1,721,036 research outputs found
Comparative effectiveness of autologous hematopoietic stem cell transplant vs Fingolimod, Natalizumab, and Ocrelizumab in highly active relapsing-remitting multiple sclerosis
No full textAbstract: Importance Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).Objective To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.Design, Setting, and Participants This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics.Exposure AHSCT vs fingolimod, natalizumab, or ocrelizumab.Main outcomes Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement.Results Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%).Conclusion In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time
Predictors of relapse risk and treatment response in AQP4-IgG positive and seronegative NMOSD : a multicentre study
No full textAbstract: Background: Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD. Methods: This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate. Results: A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group. Conclusion: Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus
Disease activity in pregnant and postpartum women with multiple sclerosis receiving ocrelizumab or other disease-modifying therapies
No full textAbstract: Background and Objectives Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods. Methods We performed a retrospective cohort study using data from the MSBase Registry including pregnancies conceived after December 31, 2010, from women aged 18 years and older, with relapsing-remitting MS or clinically isolated syndrome. Women were classified by preconception exposure to DMTs, including OCR, rituximab (RTX), natalizumab (NAT), stratified into active (NAT-A; continued >= 28 weeks of gestation, restarted 1 month postpartum) strategies, dimethyl fumarate (DMF) or low-efficacy DMTs (interferon-beta, glatiramer acetate). Annualized relapse rates (ARRs) were calculated for 12-month prepregnancy, pregnancy, and 6-month postpartum periods. Results A total of 2,009 live births from 1,744 women were analyzed, including 73 live births from 69 women treated with preconception OCR. For OCR, no within-pregnancy relapse was observed and 3 women (4.1%) experienced 1 relapse in the postpartum period (ARR 0.09 [95% CI 0.02-0.27]). For NAT-A, 3 (3.7%) of 82 women relapsed during pregnancy (0.05 [0.01-0.15]) and 4 (4.9%) relapsed during postpartum (0.10 [0.03-0.26]). However, for NAT-C, 13 (15.9%) of 82 women relapsed within pregnancy (0.32 [0.20-0.51]) and 25 (30.5%) relapsed during postpartum (0.74 [0.50-1.06]). In the low-efficacy DMT group, 101 (7.6%) of 1,329 women experienced within-pregnancy relapse (0.12 [0.10-0.14]), followed by an increase in postpartum relapse activity with 234 women (17.6%) relapsing (0.43 [0.38-0.48]). This was similarly seen in the DMF group with 13 (7.9%) of 164 women experiencing within-pregnancy relapse (0.12 [0.06-0.20]) and 25 (15.2%) of 164 relapsing postpartum (0.39 [0.26-0.57]). Our RTX cohort had 0 of 24 women experiencing within-pregnancy relapse and 3 (12.5%) of 24 experiencing postpartum relapse. Discussion Women treated with OCR or NAT-A were observed to have low relapse rates during pregnancy and postpartum. NAT-C was associated with increased risk of relapses. There was no within-pregnancy relapse in our RTX cohort, although we caution overinterpretation due to our sample size. An effective DMT strategy with a favorable safety profile for the mother and infant should be discussed and implemented well in advance of planning a family. Classification of Evidence This study provides Class III evidence that for women with relapsing-remitting MS or clinically isolated syndrome who become pregnant, ocrelizumab, rituximab, and natalizumab (continued >= 28 weeks of gestation and restarted <= 1 month postpartum) were associated with reduced risk of relapses, compared with other therapeutic strategies
Effectiveness of cladribine compared to fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting multiple sclerosis
No full textAbstract: Background: Comparisons between cladribine and other potent immunotherapies for multiple sclerosis (MS) are lacking. Objectives: To compare the effectiveness of cladribine against fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting MS. Methods: Patients with relapsing-remitting MS treated with cladribine, fingolimod, natalizumab, ocrelizumab or alemtuzumab were identified in the global MSBase cohort and two additional UK centres. Patients were followed for >= 6/12 and had >= 3 in-person disability assessments. Patients were matched using propensity score. Four pairwise analyses compared annualised relapse rates (ARRs) and disability outcomes. Results: The eligible cohorts consisted of 853 (fingolimod), 464 (natalizumab), 1131 (ocrelizumab), 123 (alemtuzumab) or 493 (cladribine) patients. Cladribine was associated with a lower ARR than fingolimod (0.07 vs. 0.12, p = 0.006) and a higher ARR than natalizumab (0.10 vs. 0.06, p = 0.03), ocrelizumab (0.09 vs. 0.05, p = 0.008) and alemtuzumab (0.17 vs. 0.04, p < 0.001). Compared to cladribine, the risk of disability worsening did not differ in patients treated with fingolimod (hazard ratio (HR) 1.08, 95% confidence interval (CI) 0.47-2.47) or alemtuzumab (HR 0.73, 95% CI 0.26-2.07), but was lower for patients treated with natalizumab (HR 0.35, 95% CI 0.13-0.94) and ocrelizumab (HR 0.45, 95% CI 0.26-0.78). There was no evidence for a difference in disability improvement. Conclusion: Cladribine is an effective therapy that can be viewed as a step up in effectiveness from fingolimod, but is less effective than the most potent intravenous MS therapies
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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