Biomedical subjects

Ruth Ann Marrie

Publications and source records attributed to Ruth Ann Marrie.

11 recordsLinked to original sources

PubMed2026

Proportionality-based association metrics in count compositional data.

Compositional data comprise vectors that describe the constituent parts of a whole. Data arising from various -omics platforms such as 16S and RNA sequencing are compositional in nature. In this kind of data, correlations between features on raw counts have no meaningful interpretation. Metrics of proportionality were formulated to address this problem. However, an inherent bias arises when these metrics are calculated empirically on count-based measures due to variability in read depths. We quantify the bias introduced by empirically calculating proportionality-based association metrics in count data. Additionally, we propose a means of estimating these metrics within a logit-normal multinomial model in pursuit of more accurate estimates. The model-based estimates are shown to outperform empirical estimates in simulated data and are applied to a mouse embryonic stem cell single-cell sequencing dataset, as well as a pediatric-onset multiple sclerosis metagenomic dataset.

Animals↗

PubMed2022

Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS. METHODS: We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center (n = 1,152), and Immune-Mediated Inflammatory Diseases study (n = 197). 25(OH)D-PGS were derived using summary statistics (p < 5 × 10-8) from a large GWAS including 485,762 individuals with circulating 25(OH)D levels measured. We included clinical and imaging outcomes: Expanded disability status scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), radiologic activity, and optical coherence tomography-derived ganglion cell inner plexiform layer (GCIPL) thickness. A subset (n = 935) had measured circulating 25(OH)D levels. We fitted multivariable models based on the outcome of interest and pooled results across studies using random effects meta-analysis. Sensitivity analyses included a modified p value threshold for inclusion in the PGS (5 × 10-5) and applying Mendelian randomization (MR) rather than using PGS. RESULTS: Initial analyses demonstrated a positive association between generated 25(OH)D-PGS and circulating 25(OH)D levels (per 1SD increase in 25[OH]D PGS: 3.08%, 95% CI: 1.77%, 4.42%; p = 4.33e-06; R2 = 2.24%). In analyses with outcomes, we did not observe an association between 25(OH)D-PGS and relapse rate (per 1SD increase in 25[OH]D-PGS: 0.98; 95% CI: 0.87-1.10), EDSS worsening (per 1SD: 1.05; 95% CI: 0.87-1.28), change in T25FW (per 1SD: 0.07%; 95% CI: -0.34 to 0.49), or change in 9HPT (per 1SD: 0.09%; 95% CI: -0.15 to 0.33). 25(OH)D-PGS was not associated with new lesion accrual, lesion volume or other imaging-based outcomes (whole brain, gray, white matter volume loss or GCIPL thinning). The results were similarly null in analyses using other p value thresholds or those applying MR. DISCUSSION: Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.

Humans↗

PubMed2006

Functional pathway-defined MRI diffusion measures reveal increased transverse diffusivity of water in multiple sclerosis.

The diffusion properties of water are sensitive to microscopic changes in the white matter of multiple sclerosis (MS) patients. Typical MRI measures of disease burden in MS demonstrate modest to poor correlation with disability. Functional MRI and DTI-based fiber tracking were used to define the interhemispheric white matter pathway connecting bilateral supplementary motor areas (SMA) in 16 MS patients sand 16 control subjects. Fractional anisotropy (FA), mean diffusivity (MD), longitudinal (lambda(1)) and transverse diffusivity (lambda(2)) were measured along this pathway in all subjects. Mean FA was 0.587 +/- 0.032 for patients and 0.608 +/- 0.020 for controls (P < 0.02). Mean MD was (0.821 +/- 0.055) x 10(-3) mm(2) s(-1) for patients and (0.770 +/- 0.020) x 10(-3) mm(2) s(-1) for controls (P < 0.004). Mean lambda(1) values were (1.462 +/- 0.099) x 10(-3) mm(2) s(-1) for patients and (1.400 +/- 0.034) x 10(-3) mm(2) s(-1) for controls (P < 0.02). Mean lambda(2) values were (0.500 +/- 0.047) x 10(-3) mm(2) s(-1) for patients and (0.454 +/- 0.027) x 10(-3) mm(2) s(-1) for controls (P < 0.001). In addition, the correlation between the Multiple Sclerosis Functional Composite (MSFC) and transverse diffusivity was -0.341 (P < 0.05). The component test of the MSFC most related to the SMA pathway studied with our MRI method (Nine-hole Peg Test) showed significant correlation with transverse diffusivity (r = 0.392, P < 0.02), indicating that probing functional pathways with MRI measures can lead to a better reflection of disease status.

Adult↗

PubMed2006

Drug Insight: interferon treatment in multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. Between 1987 and 1997, clinical trials of three preparations of recombinant interferon-beta were conducted in patients with MS, ushering in a new therapeutic era. These medications have demonstrable benefits and seem to be safe; they represent an important advance in MS treatment. All three formulations of interferon-beta had modest effects on relapses and short-term progression of disability, but the effects on MRI lesion parameters were more substantial. The benefits were greater in clinically isolated syndromes and relapsing-remitting MS than in secondary progressive MS. Although these drugs have been shown to be effective, however, their long-term impact on clinically relevant disability progression is uncertain, and there are many areas of controversy in the MS field regarding the use of these products. There is still a need for more effective treatments, which might include new agents or combination therapies.

Antibodies↗

PubMed2005

Subjective cognitive complaints relate to mild impairment of cognition in multiple sclerosis.

Cognitive impairment is common in multiple sclerosis (MS), but cannot be reliably predicted by physical impairment. The negative impact of cognitive impairment makes early detection important, but subjective cognitive complaints may be attributed to depression. We examined the relationship between subjectively reported and objectively measured cognitive impairment in MS, adjusting for mood. A neuropsychological battery, the Multiple Sclerosis Functional Composite (MSFC), the Mental Health Inventory (MHI), the Modified Fatigue Impact Scale (MFIS), the Perceived Deficits Questionnaire (PDQ) were administered to 136 patients. Demographically-adjusted cognitive scores were calculated. Subjective impairment was defined as PDQ score >2 standard deviations above that for healthy persons. We modeled the relationship of cognitive scores (independent variables) to being subjectively impaired (dependent variable) using logistic regression. Immediate Memory (IM) and Processing Speed Index (PSI) scores were non-linearly related to subjective impairment Patients were less likely to report subjective impairment if their PSI was normal (OR =0.11; 0.02-0.73) or markedly impaired (OR =0.17; 0.03-0.91), compared to mildly reduced PSI. In young patients decreases in IM were associated with increased subjective impairment (OR = 1.25; 1.07-1.47). Subjectively reported impairment reflects subtle declines in PSI and IM independent of mood, fatigue, and physical impairment Cognitive complaints should not be discounted due to depression.

Adult↗

PubMed2005

Validation of the NARCOMS Registry: pain assessment.

The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is a multiple sclerosis (MS) self-report registry with more than 24,000 participants. Participants report disability status upon enrollment, and semi-annually using Performance Scales (PS), Patient Determined Disease Steps (PDDS) and a pain question. In November 2000 and 2001, we also collected the Pain Effects Scale (PES). Our aim was to validate the NARCOMS pain question using the PES as our criterion measure. We measured correlations between the pain question and age, disease duration, various PS subscales and PDDS to assess construct validity. We correlated pain question responses in participants who reported no change in PDSS or the PS subscales between questionnaires to determine test-retest reliability. We measured responsiveness in participants who reported a substantial change in the sensory, spasticity PS subscales. The correlation between the pain question and PES was r = 0.61 in November 2000, and r = 0.64 in November 2001 (both P < 0.0001). Correlations between the pain question and age, and disease duration were low, indicating divergent validity. Correlations between the pain question and spasticity, sensory PS subscales and PDSS were moderate, indicating convergent validity. Test-retest reliability was r = 0.84 (P < 0.0001). Responsiveness was 70.7%. The pain question is a valid self-report measure of pain in MS.

Adult↗

PubMed2005

Validation of the NARCOMS registry: fatigue assessment.

Participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry report disability using Performance Scales (PS), which assess eight domains. We aimed to validate the PS fatigue subscale (PSF) using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) as external criteria. We measured correlations between the PSF and age, disease duration and PS subscales to assess construct validity. The PSF correlated strongly with the MFIS (r =0.72, P <0.0001) and FSS (r =0.75, P <0.0001). Correlations between the PSF and age, disease duration were low, indicating divergent validity. Correlations between the PSF and spasticity, sensory and mobility PS scales were moderate, indicating convergent validity. The PSF has adequate criterion and construct validity in MS.

Disability Evaluation↗

PubMed2004

Association of fatigue and brain atrophy in multiple sclerosis.

Functional imaging studies have demonstrated a relationship between fatigue and altered cerebral activation patterns in multiple sclerosis patients, but no relationship between fatigue and brain atrophy has been demonstrated. We hypothesized that the subjective complaint of fatigue would predict the severity of destructive brain pathology. We assessed the relationship between fatigue and brain atrophy longitudinally in a cohort of 134 patients previously enrolled in a 2-year clinical trial of interferon beta-1a and re-evaluated 8 years after randomization into the trial. Brain atrophy was measured using the brain parenchymal fraction (BPF), and disability was measured using the Multiple Sclerosis Functional Composite at baseline, year 2 and year 8. Fatigue was measured using the Sickness Impact Profile's Sleep and Rest Scale (SIPSR) at baseline, year 2 and year 8. Linear regression analyses were used to assess the relationship between changes in fatigue and atrophy progression. Worsening fatigue on the SIPSR during the initial 2 years was significantly associated with progressive brain atrophy over the subsequent 6 years. The relationships between fatigue and brain atrophy were independent of changes in disability, mood, or other MRI characteristics. This suggests that the subjective complaint of fatigue is linked to destructive pathologic processes in RRMS patients.

Atrophy↗

PubMed2004

Environmental risk factors in multiple sclerosis aetiology.

The epidemiology of multiple sclerosis (MS) has been intensively studied. It is conceptualised as a complex disease in which genetic and environmental factors act together to cause disease. There are temporal and geographic variations in disease risk, and risk of disease may be affected by migration between regions of differing risk. Numerous potential causal factors including infection, immunisations, physical and emotional stressors, climate, diet, and occupational exposures have been studied using various observational study designs. Thus far, no single environmental exposure has been consistently identified as a causal factor in MS, but sufficient data have accumulated that causal pathways should be postulated and tested. This review will focus on the environmental epidemiology of MS.

Environmental Exposure↗

PubMed2003

Predictors of alternative medicine use by multiple sclerosis patients.

OBJECTIVE: To determine the frequency of alternative medicine use among multiple sclerosis (MS) patients, and the factors which predict such use. METHODS: We examined 20778 MS patients enrolled in the North American Research Consortium on Multiple Sclerosis (NARCOMS) Patient Registry, residing in the USA. We used demographic and clinical data to create multivariate logistic regression models for i) lifetime use of any alternative medicine, ii) lifetime use of any alternative provider (AP), and iii) lifetime use of each of the three most common AP. RESULTS: 20387 patients provided data regarding alternative medicine use. Lifetime use of any alternative medicine was 54% and current use was 30%. Chiropractors (51%), massage therapists (34%), and nutritionists (24%) were the most commonly used AP. In all five models, use of alternative medicine was most strongly predicted by use of a conventional provider, and more modestly by disease factors indicating more severe or prolonged disease. Predictive power of the models was poor (c-index = 0.62-0.68), despite good fits for the data. CONCLUSIONS: Demographic factors play only a minimal role in predicting the use of alternative medicine in this MS population while disease factors play a slightly stronger role. There must be other factors involved that may include accessibility, social acceptability and cultural factors. Given the frequency of alternative medicine use by this patient population, further characterization of these factors is important.

Adult↗

PubMed2003

Validity and reliability of the MSQLI in cognitively impaired patients with multiple sclerosis.

Multiple sclerosis (MS) has important effects on quality of life but it is unknown how cognitive impairment affects the ability to assess or report this. Our objective was to determine whether cognitive impairment negatively affects the construct validity and the reliability of the Multiple Sclerosis Quality of Life Inventory (MSQLI). A neuropsychological test battery and the Multiple Sclerosis Functional Composite (MSFC) were administered to a sample of 136 patients referred for cognitive testing by their neurologists. Age, sex, education and ethnicity-adjusted T scores were calculated for each cognitive variable. Cognitive impairment was defined as any T score less than the fifth percentile. The MSQLI was administered prior to neuropsychological testing and readministered one to four weeks later: Correlations between the MSFC and the SF-36 were determined and compared between the cognitively impaired and unimpaired groups as the main test of construct validity. Test-retest and internal consistency reliability of each of the scales were compared for the impaired and unimpaired groups. Seventy-six (56%) patients were cognitively impaired. Construct validity and internal consistency reliability did not differ between the cognitively impaired and unimpaired groups. Test retest reliability was lower for the bladder and vision scales in the impaired group, but remained acceptable for the bladder scale (r > 0.7). Cognitive impairment, a common MS manifestation, does not appear to reduce the reliability or validity of the MSQLI as a patient self-report measure of health status and quality of life.

Adult↗