Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma.

Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

Dealing with small samples in disability research: Do not fret, Bayesian analysis is here.

PURPOSE/OBJECTIVE: Small sample sizes are a common problem in disability research. Here, we show how Bayesian methods can be applied in small sample settings and the advantages that they provide. METHOD/DESIGN: To illustrate, we provide a Bayesian analysis of employment status (employed vs. unemployed) for those with disability. Specifically, we apply empirically informed priors, based on large-sample (N = 95,593) July 2019 Current Population Survey (CPS) microdata to small subsamples (average n = 26) from July 2021 CPS microdata, defined by six specific difficulties (i.e., hearing, vision, cognitive, ambulatory, independent living, and self-care). We also conduct a sensitivity analysis, to illustrate how various priors (i.e., theory-driven, neutral, noninformative, and skeptical) impact Bayesian results (posterior distributions). RESULTS: Bayesian findings indicate that people with at least one difficulty (especially ambulatory, independent living, and cognitive difficulties) are less likely to be employed than people with no difficulties. CONCLUSIONS/IMPLICATIONS: Overall, results suggest that Bayesian analyses allow us to incorporate known information (e.g., previous research and theory) as priors, allowing researchers to learn more from small sample data than when conducting a traditional frequentist analysis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel in Relapsed or Refractory Large B-cell Lymphoma.

BACKGROUND: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. OBJECTIVE: ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. STUDY DESIGN: Patients with R/R LBCL were enrolled in Cohort 3 and received conditioning chemotherapy on Days -5 through -3 followed by a single infusion of axi-cel (2 × 106 cells/kg) on Day 0. Prophylactic tocilizumab (8 mg/kg) was administered 48 hours after axi-cel infusion. Primary endpoints were incidence and severity of CRS and NEs. Key secondary endpoints included the incidence of adverse events, objective response rate (ORR), duration of response, progression-free survival, overall survival (OS), and biomarker analyses (eg, circulating CAR T cells, cytokines, chemokines). RESULTS: Forty-two patients were enrolled in Cohort 3, 38 of whom received axi-cel. In the 24-month analysis, any-grade CRS and NEs occurred in 92% and 87% of patients, and Grade ≥3 CRS and NEs occurred in 3% and 42% of patients, respectively. One Grade 5 NE (cerebral edema) occurred. With 24-month minimum follow-up, the ORR was 63%, and 39.5% of patients had ongoing response. With 48-month follow-up, median OS was 34.8 months (95% CI, 5.4-not estimable). CAR T-cell expansion in ZUMA-1 Cohort 3 was comparable with pivotal Cohorts 1 and 2. Consistent with tocilizumab-mediated inhibition of IL-6R, serum IL-6 levels were increased relative to Cohorts 1 and 2. Grade ≥3 NEs were associated with elevated IL-6 levels, proinflammatory cytokines, and myeloid cells in the cerebrospinal fluid. CONCLUSIONS: Based on these findings, prophylactic tocilizumab is not recommended to prevent CAR T-cell-related adverse events, and beneficial effects of prophylactic levetiracetam remain uncertain in patients with R/R LBCL.

Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

PURPOSE: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy. METHODS: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events. RESULTS: Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2). CONCLUSION: In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.

The cascade of care for commercially-insured persons with opioid use disorder and comorbid HIV and HCV infections.

BACKGROUND: Opioid use disorder (OUD) significantly impacts individual and public health and exacerbated further by concurrent infectious diseases. A syndemic approach is needed to address the intertwined OUD, HIV, and HCV epidemics, including the expanded use of medications for opioid use disorder (MOUD). METHODS: To identify MOUD scale-up opportunities, we conducted a retrospective cohort study, representing commercially insured persons, and created the OUD care continuum, including HIV and HCV influences in adults (18-64 years) newly diagnosed with OUD in 2019 using Merative MarketSan data. RESULTS: Among 124,467,633 individuals, the prevalence of OUD was 0.4 % (95 % CI: 0.36 %-0.46 %; N = 497,871), with 327,277 (65.7 %, 95 % CI: 65.60 %-65.87 %) newly diagnosed in 2019. Among these newly diagnosed individuals (54 % men, mean age 44±0.01), 53,568 (27.0 %, 95 % CI: 26.4 %-27.5 %) were prescribed MOUD, with retention rates at 1, 3, and 6 months being 89.0 % (95 % CI: 88.2 %-89.8 %), 66.0 % (95 % CI: 64.8 %-67.2 %), and 50.3 % (95 % CI: 48.3 %-51.6 %), respectively. Buprenorphine was the most prescribed MOUD (79.6 %, 95 % CI: 78.6 %-80.7 %), followed by XR-NTX (14.9 %, 95 % CI:14.0 %-15.8 %) and methadone (5.5 %, 95 % CI: 4.9 %-6.1 %). Six-month retention was highest for methadone (73.4 %, 95 % CI: 73.0 %-73.8 %), however, followed by buprenorphine (55.7 %, 95 % CI: 55.3 %-57.1 %) and substantially lower for XR-NTX (12.6 %, 95 % CI: 10.6 %-14.6 %). Screening for HIV and HCV was low among OUD enrollees (11.1 %, 14.4 %), slightly higher for MOUD initiators (18.0 %, 21.6 %). Being prescribed MOUD was correlated with HCV infection (AOR: 2.54; 95 % CI: 2.41-2.68), HCV/HIV coinfection (AOR: 1.89; 95 % CI: 1.41-2.53), and hospitalization for OUD-related services (AOR: 1.14; 95 % CI: 1.11-1.17), yet hospitalization for OUD-related services was positively correlated with XR-NTX (AOR: 2.72; 95 % CI: 2.56-2.85) prescription and negatively with methadone (AOR: 0.19; 95 % CI: 0.16-0.23) prescription. Having HIV was negatively correlated with being prescribed methadone (AOR: 0.33; 95 % CI: 0.13-0.86). CONCLUSIONS: Substantial gaps in the OUD cascade persist, underscoring better implementation opportunities for MOUD prescription in hospital-based settings and expanding access to methadone beyond highly regulated sites given its low coverage yet high treatment retention.

Using nominal group technique with people who are incarcerated in Canadian federal prisons to identify barriers and solutions to improving Prison Needle Exchange Program uptake.

BACKGROUND: Prison needle exchange programs (PNEPs) are a critical component for harm reduction in prisons. Little is known about the PNEP access barriers for people who are incarcerated, but the low uptake in the Canadian program highlights these constraints. We aimed to identify the barriers and potential solutions for increasing PNEP coverage in the nine Canadian federal prisons where they operate. METHODS: Eighteen focus groups were conducted in nine prisons using nominal group technique (NGT) with two stakeholders: peer advocates and people who use or identified as potential users of the PNEP. NGT uses a round-robin technique followed by generating a list of barriers to PNEP enrolment within their prison. Participants then allocated votes to rank the highest priority barriers, followed by an identical process to generate solutions to address the top three barriers. Interview transcripts describing participant narratives during this process were de-identified and coded to generated themes. Barriers and solutions receiving >10 % of votes within respective participant groups, alongside associated narratives, are discussed more fully. RESULTS: Fear of repercussions due to drug use, lack of confidentiality, and fear of being targeted and sanctioned by correctional authorities were perceived by both stakeholder groups as the top barriers inhibiting PNEP enrolment. Stigma (peer advocates) and the application process for the program (PNEP users) were also ranked as a priority. Proposed solutions included education and external oversight of PNEP (i.e., not via correctional officers) by both groups. Peer advocates regarded improving participant confidentiality and a supervised/safe injection site as potential enablers for program participation, while PNEP users identified wrap-around services as likely to improve access. CONCLUSION: Barriers to increasing PNEP coverage in Canadian federal prisons proposed by participants highlight the importance of trust and perceived repercussions surrounding program participation. These barriers and proposed solutions highlight a need for changes in implementation to PNEP delivery if the potential health benefits of PNEPs are to be realised.

Interventions to reduce harms related to drug use among people who experience incarceration: systematic review and meta-analysis.

BACKGROUND: Mortality, suicide, self-harm, and substance use are elevated among people who are incarcerated. There is a wide range of heterogeneous interventions aimed at reducing these harms in this population. Previous reviews have focused on specific interventions or limited their findings to drug use and recidivism and have not explored interventions delivered after release from prison. Our aim is to examine the effect of interventions delivered to people who use drugs during incarceration or after release from incarceration, on a wide range of outcomes. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO databases up until Sept 12, 2023 for studies published from Jan 1, 1980 onwards. All studies evaluating the effectiveness of any intervention on drug use, recidivism outcomes, sexual or injecting risk behaviours, or mortality among people who use psychoactive drugs and who were currently or recently incarcerated were included. Studies without a comparator or measuring only alcohol use were excluded. Data extracted from each study included demographic characteristics, interventions, and comparisons. Pooled odds ratios and risk ratios were calculated using random-effects meta-analyses. FINDINGS: We identified 126 eligible studies (47 randomised controlled trials and 79 observational studies) encompassing 18 interventions; receiving opioid-agonist treatment (OAT) in prison reduced the risk of death in prison (one study; hazard ratio 0·25; 95% CI 0·13-0·48), whereas receiving OAT in the first 4 weeks following release reduced risk of death in the community (two studies; relative risk 0·24; 95% CI 0·15-0·37). Therapeutic community interventions reduced re-arrest at 6-12 months (six studies; odds ratio [OR] 0·72; 95% CI 0·55-0·95) and reincarceration at 24 months (two studies; OR 0·66; 95% CI 0·48-0·96). There was scarce evidence that OAT and syringe service provision are effective in reducing injecting risk behaviours and needle and syringe sharing. INTERPRETATION: There are effective interventions to reduce mortality and recidivism for people who use drugs who have been incarcerated. Nonetheless, there are also substantial gaps in the research examining the effect of interventions on risk behaviours and mortality during incarceration and a need for randomised designs examining outcomes for people who use drugs after release. FUNDING: Australian National Health and Medical Research Council.

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.

Myocardial Characteristics, Cardiac Structure, and Cardiac Function in Systemic Light-Chain Amyloidosis.

BACKGROUND: In systemic light-chain (AL) amyloidosis, cardiac involvement portends poor outcomes. OBJECTIVES: The authors' objectives were to detect early myocardial alterations, to analyze longitudinal changes with therapy, and to predict major adverse cardiac events (MACE) in participants with AL amyloidosis using cardiac magnetic resonance imaging (MRI). METHODS: Recently diagnosed participants were prospectively enrolled. AL amyloidosis with and without cardiomyopathy (AL-CMP, AL-non-CMP) were defined based on abnormal cardiac biomarkers and wall thickness. MRI was performed at baseline, 6 months in all participants, and 12 months in participants with AL-CMP. MACE were defined as all-cause death, heart failure hospitalization, and cardiac transplantation. Mayo stage was based on troponin T, N-terminal pro-B-type natriuretic peptide, and difference in free light chains. RESULTS: This study included 80 participants (median age 62 years, 58% men). Extracellular volume (ECV) was abnormal (>32%) in all participants with AL-CMP and in 47% of those with AL-non-CMP. ECV tended to increase at 6 months (median +2%; AL-CMP P = 0.120; AL-non-CMP P = 0.018) and returned to baseline values at 12 months in participants with AL-CMP. Global longitudinal strain (GLS) improved at 6 months (median -0.6%; P = 0.048) and 12 months (median -1.2%; P < 0.001) in participants with AL-CMP. ECV and GLS were strongly associated with MACE (P < 0.001) and improved the prognostic value when added to Mayo stage (P ≤ 0.002). No participant with ECV ≤32% had MACE, while 74% of those with ECV >48% had MACE. CONCLUSIONS: In patients with systemic AL amyloidosis, ECV detects subclinical myocardial alterations. With therapy, ECV tends to increase at 6 months and returns to values unchanged from baseline at 12 months, whereas GLS improves at 6 and 12 months in participants with AL-CMP. ECV and GLS offer additional prognostic performance over Mayo stage. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).

Clinical and Genomic Risk for Late Breast Cancer Recurrence and Survival.

BACKGROUND: The 21-gene recurrence score (RS) assay (Oncotype DX) is used to guide adjuvant chemotherapy use for patients with hormone receptor-positive, HER2 (human epidermal growth factor receptor 2)-negative, axillary node-negative breast cancer. Its role, however, in providing prognostic information for late distant recurrence when added to clinicopathologic prognostic factors is unknown. METHODS: A patient-specific meta-analysis including 10,004 women enrolled in three trials was updated using extended follow-up data from TAILORx, integrating the RS with histologic grade, tumor size, and age at surgery for the RSClin tool. Cox models integrating clinicopathologic factors and the RS were compared by using likelihood ratio (LR) tests. External validation of prognosis for distant recurrence in years 0 to 10 and 5 to 10 was performed in an independent cohort of 1098 women in a real-world registry. RESULTS: RSClin provided significantly more prognostic information than either the clinicopathologic factors (ΔLR chi-square, 86.2; P<0.001) or RS alone (ΔLR chi-square, 131.0; P<0.001). The model was prognostic in an independent cohort for distant recurrence by 10 years after diagnosis (standardized hazard ratio, 1.56; 95% confidence interval, 1.25 to 1.94), was associated with late distant recurrence risk between 5 and 10 years after diagnosis (standardized hazard ratio, 1.78; 95% confidence interval, 1.25 to 2.55), and approximated the observed 10-year distant recurrence risk (Lin concordance, 0.87) and 5- to 10-year distant recurrence risk (Lin concordance, 0.92). CONCLUSIONS: The 21-gene RS is prognostic for distant recurrence and overall survival in early breast cancer. A model integrating the 21-gene RS and clinicopathologic factors improved estimates of distant recurrence risk compared with either used individually and stratified late distant recurrence risk. (Funded by the National Cancer Institute, National Institutes of Health [U10CA180820, U10CA180794, UG1CA189859, U10CA180868, and U10CA180822] and others.).

Prognostic Value of Left Ventricular 18F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) with 18F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden in systemic light-chain (AL) amyloidosis. However, its prognostic value is not known. OBJECTIVES: The authors' aim was to evaluate the prognostic value of LV amyloid burden quantified by 18F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes. METHODS: A total of 81 participants with newly diagnosed AL amyloidosis underwent 18F-florbetapir PET/CT imaging. Amyloid burden was quantified using 18F-florbetapir LV uptake as percent injected dose. The Mayo stage for AL amyloidosis was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months. RESULTS: Among participants (median age, 61 years; 57% males), 36% experienced MACE, increasing from 7% to 63% across tertiles of LV amyloid burden (P < 0.001). LV amyloid burden was associated with MACE (HR: 1.46; 95% CI: 1.16-1.83; P = 0.001). However, this association became nonsignificant when adjusted for Mayo stage. In mediation analysis, the association between LV amyloid burden and MACE was mediated by NT-proBNP (P < 0.001), a marker of cardiomyocyte stretch and heart failure, and a component of Mayo stage. CONCLUSIONS: In this first study to link cardiac 18F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by percent injected dose predicted MACE in AL amyloidosis. This effect was not independent of Mayo stage and was mediated primarily through NT-proBNP. These findings provide novel insights into the mechanism linking myocardial amyloid deposits to MACE.

Sleep, chronotype, social jetlag, and mental health in resident physicians: a cross-sectional study.

STUDY OBJECTIVES: Social jetlag, the difference between imposed and endogenous sleep schedules, may be detrimental to resident physicians' health. The current profiles of sleep habits, particularly the differences between workdays and free days, are unknown in that population. This cross-sectional study of Quebec resident physicians aimed at assessing sleep habits on workdays and free days, and predictors of social jetlag. METHODS: Residents were recruited via their residency programs and social media to complete an online questionnaire. Measures included means of sleep duration and timing, chronotype, sleep debt, sleep disturbances, and social jetlag. A range of socio-demographic variables, lifestyle characteristics, and mental health indicators were examined as predictors of severe social jet lag using logistic regressions. RESULTS: A total of 492 residents were included in the study (mean [SD] age, 27.6 [3.6] years; 330 women [67.1%]). The mean sleep duration was 7.15h (95%CI, 7.02-7.28h) on workdays and 8.36h (95%CI, 8.18-8.54h) on free days. The mean sleep debt was 1.59h (95% CI, 1.37-1.81h), and mean social jetlag was 1.37h (95% CI, 1.28-1.47h), with 31.9% (95% CI, 25.0%-39.6%) of residents experiencing ≥2 hours of sleep debt, and 21.8% (95% CI, 16.5%-28.3%) experiencing severe social jetlag. The prevalence of sleep disturbances was 51.7% (95% CI, 44.4%-58.8%). Severe social jetlag was associated with earlier stage of training, later chronotype, decreased physical activity, increased sleep debt, and depressive symptoms. CONCLUSIONS: Many residents experience severe social jetlag, chronic sleep deprivation and sleep disturbances. Importantly, severe social jetlag was associated with depressive symptoms, suggesting a potential intervention target for promoting resident mental health.

Using nominal group technique to identify perceived barriers and facilitators to improving uptake of the Prison Needle Exchange Program in Canadian federal prisons by correctional officers and healthcare workers.

BACKGROUND: Elimination of bloodborne viruses including HIV and hepatitis C virus from prisons requires high coverage of evidence-based interventions that prevent bloodborne virus transmission, including needle and syringe programs. Canada launched a Prison Needle Exchange Program (PNEP) in nine federal prisons in 2018; however, uptake among people who inject drugs in prison remains low. We aimed to explore barriers and facilitators to improving PNEP uptake identified by correctional officers and healthcare workers. METHODS: Participants from nine federal prisons with PNEP completed focus groups using nominal group technique, a rapid mixed-method consensus strategy. Responses were generated, rank-ordered, and prioritized by each stakeholder group. We identified the highest-ranking responses (≥10 % of the overall votes) to questions about barriers and facilitators to PNEP uptake. RESULTS: Between September 2023 and February 2024, 16 focus groups were conducted with 118 participants (n = 51 correctional officers; n = 67 healthcare workers). Among correctional officers, the top perceived barriers were bullying from peers (22 %), fear of being targeted by correctional officers (14 %), and fear of repercussions due to drug use (13 %). The top facilitators were safe injection sites (30 %), provision of wrap-around services (16 %), and education of correctional officers (10 %). Among healthcare workers, the top perceived barriers were lack of confidentiality (16 %), fear of being targeted by correctional officers (12 %), and a long and complex application process (11 %). The top facilitators were education of correctional officers (29 %), delivery of PNEP by an external provider (15 %), automatic approval for participation in the PNEP (13 %), and safe injection sites (12 %). CONCLUSION: Multiple modifiable barriers and solutions to improving PNEP uptake in Canadian federal prisons were identified by correctional employees. Both participant groups identified the potential for safe injection sites and education to correctional officers as enabling PNEP uptake. These data will inform Canadian efforts to improve engagement and to expand PNEP coverage.

Associations between parental civic engagement, negative beliefs toward civic engagement and youths' future civic attitudes and behaviors.

INTRODUCTION: Civic engagement (CE) in adolescence is associated with a higher level of engagement in adulthood and is reported to be beneficial to youth's development and societal well-being. Parents are among the most influential factors in adolescents' lives. This study examined the associations between parents' own civic participation, their negative beliefs toward youth CE and their child's future CE. While prior research documented positive associations between parental civic behaviors and youth CE, the role of parental negative beliefs has remained unexplored and could act as an additional barrier to adolescents' CE. METHODS: A total of 234 adolescents (65% girls; mean age = 13.77) and their parents (79% mothers; mean age = 44.20), residing in the Canadian province of Quebec from 2016 to 2019, were recruited for this cross-sectional study. Parents completed measures of their civic activities and their negative beliefs regarding youth CE. Adolescents completed measures of future civic attitudes and behaviors. RESULTS: Hierarchical regressions revealed significant positive cross-sectional associations between parental civic behaviors and their child's future civic attitudes and behaviors. However, parental negative beliefs toward youth CE were negatively associated with youths' future civic attitudes and behaviors, even after considering parental civic behaviors and family socioeconomic status. Adolescents' age did not moderate these relationships. CONCLUSION: These findings highlight the significant role that parents could play in shaping CE of future generations. Interventions promoting youth CE should thus target both adolescents and their parents.

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.

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.