Domain Induced Dirichlet Mixture of Gaussian Processes: An Application to Predicting Disease Progression in Multiple Sclerosis Patients

2015 ◽  
Author(s):  
Yijun Zhao ◽  
Tanuja Chitnis ◽  
Brian C. Healy ◽  
Jennifer G. Dy ◽  
Carla E. Brodley
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Gaussian Processes ◽  
Dirichlet Mixture ◽  
Multiple Sclerosis Patients ◽  
Mixture Of Gaussian

scholarly journals Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mario Amatruda ◽  
Maria Petracca ◽  
Maureen Wentling ◽  
Benjamin Inbar ◽  
Kamilah Castro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Course ◽  
Primary Progressive ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
One Year ◽  
Multiple Sclerosis Patients

Abstract The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS.

Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression

2012 ◽  
Vol 18 (8) ◽  
pp. 1092-1098 ◽  
Author(s):  
CE Teunissen ◽  
M Sombekke ◽  
L van Winsen ◽  
J Killestein ◽  
F Barkhof ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Lesion Load ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
In Cis

Background: Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression. Objective: To study whether plasma isoprostane levels were related to disease progression in MS. Methods: Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters. Results: Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS). Conclusion: These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.

Disease progression among multiple sclerosis patients before and during a disease-modifying drug program: a longitudinal population-based evaluation

2009 ◽  
Vol 15 (11) ◽  
pp. 1286-1294 ◽  
Author(s):  
PJ Veugelers ◽  
JD Fisk ◽  
MG Brown ◽  
K. Stadnyk ◽  
IS Sketris ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Program Effectiveness ◽  
Population Based ◽  
Eligibility Criteria ◽  
Disease Modifying Drugs ◽  
Regression Methods ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Randomized controlled trials have demonstrated the efficacy of disease-modifying drugs (DMDs) in persons with relapsing—remitting multiple sclerosis (MS) and secondary progressive MS with superimposed relapses. However, these brief studies of selected patients have focused mainly on reducing attacks and must be complemented by evaluations in ‘realworld’ clinical settings to establish the effectiveness of DMD programs in slowing disease progression and to inform health policy and program decision-making. We assessed the effectiveness of DMDs as administered in a comprehensive publicly funded drug insurance program that provides DMDs to a geographically defined population of MS patients who meet specific eligibility criteria. Data from 1752 MS patients (10,312 assessments) seen between 1980 and 2004 at a regional MS Clinic serving the entire population of Nova Scotia, Canada were analysed. Using survival methods we observed a statistically significant reduction in disease progression to specific Expanded Disability Status Scale endpoints following the introduction of this program. Subgroup analyses of patients eligible for treatment using hierarchical linear regression methods also suggested that disease progression was slowed in patients treated with the first DMD prescribed. These findings provide evidence supporting DMD program effectiveness that can be used to inform the broader implementation of such programs.

scholarly journals A Group Cognitive Behavioural Therapy Improves Quality of Life of Multiple Sclerosis Patients and Delays Disease Progression: A Multi-Centre Controlled Trial

2018 ◽  
Vol 1 (1) ◽  
pp. 77-84
Author(s):  
Richard Devy ◽  
Philip Lehert ◽  
Marc Genty
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Disease Progression ◽  
Cognitive Behavioural Therapy ◽  
Controlled Trial ◽  
Behavioural Therapy ◽  
Group Cognitive Behavioural Therapy ◽  
Cognitive Behavioural ◽  
Multiple Sclerosis Patients

Background: Multiple Sclerosis (MS) affects quality of life (QoL). Pharmacological treatments demonstrated benefits on clinical endpoints without improving QoL. We evaluated the effects of a group Cognitive Behavioural Therapy (CBT) on QoL disease progression. Methods: One-year multi-centre controlled multivariate-matched study was organised on Relapsing-Remitting MS (RRMS) patients with Expanded Disability Status Scale (EDSS) < 4, MS duration < 2 years, treated by interferon I? in 11 French centres. For each new patient, the two best-matching patients for age, gender, EDSS, mood, illness duration baseline variables were selected in the other centres. The self-filled Two Lives Scale (TLS)-QoL10 was used at months (M) 0-3-6-9-12-15; the post-baseline mean QoL was the endpoint. We compared CBT + I? to I? alone. The effect of disease progression on QoL was evaluated by modelling, for each visit, the effect of EDSS on QoL at later visits.Results: 19 + 32 patients were recruited. Compared to placebo, improvements of 1.10 (95%CI [0.31-1.89], p = 0.009) and 1.43*** [0.72, 2.15] were observed in the CBT group on QoL and coping scales, respectively. Coping explained 81%*** [57, 100] of the effect of CBT on QoL. QoL was negatively affected by disease progression (0.95*** [-1.21; 0.63]), whereas EDSS was influenced by QoL values (-0.10*** [-0.14; -0.06]).Conclusions: We observed a clinically significant beneficial effect of CBT on QoL, the effect of CBT essentially explained by an increase of coping, a positive influence of QoL on disease progression. QoL is both the most important target for patients and a factor of slowing disease progression.

Membrane saturated fatty acids and disease progression in Multiple Sclerosis patients

2009 ◽  
Vol 24 (4) ◽  
pp. 561-568 ◽  
Author(s):  
G. M. Hon ◽  
M. S. Hassan ◽  
S. J. van Rensburg ◽  
S. Abel ◽  
R. T. Erasmus ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Fatty Acids ◽  
Disease Progression ◽  
Saturated Fatty Acids ◽  
Multiple Sclerosis Patients

Mini-Autologous Hematopoietic Stem Cell Transplantations as a New Treatment Modality for Multiple Sclerosis Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4454-4454
Author(s):  
Andrei A Novik ◽  
Vladimir Y Melnichenko ◽  
Denis A Fedorenko ◽  
Ruslana V Kruglina ◽  
Tatiana I Ionova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cell ◽  
Disease Progression ◽  
Hematopoietic Stem Cell ◽  
High Dose ◽  
Base Line ◽  
Hematopoietic Stem ◽  
Patient Reported ◽  
Multiple Sclerosis Patients

Abstract Conventional therapies do not provide satisfactory control of multiple sclerosis (MS) due to their inability to eradicate self-specific T cell clones. Recently, high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (AHSCT) was proposed as a new and promising therapy for MS patients. Taking into account the information about high risk of transplant-related mortality and severe side effects of myeloablative conditioning regimens, the rationale to use non-myeloablative regimens sounds reasonable. The goal of our research was to study the safety and efficacy of mini-AHSCT in MS patients. Fifty three patients with MS (secondary progressive – 16 patients, primary progressive – 12, progressive-relapsing – 3 and relapsing-remitting – 22) were included in this study (mean age - 30.0, range: 17–47; male/female – 23/30). The conditioning regimen included reduced or modified BEAM. Median EDSS at base-line was 4.0 (range 1.5 – 8.0). The median follow-up duration was 7 months (range 6 – 20 months). Neurological and quality of Life (QoL) evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months, and every 6 months thereafter AHSCT. MRI examinations were performed at baseline, at 6, 12 months, and at the end of follow-up. Transplantation procedure was well tolerated by the patients with no transplant-related deaths. Among 29 patients included in the efficacy analysis 15 patients (52%) experienced clinical stabilization; 14 (48%) – improvement. EDSS improved by 0.5 points in 11 patients, by 1.0 points in 2 patients, by 2.0 points in 1 patient. One patient progressed after 6 months stabilization. No active, new or enlarging lesions were registered in patients without disease progression. Out of 27 patients included in QoL analysis 21 exhibited QoL improvement and 4 – stabilization during the follow-up; QoL worsened in 2 patients. All the patients without disease progression were off therapy throughout the post-transplant period. In conclusion, mini-AHSCT may be considered as a new, safe and effective treatment for MS. The results of mini-AHSCT in MS patients are promising both in terms of clinical and patient-reported outcomes. The collection of long-term follow-up data is worthwhile to verify these findings. The rationale of evolution from myeloablative to non-myeloablative transplant regimens should be confirmed by the further studies.

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