Now showing items 1-20 of 1840

    • SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C)

      Rahman, Asif; Russell, Michael; Zheng, Wanhong; Eckrich, Daniel; Ahmed, Imtiaz (2024-05-30)
      Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.
    • UMCCTS Newsletter, May 2024

      UMass Center for Clinical and Translational Science (2024-05-06)
      This is the May 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • CD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators

      Jiang, Hao-Ching; Park, Sung Jin; Wang, I-Hao; Bear, Daniel M; Nowlan, Alexandra; Greer, Paul L (2024-04-18)
      The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian olfactory receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.
    • UMCCTS Newsletter, April 2024

      UMass Center for Clinical and Translational Science (2024-04-01)
      This is the April 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • 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 (2024-03-08)
      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. A 5-point Likert scale survey was sent to respondents to evaluate their perceptions of benefits, concerns, characteristics, and development of point-of-care technologies. The 2021 survey was distributed November 1st, 2021- February 15th, 2022, with a total of 168 independent survey responses received. Of the respondents, 59% identified as male, 73% were white, and 48% have been in practice for over 20 years. The results showed that most agreed that POCTs improve patient management (94%) and improve clinician confidence in decision making (92%). Healthcare professionals were most concerned with potentially not being reimbursed for the cost of the POCT (37%). When asked to rank the top 3 important characteristics of POCT, respondents chose accuracy, ease of use, and availability. It is important to note this survey was conducted during the COVID-19 pandemic. To achieve an even greater representation of healthcare professionals' point of view on POCTs, further work to obtain responses from a larger, more diverse population of providers is needed.
    • Social engagement and cognitive impairment among nursing home residents: The role of sensory impairment

      Xu, Shu; Jesdale, William M; Dubé, Catherine E; Nielsen, Natalia N; McPhillips, Emily A; Lapane, Kate L (2024-03-05)
      Background and objectives: Using US national nursing home data, this cross-sectional study sought to evaluate 1) the association between lack of social engagement and level of cognitive impairment; and 2) the extent to which this association differs by hearing and visual impairment. Research design and methods: Our sample included 793,846 nursing home residents aged ≥ 50 years. The Index of Social Engagement was categorized as none/lower (0, 1, 2) or higher levels (3 through 6). Cognitive Performance Scale was grouped as intact/mild (0, 1, 2), moderate (3, 4), or severe (5, 6). Multinomial models provided adjusted odds ratio (aOR) and 95 % confidence intervals (CI) between none/lower social engagement and cognitive impairment. We estimated relative excess risk due to interaction (RERI) to quantify the joint effects of social engagement and sensory impairment types. Results: Overall, 12.6 % had lower social engagement, 30.3 % had hearing impairment, and 40.3 % had visual impairment. Compared to residents with high social engagement, those with lower social engagement were more likely to have moderate/severe cognitive impairment (aORmoderate = 2.21, 95 % CI 2.17-2.26; aORsevere = 6.49, 95 % CI 6.24-6.74). The impact of low social engagement on cognitive impairment was more profound among residents with hearing impairment and/or visual impairment (RERIhearing = 3.89, 95 % CI 3.62-4.17; RERIvisual = 25.2, 95 % CI 23.9-26.6)). Discussion and implications: Residents with lower social engagement had higher levels of cognitive impairment. Residents with sensory impairments are potentially more susceptible to the negative impact of lower levels of social engagement on level of cognitive impairment.
    • UMCCTS Newsletter, March 2024

      UMass Center for Clinical and Translational Science (2024-03-01)
      This is the March 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Racial and Ethnic Disparities in Use of Colorectal Cancer Screening Among Adults With Chronic Medical Conditions: BRFSS 2012-2020

      Castañeda-Avila, Maira A; Tisminetzky, Mayra; Oyinbo, Atinuke G; Lapane, Kate L (2024-02-22)
      Introduction: People with chronic conditions and people with colorectal cancer (CRC) may share common risk factors; thus, CRC screening is important for people with chronic conditions. We examined racial and ethnic differences in the use of CRC screening among people with various numbers of chronic conditions. Methods: We included data on adult respondents aged 50 to 75 years from the Behavioral Risk Factor Surveillance System in 2012 through 2020. We categorized counts of 9 conditions as 0, 1, 2, 3, and ≥4. We classified self-reported CRC screening status as up to date or not. We used Poisson models to estimate adjusted prevalence ratios (APRs) among the different counts of chronic conditions in 4 racial and ethnic groups: Hispanic adults with limited English proficiency (LEP), Hispanic adults without LEP, non-Hispanic Black adults, and non-Hispanic White adults. Results: Overall, 66.5% of respondents were up to date with CRC screening. The prevalence of being up to date increased with the number of chronic conditions. We found disparities among racial and ethnic groups. Hispanic respondents with LEP had lower rates than non-Hispanic White adults of being up to date with CRC screening across all counts of chronic conditions (APR for 0 conditions = 0.67; 95% CI, 0.64-0.71; APR for ≥4 conditions = 0.85; 95% CI, 0.79-0.91). Hispanic respondents without LEP with 0, 1, or 2 conditions were less likely than non-Hispanic White respondents to be up to date with CRC screening. We found no significant differences between non-Hispanic Black and non-Hispanic White respondents. Conclusion: We found disparities among Hispanic BRFSS respondents with LEP, who had lower rates than non-Hispanic White respondents of being up to date with CRC screening, regardless of the number of chronic conditions. Tailored interventions are needed to address these disparities and improve screening rates, particularly among Hispanic people.
    • Persistent False Positive Covid-19 Rapid Antigen Tests

      Herbert, Carly; McManus, David D; Soni, Apurv (2024-02-22)
      Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective tools for the diagnosis of acute infection, particularly when used serially. The percentage of rapid antigen tests with false positive results is reported to be less than 1%. However, we have observed persons who repeatedly test positive with rapid antigen tests despite concurrent negative molecular tests; this infrequent phenomenon occurs predominantly among women and persons with autoimmune disorders.
    • UMCCTS Newsletter, February 2024

      UMass Center for Clinical and Translational Science (2024-02-01)
      This is the February 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Strengthening Quality Measurement to Predict Success for Total Knee Arthroplasty: Results from a Nationally Representative Total Knee Arthroplasty Cohort

      Zheng, Hua; Ash, Arlene S.; Yang, Wenyun; Liu, Shao-Hsien; Allison, Jeroan J.; Ayers, David C (2024-01-25)
      Background: When performed well on appropriate patients, total knee arthroplasty (TKA) can dramatically improve quality of life. Patient-reported outcome measures (PROMs) are increasingly used to measure outcome following TKA. Accurate prediction of improvement in PROMs after TKA potentially plays an important role in judging the surgical quality of the health-care institutions as well as informing preoperative shared decision-making. Starting in 2027, the U.S. Centers for Medicare & Medicaid Services (CMS) will begin mandating PROM reporting to assess the quality of TKAs. Methods: Using data from a national cohort of patients undergoing primary unilateral TKA, we developed an original model that closely followed a CMS-proposed measure to predict success, defined as achieving substantial clinical benefit, specifically at least a 20-point improvement on the Knee injury and Osteoarthritis Outcome Score, Joint Arthroplasty (KOOS, JR) at 1 year, and an enhanced model with just 1 additional predictor: the baseline KOOS, JR. We evaluated each model's performance using the area under the receiver operator characteristic curve (AUC) and the ratio of observed to expected (model-predicted) outcomes (O:E ratio). Results: We studied 5,958 patients with a mean age of 67 years; 63% were women, 93% were White, and 87% were overweight or obese. Adding the baseline KOOS, JR improved the AUC from 0.58 to 0.73. Ninety-four percent of those in the top decile of predicted probability of success under the enhanced model achieved success, compared with 34% in its bottom decile. Analogous numbers for the original model were less discriminating: 77% compared with 57%. Only the enhanced model predicted success accurately across the spectrum of baseline scores. The findings were virtually identical when we replicated these analyses on only patients ≥65 years of age. Conclusions: Adding a baseline knee-specific PROM score to a quality measurement model in a nationally representative cohort dramatically improved its predictive power, eliminating ceiling and floor effects and mispredictions for readily identifiable patient subgroups. The enhanced model neither favors nor discourages care for those with greater knee dysfunction and requires no new data collection. Level of evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
    • Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C [preprint]

      Preiss, Alexander; Bhatia, Abhishek; Zang, Chengxi; Aragon, Leyna V; Baratta, John M; Baskaran, Monika; Blancero, Frank; Brannock, M Daniel; Chew, Robert F; Díaz, Iván; et al. (2024-01-22)
      Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,461 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. Our primary outcome measure was a PASC computable phenotype. Secondary outcomes were the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.99, 95% confidence interval [CI] 0.96-1.01). However, its effect varied across the cognitive (RR = 0.85, 95% CI 0.79-0.90), fatigue (RR = 0.93, 95% CI 0.89-0.96), and respiratory (RR = 0.99, 95% CI 0.95-1.02) symptom clusters, suggesting that Paxlovid treatment may help prevent post-acute cognitive and fatigue symptoms more than others.
    • Practice Site Heterogeneity within and between Medicaid Accountable Care Organizations

      Dyer, Zachary; Alcusky, Matthew J; Himmelstein, Jay; Ash, Arlene S.; Kerrissey, Michaela (2024-01-20)
      The existing literature has considered accountable care organizations (ACOs) as whole entities, neglecting potentially important variations in the characteristics and experiences of the individual practice sites that comprise them. In this observational cross-sectional study, our aim is to characterize the experience, capacity, and process heterogeneity at the practice site level within and between Medicaid ACOs, drawing on the Massachusetts Medicaid and Children's Health Insurance Program (MassHealth), which launched an ACO reform effort in 2018. We used a 2019 survey of a representative sample of administrators from practice sites participating in Medicaid ACOs in Massachusetts (n = 225). We quantified the clustering of responses by practice site within all 17 Medicaid ACOs in Massachusetts for measures of process change, previous experience with alternative payment models, and changes in the practices' ability to deliver high-quality care. Using multilevel logistic models, we calculated median odds ratios (MORs) and intraclass correlation coefficients (ICCs) to quantify the variation within and between ACOs for each measure. We found greater heterogeneity within the ACOs than between them for all measures, regardless of practice site and ACO characteristics (all ICCs ≤ 0.26). Our research indicates diverse experience with, and capacity for, implementing ACO initiatives across practice sites in Medicaid ACOs. Future research and program design should account for characteristics of practice sites within ACOs.
    • Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19

      Sidky, Hythem; Hansen, Kristen A; Girvin, Andrew T; Hotaling, Nathan; Michael, Sam G; Gersing, Ken; Sahner, David K (2024-01-09)
      Background: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking. Materials and methods: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code. Results: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58-0.85]; P = 4 ×10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.
    • UMCCTS Newsletter, January 2024

      UMass Center for Clinical and Translational Science (2024-01-02)
      This is the January 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma

      Mitra, Amit Kumar; Mukherjee, Ujjal Kumar; Mazumder, Suman; Madhira, Vithal; Bergquist, Timothy; Shao, Yu Raymond; LIu, Feifan; Song, Qianqian; Su, Jing; Kumar, Shaji; et al. (2023-12-07)
      Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.
    • Single intravitreal administration of a tetravalent siRNA exhibits robust and efficient gene silencing in mouse and pig photoreceptors

      Cheng, Shun-Yun; Caiazzi, Jillian; Biscans, Annabelle; Alterman, Julia F; Echeverria, Dimas; McHugh, Nicholas; Hassler, Matthew; Jolly, Samson; Giguere, Delaney; Cipi, Joris; et al. (2023-12-05)
      Inherited retinal dystrophies caused by dominant mutations in photoreceptor (PR) cell expressed genes are a major cause of irreversible vision loss. Oligonucleotide therapy has been of interest in diseases that conventional medicine cannot target. In the early days, small interfering RNAs (siRNAs) were explored in clinical trials for retinal disorders with limited success due to a lack of stability and efficient cellular delivery. Thus, an unmet need exists to identify siRNA chemistry that targets PR cell expressed genes. Here, we evaluated 12 different fully chemically modified siRNA configurations, where the valency and conjugate structure were systematically altered. The impact on retinal distribution following intravitreal delivery was examined. We found that the increase in valency (tetravalent siRNA) supports the best PR accumulation. A single intravitreal administration induces multimonths efficacy in rodent and porcine retinas while demonstrating a good safety profile. The data suggest that this configuration can treat retinal diseases caused by PR cell expressed genes with 1-2 intravitreal injections per year.
    • FMRP deficiency leads to multifactorial dysregulation of splicing and mislocalization of MBNL1 to the cytoplasm

      Jung, Suna; Shah, Sneha; Han, Geongoo; Richter, Joel D (2023-12-04)
      Fragile X syndrome (FXS) is a neurodevelopmental disorder that is often modeled in Fmr1 knockout mice where the RNA-binding protein FMRP is absent. Here, we show that in Fmr1-deficient mice, RNA mis-splicing occurs in several brain regions and peripheral tissues. To assess molecular mechanisms of splicing mis-regulation, we employed N2A cells depleted of Fmr1. In the absence of FMRP, RNA-specific exon skipping events are linked to the splicing factors hnRNPF, PTBP1, and MBNL1. FMRP regulates the translation of Mbnl1 mRNA as well as Mbnl1 RNA auto-splicing. Elevated Mbnl1 auto-splicing in FMRP-deficient cells results in the loss of a nuclear localization signal (NLS)-containing exon. This in turn alters the nucleus-to-cytoplasm ratio of MBNL1. This redistribution of MBNL1 isoforms in Fmr1-deficient cells could result in downstream splicing changes in other RNAs. Indeed, further investigation revealed that splicing disruptions resulting from Fmr1 depletion could be rescued by overexpression of nuclear MBNL1. Altered Mbnl1 auto-splicing also occurs in human FXS postmortem brain. These data suggest that FMRP-controlled translation and RNA processing may cascade into a general dys-regulation of splicing in Fmr1-deficient cells.
    • UMCCTS Newsletter, December 2023

      UMass Center for Clinical and Translational Science (2023-12-01)
      This is the December 2023 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • 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.