Background Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS). Objective The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies. Methods The IBM ® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database. Results 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. Conclusions Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.
Background: To examine the clinical and economic burdens associated with delayed receipt of appropriate therapy among patients with Gram-negative bacteria (GNB) infections, stratified by antibiotic resistance status. Materials and Methods: Retrospective analysis using the Premier Hospital Database. Adult admissions (July 2011-September 2014) with evidence of complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, length of stay (LOS) ≥1 days and a positive GNB culture from a site consistent with infection type (culture draw date = index date) were identified and stratified by antibiotic susceptibility to index pathogens. Delayed appropriate therapy was defined as no receipt of antibiotic(s) with relevant microbiological activity on or within 2 days of index date. Inverse probability weighting and multivariate regression analyses were used to estimate the association between delayed appropriate therapy and outcomes. Generalized linear models were used to evaluate postindex duration of antibiotic therapy, LOS and total in-hospital costs. Logistic models were used to evaluate discharge destination and in-hospital mortality/discharge to hospice. Results: A total of 56,357 patients with GNB infections were identified (resistant, n = 6,055; susceptible, n = 50,302). Delayed appropriate therapy was received by 2,800 (46.2%) patients with resistant and 16,585 (33.0%) patients with susceptible infections. Using multivariate analysis, delayed appropriate therapy was associated with worse outcomes including »70% increase in LOS, »65% increase in total in-hospital costs and »20% increase in the risk of in-hospital mortality/discharge to hospice, regardless of susceptibility status. Conclusions: Our results suggest that outcomes in patients with GNB infections, regardless of resistance status, significantly improve if timely appropriate therapy can be provided.
Objective Prenatal exposure to women’s mood dysregulation is associated with variation in neurobehavioral profiles in children. Few studies have assessed these relationships during the prenatal period. Methods In 113 women in the 36th – 38th gestational week (mean age 26.3 ± 5.4 years), electrocardiogram, blood pressure, respiration, salivary cortisol, and fetal heart rate (HR) were measured during baseline, a psychological challenge (Stroop color–word matching task), and a standardized paced breathing protocol. Subjects underwent the Structured Clinical Interview for DSM-IV prior to testing and were grouped as: depressed, co–morbid for depression and anxiety, anxiety disorder only, and control. Results There was a significant main effect of maternal diagnostic group on fetal HR only during the Stroop task: fetuses of women in the co–morbid group had a greater HR increase compared to controls (p < .05). Overall, fetuses showed robust increases in HR during paced breathing (p < .0001), but there was no significant difference by maternal diagnosis. For both tasks, changes in fetal HR were independent of women’s concurrent cardiorespiratory activity. Finally, although cortisol was higher in the co-morbid group (p <.05), independent of diagnosis, there was a trend for maternal baseline cortisol to be positively associated with average fetal HR (p = .08). Conclusions These findings indicate that variation in fetal HR reactivity — an index of emerging regulatory capacities — is likely influenced by multiple acute and chronic factors associated with women’s psychobiology.
Objective: To understand how longitudinal serum neurofilament light chain (sNfL) patterns can inform its use as a prognostic biomarker in multiple sclerosis (MS) and evaluate whether sNfL reflects MS disease activity and disease-modifying therapy usage. Methods: This was a post hoc analysis of longitudinal data and samples from the ADVANCE trial (NCT00906399) of patients with relapsing–remitting MS (RRMS). sNfL was measured every 3 months for 2 years, then every 6 months for 4 years. Regression models explored how sNfL data predicted 4-year values of brain volume, expanded disability status scale score, and T2 lesions. sNfL levels were assessed in those receiving placebo, peginterferon beta-1a, and those with disease activity. Results: Baseline sNfL was a predictor of 4-year brain atrophy and development of new T2 lesions. Clinical ( p = 0.02) and magnetic resonance imaging (MRI) ( p < 0.01) outcomes improved in those receiving peginterferon beta-1a whose sNfL decreased to <16 pg/mL after 12 months versus those whose sNfL remained ⩾16 pg/mL. Mean sNfL levels decreased in peginterferon beta-1a-treated patients and increased in placebo-treated patients (–9.5% vs. 6.8%; p < 0.01). sNfL was higher and more variable in patients with evidence of active MS. Conclusion: These data support sNfL as a prognostic and disease-monitoring biomarker for RRMS.
Background:The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient’s perspective.Objective:To determine the responder definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of patients with relapsing–remitting MS (RRMS) participating in a clinical trial.Methods:Data from the SELECT trial comparing daclizumab high-yield process with placebo in patients with RRMS were used. Physical function was evaluated in SELECT using three patient-reported outcomes measures and the Expanded Disability Status Scale (EDSS). Anchor- and distribution-based methods were used to identify an RD for the MSIS-29.Results:Results across the anchor-based approach suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode). Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was selected as the most appropriate threshold for physical worsening based on corresponding changes in the EDSS (primary anchor of interest).Conclusion:These findings indicate that a ≥7.50 point worsening on the MSIS-29 PHYS is a reasonable and practical threshold for identifying patients with RRMS who have experienced a clinically significant change in the physical impact of MS.
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