Now showing items 1-20 of 27279

    • Youth Reoffending: Prevalence and Predictive Risk Factors in Two States

      Vincent, Gina M.; Skeem, Jennifer, L; Weber, Josh (2024-09-18)
      The Youth Protective Factors Study is an unprecedented multistate, multiyear examination of which risk and protective factors matter most when it comes to reoffending—particularly for more serious offenses that involve physical harm to another person (person offenses)—for youth ages 10 to 23 in the juvenile justice system. This brief is the first in a series that shares key findings to guide jurisdictions on research-based juvenile justice supervision, case planning, and service strategies to improve public safety and youth outcomes. These findings are especially pertinent during a time of rising concerns about youth crime, violence, and victimization. This brief is based on analysis of over 32,000 youth who had a new delinquency or status offense complaint over 3 years (2015–2017) in 2 states and received a risk assessment from the probation department. Most of the youth ended up on some form of supervision. Supervision could have included involvement in a diversion program, informal supervision, probation, a secure placement, or any combination of the above, and incorporates the time from their risk assessment until their case was closed (including any supervision extensions). Researchers obtained the records of all new juvenile court petitions and adult charges for these youth during supervision and for an average 2.5-year post-supervision follow-up period. The study analyzed recidivism during and after supervision, including for person offenses (offenses ranging from simple assault to robbery and homicide), and identified which risk factors were most associated with reoffending for youth overall and of different ages. The authors wish to acknowledge Emily Rogers, CSG Justice Center Research Project Manager and Luyi Jian, PhD, for the advanced data management and statistical analyses necessary for this brief We also acknowledge a terrific research team for data coordination and management: Rachael Perrault, MA, Karlie Rice, MA, Jennifer Pendleton, MA, and Kayla Carew, BS.
    • PhD nursing programs: Where are we headed?

      Fain, James A; Sullivan-Bolyai, Susan L; Bova, Carol A (2024-08-29)
      Thank you for your timely editorial, The PhD in Nursing - Questions about a Credential at a Crossroads. We agree that the future of PhD education in nursing is in peril and needs rapid solutions. Low enrollment and threats of PhD program closures are on the rise. As three former Directors of PhD Programs, we feel it is essential that we do not walk away from PhD education. Here are some of our thoughts.
    • Implementing virtual desktops for clinical research at an academic health center: a case report

      Zai, Adrian; Wong, Steven; Guilarte-Walker, Yurima; Langlois, Paul; Coleman, Brian; Soni, Apurv; McManus, David D; Luzuriaga, Katherine (2024-08-28)
      Objectives: To address the challenges of sharing clinical research data through the implementation of cloud-based virtual desktops, enhancing collaboration among researchers while maintaining data security. Materials and methods: This case study details the deployment of virtual desktops at UMass Chan Medical School (UMass Chan). The process involved forming a Research Informatics Steering Executive workgroup, identifying key requirements, implementing Amazon WorkSpaces, and establishing configurable data management for research support. Results: Key lessons include the significance of collaboration, balancing user-friendliness and functionality, flexibility in data management, maximizing virtual desktop efficiency within budget constraints, and continuous user feedback. The implementation of virtual desktops supports secure collaborative research, advancing medical knowledge and improving healthcare outcomes. Discussion: The structured approach to implementing virtual desktops addresses data security, regulatory compliance, and real-time collaboration challenges. Continuous feedback and iterative improvements have enhanced the system's effectiveness. Conclusion: The successful implementation of virtual desktops at UMass Chan demonstrates the potential for such systems to support secure, collaborative research, offering insights for similar initiatives in other academic health centers.
    • A minimally invasive endovascular approach to the cerebellopontine angle cistern enables broad CNS biodistribution of scAAV9-CB-GFP

      Benatti, Hector Ribeiro; Anagnostakou, Vania; Taghian, Toloo; Hall, Erin F; Nath, Sarah; Heilman, Carl B; Beneduce, Brandon M; Leporati, Anita; Raskett, Christopher M; Epshtein, Mark; et al. (2024-08-26)
      Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents to the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials for communicating hydrocephalus, offers a minimally invasive approach by providing endovascular access to the cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that drug delivery to the CPA cistern could yield widespread CNS distribution. Using an ovine model, we compared the biodistribution of scAAV9-CB-GFP following CPA cistern infusion with previously reported cisterna magna (CM) administration. Targeting both the CPA cistern and CM in sheep, we employed a lumbar spine-inserted microcatheter under fluoroscopy. CPA delivery of AAV9 demonstrated biodistribution and transduction in the cerebral cortices, striatum, thalamus, midbrain, cerebellum, and spinal cord, with minor liver distribution comparable to CM. The favorable safety profile in humans with hydrocephalus suggests that percutaneous endovascular injection into the CPA could offer a clinically safer and minimally invasive delivery system for CNS gene and cell-based therapies.
    • Normative Modeling of Thalamic Nuclear Volumes and Characterization of Lateralized Volume Alterations in Alzheimer's Disease Versus Schizophrenia

      Young, Taylor R; Kumar, Vinod Jangir; Saranathan, Manojkumar (2024-08-23)
      Background: Thalamic nuclei facilitate a wide range of complex behaviors, emotions, and cognition and have been implicated in neuropsychiatric disorders including Alzheimer's disease (AD) and schizophrenia. The aim of this work was to establish novel normative models of thalamic nuclear volumes and their laterality indices and investigate their changes in schizophrenia and AD. Methods: Volumes of bilateral whole thalami and 10 thalamic nuclei were generated from T1 MRI data using a state-of-the-art novel segmentation method in healthy control subjects (n=2374) and early mild cognitive impairment (MCI, n=211), late MCI (n=113), AD (n=88), and schizophrenia (n=168). Normative models for each nucleus were generated from healthy control subjects while controlling for sex, intracranial volume, and site. Extreme z-score deviations (|z|>1.96) and z-score distributions were compared across phenotypes. Z-scores were associated with clinical descriptors. Results: Increased infranormal and decreased supranormal z-scores were observed in schizophrenia and AD. Z-score shifts representing reduced volumes were observed in most nuclei in schizophrenia and AD with strong overlap in the bilateral pulvinar, medial dorsal, and centromedian nuclei. Shifts were larger in AD with evidence of a left-sided preference in early MCI while a predilection for right thalamic nuclei was observed in schizophrenia. The right medial dorsal nucleus was associated with disorganized thought and daily auditory verbal hallucinations. Conclusion: In AD, thalamic nuclei are more severely and symmetrically affected while in schizophrenia, the right thalamic nuclei are more affected. We highlight the right medial dorsal nucleus, which may mediate multiple symptoms of schizophrenia and is affected early in the disease course.
    • Teach creativity in science higher education

      Yanai, Itai; Bogler, Oliver; Carroll, Sean B; Couch, Jennifer; Dahlberg, Maria Lund; Fuhrmann, Cynthia N; Kaufman, James C; Majumdar, Sonali; Oyler-Yaniv, Jennifer; Priestley, Rodney D; et al. (2024-08-22)
      Letter to the editor addressing why creativity should be taught in higher education basic science programs.
    • Pretreatment predictors of very poor clinical outcomes in medium vessel occlusion stroke patients treated with mechanical thrombectomy

      Yedavalli, Vivek; Salim, Hamza; Musmar, Basel; Adeeb, Nimer; El Naamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kühn, Anna Luisa; Khalife, Jane; Ghozy, Sherief; et al. (2024-08-19)
      Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76. Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.
    • Exploring the social and cultural aspects of Chinese family caregivers' experience as they support loved ones with dementia transitioning into nursing homes: a qualitative study protocol

      Yuan, Yiyang; Dube, Catherine E; Xu, Shu; Lim, Emily; Qu, Shan; McPhillips, Emily A; Lapane, Kate L (2024-08-12)
      Introduction: Asian American caregivers supporting loved ones with dementia experience greater burden and more stress than other racial/ethnic groups, warranting the need for more culturally and linguistically appropriate formal support, such as in nursing homes. Transitioning loved ones into nursing homes with dementia care units is a complex process that can be impacted by a multitude of factors. Employing several established frameworks, including the socioecological model, this qualitative study will focus on the largest Asian American subgroup (people of Chinese descent) and explore the experience of family caregivers as they support the transition of their loved ones with dementia into nursing homes in the USA. Our focus will be on the nuanced influences of the Chinese language and culture and COVID-19-related social isolation and racial discrimination. Methods and analysis: Recruitment will take place starting in January 2024. Current or former Chinese caregivers for Chinese loved ones with dementia, able to communicate in Mandarin Chinese or English, and currently residing in the USA will be eligible. Key informants with intimate understanding and experience with this population will also be included. Data will be collected through 2024 using semistructured, in-depth interviews with each participant. Depending on participants' preferences, interviews will be conducted in either Mandarin Chinese or English and either in person, via Zoom or by phone. Interviews will be transcribed verbatim. Iterative thematic analysis will be employed. A coding structure will be developed based on interview questions and themes and patterns that are revealed through data immersion. Transcripts, prepared in their original language, will be dual-coded by bilingual researchers using NVivo 14. Consensus summaries of themes will be prepared. Relevant direct quotes for each thematic area will be identified (those in Chinese will be translated into English) and cited in reports and manuscripts. Ethics and dissemination: The study is approved by the UMass Chan Medical School Institutional Review Board (ID: STUDY00001376). Findings will be published in peer-review journals following the consolidated criteria for reporting qualitative research.
    • Preventing diabetes: What overweight and obese adults with prediabetes in the United States report about their providers' communication and attempted weight loss

      Demosthenes, Emmanuella J; Freedman, Jason; Hernandez, Camila; Shennette, Lisa; Frisard, Christine; Lemon, Stephenie C; Gerber, Ben S; Amante, Daniel J (2024-08-11)
      Objective: To investigate what overweight or obese adults with prediabetes in the United States report being told by providers about 1) having prediabetes, 2) diabetes risk, and 3) losing weight and the associations of these communications with attempted weight loss. Methods: Data from 2015 to 2018 National Health and Nutrition Examination Surveys (NHANES) for adults with a body mass index in the overweight or obesity ranges and HbA1c in the prediabetes range were examined (n = 2085). Patient reported data on what providers told them about having prediabetes, being at risk for diabetes, and losing weight were compared with attempted weight loss. Results: Most participants (66.4%) reported never being told they had prediabetes nor being at risk for diabetes, 13.0% reported being told they had prediabetes, 10.6% at risk for diabetes, and 8.0% both messages. 18.3% of participants reported being told to lose weight. Participants who reported being told they had prediabetes and at increased diabetes risk were more likely to report attempted weight loss (adjusted odds ratio (AOR) 1.8, 95% confidence interval (CI) 1.1-3.2). Reporting that they were told to lose weight was not significantly associated with an increase in reported weight loss attempts. Conclusions: In this cohort of individuals with overweight/obesity and prediabetic HbA1c values, low rates communications with providers about prediabetes and diabetes risk were reported. When both were discussed, patients reported greater attempted weight loss. These findings draw attention to the potential impact that provider communications about prediabetes and diabetes risk may have on lifestyle behavior change.
    • SOGI Data Collection - Proceeding, but with Caution

      Candrian, Carey; Weissman, Joel S; Tjia, Jennifer (2024-08-10)
      For more than a decade, the Joint Commission has recommended the routine collection and use of sexual orientation and gender identity (SOGI) data as a way to help the medical community understand and address the disparities that lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+) people experience throughout their lifetimes, and especially when seeking health care.... We believe health professionals and researchers need to proceed with SOGI data collection but should do so with caution.
    • Creation of a predictive calculator to determine adequacy of occlusion of the woven endobridge (WEB) device in intracranial aneurysms-A retrospective analysis of the WorldWide WEB Consortium database

      Musmar, Basel; Adeeb, Nimer; Gendreau, Julian; Horowitz, Melanie Alfonzo; Salim, Hamza Adel; Sanmugananthan, Praveen; Aslan, Assala; Brown, Nolan J; Cancelliere, Nicole M; McLellan, Rachel M; et al. (2024-08-10)
      Background: Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond-Roy classification 1 or 2) remains challenging. Objective: Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. Methods: We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. Results: A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535-0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024-0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer-Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/. Conclusion: The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.
    • Racial Disparities and Trends in Anticoagulant Use among Ambulatory Care Patients with Atrial Fibrillation and Atrial Flutter in the United States from 2007-2019

      Kan, Vincent (2024-08-08)
      Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly increasing the risk of stroke. The introduction of direct oral anticoagulants (DOACs) since 2010 has transformed anticoagulation therapy, offering an alternative to warfarin with improved safety profiles. Despite the increased adoption of DOACs, disparities in their use among different racial and ethnic groups in the United States remain understudied. Methods This study utilized a repeated cross-sectional design, analyzing data from the National Ambulatory Medical Care Survey (NAMCS) from 2007 to 2019. The study population included adults diagnosed with AF or atrial flutter (AFL). We analyzed the temporal trends of DOAC and warfarin use from 2007 to 2019. We examined the prevalence of DOAC versus warfarin use and assessed associations between race/ethnicity, patient characteristics, and DOAC utilization from 2011 to 2019. Multivariable modified Poisson regression models were used to calculate adjusted prevalence ratios (aPR) for the associations. Results From 2011 to 2019, NAMCS recorded 3,224 visits involving AF or AFL, representing a weighted estimate of 103.6 million visits. DOAC use increased significantly, with apixaban becoming the predominant anticoagulant by 2016. Non-Hispanic Black patients were less likely to use DOACs compared to non-Hispanic White patients over time (aPR 0.75; 95% CI, 0.63-0.90). Patients with Medicaid insurance were also less likely to use DOACs (aPR 0.14; 95% CI: 0.04-0.46). Conclusion Despite the shift from warfarin to DOACs for AF and AFL treatment, significant racial and socioeconomic disparities persist. Non-Hispanic Black patients and those with Medicaid insurance are less likely to use DOACs. These findings highlight the need for targeted strategies to ensure equitable access to advanced anticoagulant therapies.
    • Ten simple rules for recognizing data and software contributions in hiring, promotion, and tenure

      Puebla, Iratxe; Ascoli, Giorgio A; Blume, Jeffrey; Chodacki, John; Finnell, Joshua; Kennedy, David N; Mair, Bernard; Martone, Maryann E; Wittenberg, Jamie; Poline, Jean-Baptiste (2024-08-08)
      The ways in which promotion and tenure committees operate vary significantly across universities and departments. While committees often have the capability to evaluate the rigor and quality of articles and monographs in their scientific field, assessment with respect to practices concerning research data and software is a recent development and one that can be harder to implement, as there are few guidelines to facilitate the process. More specifically, the guidelines given to tenure and promotion committees often reference data and software in general terms, with some notable exceptions such as guidelines in [5] and are almost systematically trumped by other factors such as the number and perceived impact of journal publications. The core issue is that many colleges establish a scholarship versus service dichotomy: Peer-reviewed articles or monographs published by university presses are considered scholarship, while community service, teaching, and other categories are given less weight in the evaluation process. This dichotomy unfairly disadvantages digital scholarship and community-based scholarship, including data and software contributions [6]. In addition, there is a lack of resources for faculties to facilitate the inclusion of responsible data and software metrics into evaluation processes or to assess faculty’s expertise and competencies to create, manage, and use data and software as research objects. As a result, the outcome of the assessment by the tenure and promotion committee is as dependent on the guidelines provided as on the committee members’ background and proficiency in the data and software domains. The presented guidelines aim to help alleviate these issues and align the academic evaluation processes to the principles of open science. We focus here on hiring, tenure, and promotion processes, but the same principles apply to other areas of academic evaluation at institutions. While these guidelines are by no means sufficient for handling the complexity of a multidimensional process that involves balancing a large set of nuanced and diverse information, we hope that they will support an increasing adoption of processes that recognize data and software as key research contributions.
    • Identification of WNK1 as a Therapeutic Target to Suppress IgH/MYC Expression in Multiple Myeloma

      Ye, Tianyi (2024-08-08)
      Multiple myeloma (MM) remains an incurable hematological malignancy demanding innovative therapeutic strategies. Targeting MYC, the notorious yet traditionally undruggable oncogene, presents an appealing avenue. This thesis aims to identify and characterize novel regulators of MYC expression as therapeutic targets in MM. Using a genome-scale CRISPR/Cas9 screen, we identify the WNK lysine deficient protein kinase 1 (WNK1) as a regulator of MYC expression in MM cells. Genetic and pharmacological inhibition of WNK1 reduces MYC expression and, further, disrupts the MYC-dependent transcriptional program. Mechanistically, WNK1 inhibition attenuates the activity of the immunoglobulin heavy chain (IgH) enhancer, thus reducing MYC transcription when this locus is translocated near the MYC locus. Furthermore, we show in MM cells possessing distinct translocation profiles that WNK1 inhibition also downregulates other oncogenes frequently translocated near the IgH locus, including CCND1, FGFR3, and NSD2, broadening its potential therapeutic implications. WNK1 inhibition profoundly impacts MM cell behaviors, leading to growth inhibition, cell cycle arrest, senescence, and apoptosis. Importantly, the WNK inhibitor WNK463 inhibits MM growth in primary patient samples as well as xenograft mouse models, and exhibits synergistic effects with various anti-MM compounds. Collectively, this study uncovers WNK1 as a promising therapeutic target in MM, and suggests the utility of IgH translocations as useful biomarkers.
    • Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion

      Dmytriw, Adam A; Ghozy, Sherief; Salim, Hamza Adel; Musmar, Basel; Siegler, James E; Kobeissi, Hassan; Shaikh, Hamza; Khalife, Jane; Abdalkader, Mohamad; Klein, Piers; et al. (2024-08-06)
      Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.
    • Nirmatrelvir/Ritonavir (Paxlovid) Use Among Individuals at Risk of Severe COVID-19: An Analysis of the National COVID Cohort Collaborative (N3C)

      Xiao, Xuya; Alexander, G Caleb; Mehta, Hemalkumar B (2024-08-04)
      Purpose: Paxlovid is effective in reducing COVID-19 hospitalization and mortality. This study characterized Paxlovid use and evaluated racial/ethnic disparities over time among community-dwelling adults at high risk of progression to severe COVID-19 disease. Methods: This retrospective cohort study used the National COVID Cohort Collaborative (N3C) data and included individuals aged 18 years or older diagnosed with COVID-19 between January 2022 and December 2023. The study cohort included nonhospitalized individuals who were at high risk of COVID-19 progression, and selected the first COVID-19 episode in each quarter, including reinfection episodes. Paxlovid use was defined as receiving Paxlovid within ±5 days of a COVID-19 diagnosis. We used descriptive statistics to characterize Paxlovid use overall and by calendar quarter and race/ethnicity. We used a generalized estimating equations (GEE) models to quantify the association of race/ethnicity with Paxlovid use controlling for age, gender, and clinical characteristics. Results: Among 1 264 215 individuals at high risk of disease progression (1 404 607 episodes), Paxlovid use increased from 1.2% in January-March 2022 to 35.1% in October-December 2023. Paxlovid use was more common among non-Hispanic White individuals (23.9%) than non-Hispanic Black (16.5%) and Latinx/e (16.7%) patients. After adjusting age, gender, and clinical characteristics, Paxlovid use was less likely among non-Hispanic Black (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.68-0.70) and Latinx/e (OR 0.72, CI 0.71-0.73) patients than non-Hispanic White patients. Conclusions: Among a large, diverse cohort of community-dwelling individuals with COVID-19, nearly two out of three eligible individuals did not receive Paxlovid, and minoritized racial/ethnic groups were less likely to use Paxlovid than their non-Hispanic White individuals.
    • Investigating therapeutic nonsense suppression in a neurofibromatosis mouse model

      Wu, Chan; Shazeeb, Mohammed Salman; Mangkalaphiban, Kotchaphorn; Han, George; Peker, Ahmet; Rentiya, Zubir S; Gounis, Matthew J; Jacobson, Allan (2024-08-04)
      Neurofibromatosis type 1 (NF1) is a human genetic disorder caused by variants in the NF1 gene. Plexiform neurofibromas, one of many NF1 manifestations, are benign peripheral nerve sheath tumors occurring in up to 50% of NF1 patients. A substantial fraction of NF1 pathogenetic variants are nonsense mutations, which result in the synthesis of truncated non-functional NF1 protein (neurofibromin). To date, no therapeutics have restored neurofibromin expression or addressed the consequences of this protein's absence in NF1 nonsense mutation patients, but nonsense suppression is a potential approach to the problem. Ataluren is a small molecule drug that has been shown to stimulate functional nonsense codon readthrough in several models of nonsense mutation diseases, as well as in Duchenne muscular dystrophy patients. To test ataluren's potential applicability in nonsense mutation NF1 patients, we evaluated its therapeutic effects using three treatment regimens in a previously established NF1 patient-derived (c.2041C > T; p.Arg681X) nonsense mutation mouse model. Collectively, our experiments indicate that: i) ataluren appeared to slow the growth of neurofibromas and alleviate some paralysis phenotypes, ii) female Nf1-nonsense mutation mice manifested more severe paralysis and neurofibroma phenotypes than male mice, iii) ataluren doses with apparent effectiveness were lower in female mice than in male mice, and iv) age factors also influenced ataluren's effectiveness.
    • UMCCTS Newsletter, August 2024

      UMass Center for Clinical and Translational Science (2024-08-01)
      This is the August 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
    • Neighborhood Resources Associated With Psychological Trajectories and Neural Reactivity to Reward After Trauma

      Webb, E Kate; Stevens, Jennifer S; Ely, Timothy D; Lebois, Lauren A M; van Rooij, Sanne J H; Bruce, Steven E; House, Stacey L; Beaudoin, Francesca L; An, Xinming; Neylan, Thomas C; et al. (2024-07-31)
      Importance: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD). Objective: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward. Design, setting, and participants: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023. Exposures: Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC). Main outcome and measures: PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income). Results: In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory. Conclusions and relevance: In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.
    • Treatment of large intracranial aneurysms using the Woven EndoBridge (WEB): a propensity score-matched analysis

      Musmar, Basel; Salim, Hamza Adel; Adeeb, Nimer; Aslan, Assala; Aljeradat, Bahaa; Diestro, Jose Danilo Bengzon; McLellan, Rachel M; Algin, Oktay; Ghozy, Sherief; Dibas, Mahmoud; et al. (2024-07-31)
      The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area.