Association of Genomic Prostate Score at positive margin with recurrence after radical prostatectomy.

OBJECTIVES: To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical prostatectomy (RP) for its association with risk of subsequent biochemical recurrence (BCR). PATIENTS AND METHODS: We designed a case-cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin-fixed paraffin-embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case-cohort design. RESULTS: In univariable analysis, every 20-unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11-2.19; P = 0.011). The study is limited by its retrospective and single institution design. CONCLUSIONS: The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision-making regarding adjuvant therapy after RP.

CAR T cell Toxicities: Bedside to Bench - How Novel Toxicities Inform Laboratory Investigations.

Multiple chimeric antigen receptor (CAR) T cell therapies are FDA approved, and several are under development. While effective for some cancers, toxicities remain a limitation. The most common toxicities, i.e. cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), are well described. With increasing utilization, providers worldwide are reporting on other emergent, and often complicated toxicities. Given the evolving toxicity profiles and urgent need to catalogue these emerging and emergent CAR T toxicities and describe management approaches, the American Society of Hematology Subcommittee on Emerging Gene and Cell Therapies organized the first Scientific Workshop on CAR T cell toxicities during the annual society meeting. The workshop functioned to 1) aggregate reports of CAR T emergent toxicities, including movement disorders after BCMA CAR T, coagulation abnormalities, and prolonged cytopenias; 2) disseminate bedside to bench efforts elucidating pathophysiological mechanisms of CAR-T toxicities, including the intestinal microbiota and systemic immune dysregulation; and 3) highlight gaps in the availability of clinical tests such as cytokine measurements, which could be utilized to expand our knowledge around the monitoring of toxicities. Key themes emerged. First, while clinical manifestations may develop before the pathophysiologic mechanisms are understood, these must be studied to aid in the detection and prevention of such toxicities. Second, systemic immune dysregulation appears central to these emergent toxicities and research is needed to elucidate links between tumor, CAR T, and microbiota. Finally, there was consensus around an urgency to create a repository to capture emergent CAR-T toxicities and the real-world management.

Phenotyping revealed tolerance traits and genotypes for acidity and aluminum toxicity in European Vicia faba L.

Soil acidity is a global issue; soils with pH <4.5 are widespread in Europe. This acidity adversely affects nutrient availability to plants; pH levels <5.0 lead to aluminum (Al3+) toxicity, a significant problem that hinders root growth and nutrient uptake in faba bean (Vicia faba L.) and its symbiotic relationship with Rhizobium. However, little is known about the specific traits and tolerant genotypes among the European faba beans. This study aimed to identify response traits associated with tolerance to root zone acidity and Al3+ toxicity and potentially tolerant genotypes for future breeding efforts. Germplasm survey was conducted using 165 genotypes in a greenhouse aquaponics system. Data on the root and shoot systems were collected. Subsequently, 12 genotypes were selected for further phenotyping in peat medium, where data on physiological and morphological parameters were recorded along with biochemical responses in four selected genotypes. In the germplasm survey, about 30% of genotypes showed tolerance to acidity and approximately 10% exhibited tolerance to Al3+, while 7% showed tolerance to both. The phenotyping experiment indicated diverse morphological and physiological responses among treatments and genotypes. Acid and Al3+ increased proline concentration. Interaction between genotype and environment was observed for ascorbate peroxidase activity, malondialdehyde, and proline concentrations. Genomic markers associated with acidity and acid+Al3+-toxicity tolerances were identified using GWAS analysis. Four faba bean genotypes with varying levels of tolerance to acidity and Al3+ toxicity were identified.

Alcohol Use Disorder and HIV Risk in a National Survey of Men Who Have Sex with Men in Ukraine.

BACKGROUND: Problematic alcohol consumption is associated with risk behaviors associated with HIV transmission. Despite the high prevalence of problematic alcohol consumption in Ukraine, however, there are little empirical data examining its association with risk behaviors also associated with HIV transmission in men who have sex with men (MSM), a key population where HIV incidence is increasing, METHOD: Correlates of prevalent HIV infection and their association between drinking severity levels and behaviors also associated with increased likelihood of HIV acquisition were analyzed from a 2017 nationally representative survey (IBBS) of 4938 MSM in Ukraine using bivariate analyses and multivariate regression. RESULTS: Overall, 42.6% of MSM participants met screening criteria for alcohol use disorder (AUD), with 24.2%, 12.0%, and 6.3% meeting criteria for moderate, high, and severe risk of harm from alcohol consumption, respectively. Multivariate regression revealed that these risk categories were correlated with behaviors associated with increased HIV transmission risk, including reports of (1) > 5 sexual partners; (2) sex with a partner of unknown HIV status; (3) sex work; (4) any drug use; and (5) not testing for HIV (past year). HIV testing was infrequent, with only 44.1% having been tested in the previous year. CONCLUSION: The high prevalence of problematic alcohol use in Ukrainian MSM and its association with behaviors also associated with HIV transmission supports the importance of routine screening of MSM for AUD. Moreover, among those screening positive for a potential AUD, targeted HIV prevention strategies to scale-up pre-exposure prophylaxis, consistent condom use, and treatment for AUD are needed.

Advancing Transthyretin Amyloidosis Drug Development in an Evolving Treatment Landscape: Amyloidosis Forum Meeting Proceedings.

INTRODUCTION: Hereditary transthyretin amyloidosis (ATTRv, also referred to as hATTR; ORPHA 271861) and wild-type ATTR amyloidosis (ATTRwt; ORPHA 330001) are rare, progressive, systemic protein misfolding disorders with heterogeneous clinical presentations. ATTRv and ATTRwt amyloidosis are characterized by the deposition of amyloid fibrils in multiple organs including the heart, nerves, eyes, and soft tissues. The management of ATTR amyloidosis is complex because of its multisystemic nature and progression despite available treatment options. Morbidity is high and there are many unmet medical needs for patients. While contemporary ATTR amyloidosis cohorts are diagnosed earlier, have lower risk disease and lower mortality compared with the previous era, these advances coupled with the emergence of effective disease-modifying therapies have confounded the design of future prospective clinical trials and interpretation of historical control data. MAIN BODY: The Amyloidosis Forum is a public-private partnership between the US Food and Drug Administration Center for Drug Evaluation and Research and the nonprofit Amyloidosis Research Consortium ( www.arci.org ). This article summarizes proceedings from the 21 June 2023 Amyloidosis Forum on advancing drug development in ATTR amyloidosis in an evolving treatment landscape. The Forum focused on elements of clinical trial design to address these challenges and discussed their strengths and weaknesses from multiple stakeholder perspectives (i.e., patient, sponsor, statistician, clinician, and regulatory authorities). CONCLUSION: Given rapid evolution of natural history in ATTR amyloidosis, the utility of historical control data is limited. Leveraging contemporary real-world data is essential for clinical trial design. Evidence generation from clinical trials should address clinically relevant questions. Key factors in successful trial design must be informed by up-to-date data on natural history, prognostic factors, clinically meaningful thresholds, and sharing available clinical trial data. The Amyloidosis Forum includes the community of patients with ATTR amyloidosis, the physicians who treat them, and the sponsors and regulators who collectively stand ready to support further studies in order to develop novel effective therapies.

Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma Immunotherapy Consortium Real- World Experience.

Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.S. Impact of ALC parameters including pre-apheresis (pre-A), pre-lymphodepletion (pre-LD), absolute and percent difference from pre-A to pre-LD on clinical outcomes after ide-cel were examined using survival analysis. A new ALC profile was created based on univariate analysis that comprises 3 groups: normal (≥1 × 109/L) pre-LD ALC (LDN), low (<1 × 109/L) pre-LD ALC (LDL) + percent reduction <37.5 (%RL), and LDL ALC + percent reduction ≥37.5 (%RH). A total of 214 SOC ide-cel recipients were included in this analysis. The median patient age was 64 years (interquartile range [IQR], 57 to 69 years), median number of prior therapies was 6 (IQR, 5 to 9), and median duration of follow-up was 5.4 months (IQR, 2.1 to 8.3 months). Most patients had both low pre-A ALC (75.3%) and pre-LD ALC (77.2%), and the reduction from pre-A to pre-LD (median, .65 to .55 × 109/L) was statistically significant. Univariate analysis showed that the LDL + %RH group had significantly worse progression-free survival (PFS) and overall survival (OS) compared to the LDL + %RL and LDN ALC groups (6-month PFS: 40% versus 67.6% and 60.9%; 6-month OS: 69.5% versus 87% and 94.3%). In multivariable analysis, after adjusting for age, performance status, cytogenetic risk, use of bridging therapy, and extramedullary disease, PFS did not maintain its statistical significance; however, OS remained significantly worse for LDL + %RH group compared to the LDN ALC group (hazard ratio [HR], 4.3; 95% confidence interval [CI], 1.1 to 17), but the difference between the LDL + %RH versus %RL groups was not statistically significant (HR, 1.7; 95% CI, .8 to 4.0). Our findings indicate that low pre-LD ALC with high %R from pre-A to pre-LD was associated with inferior survival outcomes, particularly OS, in patients who received SOC ide-cel.

Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel.

Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p < 0.001). The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p < 0.0001) for the non-EMD cohort. In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.5 (1.1-2.2), p = 0.02]. The median overall survival was 14.8 months [95% CI: 9-Not reached (NR)] vs. 26.9 months (26.3 vs. NR, p = 0.006) for the EMD and non-EMD cohorts, respectively. Extramedullary disease represents an independent predictor of inferior day 90 ORR and PFS among patients treated with ide-cel.

Influence of Stigma on Engagement in HIV Care and Adherence to Antiretroviral Therapy in Specialized HIV Clinics Targeting Men Who Have Sex with Men and Transgender Women in Lima, Peru.

HIV stigma is a social determinant of health that can influence multiple health outcomes, including adherence to antiretroviral therapy (ART), engagement in HIV care, and viral suppression levels in people with HIV (PWH). In Peru, where the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW), stigma may play an important role in healthcare engagement. To understand the relationship between stigma and two outcome variables, ART adherence and engagement in HIV care in 400 MSM and TGW, we assessed factors from the Behavioral Model for Vulnerable Populations at two HIV clinics that tailor services for sexual and gender minorities. While some predisposing, need, and enabling resource factors were associated with optimal (≥ 90%) ART adherence or engagement in HIV care, none of the stigma subscales were correlated, suggesting that when LGBTQ-affirming care is provided to MSM/TGW, stigma may not influence HIV-related outcomes.

RESUMEN: El estigma hacia el VIH es un determinante social de la salud que puede influir en múltiples desenlaces, incluyendo la adherencia a la terapia antirretroviral (TAR), el compromiso con la atención del VIH y los niveles de supresión viral en personas viviendo con VIH (PVV). En el Perú, donde la epidemia del VIH se concentra en hombres que tienen sexo con hombres (HSH) y mujeres transgénero (MT), el estigma puede desempeñar un papel importante en el compromiso con la atención médica. Para comprender la relación entre el estigma y dos variables de resultado, la adherencia al TAR y el compromiso con la atención del VIH en 400 HSH y MT, evaluamos factores del Modelo de Comportamiento para Poblaciones Vulnerables en dos clínicas de VIH que adaptan sus servicios para minorías sexuales y de género. Si bien algunos factores predisponentes, de necesidad y de recursos habilitantes se asociaron con una adherencia óptima (≥ 90%) al TAR o al compromiso con la atención del VIH, ninguna de las sub-escalas de estigma estuvieron correlacionadas, sugiriendo que cuando se brinda atención que afirma a la comunidad LGBTQ a HSH/MT, el estigma puede no influir en los desenlaces relacionados con el VIH.

Mechanisms of left ventricular systolic dysfunction in light chain amyloidosis: a multiparametric cardiac MRI study.

Background: Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood. Purpose: This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis. Methods: Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass. Results: Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21 ml/min/g and correlated with MWE (r = 0.42; p < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy (n = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile (p < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; p < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; p < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden. Conclusions: In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.

Psychotic-like experiences and associated factors in resident physicians: A Canadian cross-sectional study.

AIM: Medical residency training is associated with a range of sociodemographic, lifestyle and mental health factors that may confer higher risk for psychotic-like experiences (PLEs) in residents, yet little research has examined this question. Thus, we aimed to document the prevalence and associated factors of PLEs among resident physicians. METHODS: Physicians enrolled in residency programmes in the Province of Québec, Canada (four universities) were recruited in Fall 2022 via their programme coordinators and social media. They completed an online questionnaire assessing PLEs in the past 3 months (the 15-item Community Assessment of Psychic Experiences), as well as sociodemographic characteristics, lifestyle and mental health. Analyses included survey weights and gamma regressions. RESULTS: The sample included 502 residents (mean age, 27.6 years; 65.9% women). Only 1.3% (95% CI: 0.5%, 4.0%) of residents met the screening cut-off for psychotic disorder. Factors associated with higher scores for PLEs included racialised minority status (relative difference: +7.5%; 95% CI: +2.2%, +13.2%) and English versus French as preferred language (relative difference: +7.9% 95% CI: +3.1%, +12.9%), as well as each additional point on scales of depression (relative difference: +0.8%; 95% CI: +0.3%, +1.3%) and anxiety (relative difference: +1.3%; 95% CI: +0.8%, +1.7%). In secondary analyses, racialised minority status was associated with persecutory items, but not with other PLEs. Gender, residency programmes and lifestyle variables were not associated with PLEs. CONCLUSIONS: This study found low reports of PLEs in a sample of resident physicians. Associations of PLEs with minoritised status may reflect experiences of discrimination.

Unlocking Diversity in Cardiovascular Clinical Research: Lessons from the Screening for Cardiac Amyloidosis With Nuclear Imaging in a Minority Populations Study.

BACKGROUND: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations study seeks to determine the prevalence of transthyretin cardiac amyloidosis (ATTR-CA) among older Black or Caribbean Hispanic individuals with heart failure and an increased wall thickness. We noticed varied recruitment percentages across the recruiting sites and sought to determine the factors associated with greater percentage enrollment of eligible participants. METHODS: The percentage of enrolled to eligible participants was calculated across study sites. Baseline demographic and clinical characteristics, health literacy, trust in providers, perceived discrimination, area deprivation index (ADI) and English proficiency were compared by site using Kruskal-Wallis's test or one-way ANOVA for continuous variables and the Chi-Square test or Fisher's exact test for categorical variables. Wilcoxon rank sum and Chi-Square tests, with multiple comparisons correction using the false discovery rate (FDR) method, were used as post-hoc analysis when results were statistically significant. RESULTS: Among the four recruiting sites, Boston Medical Center, Columbia University Irving Medical Center, Harlem Hospital and Yale University, which employed different recruitment approaches, the percentage of participants enrolled among eligible participants differed, with the highest rate at Harlem Hospital (n=149 of 310, 48%), followed by Yale University (n=27 of 67, 40%), Boston University (n=247 of 655, 38%), and Columbia University (n=137of 442, 32%), p <0.01. Direct recruitment by the primary cardiovascular care team providing clinical care was associated with higher percent enrolled across sites as were higher education levels and English proficiency. Enrollment differences across sites were not associated with the number of chronic diseases, physician trust, perceived discrimination, or health literacy. CONCLUSIONS: Recruitment of eligible under-represented minorities (URMs) in SCAN-MP was associated with approaches employed in recruitment, including direct initial contact by the primary cardiovascular care team providing the potential participant's clinical care. Such data may help improve approaches to more successful recruitment of URMs in clinical research.

Investigating Resistance to Antidepressants in Animal Models.

Major depressive disorder is one of the most prevalent psychiatric diseases, and up to 30-40% of patients remain symptomatic despite treatment. Novel therapies are sorely needed, and animal models may be used to elucidate fundamental neurobiological processes that contribute to human disease states. We conducted a systematic review of current preclinical approaches to investigating treatment resistance with the goal of describing a path forward for improving our understanding of treatment resistant depression. We conducted a broad literature search to identify studies relevant to the preclinical investigation of treatment resistant depression. We followed PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) guidelines and included all relevant studies. We identified 467 studies in our initial search. Of these studies, we included 69 in our systematic review after applying our inclusion/exclusion criteria. We identified 10 broad strategies for investigating treatment resistance in animal models. Stress hormone administration was the most commonly used model, and the most common behavioral test was the forced swim test. We systematically identified and reviewed current approaches for gaining insight into the neurobiology underlying treatment resistant depression using animal models. Each approach has its advantages and disadvantages, but all require careful consideration of their potential limitations regarding therapeutic translation. An enhanced understanding of treatment resistant depression is sorely needed given the burden of disease and lack of effective therapies.

ACT To Sustain: Adoptive Cell Therapy To Sustain Access to Non-Commercialized Genetically Modified Cell Therapies.

Genetically modified cell therapies (GMCT), particularly immune effector cells (IEC) such as chimeric receptor antigen (CAR) T cells, have shown promise in curing cancer and rare diseases after a single treatment course. Following close behind CAR T approvals are GMCT based on hematopoietic stem cells, such as products developed for hemoglobinopathies and other disorders. Academically sponsored GMCT products, often developed in academic centers without industry involvement, face challenges in sustaining access after completion of early phase studies when there is no commercial partner invested in completing registration trials for marketing applications. The American Society for Transplantation and Cellular Therapy (ASTCT) formed a task force named ACT To Sustain (Adoptive Cell Therapy to Sustain) to address the "valley of death" of academic GMCT products. This paper presents the task force's findings and considerations regarding financial sustainability of academically sponsored GMCT products in the absence of commercial development. We outline case scenarios illustrating barriers to maintaining access to promising GMCT developed by academic centers. The paper also delves into the current state of GMCT development, commercialization, and reimbursement, citing examples of abandoned products, cost estimates associated with GMCT manufacturing and real-world use of cost recovery. We propose potential solutions to address the financial, regulatory, and logistical challenges associated with sustaining access to academically sponsored GMCT products and to ensure that products with promising results do not languish in a "valley of death" due to financial or implementational barriers. The suggestions include aligning US Food and Drug Administration (FDA) designations with benefit coverage, allowing for cost recovery of certain products as a covered benefit, and engaging with regulators and policy makers to discuss alternative pathways for academic centers to provide access. We stress the importance of sustainable access to GMCT and call for collaborative efforts to develop regulatory pathways that support access to academically sponsored GMCT products.

Advancing Evidence Generation for Circulating Tumor DNA: Lessons Learned from A Multi-Assay Study of Baseline Circulating Tumor DNA Levels across Cancer Types and Stages.

Circulating tumor DNA (ctDNA) holds promise as a biomarker for predicting clinical responses to therapy in solid tumors, and multiple ctDNA assays are in development. However, the heterogeneity in ctDNA levels prior to treatment (baseline) across different cancer types and stages and across ctDNA assays has not been widely studied. Friends of Cancer Research formed a collaboration across multiple commercial ctDNA assay developers to assess baseline ctDNA levels across five cancer types in early- and late-stage disease. This retrospective study included eight commercial ctDNA assay developers providing summary-level de-identified data for patients with non-small cell lung cancer (NSCLC), bladder, breast, prostate, and head and neck squamous cell carcinoma following a common analysis protocol. Baseline ctDNA levels across late-stage cancer types were similarly detected, highlighting the potential use of ctDNA as a biomarker in these cancer types. Variability was observed in ctDNA levels across assays in early-stage NSCLC, indicative of the contribution of assay analytical performance and methodology on variability. We identified key data elements, including assay characteristics and clinicopathological metadata, that need to be standardized for future meta-analyses across multiple assays. This work facilitates evidence generation opportunities to support the use of ctDNA as a biomarker for clinical response.

HIV Activist Identity, Commitment, and Orientation Scale (HAICOS): Psychometric Evaluation to Assess Clinician's Propensity Towards HIV Activism in Malaysia.

HIV activism has a long history of advancing HIV treatment and is critical in dismantling HIV-related stigma. This study evaluated the psychometric quality of the HIV Activist Identity, Commitment, and Orientation Scale (HAICOS) to assess clinicians' propensity towards HIV activism in Malaysia. From November 2022 to March 2023, 74 general practitioners and primary care physicians in Malaysia participated in the study. The exploratory factor analysis (EFA) extracted an internally consistent three-factor solution with 13 items: (1) HIV activist identity and commitment, orientation towards (2) day-to-day, and (3) structural activism. The Cronbach's alpha value was 0.91, and intra-class correlation coefficient for test-retest reliability was 0.86. Stigma-related (prejudice and discrimination intent) and clinical practice (comfort in performing clinical tasks with key populations and knowledge about HIV pre-exposure prophylaxis) measures supported the construct validity of the scale. The study provided concise, structurally valid, and reliable measures to evaluate HIV activism among clinicians.

RESUMEN: El activismo del VIH tiene una larga historia de avanzar el tratamiento del VIH y es crítico para desmantelar el estigma relacionado al VIH. Este estudio evaluó la calidad psicométrica de la Escala de Identidad, Compromiso y Orientación de Activistas del VIH (HAICOS) para evaluar la propensión de los médicos hacia el activismo del VIH en Malasia. Desde noviembre del 2022 hasta marzo del 2023, 74 médicos generales y de atención primaria en Malasia participaron en este estudio. El análisis factorial exploratorio (AFE) extrajo una solución de tres factores internamente consistente con 13 ítems: (1) identidad y compromiso del activismo del VIH; orientación hacia (2) el activismo cotidiano y (3) el activismo estructural. El valor alfa de Cronbach fue de 0.91 y el coeficiente de correlación intraclase para la confiabilidad prueba-reprueba fue de 0.86. Las medidas relacionadas con el estigma (prejuicio e intención de discriminación) y la práctica clínica (comodidad realizando tareas clínicas con poblaciones claves y conocimiento sobre la profilaxis pre-exposición del VIH) respaldaron la validez de constructo de la escala. El estudio proporcionó medidas concisas, estructuralmente válidas y confiables para evaluar el activismo de VIH entre los médicos.

The impact of emergency guidance to the COVID-19 pandemic on treatment entry, retention and mortality among patients on methadone in Ukraine.

BACKGROUND AND AIMS: Ukraine's Ministry of Health released urgent COVID-19 guidelines, allowing for early implementation of take-home dosing (THD) for opioid agonist therapies (OAT) such as methadone. Enrollment in OAT and retention in the program are the most effective HIV prevention strategies for people who inject drugs (PWID). This study aimed to evaluate the impact of Ukraine's COVID-19 emergency guidance on OAT treatment enrollment, retention on treatment and mortality. DESIGN AND SETTING: Using Ukraine's national OAT registry for 252 governmental clinics across 25 regions, we conducted a 12-month comparative prospective cohort survival analysis. This study compared newly enrolled methadone patients within the initial 6 months following the COVID-19 guidance (COVID) with patients from the preceding year (pre-COVID) in a country with high adult HIV prevalence (1.2%) that is concentrated in PWID. PARTICIPANTS: In the nation-wide sample of newly enrolled PWID in Ukraine, comprising 2798 individuals, 1423 were in the COVID cohort and 1375 were in the pre-COVID cohort. The majority were male (86.7%), with an average age of 39.3 years. MEASUREMENTS: Primary outcomes were average monthly enrollment per cohort, treatment retention and mortality, with internal time-dependent predictors, including THD and optimal (> 85 mg) methadone dosing. RESULTS: Relative to the pre-COVID period, the monthly average patient enrollment was statistically significantly higher during the COVID period (283.7 versus 236.0; P < 0.0001), where patients were more likely to transition to THD and achieve optimal dosing earlier. Significant differences were observed in the proportions of person-months on THD (41 versus 13%, P < 0.0001) and optimal dosing (38 versus 31%, P < 0.0001) between the COVID and pre-COVID cohorts. Predictors of treatment retention, expressed as adjusted hazard ratios (aHR), included early THD [aHR = 1.90, 95% confidence interval (CI) = 1.47-2.45], early optimal dosing (aHR = 1.71, 95% CI = 1.37-2.13) and prior methadone treatment (aHR = 1.39, 95% CI = 1.15-1.68). These factors persisted, respectively, in the pre-COVID (aHR = 2.28, 95% CI = 1.41-3.70; aHR = 1.84, 95% CI = 1.32-2.56; and aHR = 1.36, 95% CI = 1.06-1.74) and COVID (aHR = 1.91, 95% CI = 1.40-2.59; aHR = 1.61, 95% CI = 1.20-2.16; and aHR = 1.49, 95% CI = 1.08-1.94) cohorts. Survival did not differ significantly between the two prospective cohorts. CONCLUSION: Ukraine's prompt adoption of early take-home dosing for opioid agonist therapies, such as methadone, following the emergency COVID-19 guidance appears to have increased enrollment into methadone and improved treatment retention for people who inject drugs without adverse effects on patient survival.

Autologous Hematopoietic Cell Transplantation Consolidation for First Response is Associated With Longer Survival Among Patients With Nodal Peripheral T Cell Lymphoma.

Nodal peripheral T cell lymphomas (PTCLs) are challenging subsets of non-Hodgkin lymphomas characterized by their heterogeneity and aggressive clinical behavior. Given the mixed outcomes reported in previous studies, the efficacy of autologous hematopoietic cell transplantation (auto-SCT) as a consolidation strategy following initial chemotherapy response remains uncertain. This study aims to evaluate the impact of upfront auto-SCT consolidation on overall survival (OS) and event-free survival (EFS) among patients with nodal PTCL who achieved a complete or partial response to initial chemotherapy. A retrospective cohort study was conducted at Moffitt Cancer Center, involving 123 patients with nodal PTCL treated between February 2005 and February 2021. Patients were stratified into 2 groups based on whether they received auto-SCT as part of their initial treatment strategy. Kaplan-Meier method and Cox proportional hazard models were used for statistical analysis to compare OS and EFS between groups. Patients undergoing auto-SCT after first response demonstrated significantly longer median OS (12.3 versus 4.3 yr; P = .035) and EFS (6.2 versus 2.2 yr; P = .003) compared to those who did not. Multivariate analyses indicated that auto-SCT at first response and younger age at diagnosis were favorable prognostic factors. The findings suggest that upfront auto-SCT consolidation can significantly improve long-term outcomes in patients with nodal PTCL, supporting the strategy of early auto-SCT consideration and referral following initial chemotherapy response. These results underscore the importance of integrating upfront auto-SCT into the treatment paradigm for nodal PTCL, emphasizing early referral to transplantation services to optimize patient outcomes.