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  • 1
    In: Journal of Neurology, Springer Science and Business Media LLC
    Abstract: It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case–control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1421299-7
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2005
    In:  Bulletin de l'Académie Nationale de Médecine Vol. 189, No. 6 ( 2005-06), p. 1305-1318
    In: Bulletin de l'Académie Nationale de Médecine, Elsevier BV, Vol. 189, No. 6 ( 2005-06), p. 1305-1318
    Type of Medium: Online Resource
    ISSN: 0001-4079
    Language: French
    Publisher: Elsevier BV
    Publication Date: 2005
    detail.hit.zdb_id: 2868142-3
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  • 3
    In: ECS Meeting Abstracts, The Electrochemical Society, Vol. MA2014-01, No. 40 ( 2014-04-01), p. 1482-1482
    Abstract: Dental implantology procedures necessitate surgical drilling of a hole in the jawbone to insert an artificial root over which a dental prosthesis is placed. The success factor of a dental implant is attaining successful osseointegration. This implies a deeper placed implant closest to the Inferior Alveolar Nerve (IAN) but not too close that it carries the risk of damaging this nerve-artery bundle located along the mandible line. Implications for perforating the IAN in patients can vary from temporary numbness to permanent loss of sensation in the lower facial area. Surgeons routinely use computer-assisted navigation techniques relying on static preoperative cone-beam X-ray computed tomography or other imaging methods such as Magnetic Resonance Imaging (MRI) to assess optimal anatomical distances in the patient’s jaw. However, variability of the measured IAN bundle position with these techniques is at the moment accurate to 30% at best. These techniques are known to introduce localization errors and do not benefit from in situ guidance. Therefore there is an important need for an online, in vivo probe to assess drill distances to a critical nerve-artery bundle in situ to not only avoid jaw paralysis but to improve overall outcome of the implantation. To this aim, we investigate a combined multimodal approach using Optical Coherence Tomography (OCT) for high resolution structural imaging, and functional NIR absorption detection in an optical fiber probe eventually small enough to fit into a surgical drill bit, for real-time evaluation of the distance from the probe to the IAN. We designed a reflectance fiber-optic probe to sense the pulsation of the artery (Heartbeat ~1-2Hz) in the IAN bundle, and a detection circuit board with a high gain (2 . 10 6 V/A), and very low noise (10mV RMS at output) and bandwidth (10Hz) shown on Figure 1. The success of this NIR channel for accurate real-time proximity sensing by capturing low frequency pulsing signals relies on an ultra low noise photon detection module. Measurements with this fiber probe were conducted at probe-target distances varying from 0mm (probe in contact) to 3mm. The results obtained are promising: the oscillating RMS amplitude varies as a function of distance in a similar fashion to previously published work in pulse oximetry literature [1]. The DC level also has a specific trend as a function of distance. Both AC and DC signal components can be used to extract useful distance information. Original designs using a lock-in amplifier to measure the very low RMS amplitude of the of the back-reflected light intensity, modulated by the spatially oscillating absorption changes due to flowing blood surrogate in an artery simulating tube were promising, but limited. Lock-in signal detection with a reference signal modulated at only 1-2 Hz needs filtering with long time constants. Moreover, clinical implementation with the heartbeat as the reference signal would make real-time measurement impractical. As such, we have developed a flexible optoelectronic detection platform with tunable bandwidth, gain and bias enabling the system to not be limited by electronics noise. Using custom phantoms of the jawbone and including a surrogate arterial dynamic pumping circuit, we demonstrated proof of concept for potential detection range of 0.5-4 mm at l-850nm with a source-detector separation of 1.8mm using the pulsating signal from an artery simulating tube. In compliment, a swept-source OCT at 1.3mm provided finer resolution sensitivity to the proximity of the IAN bundle in the 0-0.9mm range and offered the possibility of imaging the inhomogeneous IAN interface. Methods for calibrating and processing the data to provide robust long range NIR finding capabilities in combination with short-range high precision OCT imaging towards a complete clinical solution will be discussed.
    Type of Medium: Online Resource
    ISSN: 2151-2043
    Language: Unknown
    Publisher: The Electrochemical Society
    Publication Date: 2014
    detail.hit.zdb_id: 2438749-6
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  • 4
    In: Biomedical Optics Express, Optica Publishing Group, Vol. 5, No. 1 ( 2014-01-01), p. 16-
    Type of Medium: Online Resource
    ISSN: 2156-7085 , 2156-7085
    Language: English
    Publisher: Optica Publishing Group
    Publication Date: 2014
    detail.hit.zdb_id: 2572216-5
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  • 5
    In: Journal of Physics: Conference Series, IOP Publishing, Vol. 276 ( 2011-02-01), p. 012114-
    Type of Medium: Online Resource
    ISSN: 1742-6596
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2011
    detail.hit.zdb_id: 2166409-2
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  • 6
    In: Brain, Oxford University Press (OUP), Vol. 143, No. 9 ( 2020-09-01), p. 2742-2756
    Abstract: In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments (‘therapeutic lag’) on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 7
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 20, No. 11 ( 2014-10), p. 1511-1522
    Abstract: The aim was to analyse risk of relapse phenotype recurrence in multiple sclerosis and to characterise the effect of demographic and clinical features on this phenotype. Methods: Information about relapses was collected using MSBase, an international observational registry. Associations between relapse phenotypes and history of similar relapses or patient characteristics were tested with multivariable logistic regression models. Tendency of relapse phenotypes to recur sequentially was assessed with principal component analysis. Results: Among 14,969 eligible patients (89,949 patient-years), 49,279 phenotypically characterised relapses were recorded. Visual and brainstem relapses occurred more frequently in early disease and in younger patients. Sensory relapses were more frequent in early or non-progressive disease. Pyramidal, sphincter and cerebellar relapses were more common in older patients and in progressive disease. Women presented more often with sensory or visual symptoms. Men were more prone to pyramidal, brainstem and cerebellar relapses. Importantly, relapse phenotype was predicted by the phenotypes of previous relapses. (OR = 1.8–5, p = 10 -14 ). Sensory, visual and brainstem relapses showed better recovery than other relapse phenotypes. Relapse severity increased and the ability to recover decreased with age or more advanced disease. Conclusion: Relapse phenotype was associated with demographic and clinical characteristics, with phenotypic recurrence significantly more common than expected by chance.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2008225-3
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  • 8
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 94, No. 9 ( 2023-09), p. 707-717
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
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    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 1480429-3
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  • 9
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 24 ( 2022-06-14), p. e2401-e2412
    Abstract: The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS. Methods This observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration’s Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS. Results The 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35′ and 56°16′) were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes 〈 40°, more severe disease was associated with higher latitudes (β = 0.08, 95% CI 0.04–0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes 〈 40° (β = −0.02, 95% CI −0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 years (β = − 0.5, 95% CI −0.6 to 0.4) and 18 years (β = − 0.6, 95% CI −0.7 to 0.4), as well as with lower lifetime UVB exposure at the time of disability assessment (β = −1.0, 95% CI −1.1 to 0.9). Discussion In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 10
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 2 ( 2021-01-12), p. e214-e227
    Abstract: To compare the effectiveness of glatiramer acetate (GA) vs intramuscular interferon beta-1a (IFN-β-1a), we applied a previously published statistical method aimed at identifying patients' profiles associated with efficacy of treatments. Methods Data from 2 independent multiple sclerosis datasets, a randomized study (the Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis [CombiRx] trial, evaluating GA vs IFN-β-1a) and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors. Results The overall ARR ratio of GA to IFN-β-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration, and Expanded Disability Status Scale score) detected differential response of GA vs IFN-β-1a: in the trial, patients with the largest benefit from GA vs IFN-β-1a (lower score quartile) had an ARR ratio of 0.40 (95% confidence interval [CI] 0.25–0.63), those in the 2 middle quartiles of 0.90 (95% CI 0.61–1.34), and those in the upper quartile of 1.14 (95% CI 0.59–2.18) (heterogeneity p = 0.012); this result was validated on MSBase, with the corresponding ARR ratios of 0.58 (95% CI 0.46–0.72), 0.92 (95% CI 0.77–1.09,) and 1.29 (95% CI 0.97–1.71); heterogeneity p 〈 0.0001). Conclusions We demonstrate the possibility of a criterion, based on patients' characteristics, to choose whether to treat with GA or IFN-β-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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