Medicine (RMH) - Research Publications
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ItemEffect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years(LIPPINCOTT WILLIAMS & WILKINS, 2021-02-02)OBJECTIVE: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients. METHODS: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity. RESULTS: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, p = 0.0016), worsening of disability (0.56, 0.38-0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p = 10-9) and worsening of disability (0.81, 0.67-0.99, p = 0.043). CONCLUSION: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
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ItemEffectiveness of multiple disease-modifying therapies in relapsing-remitting multiple sclerosis: causal inference to emulate a multiarm randomised trial(BMJ PUBLISHING GROUP, 2023-12)BACKGROUND: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years. METHODS: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement. RESULTS: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability. CONCLUSIONS: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously.
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ItemVariability of the response to immunotherapy among subgroups of patients with multiple sclerosis(WILEY, 2023-04)BACKGROUND AND PURPOSE: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). METHODS: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. RESULTS: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. CONCLUSIONS: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.
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ItemDisability accrual in primary and secondary progressive multiple sclerosis(BMJ Publishing Group, 2023-04-17)Background: Some studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS. Methods: We compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS. Results: Included patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2-47.3) vs 43.9 (43.3-44.4); p<0.001), greater baseline disability, slower disability accrual (HR 0.86 (0.78-0.94); p<0.001) and similar age at wheelchair dependence. Conclusions: We demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials.
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ItemNo Preview AvailableCoronavirus Disease 2019 (COVID-19) in Conakry, Republic of Guinea: Analysis and Relationship with Meteorological Factors(Scientific Research Publishing, Inc., 2021)
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ItemAnalysis of Rainfall Dynamics in Conakry, Republic of Guinea(Scientific Research Publishing, Inc., 2020)
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ItemHydropluviometric variability in non-Sahelian West Africa: Case of the Koliba/Corubal River Basin (Guinea and Guinea-Bissau)(Copernicus GmbH, 2020-09-15)Abstract. The Koliba/Corubal River watershed is poorly documented due to the hydrometric measurements shutdown and gaps in the very short hydropluviometric timeseries. The purpose of this study is to analyze the variability of rainfall in the Basin, by simulating flows using the GR2M rain-flow model and extending the discharge timeseries. From the regional vector method, the rainfall timeseries were homogenized, and the gaps filled by the estimated values. The rank correlation and Pettitt test on annual rainfall amounts (1924–2015) indicate breaks in 1958, 1967 and 1969, leading to rainfall deficits ranging from 9.7 % to 20.2 %. For some stations, the segmentation method shows a recovery of rainfall towards the end of the 1980s (Gaoual, Mali) and the early 2000s (Gabu). The analysis of the temporal distribution of the Monthly Rainfall Coefficients shows an improvement of the contributions of a few months during the period after rupture. From a hydrological point of view, the correlation between the mean annual rainfall and the runoff has allowed to extend the flow timeseries. The mean monthly rainfall calculated using the inverse square of distance method, the Potential Evapotranspiration, and the flow rates were used to calibrate and validate the model to determine the parameters that better transform rainfall in flow. The values of the Nash criteria close to 100 have made it possible to extend the monthly flow data from Koliba/Corubal to Gaoual, Cade and Tche-Tche until 2015.
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ItemNo Preview AvailableImpact of different heat wave definitions on daily mortality in Bandafassi, Senegal.(Public Library of Science (PLoS), 2021)OBJECTIVE: The aim of this study is to find the most suitable heat wave definition among 15 different ones and to evaluate its impact on total, age-, and gender-specific mortality for Bandafassi, Senegal. METHODS: Daily weather station data were obtained from Kedougou situated at 17 km from Bandafassi from 1973 to 2012. Poisson generalized additive model (GAM) and distributed lag non-linear model (DLNM) are used to investigate the effect of heat wave on mortality and to evaluate the nonlinear association of heat wave definitions at different lag days, respectively. RESULTS: Heat wave definitions, based on three or more consecutive days with both daily minimum and maximum temperatures greater than the 90th percentile, provided the best model fit. A statistically significant increase in the relative risk (RRs 1.4 (95% Confidence Interval (CI): 1.2-1.6), 1.7 (95% CI: 1.5-1.9), 1.21 (95% CI: 1.08-1.3), 1.2 (95% CI: 1.04-1.5), 1.5 (95% CI: 1.3-1.8), 1.4 (95% CI: 1.2-1.5), 1.5 (95% CI: 1.07-1.6), and 1.5 (95% CI: 1.3-1.8)) of total mortality was observed for eight definitions. By using the definition based on the 90th percentile of minimum and maximum temperature with a 3-day duration, we also found that females and people aged ≥ 55 years old were at higher risks than males and other different age groups to heat wave related mortality. CONCLUSION: The impact of heat waves was associated with total-, age-, gender-mortality. These results are expected to be useful for decision makers who conceive of public health policies in Senegal and elsewhere. Climate parameters, including temperatures and humidity, could be used to forecast heat wave risks as an early warning system in the area where we conduct this research. More broadly, our findings should be highly beneficial to climate services, researchers, clinicians, end-users and decision-makers.
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ItemNo Preview AvailableElectro-generation of hydrogen peroxide using a graphite cathode from exhausted batteries: study of influential parameters on electro-Fenton process(TAYLOR & FRANCIS LTD, 2020-05-11)In this work, the study of hydrogen peroxide (H2O2) electro-generation using graphite from exhausted batteries (Gr-Bat) was conducted. Linear sweep voltammetry and electrolysis experiments were carried out in a single compartment electrochemical cell. Study of the possibility to use this electrode revealed that it presents, as vitreous carbon (VC) electrode, a reduction of oxygen with two successive waves (bi-electronic reduction). The first wave corresponds to the reduction of O2 to H2O2, while the second one corresponds to the reduction of H2O2 to H2O. The cathodic potentials for electro-generation of H2O2 appeared at -600 and -700 mV vs. Ag/AgCl for Gr-Bat and VC electrodes, respectively. Subsequently, electrolysis experiments were conducted by imposing the potentials required for H2O2 formation. The effect of several operating parameters on H2O2 production, such as the nature and concentration of the electrolyte, the pH, the presence of ferrous ions and O2 injection were studied using Gr-Bat and VC electrodes, respectively. For both electrodes, the acidic medium was more favorable for H2O2 electro-generation. The oxygen injection in solution promoted an increase of H2O2 concentration, but its effect was more pronounced in the case of VC electrode. Application for crystal violet degradation by electro-Fenton revealed that Gr-Bat had the best purification performance. A removal rate of 73.18% was obtained with Gr-Bat electrode against 62.27% with VC electrode for an electrolysis time of 120 min. This study has demonstrated the possibility of recycling Gr-Bat by using them as cathode materials in the electro-Fenton process.
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ItemIntegration of QTL, Transcriptome and Polymorphism Studies Reveals Candidate Genes for Water Stress Response in Tomato(MDPI, 2020-08)Water deficit (WD) leads to significant phenotypic changes in crops resulting from complex stress regulation mechanisms involving responses at the physiological, biochemical and molecular levels. Tomato growth and fruit quality have been shown to be significantly affected by WD stress. Understanding the molecular mechanism underlying response to WD is crucial to develop tomato cultivars with relatively high performance under low watering conditions. Transcriptome response to WD was investigated through the RNA sequencing of fruit and leaves in eight accessions grown under two irrigation conditions, in order to get insight into the complex genetic regulation of WD response in tomato. Significant differences in genotype WD response were first observed at the phenotypic level for fruit composition and plant development traits. At the transcriptome level, a total of 14,065 differentially expressed genes (DEGs) in response to WD were detected, among which 7393 (53%) and 11,059 (79%) were genotype- and organ-specific, respectively. Water deficit induced transcriptome variations much stronger in leaves than in fruit. A significant effect of the genetic background on expression variation was observed compared to the WD effect, along with the presence of a set of genes showing a significant genotype x watering regime interaction. Integrating the DEGs with previously identified WD response quantitative trait loci (QTLs) mapped in a multi-parental population derived from the crossing of the eight genotypes narrowed the candidate gene lists to within the confidence intervals surrounding the QTLs. The results present valuable resources for further study to decipher the genetic determinants of tomato response to WD.