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Abstract: In the U.S. South, over half of new HIV diagnoses occur among Black Americans with research lagging for women who face increased HIV rates and low PrEP uptake, among other health inequities. Community engaged research is a promising method for reversing these trends with established best practices for building infrastructure, implementing research, and translating evidence-based interventions into clinical and community settings. Using the 5Ws of Racial Equity in Research Framework (5Ws) as a racial equity lens, the following paper models a review of a salon-based intervention to improve PrEP awareness and uptake among Black women that was co-developed with beauty salons, stylists, and Black women through an established community advisory council. In this paper we demonstrate how the 5Ws framework was applied to review processes, practices, and outcomes from a community-engaged research approach. The benefits of and challenges to successful collaboration are discussed with insights for future research and community impact., (Copyright © 2024 Association of Nurses in AIDS Care.)

Background: Black cis-gender women are disparately affected by HIV and require prioritization in prevention efforts, including pre-exposure prophylaxis (PrEP). Preparing trusted community leaders such as salon stylists as health-based opinion leaders may be promising to increasing awareness, knowledge, and uptake of PrEP among Black women. We sought to develop training and better understand stylists who may participate in a salon-based PrEP intervention for Black women., Methods: A community-research partnership designed a stylist training workshop for stylists with a majority Black women clientele. A two-session workshop focused on HIV knowledge, HIV prevention including PrEP, and the role of an opinion leader to influence community social and health norms. An exploratory research design and analysis was conducted to examine stylists and provide training feedback., Conclusions: Stylists showed a high level of knowledge and willingness to serve as an opinion leader in their salons and with their communities. Stylists also verified medical mistrust in the healthcare system that makes community-based interventions attractive. This article discusses how the training was piloted and accepted by stylists., (© 2023 Wiley Periodicals LLC.)

Improved biomarkers are required to guide the optimal use of autologous stem cell transplantation (ASCT) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples, post-ASCT peripheral blood mononuclear cell (PBMC), and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples. After a median post-ASCT follow-up of 60 months, the 5-year progression-free survival (PFS) was 48%. MRD was detected in of 23/98 (23%) ASC samples and was associated with very poor PFS (5-year PFS 13% vs 53%, P < .001) and inferior overall survival (52% vs 68%, P = .05). The sensitivity and specificity of ASC MRD positivity for progression and death were 36% and 93%, respectively. Positive ASC MRD remained a significant predictor of PFS in multivariable analysis (hazard ratio [HR], 3.7; P < .001). Post-ASCT surveillance MRD testing of plasma, but not PBMC samples, reliably identified patients with an impending relapse. A positive plasma MRD result was associated with inferior PFS (HR, 3.0; P = .016) in a multivariable analysis. The median lead time from MRD detection to relapse was 62 days (range, 0-518 days). In conclusion, the detection of MRD in ASC samples is associated with a very high risk of relapse, justifying alternative treatment strategies or trials of novel consolidation options in these patients. Furthermore, post-ASCT MRD monitoring may facilitate the evaluation of the early initiation of treatment at molecular relapse. This trial has been registered at www.clinicaltrials.gov as #NCT02362997., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: In the United States, Black cisgender women account for one in five new HIV infections with Black Americans, accounting for 57% of new diagnoses in the South. Pre-exposure prophylaxis (PrEP) is 99% effective at preventing HIV. Still, Black women's uptake remains at 2% due to multiple documented barriers, including lack of awareness and knowledge, mistrust, stigma, and low perceived risk. Culturally relevant interventions leveraging trusted venues, such as beauty salons, can overcome these barriers. This article reports preliminary results of an intervention to improve PrEP knowledge and awareness, PrEP stigma, PrEP trust, and uptake among Black cisgender women. This multilevel, mixed-methods study used a community-engagement approach to develop and pilot a salon-based intervention, Using PrEP and Doing it for Ourselves (UPDOs) Protective Styles. The intervention improved knowledge, awareness, and trust around PrEP among Black cisgender women. PrEP use stigma within interpersonal relationships decreased, but low perceived risk and social stigma remained constant. Culturally and socially acceptable interventions like UPDOs Protective Styles can model health care delivery to improve trust, thus improving uptake over time for this population., (Copyright © 2023 Association of Nurses in AIDS Care.)

While most patients with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Novel biomarkers are needed to identify high-risk patients earlier. We hypothesized that interim positron emission tomography (PET) would predict progression-free survival (PFS) in this population. We retrospectively identified 128 patients with grade 1-3A FL who had an interim PET after 2-4 cycles of frontline CIT at 2 academic centers. PET scans were analyzed using Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Interim PET DS was a significant predictor of PFS ( P < 0.003). Patients with a DS of 3 had outcomes similar to those of patients with a DS of 4, so were categorized as PET-positive for additional analyses. Interim PET remained a strong predictor of PFS (DS 3-5, hazard ratio [HR] 2.4, P = 0.006) in a multivariable analysis and was also an early predictor of both a positive end-of-treatment PET ( P < 0.001) and progression of disease within 24 months (POD24) ( P = 0.006). An optimal ΔSUVmax cutoff of 75% was selected using the bootstrap method. ΔSUVmax <75% was also a significant predictor of PFS on univariable and multivariable analyses (HR 2.8, P < 0.003). In a separate cohort of 50 patients with high-grade FL, interim PET interpreted using either DS ( P < 0.001) or ΔSUVmax75% ( P = 0.034) was also a significant predictor of inferior PFS. In conclusion, interim PET is an independent predictor of PFS and may be useful as a tool for response-adapted treatment strategies in FL., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Improved biomarkers are needed to guide patient selection for autologous stem cell transplantation (ASCT) and post-ASCT maintenance therapies in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the prognostic value of minimal residual disease (MRD) using immunoglobulin-based high-throughput sequencing (Ig-HTS), we analyzed pre- and post-ASCT peripheral blood and pre-ASCT apheresis stem cell (ASC) samples in 36 cHL patients. A tumor clonotype was detected in only 12 patients (33%). Among these patients, MRD within plasma samples was closely associated with impending relapse. All patients (n = 3) with detectable MRD in any post-ASCT plasma sample relapsed (100% specificity), and MRD was not detected in any patients in remission. MRD testing from cellular specimens (peripheral blood mononuclear cell or ASC samples) was not associated with relapse. In this small cohort, plasma-based MRD testing appeared to be a promising biomarker in cHL, but given low clonotype detection rates with Ig-HTS, alternative MRD approaches should be investigated.

Background: Fear of recurrence (FoR) is prevalent among breast cancer survivors (BCS) and may be exacerbated by avoidance coping. This study examined BCS with avoidance coping and their engagement in a FoR eHealth intervention (FoRtitude)., Methods: BCS (N = 196) with elevated FoR participated in FoRtitude. Patient-reported measures assessed avoidance coping with FoR and baseline emotional and behavioral health. Intervention engagement was measured quantitatively (e.g., website logins, telecoaching attendance) and qualitatively (i.e., telecoaching notes)., Results: 38 BCS (19%) endorsed avoidance coping, which was associated with more severe post-traumatic anxiety-related symptoms and worse global mental health (ps < .05), but not anxiety (p = .19), depression (p = .11), physical health (p = .12), alcohol consumption (p = .85), or physical activity (p = .39). Avoidance coping was not associated with engagement levels (ps > .05) but did characterize engagement-related motivators and barriers., Conclusions: Avoidance coping was not a barrier to FoRtitude engagement. eHealth delivery is a promising modality for engaging survivors with avoidance coping in FoR interventions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: More than half of US veterans seek care outside of the Veterans Health Administration. Physical and mental healthcare needs can be complicated by experiences during military service. Community clinicians can deliver more holistic and comprehensive care to veterans through understanding the unique needs of the veteran population., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Pharmacists provide care in a complex adaptive system, which requires action and teamwork to address unexpected outcomes. We assessed practicing pharmacists' self-views of growth mindset and team communication across multiple practice settings., Design: The validated Growth Mindset and Team Communication (GMTC) tool, a multicomponent quantitative and qualitative survey instrument was used to conduct a descriptive study of pharmacist self views., Setting and Participants: Survey instrument was distributed electronically to all licensed North Carolina pharmacists., Outcome Measures: The survey consisted of 4 sections: (1) growth mindset self-evaluation (14 questions), (2) team communication self-evaluation (13 questions), (3) description of previous teamwork experience (1 question), and (4) demographics (8 questions). Data were analyzed using descriptive statistics, and responses to the open-ended question were assessed using qualitative content analysis., Results: A total of 507 pharmacists participated in the survey. Participants reported primary practice settings, 42.1% in community, 38.9% in health system, and 17.3% in other settings, and 52.1% reported more than 20 years' total pharmacy experience. The total GMTC scale average score was 81.9 ± 7.9 out of 108 possible points. The growth mindset subscale indicated an overall average score of 43.5 ± 4.4 out of 56 possible points The team communication subscale indicated an overall average score of 38.3 ± 5.2 out of 52 possible points. The self-view of a growth mindset was not affected by years of pharmacy experience or primary practice site, but additional teamwork credentials were positively correlated with the overall GMTC score driven by the team communication subscale., Conclusions: A growth mindset is prevalent among experienced pharmacists from multiple practice settings. Pharmacists recognize teamwork as an essential work element and rate their team communication skills highly., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Autologous stem cell transplantation (ASCT) is a standard of care for patients with chemosensitive, relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) and diffuse large B cell lymphoma (DLBCL). Whereas the clinical benefit of ASCT has traditionally been attributed solely to cytoreduction from intensive chemotherapy, ASCT has important immunogenic effects that may contribute to its antitumor efficacy and could provide a favorable immune environment for post-ASCT immune-based maintenance treatments. We previously reported clinical results of a phase II trial (ClinicalTrials.gov identifier NCT02362997) testing 8 doses of pembrolizumab maintenance therapy after ASCT for patients with R/R cHL or DLBCL. To clarify the impact of pembrolizumab on immune reconstitution, we compared the kinetics of peripheral blood immune cell recovery after ASCT for trial patients receiving pembrolizumab maintenance to those of a contemporaneous control cohort of similar patients undergoing ASCT without pembrolizumab maintenance. This study was conducted to characterize the impact of post-ASCT pembrolizumab maintenance therapy on immune reconstitution for patients with R/R DLBCL and cHL and to identify candidate biomarkers of efficacy and immune-related adverse events (irAEs). Peripheral blood (PB) mononuclear cell samples were prospectively collected at 1 to 18 months after ASCT and analyzed by flow cytometry using a panel of fluorophore-conjugated monoclonal antibodies to identify B cells, natural killer (NK) cells, and various dendritic cell (DC) and T cell subsets. A median of 5 (range, 1 to 8) post-ASCT PB samples were collected from 144 patients (59 in the pembrolizumab group and 85 in the control group). Clinical characteristics of the 2 cohorts were similar. Compared with cHL patients, DLBCL patients (all of whom received anti-CD20 monoclonal antibody therapy before ASCT) had delayed CD19 + cell reconstitution that persisted for at least 18 months after ASCT. No other differences in immune reconstitution based on lymphoma subtype were observed. Post-ASCT pembrolizumab maintenance therapy was associated with an elevation in circulating DCs (driven by higher levels of plasmacytoid and immature DCs) that persisted for the duration of pembrolizumab treatment, along with a significant reduction in PD-1 + T cells that persisted for 6 to 12 months after completion of pembrolizumab therapy. Despite the key role of T cells in mediating the effects of PD-1 blockade, pembrolizumab maintenance did not affect recovery of any T cell subsets. In an exploratory analysis, a higher baseline CD4 + terminal effector memory cell count (defined as CD3 + CD4 + CD45RA + CD62L - ) was associated with inferior progression-free survival (PFS), but only among patients who received pembrolizumab maintenance (P = .003). As continuous variables, lower absolute levels of NK cells (P = .009), PD-1 + CD4 + T cells (P = .005), and PD-1 + CD8 + T cells (P = .005) before pembrolizumab initiation were each associated with a higher risk of grade 2+ irAEs. Our findings indicate that post-ACST pembrolizumab maintenance therapy is associated with a persistent elevation of circulating DCs, but its impact on the reconstitution of other immune cells in peripheral blood appears limited. Our study suggests that early features of post-ASCT immune reconstitution could be associated with PFS and the risk of irAE and warrant additional investigation. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., Competing Interests: Declaration of Competing Interest R.W.M.: Consulting for Genmab; research funding from Bristol Myers Squibb and Merck. J.R.B.: Consulting for AbbVie, Acerta/Astra-Zeneca, BeiGene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Eli Lilly, Genentech/Roche, Janssen, MEI Pharma, MorphoSys, Nextcea, Novartis, Pfizer, and Rigel; research funding from Gilead, Loxo/Lilly, SecuraBio, Sun, and TG Therapeutics; Data and Safety Monitoring Board for Invectys. J.L.C.: Consulting for Incyte and MorphoSys; research funding from Bayer and AbbVie. M.S.D.: Consulting for AbbVie, Adaptive Biotechnologies, Ascentage Pharma, AstraZeneca, BeiGene, BMS, Celgene, Eli Lilly, Genentech, Janssen, Takeda, and TG Therapeutics; research support from AbbVie, Ascentage Pharma, AstraZeneca, BMS, Genentech, MEI Pharma, Novartis, Surface Oncology, TG Therapeutics, and Verastem; honoraria from Research to Practice and Aptitude Health. E.J.: Consulting for Syros and Takeda; research funding from Acerta, Janssen, Novartis, and Pharmacyclics. C.A.J.: Consulting for Kite Pharma/Gilead, Novartis, BMS/Celgene, Precision Biosciences, Nkarta, bluebird bio, Epizyme, Lonza, AbbVie, and Ipsen; research funding from Kite Pharma/Gilead and Pfizer. P.B.D.: Advisory board for Kite Pharma/Gilead. Y.N.: Consulting for Affimed and Novo Nordisk; research funding from Novartis, Biosecura, Astra-Zeneca, Affimed, and Takeda. Y.-B.C.: Consulting for Incyte, Magenta, Gamida Cell, Daiichi, Equilium, Celularity, and Actinium. A.F.H.: Consulting for Bristol Myers Squibb, Genentech, Merck, Seattle Genetics, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda, and Tubulis; research funding from Bristol Myers Squibb, Genentech, Merck, Seattle Genetics, Kite Pharma, Gilead Sciences, AstraZeneca, and ADC Therapeutics. P.A.: Consulting for Merck, BMS, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, MorphoSys, Daiichi Sankyo, Miltenyi Biotech, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, Astra Zeneca, and Genentech; research funding (institutional) from Merck, BMS, Affimed, Adaptive, Roche, Tensha, Otsuka, Sigma Tau, Genentech, IGM, and Kite Pharma; honoraria from Merck and BMS. J.R.: Consulting for Akron Biotech, Blackstone Life Sciences Advisors, Clade Therapeutics, Garuda Therapeutics, Immunitas Therapeutics, LifeVault Bio, Novartis, Rheos Medicines, Talaris Therapeutics, and TScan Therapeutics; research grant support from Amgen, Equillium, Novartis, and Kite Pharma/Gilead; Data and Safety Monitoring Board for Avrobio. The other authors have no conflicts of interest to report., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Drug-drug interactions (DDIs) are a serious problem in the healthcare system, leading to excess healthcare utilization and costs. We conducted a second prospective randomized, controlled trial to further establish the real-world clinical utility of a novel assay that objectively identifies potentially serious DDIs in real-world patients. Re-recruiting primary care physicians (PCPs) from our first randomized, controlled, simulated-patients study on DDIs, we experimentally introduced a definitive, urine-based mass spectrometry test intervention that the physicians could use when caring for their eligible patients. Patients were eligible if taking four or more prescription medications or suspected of taking other non-prescribed substances with potential medication interactions. The primary outcome was whether DDI testing changed clinical care. We explored a secondary outcome to see if the change in practice improved symptoms in patients with potential DDIs. A total of 169 control and 162 intervention patients were enrolled in the study, and their medical records were abstracted. In real-world patients, intervention physicians identified and/or treated a DDI at 3.0x the rate in their patient population compared to controls (21.6% vs. 7.1%, p < 0.001). Intervention physicians were more likely to discontinue or adjust the interacting agent compared to controls (62.9% vs. 8.3%, p = 0.001), and patient-reported symptoms also significantly declined (29.6% vs. 20.1%, p = 0.045). These results were nearly identical to concurrent measurements that used simulated patients, wherein intervention was more likely to both make a DDI diagnosis (56.3% vs. 21.6%, p < 0.001) and stop the interacting medications (58.3% versus 26.6%, p < 0.001). Bringing a new diagnostic test to market, particularly for an under-recognized clinical problem, requires robust data on both clinical validity and clinical utility. The results of this follow-up study showed that the use of DDI testing in real-world patients significantly improved (1) primary care patient management of drug interactions and (2) patient outcomes.

Objective. To determine the impact of a workshop on the growth mindset and team communication of first year Doctor of Pharmacy (PharmD) students. Methods. A multi-week workshop was developed for first year pharmacy students. The workshop included completion of the StrengthsFinder 2.0, a session on identifying individual and team member strengths, a session on situational communication and conflict resolution models, and a work-up of two pharmacy scenarios requiring conflict resolution. The workshop was delivered to two intervention groups (fall 2019 and fall 2018) and compared to a control group (fall 2017). A pre-post survey was administered to measure change in students' growth mindset and team communication using the validated Growth Mindset and Team Communication (GMTC) tool. Data were analyzed using descriptive statistics, independent sample t tests, and chi-square tests to compare difference and association. Focus groups were conducted in fall 2017 and fall 2018 to assess students' views regarding teamwork. Results. Team communication subscale scores increased significantly among students in the intervention group while there was no significant change in these scores among students in the control group. The focus groups reflected that students had overall positive views about team communication and collaboration, which were also supported by discussions of advantages and challenges during teamwork. Conclusion. A teamwork workshop affected pharmacy students' communication skills. Future work should focus on longitudinal measurement of students' self-views to determine the long-term impact of teamwork training interventions., (© 2021 American Association of Colleges of Pharmacy.)

T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) characterized by rare malignant B cells within a robust but ineffective immune cell infiltrate. The mechanistic basis of immune escape in TCRLBCL is poorly defined and not targeted therapeutically. We performed a genetic and quantitative spatial analysis of the PD-1/PD-L1 pathway in a multi-institutional cohort of TCRLBCLs and found that malignant B cells harbored PD-L1/PD-L2 copy gain or amplification in 64% of cases, which was associated with increased PD-L1 expression (P = .0111). By directed and unsupervised spatial analyses of multiparametric cell phenotypic data within the tumor microenvironment, we found that TCRLBCL is characterized by tumor-immune "neighborhoods" in which malignant B cells are surrounded by exceptionally high numbers of PD-L1-expressing TAMs and PD-1+ T cells. Furthermore, unbiased clustering of spatially resolved immune signatures distinguished TCRLBCL from related subtypes of B-cell lymphoma, including classic Hodgkin lymphoma (cHL) and DLBCL-NOS. Finally, we observed clinical responses to PD-1 blockade in 3 of 5 patients with relapsed/refractory TCRLBCL who were enrolled in clinical trials for refractory hematologic malignancies (NCT03316573; NCT01953692), including 2 complete responses and 1 partial response. Taken together, these data implicate PD-1 signaling as an immune escape pathway in TCRLBCL and also support the potential utility of spatially resolved immune signatures to aid the diagnostic classification and immunotherapeutic prioritization of diverse tumor types., (© 2021 by The American Society of Hematology.)

Objective: The objective of this study was to develop and conduct psychometric validation of a tool to assess self-views of a growth mindset and team communication skills among pharmacists., Design: The Mindset and Team Communication Tool was developed to assess self-views of growth mindset and team communication. The survey consisted of 2 parts: (1) 14 items on growth mindset and (2) 13 items on team communication; a 4-point Likert scale of agreement was used as an option to answer all items., Setting and Participants: The survey was administered to first-year student pharmacists from 2017 to 2019. The participants completed a presurvey at the beginning of the semester and a postsurvey at the end of the semester (3-month follow-up period)., Outcome Measures: Psychometric validation was performed by assessing the following properties: face and content validity, internal consistency reliability, construct validity, test-retest reliability, responsiveness validity, and convergent validity., Results: A total of 174 participants completed both the pre- and postsurvey (response rate = 92.7%). Internal consistency reliability demonstrated a Cronbach alpha coefficient of 0.827. Construct validity showed that all measures, except for 6 items, loaded highly onto 2 components. Test-retest reliability revealed a statistically significantly positive relationship between the pre- and postsurvey scores. Responsiveness validity demonstrated a statistically significant improvement in the score when an intervention was provided. Convergent validity showed no correlation between the tool score and course grades., Conclusion: The Mindset and Team Communication Tool demonstrated validity and reliability across a robust set of psychometric values and provides a foundation to describe pharmacists' self-views and explore associations of these views with behavior in teamwork-based environments., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Impact of medication-related problems (MRPs) on persistently high hospital readmission rates are not well described. Objective: The purpose of this study was to determine the rate and type of MRPs attributed to rehospitalization within 30 days of discharge from a general internal medicine hospitalists' service at a nonacademic medical center. Methods: A retrospective cohort study was conducted evaluating consecutive patients readmitted within 30-days after discharge to home from an internal medicine hospitalist service. Readmissions attributed to MRPs in physician documentation were systematically classified as indication, effectiveness, adverse drug reaction, or nonadherence problems and evaluated for possible preventability. Descriptive statistics were used to describe the rate and type of MRP. Results: Evaluation of consecutive 30-day readmissions (n = 203) to a nonteaching community hospital identified 50.2% of admissions attributed to MRPs. MRPs (n = 102) were categorized as problems of indication (34.3%), efficacy (19.6%), adverse drug events (18.6%), and nonadherence (27.5%). One third of 30-day readmissions in this cohort were attributed to potentially preventable MRPs. Conclusion: MRPs are frequently implicated in 30-day hospital readmissions in a nonteaching community hospital representing an opportunity for context-specific improvements., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Disease relapse remains the leading cause of failure after autologous stem cell transplantation (ASCT) for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). We conducted a phase 2, multicenter, single-arm study of the anti-PD-1 monoclonal antibody pembrolizumab given after ASCT in patients with chemosensitive DLBCL, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary endpoint) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Twenty-nine patients were treated on this study; 62% completed all 8 cycles. Seventy-nine percent of patients experienced at least one grade 3 or higher adverse event, and 34% experienced at least one grade 2 or higher immune-related adverse event. Overall, 59% of patients were alive and progression free at 18 months, which did not meet the primary endpoint. The 18-month overall survival was 93%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with R/R DLBCL, but the PFS did not meet the protocol-specific primary objective and therefore does not support a larger confirmatory study. This trial was registered at www.clinicaltrials.gov as #NCT02362997., (© 2020 by The American Society of Hematology.)

Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997., (© 2019 by The American Society of Hematology.)

Demonstrating clinical utility for diagnostic tests and securing coverage and reimbursement requires high quality and, ideally, randomized controlled trial (RCT) data. Traditional RCTs are often too costly, slow, and cumbersome for diagnostic firms. Alternative data options are needed. We evaluated four RCTs using virtual patients to demonstrate clinical utility. Each study used a similar pre-post intervention, two round design to facilitate comparison. Representative samples of physicians were recruited and randomized into control and intervention arms. All physicians were asked to care for their virtual patients during two assessment rounds, separated by a multi-week time interval. Between rounds, intervention physicians reviewed educational materials on the diagnostic test. All physician responses were scored against evidence-based care criteria. RCTs using virtual patients can demonstrate clinical utility for a variety of diagnostic test types, including: (1) an advanced multi-biomarker blood test, (2) a chromosomal microarray, (3) a proteomic assay analysis, and (4) a multiplex immunofluorescence imaging platform. In two studies, utility was demonstrated for all targeted patient populations, while in the other two studies, utility was only demonstrated for a select sub-segment of the intended patient population. Of these four tests, two received positive coverage decisions from Palmetto, one utilized the study results to support commercial payer adjudications, and the fourth company went out of business. RCTs using virtual patients are a cost-effective approach to demonstrate the presence or absence of clinical utility.

Background: Drug-drug interactions (DDIs) are ubiquitous, harmful and a leading cause of morbidity and mortality. With an aging population, growth in polypharmacy, widespread use of supplements, and the rising opioid abuse epidemic, primary care physicians (PCPs) are increasingly challenged with identifying and preventing DDIs. We set out to evaluate current clinical practices related to identifying and treating DDIs and to determine if opportunities to increase prevention of DDIs and their adverse events could be identified., Methods: In a nationally representative sample of 330 board-certified family and internal medicine practitioners, we evaluated whether PCPs assessed DDIs in the care they provided for three simulated patients. The patients were taking common prescription medications (e.g. opioids and psychiatric medications) along with other common ingestants (e.g. supplements and food) and presented with symptoms of DDIs. Physicians were scored on their ability to inquire about the patient's medications, investigate possible DDIs, evaluate the patient, and provide treatment recommendations. We scored the physicians' care recommendations against evidence-based criteria, including overall care quality and treatment for DDIs., Results: Average overall quality of care score was 50.5% ± 12.0%. Despite >99% self-reported use of medication reconciliation practices and tools, physicians identified DDIs in only 15.3% of patients, with 15.5% ± 20.3% of DDI-specific treatment by the physicians., Conclusions: PCPs in this study did not recognize or adequately treat DDIs. Better methods are needed to screen for DDIs in the primary care setting.

Drug⁻drug interactions (DDIs) are a leading cause of morbidity and mortality. New tools are needed to improve identification and treatment of DDIs. We conducted a randomized controlled trial to assess the clinical utility of a new test to identify DDIs and improve their management. Primary care physicians (PCPs) cared for simulated patients presenting with DDI symptoms from commonly prescribed medications and other ingestants. All physicians, in either control or one of two intervention groups, cared for six patients over two rounds of assessment. Intervention physicians were educated on the DDI test and given access to these test reports when caring for their patients in the second round. At baseline, we saw no significant differences in making the DDI diagnosis ( p = 0.071) or DDI-related treatment ( p = 0.640) between control and intervention arms. By round two, providers who accessed the DDI test performed significantly better in making the DDI diagnosis (+41.6%) and performing DDI-specific treatment (+12.2%) than in the previous round, and were 9.8 and 20.4 times more likely to diagnose and identify the DDI ( p < 0.001 for all). The introduction of a definitive DDI test significantly increased identification, appropriate management, and counseling of DDIs among PCPs, which has the potential to improve clinical care.

The College of Veterinary Medicine and Biomedical Sciences (CVMBS) at Texas A&M University (TAMU) has developed a multifaceted program in partnership with the Brazos Animal Shelter to provide teaching opportunities with shelter animals during all four years of the professional curriculum. In the first three semesters of the professional program, students working in small groups spend two hours per semester at the shelter performing physical examinations, administering vaccinations and anthelmintics, completing heartworm or FeLV/FIV testing, and performing simple medical treatments. In an expanded fourth-year program, groups of six students spend 16 contact hours at the shelter during two-week rotations, completing similar tasks. Through this program, each student practices animal-handling skills and routine procedures on an average of 150 to 200 dogs and cats. In addition, during third- and fourth-year surgery courses, student teams spay or neuter an average of 12 to 18 dogs or cats each week. More than 800 animals are spayed/neutered annually through this program, and each student directly participates in 12 to 15 spay/neuter survival surgeries. The program represents a creative approach to veterinary training that conscientiously uses animal resources in a positive fashion. We believe that this is a successful partnership between a state-supported veterinary college and a non-profit shelter that benefits both agencies. We encourage other veterinary colleges to explore similar partnership opportunities to provide optimal training for professional students while using animal resources efficiently.

A 16-month-old boy, diagnosed at age 3 months with osteopetrosis, was treated since age 6 months with rhIFN-gamma in combination with rhM-CSF. The child developed acute respiratory distress within 1 hr of a paternal platelet transfusion. Both the child and the father were blood group type O, and platelets were collected the previous day from the father. Chest X-ray revealed right pulmonary consolidation and a complete "whiteout" on the left. By 24 hr, the lungs had the appearance of adult respiratory distress syndrome (ARDS). Over the course of the next 11 days, the child remained intubated and hypotensive, and died of respiratory insufficiency 11 days later. ARDS was confirmed at autopsy. Pre- and posttransfusion patient's sera, as well as paternal serum, were tested by granulocyte agglutination and flow cytometry against granulocytes (PMN) from the patient, father, mother, and routine cell-panel donors and lymphocytes for the presence of neutrophil-specific and lymphocyte (HLA) antibodies, to rule out classical transfusion-related acute lung injury (TRALI). Both the patient's and the paternal sera were devoid of antibodies, but the patient's neutrophils demonstrated strong binding of cytophilic IgG accompanied by extremely low serum IgG and IgG1 levels. Since rhIFN-gamma is known to upregulate Fc gamma receptor type I (Fc(gamma)RI) with high affinity for IgG1, the binding of cytophilic IgG suggests that the patient's neutrophils may have been activated in vivo. The case report of another child with osteopetrosis has also been described. Although the blood specimen was not available for serological studies, this 4 1/2-year-old child treated with rhIFN-gamma and rhM-CSF also died of adult respiratory distress syndrome, with similar clinical presentations.

High-dose chemoradiotherapy in conjunction with autologous bone marrow transplantation has been used in the treatment of advanced stage neuroblastoma. Because of frequent marrow involvement, marrow purging methods, such as the immunomagnetic technique, have been developed. Current cost constraints force institutions to consider in-house purging versus submission of marrow to purging centers. Our analysis demonstrates that 15 procedures per year are needed to justify an up-front investment in equipment and supplies with a break-even period of 5 years. This number is also required to keep technical proficiency current without frequent retraining of personnel. The analysis includes start-up costs for institutions without a bone marrow processing laboratory, as well as for institutions already processing marrow or peripheral blood stem cells. For institutions performing fewer procedures per year, submission of marrow to purging centers is more cost effective than in-housing purging.

The noninfectious complications of blood transfusion consist of a diverse group of immune-mediated transfusion reactions that range from immediate life-threatening to subclinical reactions. Each reaction involves the recognition and interaction of the both the humoral and cellular immune systems. In the past, many of the noninfectious complications of transfusion were attributed solely to antigen-antibody interactions. Today, an emerging body of evidence suggests that cytokines and cytokine inhibitors play a central role in the pathophysiology of immune-mediated transfusion reactions and account for the broad diversity of clinical presentations.

The separation of bone marrow (BM) constituents, BM cell purging, and cryopreservation of BM and peripheral blood stem cells (PBSC) are frequently performed in the clinical laboratories. In 1991, recognizing the increasing involvement of transfusion services in BM and PBSC processing, the American Association of Blood Banks (AABB) established standards that, in general, held BM and PBSC processing to the same standards as applied to blood components. In 1993, the AABB defined the information that was required on the container label, but did not establish a uniform system of labeling for BM/PBSC preparations. We present a system of labeling for definitive identification of allogeneic BM and autologous BM/PBSC collections that identifies all components derived from the original product from the time of collection to final infusion or disposal. This system avoids the risk of component misidentification, particularly when multiple collections are processed simultaneously. Our transfusion service computer system was adapted with BM/PBSC component names and abbreviated codes to provide a singular validated mechanism for labeling, tracking, and final disposition of these products. We propose the adaptation of a "universal system" for BM/PBSC labeling for AABB accredited transfusion services utilizing the existing guidelines for labeling of blood and blood components.

Predictive values for patient engraftment in neuroblastoma have not been defined. By analyzing the parameters available to us at the time of harvest and post-harvest, we found that the MNC/kg after purging demonstrated significant correlation with patient engraftment as measured by the patient's time to reach a WBC count of 1,000/microL and an ANC count of 500/microL. Platelet and red cell independence was difficult to measure as some of these patients remain platelet- and red cell-dependent for extended periods of time. Platelet refractoriness, alloimmunization, infection and many other factors can delay platelet and red cell recovery following transplantation. A larger number of patients is needed to assess a correlation between the parameters analyzed and platelet and red cell recovery, as well as to validate our observation with myeloid recovery.

The 13th edition of the standards of the American Association of Blood Banks specified storage at 1 to 6 degrees C for cryoprecipitated anti-hemophilic factor (Cryo) administered up to 6 hours after thawing if the Cryo is used for factor VIII (FVIII) content (Standard J4.210). Previous editions specified room-temperature (RT) storage for up to 6 hours. Currently, the temperature specification has been deleted. There are few data addressing the optimal storage temperature and maximum storage time for FVIII and fibrinogen in thawed Cryo. Thirty bags of Cryo were assayed for FVIII and fibrinogen. Each bag was divided into two aliquots; one was stored at RT and the other at 1 to 6 degrees C. Assays were performed immediately after thawing (Base) and 6 and 24 hours after thawing, respectively. All samples were filtered through 200-mu blood component infusion sets before assay. Three hundred analyses were performed, 150 each for FVIII and fibrinogen by conventional clotting technique. Data were analyzed by using a paired t test. Cryo stored at 1 to 6 degrees C for 6 and 24 hours showed an FVIII loss of 35 percent (p less than 0.0001) and 63 percent (p less than 0.0001), respectively. Cryo stored at RT for 6 and 24 hours had an FVIII loss of 8 percent (p greater than 0.05) and 20 percent (p less than 0.0001). Cryo stored at 1 to 6 degrees C for 6 and 24 hours had a fibrinogen loss of 20 percent (p less than 0.0001) and 43 percent (p less than 0.0001). Cryo stored at RT for 6 hours had no fibrinogen loss and a 2 percent loss at 24 hours (p greater than 0.05). These preliminary data show a significant loss of FVIII and fibrinogen activity in Cryo stored at 1 to 6 degrees C and filtered before assay. The FVIII and fibrinogen activity at RT is clearly maintained up to 6 hours after thawing.

Proximal interphalangeal (PIP) joint fracture-subluxations represent a small component of hyperextension injuries to the finger. Six unstable PIP fracture-subluxations that were not amenable to nonoperative treatment underwent open reduction and internal fixation. Among the patients, the technique of open reduction and internal fixation with temporary transarticular K-wire fixation and early protected range of motion has been found to result in a good range of motion with minimal complaints on follow-up.

Irradiation of stored red blood cells (RBC) is increasingly utilized for patients who are immunosuppressed or on chemotherapeutic regimens. With the growing demand for irradiated cellular blood products, there has been an increasing need for transfusion services to store previously irradiated blood until needed for transfusion. The effect of irradiation on aging stored RBC has not been studied to date. Five units each of group A, RBC collected in CPD-Adsol (AS-1) with a prior shelf-life of 10, 20, 30, and 40 days, respectively, were divided equally utilizing a sterile docking device and stored at 1 to 6 degrees C. Baseline samples from each bag were obtained for the measurement of extracellular potassium (K+), plasma free hemoglobin (PFH), total lactate dehydrogenase (LD), and erythrocyte 2,3-DPG activity. One of each pair received 2,000 rads of gamma irradiation. Samples were obtained at 3 and 7 days post-irradiation, and multiples of 7 days until expiration. All irradiated units reached a state of K+ equilibrium at 60 to 70 mmol per L irrespective of the length of previous storage with an inverse relationship of RBC age at irradiation and the time required to reach the state of equilibrium. Increased K+ leakage from irradiated aging RBC suggests the need for including in vivo studies of cell survival to establish a post-irradiation storage life. Length of storage prior to irradiation had no effect on PFH, LD activity, and 2,3-diphosphoglycerate (2,3-DPG) activity compared to paired controls.

Red blood cells (pRBC) collected in citrate, phosphate, dextrose, adenine-formula 1 (CPDA-1) and citrate, phosphate, dextrose-adenine, manitol saline solution (CPD-ADSOL [AS-1]) anticoagulants are increasingly being stored for variable periods in transfusion service inventories following irradiation. While anecdotal reports of increased K+ following irradiation and storage have recently appeared in the literature, concomitant in vitro biochemical changes resulting from differences in anticoagulants have not been reported. Utilizing two venipunctures, two units each of 225 mL of blood from five volunteers were collected in anticoagulant-adjusted CPDA-1 and AS-1 bags. Within two hours of collection, each unit was equally divided. One of each pair was irradiated (2000 rads). Samples were analyzed on Days 0, 1, 3, 7, and every seven days to expiration. Irradiation resulted in a 2.3 fold increase in K+ during the first seven days of storage for both anticoagulants, although significantly greater K+ levels were observed in the CPDA-1 pairs compared to the AS-1 pairs. Comparison of glucose utilization, plasma free hemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and lactate dehydrogenase between control and irradiated CPDA-1 and AS-1 pairs and between anticoagulants were documented.

A 44-year-old Caucasian female was admitted with a subarachnoid hemorrhage owing to a multilobular tubular anterior communicating artery aneurysm. Eleven days after the original craniotomy, an epidural hematoma was evacuated. The patient was placed on empiric nafcillin antimicrobial coverage (two g every six hours). Within 24 hours, the onset of epistaxis and oozing of blood from the endotracheal tube and craniotomy site was noted. Recurrent subdural and epidural hematomas necessitated a third emergent craniotomy. The development of an acquired qualitative platelet defect was suggested by the findings of a prolonged template bleeding time and markedly abnormal platelet aggregation/ATP release studies despite a normal platelet count. Nafcillin therapy was immediately discontinued. Clinical bleeding resolved. Subsequent bleeding times and platelet aggregation studies confirmed the nafcillin-induced platelet dysfunction.