history of memory impairment, SCD endorsement, and education consistently predicted scores on future directives. A significant interaction between E4+ and SCD endorsement on future directive scores was noted (OR = 163.06, 9.5-2,799.8). E4 + carrier status was associated with physical activity ( W = 60,148, P = .005) but not dietary habits scores., Conclusions: Our findings indicate that disclosure led to a change in future directives but not protective health behaviors, specifically in E4 carriers. Future work will explore whether pairing disclosure with education about the role of lifestyle factors in AD risk and providing guidelines on making risk-lowering lifestyle modifications as an intervention approach leads to positive change., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Plasma biomarkers have recently emerged for the diagnosis, assessment, and disease monitoring of Alzheimer's disease (AD), but have yet to be fully validated in preclinical AD. In addition to AD pathologic plasma biomarkers (amyloid-β (Aβ) and phosphorylated tau (p-tau) species), a proteomic panel can discriminate between symptomatic AD and cognitively unimpaired older adults in a dementia clinic population., Objective: Examine the added value of a plasma proteomic panel, validated in symptomatic AD, over standard AD pathologic plasma biomarkers and demographic and genetic (apolipoprotein ( APOE ) ɛ4 status) risk factors in detecting preclinical AD., Methods: 125 cognitively unimpaired older adults (mean age = 66 years) who completed Aβ PET and plasma draw were analyzed using multiple regression with Aβ PET status (positive versus negative) as the outcome to determine the best fit for predicting preclinical AD. Model 1 included age, education, and gender. Model 2 and 3 added predictors APOE ɛ4 status (carrier versus non-carrier) and AD pathologic blood biomarkers (Aβ 42/40 ratio, p-tau181), respectively. Random forest modeling established the 5 proteomic markers from the proteomic panel that best predicted Aβ PET status, and these markers were added in Model 4., Results: The best model for predicting Aβ PET status included age, years of education, APOE ɛ4 status, Aβ 42/40 ratio, and p-tau181. Adding the top 5 proteomic markers did not significantly improve the model., Conclusions: Proteomic markers in plasma did not add predictive value to standard AD pathologic plasma biomarkers in predicting preclinical AD in this sample., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JA receives funding from R21AG074153, R01AG079241, and the Warren Alpert Foundation. AL receives funding from R01AG068990, U24AG057437, U01AG057195 and the Alzheimer's Association.

Despite the association of neighborhood quality with poorer adult health, limited research has explored the association between neighborhood disadvantage, e.g. Area Deprivation Index (ADI), and older Black adults' health, prospectively. This observational study examined the association between ADI and changes in longitudinal physical health within older Black adults. The analytic sample ( n  = 317) included data from waves 1 & 2 of the Baltimore Study of Black Aging: Patterns of Cognitive Aging (BSBA-PCA). Study variables included the Area Deprivation Index (ADI), objective (e.g. average heart rate) and subjective (e.g. activities of daily living) measures of physical health. Multiple linear regression models were conducted controlling for sociodemographic and social support characteristics. Participants living in more disadvantaged neighborhoods, based on national and state ADIs, were more likely to have a decreasing heart rate even after adjusting for covariates. Likewise, participants reporting increasing levels of ADL difficulty were living in a neighborhood with greater disadvantage based on national and state ADI rankings. Significant social support received and ADI (national and state) interactions were observed for average heart rate. The findings suggest that research on the effect of neighborhood quality and social support can enhance our understanding of its impact on older Black adults' health prospectively.

Extracellular vesicles (EVs) show promise in drug loading and delivery for medical applications. However, the lack of scalable manufacturing processes hinders the generation of clinically suitable quantities, thereby impeding the translation of EV-based therapies. Current EV production relies heavily on non-physiological two-dimensional (2D) cell culture or bioreactors, requiring significant resources. Additionally, EV-derived ribonucleic acid cargo in three-dimensional (3D) and 2D culture environments remains largely unknown. In this study, we optimized the biofabrication of 3D auxetic scaffolds encapsulated with human embryonic kidney 293 T (HEK293 T) cells, focusing on enhancing the mechanical properties of the scaffolds to significantly boost EV production through tensile stimulation in bioreactors. The proposed platform increased EV yields approximately 115-fold compared to conventional 2D culture, possessing properties that inhibit tumor progression. Further mechanistic examinations revealed that this effect was mediated by the mechanosensitivity of YAP/TAZ. EVs derived from tensile-stimulated HEK293 T cells on 3D auxetic scaffolds demonstrated superior capability for loading doxorubicin compared to their 2D counterparts for cancer therapy. Our results underscore the potential of this strategy for scaling up EV production and optimizing functional performance for clinical translation., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: The Youth Health Ambassador Programme (YHAP) is a health educational program aimed at empowering youths to become health ambassadors in the community through raising their health awareness and training them in primary health prevention. This study evaluates the effectiveness of YHAP in improving the knowledge, attitudes, and practices (KAP) of participants in physical and mental health., Materials and Methods: This study followed a single-group quasi-experimental design, with a pre- and postworkshop KAP survey. Participants were junior college (JC) and polytechnic students in Singapore enrolled in YHAP. In total, 131 responses were analyzed for changes in KAP for physical and mental health before and after the program. This article also studied the participants' barriers to educating others, including environment factors, intrinsic factors, and receptiveness of the target audience., Results: Mean scores of all six KAP domains increased from the preworkshop survey to the postworkshop survey, with significant improvements ( P < 0.05) in all domains except mental health knowledge. Individually, 16 out of 29 questions in the KAP sections had a significant increment in mean score after the program ( P < 0.05). Mean scores for intrinsic barriers also decreased significantly ( P < 0.001) postintervention, indicating that participants were less likely to agree that intrinsic factors were a barrier to educating people around them about health postintervention., Conclusion: YHAP is effective in improving the KAP of physical health and the attitudes and practices of mental health JC and polytechnic students and may reduce the effect of intrinsic barriers that participants face when teaching others., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Education and Health Promotion.)

Background: Patients with opioid use disorder (OUD) have increased emergency and hospital utilization. The PROUD trial showed that implementation of office-based addiction treatment (OBAT) increased OUD medication treatment compared to usual care, but did not decrease acute care utilization in patients with OUD documented pre-randomization (clinicaltrials.gov/study/NCT03407638). This paper reports secondary emergency and hospital utilization outcomes in patients with documented OUD in the PROUD trial., Methods: This cluster-randomized implementation trial was conducted in 12 clinics from 6 diverse health systems (March 2015-February 2020). Patients who visited trial clinics and had an OUD diagnosis within 3 years pre-randomization were included in primary analyses; secondary analyses added patients with OUD who were new to the clinic or with newly-documented OUD post-randomization. Outcomes included days of emergency care and hospital utilization over 2 years post-randomization. Explanatory outcomes included measures of OUD treatment. Patient-level analyses used mixed-effect regression with clinic-specific random intercepts., Results: Among 1988 patients with documented OUD seen pre-randomization (mean age 49, 53 % female), days of emergency care or hospitalization did not differ between intervention and usual care; OUD treatment also did not differ. In secondary analyses among 1347 patients with OUD post-randomization, there remained no difference in emergency or hospital utilization despite intervention patients receiving 32.2 (95 % CI 4.7, 59.7) more days of OUD treatment relative to usual care., Conclusions: Implementation of OBAT did not reduce emergency or hospital utilization among patients with OUD, even in the sample with OUD first documented post-randomization in whom the intervention increased treatment., Competing Interests: Declaration of Competing Interest All authors reviewed and approved the final article. Jennifer F. Bobb has no disclosures. Andrea Altschuler has no disclosures. Hongxiang Qiu has no disclosures. Abigail G. Matthews has no disclosures. Jennifer McCormack has no disclosures. Dr. Campbell has received support managed through her institution from the Industry PMR Consortium, a consortium of companies conducting post marketing studies required by the Food and Drug Administration that assess risks related to opioid analgesic use. Outside of this study, Paige Wartko received funding in the past year from a contract awarded to the Harvard Department of Population Medicine from GlaxoSmithKline to assess medication use in pregnancy and funding from a research contract awarded to Kaiser Permanente Washington Health Research Institute from Syneos Health to conduct Food and Drug Administration-mandated post-marketing research on the risks of opioid analgesic use. Dr. Saxon has received an honorarium from Indivior, Inc., travel support from Alkermes, Inc., and royalties from UpToDate. Onchee Yu received research grant funded by Bayer. Jeffrey Samet has no disclosures. Dr. Boudreau previously received funding from a research contract awarded to Kaiser Permanente Washington Health Research Institute (KPWHRI) from Syneos Health to conduct Food and Drug Administration-mandated post-marketing research on the risks of opioid analgesic use. Dr. Boudreau was an employee of KPWHRI at the time the study was conducted but is now an employee of Genentech, Inc. Amy K. Lee has no disclosures Dr. Glass reports that Pear Therapeutics Inc provided digital therapeutic prescriptions at no cost to Kaiser Permanente Washington during a quality improvement pilot study that he led. Kathrine A. Bradley has no disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

COVID-19 spread across the nation with Black Americans experiencing twice of the prevalence of deaths than White Americans. Black American college students are facing a unique set of biopsychosocial costs including less retention and poorer mental health. Therefore, the purpose of this study was to examine how Historically Black College or University (HBCU) students contextualize COVID-19. Interviews were conducted with 19 participants and lasted 40-60 minutes. They discussed topics including: their COVID-19 knowledge, precautionary measures, and barriers and promoters of school success were covered. Data were coded through semi-open coding and discussed among the research team. Responses were summarized by eight themes: emotional responses, colorblind rhetoric, lack of healthcare, essential work, distrust for the medical field, barriers to precautions like supply shortages and environmental factors, and poor baseline health. These findings may be used to develop interventions that moderate the impact of COVID-19 and future pandemics on mental health.

Background: Proton therapy (PT) has unique biologic properties with excellent clinical outcomes for the management of localized prostate cancer. Here, we aim to characterize the toxicity of PT for patients with localized prostate cancer and propose mitigation strategies using a large institutional database., Methods: We reviewed medical records of 2772 patients with localized prostate cancer treated with definitive PT between May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 849]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 117]. Descriptive statistics and Kaplan-Meier estimates assessed toxicity and freedom from biochemical relapse (FFBR)., Results: Median follow-up was 7.0 years. The median dose was 78 Gy(RBE)(range: 72-79.2 Gy) in 2.0 Gy(RBE) fractions; 63 % of patients received 78 Gy(RBE) in 39 fractions, and 29 % received 76 Gy(RBE) in 38 fractions. Overall rates of late grade ≥3 GU and GI toxicity were 0.87 % and 1.01 %, respectively. Two patients developed grade 4 late GU toxicity and seven patients with grade 4 late GI toxicity. All patients experiencing severe late grade 4 toxicities were treated to 78 Gy(RBE) in 39 fractions with 80 Gy(RBE) dose to the anterior rectal wall and/or bladder neck. The 10-year FFBR rates for patients with LR to U-IR disease were compared between those treated with 76 and 78 Gy(RBE); the rates were 94.5 % (95 % confidence interval [CI] 92.4-96.0 %) and 93.2 % (95 % CI 91.3-95.7 %), respectively (log-rank p = 0.22)., Conclusions: Proton therapy is associated with low rates of late grade ≥3 GU and GI toxicity. While rare, late grade 4 toxicities occurred in nine (0.3 %) patients. De-escalation to a total dose of 76 Gy(RBE) yields excellent clinical outcomes for patients with LR to U-IR disease with the potential for significant reductions in grade ≥3 late toxicity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommends the paper-based or computerized Alcohol Symptom Checklist to assess alcohol use disorder (AUD) symptoms in routine care when patients report high-risk drinking. However, it is unknown whether Alcohol Symptom Checklist response characteristics differ when it is administered online (eg, remotely via an online electronic health record [EHR] patient portal before an appointment) versus in clinic (eg, on paper after appointment check-in)., Objective: This study evaluated the psychometric performance of the Alcohol Symptom Checklist when completed online versus in clinic during routine clinical care., Methods: This cross-sectional, psychometric study obtained EHR data from the Alcohol Symptom Checklist completed by adult patients from an integrated health system in Washington state. The sample included patients who had a primary care visit in 2021 at 1 of 32 primary care practices, were due for annual behavioral health screening, and reported high-risk drinking on the behavioral health screen (Alcohol Use Disorder Identification Test-Consumption score ≥7). After screening, patients with high-risk drinking were typically asked to complete the Alcohol Symptom Checklist-an 11-item questionnaire on which patients self-report whether they had experienced each of the 11 AUD criteria listed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) over a past-year timeframe. Patients could complete the Alcohol Symptom Checklist online (eg, on a computer, smartphone, or tablet from any location) or in clinic (eg, on paper as part of the rooming process at clinical appointments). We examined sample and measurement characteristics and conducted differential item functioning analyses using item response theory to examine measurement consistency across these 2 assessment modalities., Results: Among 3243 patients meeting eligibility criteria for this secondary analysis (2313/3243, 71% male; 2271/3243, 70% White; and 2014/3243, 62% non-Hispanic), 1640 (51%) completed the Alcohol Symptom Checklist online while 1603 (49%) completed it in clinic. Approximately 46% (752/1640) and 48% (764/1603) reported ≥2 AUD criteria (the threshold for AUD diagnosis) online and in clinic (P=.37), respectively. A small degree of differential item functioning was observed for 4 of 11 items. This differential item functioning produced only minimal impact on total scores used clinically to assess AUD severity, affecting total criteria count by a maximum of 0.13 criteria (on a scale ranging from 0 to 11)., Conclusions: Completing the Alcohol Symptom Checklist online, typically prior to patient check-in, performed similarly to an in-clinic modality typically administered on paper by a medical assistant at the time of the appointment. Findings have implications for using online AUD symptom assessments to streamline workflows, reduce staff burden, reduce stigma, and potentially assess patients who do not receive in-person care. Whether modality of DSM-5 assessment of AUD differentially impacts treatment is unknown., (©Theresa E Matson, Amy K Lee, Malia Oliver, Katharine A Bradley, Kevin A Hallgren. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.07.2024.)

Introduction: Examination under anesthesia (EUA) (stress fluoroscopy) is commonly done after pelvic ring injury to identify occult instability because unstable disruptions may displace causing morbidity. The force applied during EUA for these injuries has not been standardized. The purpose of this study was to examine the forces used during the EUA by experienced orthopaedic trauma pelvic surgeons., Methods: Orthopaedic traumatologists performed simulated EUA on a cadaver at two North American pelvis and acetabular courses using internal rotation (IR), external rotation, and push-pull maneuvers while wearing a handheld dynamometer to measure force. All surgeons used a comparable method, and each performed EUA multiple times. Maximum forces were measured in Newton (N)., Results: Eighteen surgeons participated. Four had been practicing for <5 years, six for 5 to 10 years, six for 11 to 20 years, and two for >20 years. Surgeons applied a force ranging from 40.4 to 374.9 N during IR, 72.9 to 338.4 N during external rotation, and 25 to 323 N during push-pull, with notable variability seen between surgeons. Three surgeons (18%) had >50-N variability on serial trials of a single EUA maneuver (IR)., Discussion: This is the first study evaluating the forces applied during pelvic EUA used to assess ring stability. Notable variability existed among surgeons performing EUA and in serial examinations by the same surgeon. Additional study is needed to standardize the displacement measured and threshold for instability that guides management., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Background: To assess the clinical outcomes and identify the ideal indication for implementing dorsal distal radioulnar joint (DRUJ) capsular imbrication after triangular fibrocartilage complex (TFCC) repair in cases of DRUJ instability., Methods: We conducted a retrospective study on patients who underwent arthroscopic TFCC repair between 2016 and 2021. Inclusion criteria comprised a symptomatic ulna fovea sign for over 6 months and dorsal DRUJ subluxation on magnetic resonance imaging. A total of 225 patients were divided into two groups: Group 1 (135 cases) with a negative ballottement test after "Cross-form TFCC repair" (CR) and Group 2 (90 cases) with a positive ballottement test after "Cross-form TFCC repair" and augmented DRUJ stability through dorsal DRUJ capsular imbrication (CR + DCI). Pain visual analog scale score (VAS), grip strength, modified Mayo Wrist Score (MMWS), wrist range of motion (ROM), and patient-reported outcomes (PROMs) were assessed for a minimum of 3 years postoperatively., Results: Both groups showed significant improvements in pain VAS score, grip strength, wrist ROM, MMWS, and PROMs between the preoperative and postoperative periods (all P < 0.05). Recurrent DRUJ instability occurred in 3.7% and 1.1% of patients in the "CR" and "CR + DCI" groups, respectively, with a significant difference. Despite the "CR + DCI" group initially exhibiting inferior ROM compared with the "CR" group, subsequently, no significant difference was noted between them., Conclusions: Dorsal DRUJ capsular imbrication effectively reduces postoperative DRUJ instability rates, enhances grip strength, and maintains wrist ROM in patients with a positive intra-operative ballottement test after arthroscopic TFCC repair., (© 2024. The Author(s).)

Background: Medulloblastoma (MB) is the most malignant childhood brain cancer. Group 3 MB subtype accounts for about 25% of MB diagnoses and is associated with the most unfavorable outcomes. Herein, we report that more than half of group 3 MB tumors express melanoma antigens (MAGEs), which are potential prognostic and therapeutic markers. MAGEs are tumor antigens, expressed in several types of adult cancers and associated with poorer prognosis and therapy resistance; however, their expression in pediatric cancers is mostly unknown. The aim of this study was to determine whether MAGEs are activated in pediatric MB., Methods: To determine MAGE frequency in pediatric MB, we obtained formalin-fixed paraffin-embedded tissue (FFPE) samples of 34 patients, collected between 2008 - 2015, from the Children's Medical Center Dallas pathology archives and applied our validated reverse transcription quantitative PCR (RT-qPCR) assay to measure the relative expression of 23 MAGE cancer-testis antigen genes. To validate our data, we analyzed several published datasets from pediatric MB patients and patient-derived orthotopic xenografts, totaling 860 patients. We then examined how MAGE expression affects the growth and oncogenic potential of medulloblastoma cells by CRISPR-Cas9- and siRNA-mediated gene depletion., Results: Our RT-qPCR analysis suggested that MAGEs were expressed in group 3/4 medulloblastoma. Further mining of bulk and single-cell RNA-sequencing datasets confirmed that 50-75% of group 3 tumors activate a subset of MAGE genes. Depletion of MAGEAs, B2, and Cs alter MB cell survival, viability, and clonogenic growth due to decreased proliferation and increased apoptosis., Conclusions: These results indicate that targeting MAGEs in medulloblastoma may be a potential therapeutic option for group 3 medulloblastomas., Key Points: Several Type I MAGE CTAs are expressed in >60% of group 3 MBs. Type I MAGEs affect MB cell proliferation and apoptosis. MAGEs are potential biomarkers and therapeutic targets for group 3 MBs., Importance of the Study: This study is the first comprehensive analysis of all Type I MAGE CTAs ( MAGEA , -B , and -C subfamily members) in pediatric MBs. Our results show that more than 60% of group 3 MBs express MAGE genes, which are required for the viability and growth of cells in which they are expressed. Collectively, these data provide novel insights into the antigen landscape of pediatric MBs. The activation of MAGE genes in group 3 MBs presents potential stratifying and therapeutic options.

Objective: Determine whether continuous glucose monitor (CGM) metrics can provide actionable advance warning of an emergency department (ED) visit or hospitalization for hypoglycemic or hyperglycemic (dysglycemic) events. Research Design and Methods: Two nested case-control studies were conducted among insulin-treated diabetes patients at Kaiser Permanente, who shared their CGM data with their providers. Cases included dysglycemic events identified from ED and hospital records (2016-2021). Controls were selected using incidence density sampling. Multiple CGM metrics were calculated among patients using CGM >70% of the time, using CGM data from two lookback periods (0-7 and 8-14 days) before each event. Generalized estimating equations were specified to estimate odds ratios and C-statistics. Results: Among 3626 CGM users, 108 patients had 154 hypoglycemic events and 165 patients had 335 hyperglycemic events. Approximately 25% of patients had no CGM data during either lookback; these patients had >2 × the odds of a hypoglycemic event and 3-4 × the odds of a hyperglycemic event. While several metrics were strongly associated with a dysglycemic event, none had good discrimination. Conclusion: Several CGM metrics were strongly associated with risk of dysglycemic events, and these can be used to identify higher risk patients. Also, patients who are not using their CGM device may be at elevated risk of adverse outcomes. However, no CGM metric or absence of CGM data had adequate discrimination to reliably provide actionable advance warning of an event and thus justify a rapid intervention.

Background: This study aimed to examine the association between risk of brain tumors and radiofrequency (RF) exposure from mobile phones among young people in Korea and Japan., Methods: This case-control study of brain tumors in young people was conducted in Korea and Japan under the framework of the international MOBI-Kids study. We included 118 patients diagnosed with brain tumors between 2011 and 2015 and 236 matched appendicitis controls aged 10-24 years. Information on mobile phone use was collected through face-to-face interviews. A detailed RF exposure algorithm, based on the MOBI-Kids algorithm and modified to account for the specificities of Japanese and Korean phones and networks, was used to calculate the odds ratios (ORs) for total cumulative specific energy using conditional logistic regression., Results: The adjusted ORs in the highest tertile of cumulative call time at 1 year before the reference date were 1.61 (95% confidence interval [CI], 0.72-3.60) for all brain tumors and 0.70 (95% CI, 0.16-3.03) for gliomas, with no indication of a trend with exposure. The ORs for glioma specifically, were below 1 in the lowest exposure category., Conclusion: This study provided no evidence of a causal association between mobile phone use and risk of brain tumors as a whole or of glioma specifically. Further research will be required to evaluate the impact of newer technologies of communication in the future.

Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD + ) levels are hallmarks of skeletal muscle ageing and sarcopenia 1-3 , but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid 4 , NAD + levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD + pool and increases NAD + levels in Caenorhabditis elegans, mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss-Handler pathway 5,6 across models. In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD + -dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD + -boosting strategy with therapeutic potential for age-associated muscle decline., (© 2024. The Author(s).)

Background: Narrative discourse, or storytelling, is used in daily conversation and requires higher-level language and social communication skills that are not always captured by standardised assessments of language. Many autistic individuals and individuals with fetal alcohol spectrum disorders (FASD) have difficulties with both social communication and language skills, and narrative discourse analysis offers an ecologically relevant approach to assessing those challenges., Aims: This study investigated narrative discourse in individuals with autism and FASD, as well as an age- and sex-matched comparison group., Methods and Procedures: Narratives from 45 adolescents and adults, 11 with autism, 11 with FASD and 23 age- and sex-matched comparison participants were elicited using a wordless storybook. They were then transcribed orthographically, formatted to the Systematic Analyses of Language Transcript (SALT) convention and scored based on the SALT Narrative Scoring Scheme (NSS), a standardised language analysis protocol. In addition to the NSS total score, which assesses the overall structure and cohesion of the narratives produced, local and global measures of language ability were also employed. The local language measures included the number of mental state and temporal relation terms produced, while the global language measures included mean length of utterance, total different words, total words, total utterances, rate of speech, the number of mazes (e.g., repetitions, 'um', 'uh' or self-corrections) per total word and the NSS total score., Outcomes and Results: Using the SALT Language Sample Analysis tool, our results revealed that on global language measures, group differences were found on rate of speech, number of mazes per total words and the description of conflict/resolution in the narratives produced. The autism group produced significantly more mazes per total word and scored higher on the NSS conflict/resolution category score compared to the FASD and comparison groups. Both the autism and FASD groups spoke at a lower rate than the comparison group. On local language measures of narrative production, all groups were comparable, on average., Conclusions and Implications: While many aspects of narrative discourse in the autism and FASD groups were similar to each other and to the comparison group, we observed group differences on global measures of narrative production and significant individual variability within groups, suggesting that narrative abilities considered at an individual level may provide important clinical information for intervention planning. Future research should also consider additional variables that influence narrative discourse, such as motivation, distractibility or decision-making of individual participants., What This Paper Adds: What is already known on the subject Narrative discourse, or storytelling, is used in daily conversational interactions and reveals higher-level language skills that may not be well captured by standardised assessments of language. Many autistic individuals and individuals with fetal alcohol spectrum disorders (FASD) show difficulty with pragmatic and expressive language skills. What this paper adds to existing knowledge We found that many aspects of the narratives produced by the adolescents/young adults in the autism and FASD groups were comparable to each other and to the neurotypical group. However, the groups differed on three global measures of narrative production: rate of speech, number of mazes per total words and the description of conflict/resolution in the narratives produced. Also, significant variability was observed within groups, suggesting that narrative abilities should be considered at an individual level as opposed to their clinical groups. What are the potential or actual clinical implications of this work? This study showed that narrative discourse is an appropriate task that can be added to routine clinical assessments of language abilities in autistic adolescents/young adults as well as those with FASD or typical development and has the potential to reveal higher-level, real-world language skills. An important clinical implication of this study is that narrative language abilities should be considered at an individual level and individual-tailored interventions based on ability level due to the variability observed across individuals., (© 2023 Royal College of Speech and Language Therapists.)

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments., Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization., Design, Setting, and Participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after., Intervention: The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine., Main Outcomes and Measures: The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up., Results: During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70)., Conclusions and Relevance: The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD., Trial Registration: ClinicalTrials.gov Identifier: NCT03407638.

Physical activity and exercise (PAE) improve quality of life and reduce the effects of chronic diseases. Primary care physicians (PCPs) play an important role to encourage PAE in patients. We aim to assess PCPs' current PAE consultation practices and their enablers/barriers in daily clinical practice. We had 64 PCPs (age [35.3 ​± ​4.7] y, 47 women) that completed self-administered questionnaires on PAE consultation practices, training, and confidence levels. PCPs ( n  ​= ​42) also completed the International Physical Activity Questionnaire-Short Form to assess their physical activity (PA) levels. We conducted correlation, one-way analysis of variance and a linear regression to assess the associations between enablers, barriers and PA levels to PAE consultation practices. On average, PCPs consulted on PAE in 49.7% of their daily clinical appointments. Majority of PCPs (70%) strongly agreed that more PAE knowledge were needed to increase consultation practices. Top three barriers related ( p  ​< ​0.001) to practices were lack of PAE education ( r  ​= ​0.47), patients' preference of pharmaceutical interventions ( r  ​= ​0.45) and lack of continuing education in PAE for PCPs ( r  ​= ​0.37). Physically active PCPs (health-enhancing PA levels, n  ​= ​6) gave significantly more daily consultations in PAE, 73.2% ​± ​21.9%, compared to inactive PCPs ( n  ​= ​13), 37.4% ​± ​22.8% ( p  ​= ​0.013). In our regression output, PCPs who had higher PA levels consulted more on PAE daily ( R 2  ​= ​0.38, p  ​< ​0.001) while controlling for age. Conclusion, PCPs require more knowledge on PAE and need be physically active themselves to increase PAE consultation for patients in their daily practice. Medical education should consider including more PA and exercise topics that may benefit both physicians and their patients., Competing Interests: None of authors have any conflicts and interest regarding this manuscript submission., (© 2023 Chengdu Sport University. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)