33 research outputs found
Demographics and baseline disease characteristics of Black and Hispanic patients with multiple sclerosis in the open-label, single-arm, multicenter, phase IV CHIMES trial
BACKGROUND: Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented in multiple sclerosis (MS) clinical trials, exhibit greater disease severity and more rapid disease progression than White patients with MS (WpwMS). The lack of diversity and inclusion in clinical trials, which may be due to barriers at the system, patient and study levels, impacts the ability to effectively assess risks, benefits and treatment responses in a generalized patient population.
METHODS: CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), an open-label, single-arm, multicenter, phase IV study of self-identified BpwMS and HpwMS aged 18-65 years with relapsing MS and an Expanded Disability Status Score (EDSS) of ≤5.5, was developed in collaboration with patients with MS, national advocacy groups and clinical researchers. Patients were enrolled at study centers across the US, including Puerto Rico, and 1 site in Kenya.
RESULTS: A total of 182 patients enrolled in CHIMES: 113 (62.1%) were BpwMS, and 69 (37.9%) were HpwMS; the mean (SD) baseline EDSS score was 2.4 (1.4), and 62.6% of patients were treatment naive. Using the pooled non-BpwMS/HpwMS group in the OPERA ocrelizumab trials as a reference population, patients enrolled in CHIMES were younger, had a higher mean body mass and had a greater T2 lesion volume but similar T2 lesion number on MRI.
CONCLUSION: BpwMS and HpwMS have been consistently underrepresented in clinical trials, limiting the understanding of disease biology and response to treatment in this population. Data from the CHIMES study revealed differences in demographics and some baseline disease characteristics and disease burden between BpwMS and HpwMS vs WpwMS. These differences could have an impact when assessing clinical outcomes in BpwMS and HpwMS.
GOV IDENTIFIER: NCT04377555
Demographics and baseline disease characteristics of patients with relapsing multiple sclerosis from Kenya participating in the CHIMES trial
Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner
HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC) -α and -δ, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC) involving stress induced AMP Kinase (AMPK) inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs
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Variables Associated with Patient Activation in Persons with Multiple Sclerosis
Identifying variables associated with patient activation in the multiple sclerosis population could serve to facilitate better multiple sclerosis self-management behaviors. Using a cross-sectional survey design, 199 participants were recruited from a multiple sclerosis center in the Southeastern United States. Depression, multiple sclerosis quality of life, and multiple Sclerosis self-efficacy were all significantly correlated with patient activation. Results of a hierarchical regression indicated that patient activation was significantly related to educational attainment, depression, and self-efficacy but not to quality of life. The results suggest several possible targets for intervention to increase patient activation, including health literacy, depression symptoms, and self-efficacy for multiple sclerosis disease management
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Expert Perspectives on COVID-19 Vaccination for People Living with Multiple Sclerosis
COVID-19 vaccines are safe for people living with MS on or off disease-modifying therapies and are important for the prevention of COVID-19. Antibody responses for individuals on certain DMTs may be diminished, however, T-cell responses may be preserved in those individuals. Data are lacking regarding optimal timing of vaccinations, and delaying disease-modifying therapies may increase the risk of disease activity and progression. In this perspective podcast, the authors recommend COVID-19 vaccination as soon as possible, regardless of timing considerations, in most cases.
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Memory-Based Prediction Deficits and Dorsolateral Prefrontal Dysfunction in Schizophrenia
BackgroundTheories suggest that people with schizophrenia (SZ) have problems generating predictions based on past experiences. The dorsolateral prefrontal cortex (DLPFC) and hippocampus participate in memory-based prediction. We used functional magnetic resonance imaging to investigate DLPFC and hippocampal function in healthy control (HC) subjects and people with SZ during memory-based prediction.MethodsPrior to scanning, HC subjects (n = 54) and people with SZ (n = 31) learned 5-object sequences presented in fixed or random orders on each repetition. During scanning, participants made semantic decisions (e.g., "Can this object fit in a shoebox?") on a continuous stream of objects from fixed and random sequences. Sequence prediction was demonstrated by faster semantic decisions for objects in fixed versus random sequences because memory could be used to anticipate and more efficiently process semantic information about upcoming objects in fixed sequences. Representational similarity analyses were used to determine how each sequence type was represented in the posterior hippocampus and DLPFC.ResultsSequence predictions were reduced in individuals with SZ relative to HC subjects. Representational similarity analyses revealed stronger memory-based predictions in the DLPFC of HC subjects than people with SZ, and DLPFC representations correlated with more successful predictions in HC subjects only. For the posterior hippocampus, voxel pattern similarity was increased for fixed versus random sequences in HC subjects only, but no significant between-group differences or correlations with prediction success were observed.ConclusionsIndividuals with SZ are capable of learning temporal sequences; however, they are impaired using memory to predict upcoming events as efficiently as HC subjects. This deficit appears related to disrupted neural representation of sequence information in the DLPFC
Advancing Care and Outcomes for African American Patients With Multiple Sclerosis.
Multiple sclerosis (MS) has historically been underdiagnosed and undertreated among African Americans. Recent evidence suggests that African Americans with MS have a different clinical presentation, increased disease incidence and burden, and worsened long-term outcomes versus their White counterparts. Due to limited data available for African Americans in MS clinical trials, it is difficult to make informed, generalizable conclusions about the natural history, prognosis, and therapeutic response in this population. In this narrative review, we highlight the nature and magnitude of the health disparities experienced by African Americans with MS and underscore the pressing need to increase knowledge about and understanding of MS disease manifestations in this group. Additionally, we describe the mission and objectives of the recently established National African Americans with Multiple Sclerosis Registry (NAAMSR), which is intended to be a platform to advance the care of African Americans with MS and address health disparities they may experience
Intercalated Organic−Inorganic Perovskites Stabilized by Fluoroaryl−Aryl Interactions
Real-World Safety and Effectiveness of Dimethyl Fumarate in Black or African American Patients with Multiple Sclerosis: 3-Year Results from ESTEEM.
INTRODUCTION: Black or African American (black/AA) patients with multiple sclerosis (MS) are reported to exhibit greater disease severity compared with non-black or non-AA patients. Whether differences exist in response to MS disease-modifying therapies remains uncertain, as MS clinical trials have included low numbers of non-white patients. We evaluated real-world safety and effectiveness of dimethyl fumarate (DMF) on MS disease activity in black/AA patients.
METHODS: ESTEEM is an ongoing, 5-year, multinational, prospective study evaluating long-term safety and effectiveness of DMF in patients with MS. This interim analysis included patients newly prescribed DMF in routine practice at 394 sites globally.
RESULTS: Overall, 4897 non-black/non-AA and 187 black/AA patients were analyzed; median (range) follow-up 18 (2-37) months. Unadjusted annualized relapse rates (ARRs) for 12 months before DMF initiation versus 36 months post DMF initiation, respectively, were: non-black/non-AA patients, 0.83 (95% CI 0.80-0.85) versus 0.10 (95% CI 0.09-0.10), 88% lower ARR (P \u3c 0.0001); black/AA patients, 0.68 (95% CI 0.58-0.80) versus 0.07 (95% CI 0.05-0.10), 90% lower ARR (P \u3c 0.0001). In total, 35 (19%) black/AA patients reported adverse events leading to treatment discontinuation; gastrointestinal disorders were most common (7%), consistent with non-black/non-AA patients (8%). Median lymphocyte counts decreased by 22% in the first year (vs 36% in non-black/non-AA patients), then remained stable and above lower limit of normal in most patients.
CONCLUSIONS: Relapse rates remained low in black/AA patients, consistent with non-black/non-AA patients. The safety profile of DMF in black/AA patients was consistent with that in the non-black/non-AA ESTEEM population, although lymphocyte decrease was less pronounced in black/AA patients