scholarly journals Effectiveness and safety of dimethyl fumarate in progressive multiple sclerosis

2021 ◽  
Vol 7 (2) ◽  
pp. 205521732110108
Author(s):  
Vanessa F Moreira Ferreira ◽  
Yanqing Liu ◽  
Brian C Healy ◽  
James M Stankiewicz
Keyword(s):  
Multiple Sclerosis ◽  
Proportional Hazards ◽  
Dimethyl Fumarate ◽  
Progressive Multiple Sclerosis ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Cox Proportional Hazards Models ◽  
Disability Status ◽  
Clinically Significant ◽  
One Year

Background There is limited data analyzing the safety and effectiveness of dimethyl fumarate (DMF) in the progressive multiple sclerosis (PMS) population. Objective To analyze the safety and effectiveness of DMF in patients with PMS. Methods We used Cox proportional hazards models to compare the time to confirmed worsening and improvement on the Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) between patients treated with DMF and glatiramer acetate (GA) for at least one year. Results We included 46 patients treated with DMF and 42 patients treated with GA. The safety and tolerability of GA and DMF were consistent with established profiles. There was no difference in confirmed EDSS progression. A trend towards reduced T25FW was seen in the DMF compared to GA after adjustment (HR = 0.86; 95% CI:0.37, 1.98; p = 0.72 and HR = 0.60; 95% CI:0.27, 1.34; p = 0.21, respectively). Conclusion Dimethyl fumarate showed a trend towards reduction in T25FW but no evidence of clinically significant impact on EDSS. The small sample precluded definitive determination.

scholarly journals Safety and Tolerability of Subcutaneous Cladribine Therapy in Progressive Multiple Sclerosis

1998 ◽  
Vol 25 (4) ◽  
pp. 295-299 ◽  
Author(s):  
R. Selby ◽  
J. Brandwein ◽  
P. O'Connor
Keyword(s):  
Multiple Sclerosis ◽  
Lymphocyte Count ◽  
Antineoplastic Agent ◽  
Absolute Lymphocyte Count ◽  
Progressive Multiple Sclerosis ◽  
Disability Status ◽  
Chronic Progressive Multiple Sclerosis ◽  
Clinically Significant ◽  
One Year ◽  
Post Therapy

ABSTRACT:Objective:To evaluate the safety and tolerability of subcutaneous (s.c.) cladribine therapy in patients with chronic progressive multiple sclerosis (CPMS), and to evaluate the effects on lymphocyte subsets.Background:Cladribine, a synthetic antineoplastic agent with immunosuppressive effects, may favourably affect the course of CPMS. However results of a previous reported clinical trial showed significant myelosuppression in some patients.Design/Methods:19 patients with severe (mean extended disability status score [EDSS] = 6.7) CPMS were treated on a compassionate basis with cladribine 0.07 mg/kg/ day s.c. for 5 days per cycle, repeated every 4 weeks for a total of 6 cycles. Patients underwent clinical evaluation, EDSS, and hematologic analysis before, during, and following therapy.Results:The treatment was very well tolerated with no clinically significant side effects observed. Between baseline and the end of cycle 6, mean decreases were noted in absolute lymphocyte count from 1697 to 463 (p = 0.000012), CD4 count from 865 to 187 (p = 0.0000008), CD8 from 418 to 165 (p = 0.005) and CD19 from 197 to 26 (p = 0.000002). Platelet, granulocyte and RBC counts were unaffected. Approximately one year after completion of therapy, some recovery of CD4 and CD8 counts had occurred although both counts remained suppressed compared to baseline (302 and 227 respectively); the CD19 count had recovered essentially to normal by one year. EDSS scores post-therapy revealed some deterioration in 8 patients and stable scores in the remaining 11. Global patient evaluations of the treatment were mixed.Conclusions:Cladribine therapy, at lower doses than previously reported, was remarkably well tolerated in CPMS, with no significant myelosuppression. Profound effects occurred in total lymphocyte count and CD4, CD8 and CD19 subsets.

Suicide risk within one year of cognitive impairment diagnosis in older adults: a nationwide retrospective cohort study

2019 ◽  
Author(s):  
Jae Woo Choi ◽  
Kang Soo Lee ◽  
Euna Han
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mental Disorders ◽  
Suicide Risk ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
One Year

Abstract Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.

scholarly journals Childhood body mass index and multiple sclerosis risk: a long-term cohort study

2013 ◽  
Vol 19 (10) ◽  
pp. 1323-1329 ◽  
Author(s):  
Kassandra L Munger ◽  
Joan Bentzen ◽  
Bjarne Laursen ◽  
Egon Stenager ◽  
Nils Koch-Henriksen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Body Mass Index ◽  
Body Mass ◽  
School Health ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Z Score ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Unit Increase

Background: Obesity in late adolescence has been associated with an increased risk of multiple sclerosis (MS); however, it is not known if body size in childhood is associated with MS risk. Methods: Using a prospective design we examined whether body mass index (BMI) at ages 7–13 years was associated with MS risk among 302,043 individuals in the Copenhagen School Health Records Register (CSHRR). Linking the CSHRR with the Danish MS registry yielded 774 MS cases (501 girls, 273 boys). We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among girls, at each age 7–13 years, a one-unit increase in BMI z-score was associated with an increased risk of MS (HRage 7=1.20, 95% CI: 1.10–1.30; HRage 13=1.18, 95% CI: 1.08–1.28). Girls who were ≥95th percentile for BMI had a 1.61–1.95-fold increased risk of MS as compared to girls <85th percentile. The associations were attenuated in boys. The pooled HR for a one-unit increase in BMI z-score at age 7 years was 1.17 (95% CI: 1.09–1.26) and at age 13 years was 1.15 (95% CI: 1.07–1.24). Conclusion: Having a high BMI in early life is a risk factor for MS, but the mechanisms underlying the association remain to be elucidated.

Socioeconomic status and disability progression in multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (13) ◽  
pp. e1497-e1506 ◽  
Author(s):  
Katharine E. Harding ◽  
Mark Wardle ◽  
Robert Carruthers ◽  
Neil Robertson ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Socioeconomic Status ◽  
Drug Exposure ◽  
Proportional Hazards ◽  
Meta Analysis ◽  
Random Effect ◽  
Cox Proportional Hazards ◽  
Disability Progression ◽  
Cox Proportional Hazards Models ◽  
Neighborhood Level

ObjectiveTo examine the association between socioeconomic status (SES) and disability outcomes and progression in multiple sclerosis (MS).MethodsHealth administrative and MS clinical data were linked for 2 cohorts of patients with MS in British Columbia (Canada) and South East Wales (UK). SES was measured at MS symptom onset (±3 years) based on neighborhood-level average income. The association between SES at MS onset and sustained and confirmed Expanded Disability Status Scale (EDSS) 6.0 and 4.0 and onset of secondary progression of MS (SPMS) were assessed using Cox proportional hazards models. EDSS scores were also examined via linear regression, using generalized estimating equations (GEE) with an exchangeable working correlation. Models were adjusted for onset age, sex, initial disease course, and disease-modifying drug exposure. Random effect models (meta-analysis) were used to combine results from the 2 cohorts.ResultsA total of 3,113 patients with MS were included (2,069 from Canada; 1,044 from Wales). A higher SES was associated with a lower hazard of reaching EDSS 6.0 (adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI] 0.89–0.91), EDSS 4.0 (aHR 0.93, 0.88–0.98), and SPMS (aHR 0.94, 0.88–0.99). The direction of findings was similar when all EDSS scores were included (GEE: β = −0.13, −0.18 to −0.08).ConclusionsLower neighborhood-level SES was associated with a higher risk of disability progression. Reasons for this association are likely to be complex but could include factors amenable to modification, such as lifestyle or comorbidity. Our findings are relevant for planning and development of MS services.

scholarly journals Risk of schizophrenia and bipolar disorder in patients with multiple sclerosis: record-linkage studies

2019 ◽  
Author(s):  
Ute-Christiane Meier ◽  
Sreeram V Ramagopalan ◽  
Michael J Goldacre ◽  
Raph Goldacre
Keyword(s):  
Multiple Sclerosis ◽  
Bipolar Disorder ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Primary Reason ◽  
Hospital Record ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Potential Association ◽  
Shared Risk

AbstractBackgroundThe epidemiology of psychiatric comorbidity in multiple sclerosis (MS) remains poorly understood.ObjectiveWe aimed to determine the risk of schizophrenia and bipolar disorder in MS patients.Material and MethodsRetrospective cohort analyses were performed using an all-England national linked Hospital Episode Statistics (HES) dataset (1999-2016) and to determine whether schizophrenia or bipolar disorder are more commonly diagnosed subsequently in people with MS (n=128,194), and whether MS is more commonly diagnosed subsequently in people with schizophrenia (n=384,188) or bipolar disorder (n=203,592), than would be expected when compared with a reference cohort (∼15 million people) after adjusting for age and other factors. Adjusted hazard ratios (aHRs) were calculated using Cox proportional hazards models.ResultsFindings were dependent on whether the index and subsequent diagnoses were selected as the primary reason for hospital admission or were taken from anywhere on the hospital record. When searching for diagnoses anywhere on the hospital record, there was a significantly elevated risk of subsequent schizophrenia (aHR 1.51, 95% confidence interval (CI) 1.40 to 1.60) and of bipolar disorder (aHR 1.14, 95% CI 1.04 to 1.24) in people with prior-recorded MS and of subsequent MS in people with prior-recorded schizophrenia (aHR 1.26, 1.15-1.37) or bipolar disorder (aHR 1.73, 1.57-1.91), but most of these associations were reduced to null when analyses were confined to diagnoses recorded as the primary reason for admission.ConclusionFurther research is needed to investigate the potential association between MS and schizophrenia and/or bipolar disorder as it may shed light on underlying pathophysiology and help identify potential shared risk factors.

scholarly journals Infectious Diseases Consultation Reduces 30-Day and 1-Year All-Cause Mortality for Multidrug-Resistant Organism Infections

2018 ◽  
Vol 5 (3) ◽  
Author(s):  
Jason P Burnham ◽  
Margaret A Olsen ◽  
Dustin Stwalley ◽  
Jennie H Kwon ◽  
Hilary M Babcock ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Proportional Hazards ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Resistant Organism ◽  
Tertiary Referral Center ◽  
Cox Proportional Hazards Models ◽  
Polymicrobial Infections

Abstract Background Multidrug-resistant organism (MDRO) infections are associated with high mortality and readmission rates. Infectious diseases (ID) consultation improves clinical outcomes for drug-resistant Staphylococcus aureus bloodstream infections. Our goal was to determine the association between ID consultation and mortality following various MDRO infections. Methods This study was conducted with a retrospective cohort (January 1, 2006–October 1, 2015) at an academic tertiary referral center. We identified patients with MDROs in a sterile site or bronchoalveolar lavage/bronchial wash culture. Mortality and readmissions within 1 year of index culture were identified, and the association of ID consultation with these outcomes was determined using Cox proportional hazards models with inverse weighting by the propensity score for ID consultation. Results A total of 4214 patients with MDRO infections were identified. ID consultation was significantly associated with reductions in 30-day and 1-year mortality for resistant S. aureus (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.63; and HR, 0.73, 95% CI, 0.61–0.86) and Enterobacteriaceae (HR, 0.41; 95% CI, 0.27–0.64; and HR, 0.74; 95% CI, 0.59–0.94), and 30-day mortality for polymicrobial infections (HR, 0.51; 95% CI, 0.31–0.86) but not Acinetobacter or Pseudomonas. For resistant Enterococcus, ID consultation was marginally associated with decreased 30-day mortality (HR, 0.81; 95% CI, 0.62–1.06). ID consultation was associated with reduced 30-day readmission for resistant Enterobacteriaceae. Conclusions ID consultation was associated with significant reductions in 30-day and 1-year mortality for resistant S. aureus and Enterobacteriaceae, and 30-day mortality for polymicrobial infections. There was no association between ID consultation and mortality for patients with resistant Pseudomonas, Acinetobacter, or Enterococcus, possibly due to small sample sizes. Our results suggest that ID consultation may be beneficial for patients with some MDRO infections.

scholarly journals Efficacy and tolerability of oral versus injectable disease-modifying therapies for multiple sclerosis in clinical practice

2016 ◽  
Vol 2 ◽  
pp. 205521731667786 ◽  
Author(s):  
Erin E Longbrake ◽  
Anne H Cross ◽  
Amber Salter
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Proportional Hazards ◽  
Dimethyl Fumarate ◽  
Cox Proportional Hazards ◽  
Oral Disease ◽  
Sensitivity Analyses ◽  
Drug Discontinuation ◽  
Disease Modifying Therapies ◽  
Disease Modifying

Background The advent of oral disease-modifying therapies fundamentally changed the treatment of multiple sclerosis. Nevertheless, impressions of their relative efficacy and tolerability are primarily founded on expert opinion. Objective The purpose of this study was to determine whether oral disease-modifying therapies were better tolerated and/or more effective for controlling multiple sclerosis compared to injectable therapies in clinical practice. Methods Single-center, retrospective cohort study. 480 patients initiated oral (fingolimod, teriflunomide, or dimethyl fumarate) or injectable therapy between March 2013–March 2015 and follow-up data was collected for 5–31 months. Outcomes included on-drug multiple sclerosis activity and drug discontinuation. Cox proportional hazards models were used to control for baseline differences and sensitivity analyses using propensity-weighted matching were performed. Results A higher proportion of teriflunomide-treated patients experienced multiple sclerosis activity compared to those treated with injectable therapies ( p = 0.0053) in the adjusted model. Breakthrough multiple sclerosis was equally prevalent among fingolimod and dimethyl fumarate-treated compared to injectable therapy-treated patients. Of patients initiating a disease-modifying therapy, 32–46% discontinued or switched treatments during the study. After controlling for baseline differences, discontinuation rates were comparable across treatment groups. Conclusions In this cohort, oral and injectable disease-modifying therapies were equally well tolerated, but teriflunomide appeared less effective for controlling multiple sclerosis activity than injectable therapies. Further study is needed.

scholarly journals FAMILY CAREGIVER FACTORS AND HOSPITALIZATION IN DISABLED OLDER ADULTS WITH AND WITHOUT DEMENTIA

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S739-S739
Author(s):  
Halima Amjad ◽  
John Mulcahy ◽  
Judith D Kasper ◽  
Julia Burgdorf ◽  
David L Roth ◽  
...  
Keyword(s):  
Older Adults ◽  
Family Caregiver ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Term Care ◽  
Adults With Disabilities ◽  
Hospitalization Rates ◽  
Cox Proportional Hazards Models ◽  
Care Survey ◽  
One Year

Abstract Older adults with disabilities commonly rely on family caregivers’ help, yet effects of caregiver factors on patient outcomes are poorly understood. Within this population, dementia is common. Our objective was to evaluate the association between caregiver factors and risk of hospitalization in disabled older adults with and without dementia. We examined 2,589 community-living older adults with mobility/self-care disability and their primary family caregiver in four waves of the National Long-Term Care Survey and National Health and Aging Trends Study. We used Cox proportional hazards models to examine risk of one-year, Medicare claims-derived, all-cause hospitalization as a function of caregiver factors, adjusting for older adult characteristics (sociodemographics, comorbidities, healthcare utilization) and survey year, considering dementia a characteristic of interest. Among disabled older adults, 38% were hospitalized over one year, and 31% had probable dementia. Hospitalization rates were similar for older adults with and without dementia (39.5% and 37.3% respectively); dementia was not associated with hospitalization risk (HR 1.09, 95% CI 0.95-1.26). Older adults demonstrated greater risk of hospitalization if their caregiver was male (HR 1.31, 95% CI 1.10-1.56), new to caregiving (HR 1.61, 95% CI 1.27-2.04 for &lt; 1 year versus ≥ 4 years), or helped with healthcare tasks (HR 1.21, 95% CI 1.04-1.41). The association between most caregiving factors and hospitalization risk did not differ by dementia status. Results suggest that strategies to reduce hospitalization in older adults with disabilities could target select caregivers using similar strategies in populations with and without dementia.

scholarly journals Teriflunomide Safety and Efficacy in Advanced Progressive Multiple Sclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Vanessa F. Moreira Ferreira ◽  
Danielle Caefer ◽  
Natalie Erlich-Malona ◽  
Brian C. Healy ◽  
Tanuja Chitnis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Confidence Interval ◽  
Glatiramer Acetate ◽  
Progressive Multiple Sclerosis ◽  
Small Sample ◽  
Cox Proportional Hazards Model ◽  
Safety And Efficacy ◽  
Status Score ◽  
Disability Status ◽  
Multiple Sclerosis Population

Objectives. To explore the safety and efficacy profile of teriflunomide in progressive multiple sclerosis. Methods. We conducted a single-center retrospective observational analysis of a progressive multiple sclerosis population, assessing safety and efficacy in patients treated at least one year with teriflunomide or glatiramer acetate. Sustained progression of expanded disability status scale and sustained worsening of timed 25-foot walk were compared using a Cox proportional hazards model. Results. Teriflunomide group ( n = 29 ) mean characteristics: age = 58 years ( SD ± 7.6 ), disease   duration = 16.7 years ( SD ± 9.5 ), expanded   disability   status   score = 5.9 ( SD ± 1.3 ), and follow − up = 32.4 months ( SD ± 13.6 ). Glatiramer acetate group ( n = 30 ) mean characteristics: age = 52.4 years ( SD ± 11.3 ), disease   duration = 15.1 years ( SD ± 10.4 ), expanded   disability   status   score = 5.7 ( SD ± 1.6 ), and follow − up = 46.9 months ( SD ± 43.9 ). Both treatments were well tolerated without serious side effects. After adjustment for age, sex, and baseline expanded disability status score, sustained expanded disability status score progression did not differ between groups ( hazard   ratio = 1.17 ; 95% confidence interval: 0.45, 3.08; p = 0.75 ). Sustained timed 25-foot walk worsening after adjustment also did not differ ( hazard   ratio = 0.56 ; 95% confidence interval: 0.2, 1.53; p = 0.26 ). Conclusion. In an advanced progressive multiple sclerosis population, no substantial differences in tolerability, safety, sustained EDSS progression, or sustained T25FW worsening over time were observed between glatiramer acetate and teriflunomide-treated groups. The small sample precluded definitive determination.

scholarly journals No association between dietary sodium intake and the risk of multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 89 (13) ◽  
pp. 1322-1329 ◽  
Author(s):  
Marianna Cortese ◽  
Changzheng Yuan ◽  
Tanuja Chitnis ◽  
Alberto Ascherio ◽  
Kassandra L. Munger
Keyword(s):  
Multiple Sclerosis ◽  
Fixed Effects ◽  
Proportional Hazards ◽  
Sodium Intake ◽  
Cox Proportional Hazards ◽  
Dietary Sodium ◽  
Health Study ◽  
Cox Proportional Hazards Models ◽  
Using Data

Objective:To prospectively investigate the association between dietary sodium intake and multiple sclerosis (MS) risk.Methods:In this cohort study, we assessed dietary sodium intake by a validated food frequency questionnaire administered every 4 years to 80,920 nurses in the Nurses' Health Study (NHS) (1984–2002) and to 94,511 in the Nurses' Health Study II (NHSII) (1991–2007), and calibrated it using data from a validation study. There were 479 new MS cases during follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the effect of energy-adjusted dietary sodium on MS risk, adjusting also for age, latitude of residence at age 15, ancestry, body mass index at age 18, supplemental vitamin D intake, cigarette smoking, and total energy intake in each cohort. The results in both cohorts were pooled using fixed effects models.Results:Total dietary intake of sodium at baseline was not associated with MS risk (highest [medians: 3.2 g/d NHS; 3.5 g/d NHSII] vs lowest [medians: 2.5 g/d NHS; 2.8 g/d NHSII] quintile: HRpooled 0.98, 95% CI 0.74–1.30, p for trend = 0.75). Cumulative average sodium intake during follow-up was also not associated with MS risk (highest [medians: 3.3 g/d NHS; 3.4 g/d NHSII] vs lowest [medians: 2.7 g/d NHS; 2.8 g/d NHSII] quintile: HRpooled 1.02, 95% CI 0.76–1.37, p for trend = 0.76). Comparing more extreme sodium intake in deciles yielded similar results (p for trend = 0.95).Conclusions:Our findings suggest that higher dietary sodium intake does not increase the risk of developing MS.

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