Publications by authors named "Gray O"
Background: Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories.
View Article and Find Full Text PDFArticle Synopsis
- * Machine learning models were applied to predict confirmed disability progression after two years, achieving a ROC-AUC score of 0.71, indicating moderate accuracy, while historical disability was found to be a stronger predictor than treatment or relapse history.
- * The research followed strict guidelines and made its coding accessible for others to facilitate future benchmarking in predicting disability progression in MS patients.
Background: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset.
Methods: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted.
Article Synopsis
- Non-specific immunosuppressants (NSIS) are still widely used for treating multiple sclerosis (MS) despite safety concerns, particularly in resource-limited areas.
- The study analyzed MSBase registry data to compare treatment outcomes of adults with relapsing-remitting MS (RRMS) using dimethyl fumarate (DMF) versus NSIS between January 2014 and April 2022.
- Results showed that while annualized relapse rates were similar, DMF led to longer times before treatment discontinuation and confirmed disability progression, supporting its use over NSIS for RRMS patients.
Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study.
J Neurol Neurosurg Psychiatry
October 2024
Background: It remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.
Methods: This large-scale cohort study included persons with MS with CSF data documented in the MSBase registry. CSF parameters to predict time to reach confirmed Expanded Disability Status Scale (EDSS) scores 4, 6 and 7 and annualised relapse rate in the first 2 years after diagnosis (ARR2) were assessed using (cox) regression analysis.
Article Synopsis
- - The study aimed to analyze real-world treatment persistence rates of disease-modifying therapies (DMTs) for individuals with multiple sclerosis (MS), examining factors that lead to discontinuation of these treatments.
- - Data from 4,366 patients with relapse-onset MS were collected from 13 specialist centers in the UK, finding a median persistence of 4.3 years on any DMT, with adverse events and lack of efficacy being the top reasons for stopping treatment.
- - Results indicated that immune reconstituting therapies like alemtuzumab may provide more prolonged DMT options compared to traditional therapies, emphasizing the importance of understanding DMT persistence for better treatment strategies.
Background: The Big Multiple Sclerosis Data (BMSD) network ( https://bigmsdata.org ) was initiated in 2014 and includes the national multiple sclerosis (MS) registries of the Czech Republic, Denmark, France, Italy, and Sweden as well as the international MSBase registry. BMSD has addressed the ethical, legal, technical, and governance-related challenges for data sharing and so far, published three scientific papers on pooled datasets as proof of concept for its collaborative design.
View Article and Find Full Text PDFArticle Synopsis
- Vascular health is influenced by mechanical forces from blood flow, with disorders like atherosclerosis more common at bends and junctions in blood vessels.
- Research identified specific gene regulatory regions (super-enhancers) in endothelial cells that respond differently to healthy unidirectional flow versus disturbed flow associated with atherosclerosis.
- Using gene editing techniques, the study confirmed the role of these super-enhancers in regulating antioxidant and prothrombotic genes, providing insights into how flow affects vascular health at a molecular level.
Aim: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS).
Methods: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups.
Article Synopsis
- This study investigates the relationship between environmental factors and progressive-onset multiple sclerosis (POMS) compared to relapse-onset multiple sclerosis (ROMS), aiming to better understand the causes of POMS.
- Data is drawn from two major studies, including a sample of 155 POMS, 204 ROMS, and 558 controls, ensuring that the POMS sample is representative of the broader Australian POMS population.
- The research addresses various methodological challenges, such as biases and differences between POMS and controls, and will present findings on the associations in future publications.
Article Synopsis
- This study examines the effectiveness of six different therapies for treating relapsing-remitting multiple sclerosis (RRMS) over 5 years, using a large dataset from 74 centers across 35 countries.
- Researchers found that natalizumab and fingolimod were more effective in reducing relapses and worsening disability compared to other therapies like dimethyl fumarate, teriflunomide, glatiramer acetate, and interferon beta.
- The findings highlight the potential of marginal structural models (MSMs) to simulate clinical trials and compare various treatment outcomes in real-world patient populations.
Article Synopsis
- The study investigates geographical differences in the risk of secondary progressive multiple sclerosis (SPMS) and how these may be influenced by factors like latitude and treatment types.
- It utilizes data from a global patient registry, focusing on relapsing-remitting multiple sclerosis patients and factors such as age, sex, and treatment efficacy.
- The research analyzes data from over 51,000 patients across 27 countries to establish patterns in the progression from relapsing-remitting to secondary progressive phases of the disease.
Article Synopsis
- Ocrelizumab, a targeted monoclonal antibody for treating relapsing-remitting MS, significantly reduces relapse rates and disability compared to interferon beta 1a, while rituximab is often used off-label as an alternative.
- This study aimed to determine if rituximab's effectiveness is comparable (noninferior) to that of ocrelizumab in treating relapsing-remitting MS.
- The observational study included over 1600 patients from MS registries with matched baseline characteristics, focusing on annual relapse rates as the primary outcome measure.
Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.
Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS.
Methods: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'.
Background: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic has made neurology clinic waiting times longer. To prevent a build-up of patients waiting, we introduced a neurology advanced referral management system (NARMS) to deal with new referrals from GPs, using advice, investigations, or the telephone, as alternatives to face-to-face (FF) assessment.
Methods: For six months, electronic referrals from GPs were triaged to the above categories.
Article Synopsis
- Every decision we make involves a trade-off between using what we know (exploiting) and trying new options (exploring) that could lead to better or worse results.
- Research on patients with deep brain stimulation (DBS) for dystonia showed that stimulating a specific part of the brain called the globus pallidus interna increased exploratory choices in a decision-making task.
- The study found that this enhanced exploration linked to how the brain processes information and its connections, suggesting that the basal ganglia can influence our decision-making strategies when faced with choices between exploring and exploiting.
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.
In Tibetans, noncoding alleles in -whose protein product hypoxia-inducible factor 2α (HIF-2α) drives the response to hypoxia-carry strong signatures of positive selection; however, their functional mechanism has not been systematically examined. Here, we report that high-altitude alleles disrupt the activity of four enhancers in one or more cell types. We further characterize one enhancer (ENH5) whose activity is both allele specific and hypoxia dependent.
View Article and Find Full Text PDFArticle Synopsis
- This study looks at how to predict long-term disability in people with multiple sclerosis (MS) after they show signs of worsening over six months.
- Researchers checked data from thousands of patients to figure out who is more likely to have lasting problems.
- They found that things like age, sex, and how MS affects the person can help tell if someone will continue to get worse, which can help doctors in future treatments.
Article Synopsis
- The study aimed to explore how the latitude of residence and UVB radiation exposure affects the severity of multiple sclerosis (MS) among patients, using data from the MSBase registry.
- Results indicated that patients living at higher latitudes (above 40°) experienced more severe MS symptoms, while this trend was not observed in those living below this latitude.
- Additionally, lower UVB exposure during childhood (ages 6 and 18) was linked to faster progression of disability in MS, suggesting the importance of environmental factors in disease severity.
Aims: To scope the key performance indicators (KPIs) used in nursing and midwifery across the United Kingdom and Republic of Ireland and explore how they influence practice in healthcare organizations.
Design: The study adopted a sequential, exploratory mixed-methods design.
Methods: Phase 1 incorporated a multiple-choice questionnaire completed by 77 Directors of Nursing recruited using voluntary response sampling.
Background: L.is a well-established medicinal herb used for millennia to treat parasites and fever-related ailments caused by various microbes. Although effective against many infectious agents, the plant is not a miracle cure and there are infections where it has proved ineffective or limited.
View Article and Find Full Text PDFThe MSBase pregnancy, neonatal outcomes, and women's health registry.
Ther Adv Neurol Disord
April 2021
Background: Family planning and pregnancy decisions are key considerations in the management of women with multiple sclerosis (MS), who are typically diagnosed between the ages of 20-40 years. Despite a strong evidence base that pregnancy is not harmful for women with MS, many knowledge gaps remain. These include: best management strategies through pregnancy in the era of highly effective disease-modifying therapies (DMT); foetal risks associated with DMT exposure or in relation to breastfeeding; knowledge base around the use of assisted reproductive technologies; the long-term impact of pregnancy on disease outcomes, as well as the impact of long-term DMT use on women's health and cancer risk.
View Article and Find Full Text PDFObjective: 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.