Now showing items 21-40 of 1843

    • POINT-OF-CARE TECHNOLOGY CLINICIAN-FACING SURVEY Dataset for Sampling of Healthcare Professionals’ Perspective on Point-of-Care Technologies from 2019-2021: a survey of benefits, concerns, and development

      Orwig, Taylor; Sutaria, Shiv; Wang, Ziyue; Howard-Wilson, Sakeina; Dunlap, Denise; Lilly, Craig M; Buchholz, Bryan; McManus, David D.; Hafer, Nathaniel (2023-11-27)
      Point-of-care technology (POCT) plays a vital role in modern healthcare by providing a fast diagnosis, improving patient management, and extending healthcare access to remote and resource-limited areas. The objective of this study was to understand how healthcare professionals in the United States perceived POCTs during 2019-2021 to assess the decision-making process of implementing these newer technologies into everyday practice.
    • Differential Viral Dynamics by Sex and Body Mass Index During Acute SARS-CoV-2 Infection: Results from a Longitudinal Cohort Study

      Herbert, Carly; Manabe, Yukari C; Filippaios, Andreas; Lin, Honghuang; Wang, Biqi; Achenbach, Chad; Kheterpal, Vik; Hartin, Paul; Suvarna, Thejas; Harman, Emma; et al. (2023-11-16)
      Background: There is evidence of an association of severe COVID-19 outcomes with increased body mass index (BMI) and male sex. However, few studies have examined the interaction between sex and BMI on SARS-CoV-2 viral dynamics. Methods: Participants conducted RT-PCR testing every 24-48 hours over a 15-day period. Sex and BMI were self-reported, and Ct values from E-gene were used to quantify viral load. Three distinct outcomes were examined using mixed effects generalized linear models, linear models, and logistic models, respectively: all Ct values (Model 1); nadir Ct value (model 2); and strongly detectable infection (at least one Ct value ≤28 during their infection) (Model 3). An interaction term between BMI and sex was included, and inverse logit transformations were applied to quantify the differences by BMI and sex using marginal predictions. Results: In total, 7,988 participants enrolled in this study, and 439 participants (Model 1) and 309 (Model 2 and 3) were eligible for these analyses. Among males, increasing BMI was associated with lower Ct values in a dose-response fashion. For participants with BMIs greater than 29, males had significantly lower Ct values and nadir Ct values than females. In total, 67.8% of males and 55.3% of females recorded a strongly detectable infection; increasing proportions of men had Ct values <28 with BMIs of 35 and 40. Conclusions: We observed sex-based dimorphism in relation to BMI and COVID-19 viral load. Further investigation is needed to determine the cause, clinical impact, and transmission implications of this sex-differential effect of BMI on viral load.
    • UMCCTS Newsletter, November 2023

      UMass Center for Clinical and Translational Science (2023-11-01)
      This is the November 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Prevalence and predictors of shared decision-making in goals-of-care clinician-family meetings for critically ill neurologic patients: a multi-center mixed-methods study

      Fleming, Victoria; Prasad, Abhinav; Ge, Connie; Crawford, Sybil; Meraj, Shazeb; Hough, Catherine L; Lo, Bernard; Carson, Shannon S; Steingrub, Jay; White, Douglas B; et al. (2023-10-21)
      Background: Shared decision-making is a joint process where patients, or their surrogates, and clinicians make health choices based on evidence and preferences. We aimed to determine the extent and predictors of shared decision-making for goals-of-care discussions for critically ill neurological patients, which is crucial for patient-goal-concordant care but currently unknown. Methods: We analyzed 72 audio-recorded routine clinician-family meetings during which goals-of-care were discussed from seven US hospitals. These occurred for 67 patients with 72 surrogates and 29 clinicians; one hospital provided 49/72 (68%) of the recordings. Using a previously validated 10-element shared decision-making instrument, we quantified the extent of shared decision-making in each meeting. We measured clinicians' and surrogates' characteristics and prognostic estimates for the patient's hospital survival and 6-month independent function using post-meeting questionnaires. We calculated clinician-family prognostic discordance, defined as ≥ 20% absolute difference between the clinician's and surrogate's estimates. We applied mixed-effects regression to identify independent associations with greater shared decision-making. Results: The median shared decision-making score was 7 (IQR 5-8). Only 6% of meetings contained all 10 shared decision-making elements. The most common elements were "discussing uncertainty"(89%) and "assessing family understanding"(86%); least frequent elements were "assessing the need for input from others"(36%) and "eliciting the context of the decision"(33%). Clinician-family prognostic discordance was present in 60% for hospital survival and 45% for 6-month independent function. Univariate analyses indicated associations between greater shared decision-making and younger clinician age, fewer years in practice, specialty (medical-surgical critical care > internal medicine > neurocritical care > other > trauma surgery), and higher clinician-family prognostic discordance for hospital survival. After adjustment, only higher clinician-family prognostic discordance for hospital survival remained independently associated with greater shared decision-making (p = 0.029). Conclusion: Fewer than 1 in 10 goals-of-care clinician-family meetings for critically ill neurological patients contained all shared decision-making elements. Our findings highlight gaps in shared decision-making. Interventions promoting shared decision-making for high-stakes decisions in these patients may increase patient-value congruent care; future studies should also examine whether they will affect decision quality and surrogates' health outcomes.
    • UMCCTS Newsletter, October 2023

      UMass Center for Clinical and Translational Science (2023-10-02)
      This is the October 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Awake intracerebroventricular delivery and safety assessment of oligonucleotides in a large animal model

      Benatti, Hector Ribeiro; Prestigiacomo, Rachel D; Taghian, Toloo; Miller, Rachael; King, Robert; Gounis, Matthew J; Celik, Ugur; Bertrand, Stephanie; Tuominen, Susan; Bierfeldt, Lindsey; et al. (2023-09-26)
      Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking. The use of intracerebroventricular (i.c.v.) catheters offers a solution for repeated dosing; however, fixation techniques in large animal models are not standardized and are not reliable. Here we describe a novel surgical technique in a sheep model for i.c.v. delivery of neurotherapeutics based on the fixation of the i.c.v. catheter with a 3D-printed anchorage system composed of plastic and ceramic parts, compatible with magnetic resonance imaging, computed tomography, and electroencephalography (EEG). Our technique allowed tracking electrical brain activity in awake animals via EEG and video recording during and for the 24-h period after administration of a novel oligonucleotide in sheep. Its anchoring efficiency was demonstrated for at least 2 months and will be tested for up to a year in ongoing studies.
    • Effectiveness of various COVID-19 vaccine regimens among 10.4 million patients from the National COVID Cohort Collaborative during Pre-Delta to Omicron periods - United States, 11 December 2020 to 30 June 2022

      Fu, Yuanyuan; Wu, Kaipeng; Wang, Zhanwei; Yang, Hua; Chen, Yu; Wu, Lang; Yanagihara, Richard; Hedges, Jerris R; Wang, Hongwei; Deng, Youping (2023-09-22)
      Objective: This study reports the vaccine effectiveness (VE) of COVID-19 vaccine regimens in the United States, based on the National COVID Cohort Collaborative (N3C) database. Methods: Data from 10.4 million adults, enrolled in the N3C from 11 December 2020 to 30 June 2022, were analyzed. VE against infection and death outcomes were evaluated across 13 vaccine regimens in recipient cohorts during the Pre-Delta, Delta, and Omicron periods. VE was estimated as (1-odds ratio) × 100% by multivariate logistic regression, using the unvaccinated cohort as reference. Results: Natural immunity showed a highly protective effect (70.33%) against re-infection, but the mortality risk among the unvaccinated population was increased after re-infection; vaccination following infection reduced the risk of re-infection and death. mRNA-1273 full vaccination plus mRNA-1273 booster showed the highest anti-infection effectiveness (47.59%) (95% CI, 46.72-48.45) in the overall cohort. In the type 2 diabetes cohort, VE against infection was highest with BNT162b2 full vaccination plus mRNA-1273 booster (61.19%) (95% CI, 53.73-67.75). VE against death was also highest with BNT162b2 full vaccination plus mRNA-1273 booster (89.56%) (95% CI, 85.75-92.61). During the Pre-Delta period, all vaccination regimens showed an anti-infection effect; during the Delta period, only boosters, mixed vaccines, and Ad26.COV2.S vaccination exhibited an anti-infection effect; during the Omicron period, none of the vaccine regimens demonstrated an anti-infection effect. Irrespective of the variant period, even a single dose of mRNA vaccine offered protection against death, thus demonstrating survival benefit, even in the presence of infection or re-infection. Similar patterns were observed in patients with type 2 diabetes. Conclusions: Although the anti-infection effect declined as SARS-CoV-2 variants evolved, all COVID-19 mRNA vaccines had sustained effectiveness against death. Vaccination was crucial for preventing re-infection and reducing the risk of death following SARS-CoV-2 infection.
    • Association of neighborhood-level sociodemographic factors with Direct-to-Consumer (DTC) distribution of COVID-19 rapid antigen tests in 5 US communities

      Herbert, Carly; Shi, Qiming; Baek, Jonggyu; Wang, Biqi; Kheterpal, Vik; Nowak, Christopher; Suvarna, Thejas; Singh, Aditi; Hartin, Paul; Durnam, Basyl; et al. (2023-09-22)
      Background: Many interventions for widescale distribution of rapid antigen tests for COVID-19 have utilized online, direct-to-consumer (DTC) ordering systems; however, little is known about the sociodemographic characteristics of home-test users. We aimed to characterize the patterns of online orders for rapid antigen tests and determine geospatial and temporal associations with neighborhood characteristics and community incidence of COVID-19, respectively. Methods: This observational study analyzed online, DTC orders for rapid antigen test kits from beneficiaries of the Say Yes! Covid Test program from March to November 2021 in five communities: Louisville, Kentucky; Indianapolis, Indiana; Fulton County, Georgia; O'ahu, Hawaii; and Ann Arbor/Ypsilanti, Michigan. Using spatial autoregressive models, we assessed the geospatial associations of test kit distribution with Census block-level education, income, age, population density, and racial distribution and Census tract-level Social Vulnerability Index. Lag association analyses were used to measure the association between online rapid antigen kit orders and community-level COVID-19 incidence. Results: In total, 164,402 DTC test kits were ordered during the intervention. Distribution of tests at all sites were significantly geospatially clustered at the block-group level (Moran's I: p < 0.001); however, education, income, age, population density, race, and social vulnerability index were inconsistently associated with test orders across sites. In Michigan, Georgia, and Kentucky, there were strong associations between same-day COVID-19 incidence and test kit orders (Michigan: r = 0.89, Georgia: r = 0.85, Kentucky: r = 0.75). The incidence of COVID-19 during the current day and the previous 6-days increased current DTC orders by 9.0 (95% CI = 1.7, 16.3), 3.0 (95% CI = 1.3, 4.6), and 6.8 (95% CI = 3.4, 10.2) in Michigan, Georgia, and Kentucky, respectively. There was no same-day or 6-day lagged correlation between test kit orders and COVID-19 incidence in Indiana. Conclusions: Our findings suggest that online ordering is not associated with geospatial clustering based on sociodemographic characteristics. Observed temporal preferences for DTC ordering can guide public health messaging around DTC testing programs.
    • Predictive models of long COVID

      Antony, Blessy; Blau, Hannah; Casiraghi, Elena; Loomba, Johanna J; Callahan, Tiffany J; Laraway, Bryan J; Wilkins, Kenneth J; Antonescu, Corneliu C; Valentini, Giorgio; Williams, Andrew E; et al. (2023-09-04)
      Background: The cause and symptoms of long COVID are poorly understood. It is challenging to predict whether a given COVID-19 patient will develop long COVID in the future. Methods: We used electronic health record (EHR) data from the National COVID Cohort Collaborative to predict the incidence of long COVID. We trained two machine learning (ML) models - logistic regression (LR) and random forest (RF). Features used to train predictors included symptoms and drugs ordered during acute infection, measures of COVID-19 treatment, pre-COVID comorbidities, and demographic information. We assigned the 'long COVID' label to patients diagnosed with the U09.9 ICD10-CM code. The cohorts included patients with (a) EHRs reported from data partners using U09.9 ICD10-CM code and (b) at least one EHR in each feature category. We analysed three cohorts: all patients (n = 2,190,579; diagnosed with long COVID = 17,036), inpatients (149,319; 3,295), and outpatients (2,041,260; 13,741). Findings: LR and RF models yielded median AUROC of 0.76 and 0.75, respectively. Ablation study revealed that drugs had the highest influence on the prediction task. The SHAP method identified age, gender, cough, fatigue, albuterol, obesity, diabetes, and chronic lung disease as explanatory features. Models trained on data from one N3C partner and tested on data from the other partners had average AUROC of 0.75. Interpretation: ML-based classification using EHR information from the acute infection period is effective in predicting long COVID. SHAP methods identified important features for prediction. Cross-site analysis demonstrated the generalizability of the proposed methodology. Funding: NCATS U24 TR002306, NCATS UL1 TR003015, Axle Informatics Subcontract: NCATS-P00438-B, NIH/NIDDK/OD, PSR2015-1720GVALE_01, G43C22001320007, and Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231.
    • UMCCTS Newsletter, September 2023

      UMass Center for Clinical and Translational Science (2023-08-31)
      This is the September 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Who is pregnant? Defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C)

      Jones, Sara E; Bradwell, Katie R; Chan, Lauren E; McMurry, Julie A; Olson-Chen, Courtney; Tarleton, Jessica; Wilkins, Kenneth J; Ly, Victoria; Ljazouli, Saad; Qin, Qiuyuan; et al. (2023-08-16)
      Objectives: To define pregnancy episodes and estimate gestational age within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and methods: We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS), and applied it to EHR data in the N3C (January 1, 2018-April 7, 2022). HIPPS combines: (1) an extension of a previously published pregnancy episode algorithm, (2) a novel algorithm to detect gestational age-specific signatures of a progressing pregnancy for further episode support, and (3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated pregnancy cohorts based on gestational age precision and pregnancy outcomes for assessment of accuracy and comparison of COVID-19 and other characteristics. Results: We identified 628 165 pregnant persons with 816 471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, abortions), and 23.3% had unknown outcomes. Clinician validation agreed 98.8% with HIPPS-identified episodes. We were able to estimate start dates within 1 week of precision for 475 433 (58.2%) episodes. 62 540 (7.7%) episodes had incident COVID-19 during pregnancy. Discussion: HIPPS provides measures of support for pregnancy-related variables such as gestational age and pregnancy outcomes based on N3C data. Gestational age precision allows researchers to find time to events with reasonable confidence. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational age that addresses data inconsistency and missingness in EHR data.
    • Can psychological interventions prevent or reduce risk for perinatal anxiety disorders? A systematic review and meta-analysis

      Zimmermann, Martha; Julce, Clevanne; Sarkar, Pooja; McNicholas, Eileen; Xu, Lulu; Carr, Catherine W.; Boudreaux, Edwin D; Lemon, Stephenie C; Byatt, Nancy (2023-08-16)
      Objective: Little is known about the extent to which interventions can prevent perinatal anxiety disorders. We conducted a systematic review and meta-analysis to examine whether interventions can decrease the onset and symptoms of perinatal anxiety among individuals without an anxiety disorder diagnosis. Method: We conducted a comprehensive literature search across five databases related to key concepts: (1) anxiety disorders/anxiety symptom severity (2) perinatal (3) interventions (4) prevention. We included studies that examined a perinatal population without an anxiety disorder diagnosis, included a comparator group, and assessed perinatal anxiety. We included interventions focused on perinatal anxiety as well as interventions to prevent perinatal depression or influence related outcomes (e.g., physical activity). Results: Thirty-six studies were included. No study assessing the incidence of perinatal anxiety disorder (n = 4) found a significant effect of an intervention. Among studies assessing anxiety symptom severity and included in the quantitative analysis (n = 30), a meta-analysis suggested a small standardized mean difference of -0.31 (95% CI [-0.46, -0.16], p < .001) for anxiety at post intervention, favoring the intervention group. Both mindfulness (n = 6), and cognitive behavioral therapy approaches (n = 10) were effective. Conclusions: Interventions developed for perinatal anxiety were more effective than interventions to prevent perinatal depression. Psychological interventions show promise for reducing perinatal anxiety symptom severity, though interventions specifically targeting anxiety are needed.
    • UMCCTS Newsletter, August 2023

      UMass Center for Clinical and Translational Science (2023-08-02)
      This is the August 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Comparative safety of adding serotonin and norepinephrine reuptake inhibitors (SNRIs) versus nonsteroidal anti-inflammatory drugs (NSAIDs) to short-acting opioids for non-malignant pain in nursing homes

      Liu, Shao-Hsien; Yuan, Yiyang; Baek, Jonggyu; Nunes, Anthony P; Pawasauskas, Jayne; Hume, Anne L; Lapane, Kate L (2023-08-02)
      Background: The comparative safety of serotonin and norepinephrine reuptake inhibitors (SNRIs) as adjuvants to short-acting opioids in older adults is unknown even though SNRIs are commonly used. We compared the effects of SNRIs versus nonsteroidal anti-Inflammatory drugs (NSAIDs) on delirium among nursing home residents when SNRIs or NSAIDs were added to stable regimens of short-acting opioids. Methods: Using 2011-2016 national Minimum Data Set (MDS) 3.0 and Medicare claims data to implement a new-user design, we identified a cohort of nursing home residents receiving short-acting opioids who initiated either an SNRI or an NSAID. Delirium was defined from the Confusion Assessment Method in MDS 3.0 assessments and ICD9/10 codes using Medicare hospitalization claims. Propensity score matching balanced underlying differences for initiating treatments on 39 demographic and clinical characteristics (nSNRIs = 5350; nNSAIDs = 5350). Fine and Gray models provided hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for the competing risk of death. Results: Hydrocodone was the most commonly used short-acting opioid (48%). Residents received ~23 mg daily oral morphine equivalent at the time of SNRIs/NSAIDs initiation. The majority were women, non-Hispanic White, and aged ≥75 years. There were no differences in any of the confounders after propensity matching. Over 1 year, 10.8% of SNRIs initiators and 8.9% of NSAIDs initiators developed delirium. The rate of delirium onset was similar in SNRIs and NSAID initiators (HR(delirium in nursing home or hospitalization for delirium):1.10; 95% CI: 0.97-1.24; HR(hospitalization for delirium): 1.06; 95% CI: 0.89-1.25), and were similar regardless of baseline opioid daily dosage. Conclusions: Among nursing home residents, adding SNRIs to short-acting opioids does not appear to increase risk of delirium relative to initiating NSAIDs. Understanding the comparative safety of pain regimens is needed to inform clinical decisions in a medically complex population often excluded from clinical research.
    • Immunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T-cell epitopes specific to seasonal coronaviruses or cross-reactive with SARS-CoV-2

      Becerra-Artiles, Aniuska; Nanaware, Padma P; Muneeruddin, Khaja; Weaver, Grant; Shaffer, Scott A; Calvo-Calle, J Mauricio; Stern, Lawrence J (2023-07-27)
      Seasonal "common-cold" human coronaviruses are widely spread throughout the world and are mainly associated with mild upper respiratory tract infections. The emergence of highly pathogenic coronaviruses MERS-CoV, SARS-CoV, and most recently SARS-CoV-2 has prompted increased attention to coronavirus biology and immunopathology, but the T-cell response to seasonal coronaviruses remains largely uncharacterized. Here we report the repertoire of viral peptides that are naturally processed and presented upon infection of a model cell line with seasonal coronavirus OC43. We identified MHC-bound peptides derived from each of the viral structural proteins (spike, nucleoprotein, hemagglutinin-esterase, membrane, and envelope) as well as non-structural proteins nsp3, nsp5, nsp6, and nsp12. Eighty MHC-II bound peptides corresponding to 14 distinct OC43-derived epitopes were identified, including many at very high abundance within the overall MHC-II peptidome. Fewer and less abundant MHC-I bound OC43-derived peptides were observed, possibly due to MHC-I downregulation induced by OC43 infection. The MHC-II peptides elicited low-abundance recall T-cell responses in most donors tested. In vitro assays confirmed that the peptides were recognized by CD4+ T cells and identified the presenting HLA alleles. T-cell responses cross-reactive between OC43, SARS-CoV-2, and the other seasonal coronaviruses were confirmed in samples of peripheral blood and peptide-expanded T-cell lines. Among the validated epitopes, spike protein S903-917 presented by DPA1*01:03/DPB1*04:01 and S1085-1099 presented by DRB1*15:01 shared substantial homology to other human coronaviruses, including SARS-CoV-2, and were targeted by cross-reactive CD4 T cells. Nucleoprotein N54-68 and hemagglutinin-esterase HE128-142 presented by DRB1*15:01 and HE259-273 presented by DPA1*01:03/DPB1*04:01 are immunodominant epitopes with low coronavirus homology that are not cross-reactive with SARS-CoV-2. Overall, the set of naturally processed and presented OC43 epitopes comprise both OC43-specific and human coronavirus cross-reactive epitopes, which can be used to follow CD4 T-cell cross-reactivity after infection or vaccination, and to guide selection of epitopes for inclusion in pan-coronavirus vaccines.
    • Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

      O'Halloran, Jane A; Ko, Emily R; Anstrom, Kevin J; Kedar, Eyal; McCarthy, Matthew W; Panettieri, Reynold A; Maillo, Martin; Nunez, Patricia Segura; Lachiewicz, Anne M; Gonzalez, Cynthia; et al. (2023-07-25)
      Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, setting, and participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main outcomes and measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial registration: ClinicalTrials.gov Identifier: NCT04593940.
    • Challenges and solutions to superior chimeric antigen receptor-T design and deployment for B-cell lymphomas

      Gao, Jenny; Dahiya, Saurabh; Patel, Shyam A (2023-07-24)
      Chimeric antigen receptor-T (CAR-T) therapies represent a major breakthrough in cancer medicine, given the ex vivo-based technology that harnesses the power of one's own immune system. These therapeutics have demonstrated remarkable success for relapsed/refractory B-cell lymphomas. Although more than a decade has passed since the initial introduction of CAR-T therapeutics for patients with leukaemia and lymphoma, there is still significant debate as to where CAR-T therapeutics fit into the management paradigm, as consensus guidelines are limited. Competing interventions deployed in subsequent lines of therapy for aggressive lymphoma include novel targeted agents, bispecific antibodies, and time-honoured stem cell transplant. In this focused review, we discuss the major obstacles to advancing the therapeutic reach for CAR-T products in early lines of therapy. Such barriers include antigen escape, "cold" tumour microenvironments, host inflammation and CAR-T cell exhaustion. We highlight solutions including point-of-care CAR-T manufacturing and early T lymphopheresis. We review the evidence basis for early CAR-T deployment for B-cell lymphomas in light of the recent Food and Drug Administration (FDA) approval of three first-in-class anti-CD3/CD20 bispecific antibodies-mosunetuzumab, epcoritamab and glofitamab. We propose practical recommendations for 2024.
    • Pediatric High Blood Pressure Follow-up Guideline Adherence in a Massachusetts Healthcare System

      Goulding, Melissa; Ryan, Grace W; Frisard, Christine; Stevens, Elise M; Person, Sharina D.; Goldberg, Robert J.; Garg, Arvin; Lemon, Stephenie C (2023-07-22)
      Objectives: To describe adherence to the American Academy of Pediatrics' (AAP) 2017 clinical practice guidelines for follow-up after high blood pressure (BP) screening by pediatric and family medicine providers in a Massachusetts healthcare system and to assess differences in receipt of follow-up according to child- and clinic-level factors. Methods: Electronic health record data were analyzed for children aged 3-17 years who had an outpatient primary care visit during 2018 with a high BP screening (according to AAP guidelines). We classified AAP guideline adherent follow-up as BP follow-up within 6 months after an elevated finding (+2-week buffer) and within 2 weeks after a hypertensive finding (+2-week buffer). Differences in receipt of guideline adherent follow-up by child- and clinic-level factors were assessed via multilevel mixed effects logistic regression models. Results: The median age of the 4,563 included children was 12 years and 43% were female. Overall, guideline adherent follow-up was received by 17.7% of children within the recommended time interval; 27.4% for those whose index BP was elevated and 5.4% for those whose BP was hypertensive. Modeling revealed older children and those belonging to clinics with more providers, smaller patient panels, and smaller proportion of Medicaid patients were more likely to receive adherent follow-up. Conclusion: Few children received guideline adherent BP follow-up and most differences in adherence were related to clinic resources. System level interventions are needed to improve BP follow-up.
    • Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection : A Prospective Cohort Study

      Soni, Apurv; Herbert, Carly; Lin, Honghuang; Yan, Yi; Pretz, Caitlin; Stamegna, Pamela; Wang, Biqi; Orwig, Taylor; Wright, Colton; Tarrant, Seanan; et al. (2023-07-04)
      Background: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established. Objective: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants. Design: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days. Setting: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home. Participants: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result. Measurements: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status. Results: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals. Limitation: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours. Conclusion: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours. Primary funding source: National Institutes of Health RADx Tech program.
    • UMCCTS Newsletter, July 2023

      UMass Center for Clinical and Translational Science (2023-07-03)
      This is the July 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.