scholarly journals Clinical and Laboratory Associations with Methotrexate Metabolism Gene Polymorphisms in Rheumatoid Arthritis

2020 ◽  
Vol 10 (4) ◽  
pp. 149
Author(s):  
Leon G. D’Cruz ◽  
Kevin G. McEleney ◽  
Kyle B. C. Tan ◽  
Priyank Shukla ◽  
Philip V. Gardiner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Plasma Concentrations ◽  
Systemic Autoimmune Disease ◽  
Single Nucleotide ◽  
Pain Scores ◽  
Metabolite Concentrations ◽  
Lower Pain ◽  
Plasma Metabolite ◽  
The Relationship

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD-metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease collected at two intervals. Taqman probes were used to discriminate single-nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p < 0.05) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles have significantly higher (p < 0.001) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p < 0.05) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit whilst minimizing toxicity.

scholarly journals Clinical and Laboratory Associations with Methotrexate Metabolism Gene Polymorphisms in Rheumatoid Arthritis

2020 ◽  
Author(s):  
Leon D'Cruz ◽  
Kevin McEleney ◽  
Kyle Tan ◽  
Priyank Shukla ◽  
Philip Gardiner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Plasma Concentrations ◽  
Systemic Autoimmune Disease ◽  
Single Nucleotide ◽  
Pain Scores ◽  
Metabolite Concentrations ◽  
Lower Pain ◽  
Plasma Metabolite ◽  
The Relationship

Rheumatoid arthritis (RA); is a chronic systemic autoimmune disease which causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease, collected at two intervals. Taqman-probes were used to discriminate single nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p&lt;0.05, C.I. 95%) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles in the have significantly higher (p&lt;0.001, 95% C.I) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p&lt;0.05, 95% C.I.) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit, whilst minimizing toxicity.

scholarly journals AB0101 THE IMPACT OF TIME SPAN TO ACHIEVE BOOLEAN REMISSION FOR MAINTAINING DISEASE ACTIVITY AFTER ACQUISITION IN RHEUMATOID ARTHRITIS PATIENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1079.1-1079
Author(s):  
I. Yoshii
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Remission Rate ◽  
Mean Value ◽  
Time Span ◽  
Mean Values ◽  
The Mean ◽  
The Relationship

Background:Boolean remission criteria is one most popular and stringent criteria in treating patient with rheumatoid arthritis (RA), because it may guarantees a stable clinical course after attaining remission.Objectives:Impact of time span from initiation to achieving Boolean remission on maintaining disease activity, daily activities, and quality of life after attaining Boolean remission was investigated from daily clinical practice data.Methods:685 patients with RA since August 2010 under the T2T strategy were treated. They were monitored for their TJC, SJC, PGA, EGA, CRP, and disease activity indices such as CDAI, SDAI, DAS28, and Boolean criteria at every visit. HAQ-DI score, pain score using visual analog scale (PS-VAS), and EQ-5D were also monitored, and the quality of life score (QOLS) calculated from EQ-5D was determined at every visit from the time of diagnosis (baseline).Of 685 patients, 465 patients had achieved Boolean remission >1 times, and were consecutively followed up for >3 years. These patients were enrolled in the study. Time span from the first visit to first Boolean remission was calculated. The relationship between the time span and each of background parameters, and the relationship between the time span and each of the mean values of the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at the first Boolean remission and thereafter was evaluated statistically.Patients were subsequently divided into the G ≤ 6 and G > 6 groups based on the achievement of first Boolean remission within two groups: time span G ≤ 6 months and G > 6 months. The two groups were compared with regard to the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at first visit and at the time of first Boolean remission, and the mean values of these parameters after remission were evaluated statistically. Moreover, changes of these parameters and the mean Boolean remission rate after the first remission, and SDAI remission rate at the first Boolean remission to thereafter were compared between the two groups statistically.Results:Out of 465 patients, females comprised 343 (73.7%), and the mean age was 67.8 years (range, from 21–95 years). The mean disease duration at first visit was 6.1 years (range, from 1 months–45 years). The mean follow up length was 88.1 months (range: 36–122 months; median: 85 months) and mean time span from the first visit to the first Boolean remission was 8.1 months. The mean SDAI score, HAQ score, PS-VAS, and the QOLS at first visit were 13.3, 0.467, 33.2, and 0.834, respectively. Among the study parameters, PS-VAS and QOLS were significantly correlated with the time span. For parameters at the first Boolean remission, HAQ-DI score, PS-VAS, and QOLS demonstrated significant correlation with the time span, whereas SDAI, HAQ-DI score, PS-VAS, SHS, and QOLS after the Boolean remission demonstrated significant correlation with the time span.The comparison between the G ≤ 6 and the G > 6 groups revealed that the disease duration, HAQ score, and PS-VAS at baseline in the G > 6 were significantly higher than that in the G ≤ 6 group, and QOLS in the G ≤ 6 group was significantly higher than that in the G > 6 group at baseline. Similarly, the HAQ score and PS-VAS at the first Boolean remission in the G > 6 group were significantly higher than that in the G ≤ 6 group, whereas QOLS in the G ≤ 6 group demonstrated no significant difference compared with that in the G > 6 group.The mean value of the SDAI score after the first Boolean remission in the G > 6 group was significantly higher than that in the G ≤ 6 group. Similarly, the SDAI score, HAQ score, and PS-VAS after the first Boolean remission in the G > 6 group were also significantly higher than those in the G ≤ 6 group, and the mean value of the QOLS in the G ≤ 6 group were significantly higher than that in the G > 6 group. The Boolean remission rate and SDAI remission rate after the first Boolean remission were significantly higher in the G ≤ 6 group than those in the G > 6 group.Conclusion:Attaining Boolean remission ≤ 6 months for RA has significant benefit for more stable disease control, that leads good maintenance of ADL.Disclosure of Interests:None declared

Quality of Life and Outcomes in Multiple Myeloma Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2605-2605
Author(s):  
Shilpa Paul ◽  
Samith T. Kochuparambil ◽  
Carrie A Thompson ◽  
Tait D. Shanafelt ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Serum Albumin ◽  
Mayo Clinic ◽  
Multivariable Analysis ◽  
Pain Scores ◽  
Patient Reported ◽  
The Impact ◽  
The Relationship

Abstract Background: Multiple Myeloma (MM) patients have a substantially reduced Health related Quality of Life (HQOL) at diagnosis (dx) due to disease related symptoms like bone pain (58%) and fatigue (32%). HQOL monitoring is becoming increasingly important, owing to improved survival and the impact of treatment-related toxicity. As a result HQOL assessments are increasingly being used in clinical trials, but the literature regarding the relationship between HQOL and outcomes in MM is sparse. We used the Mayo Clinic “Hematology Patient Reported Symptom Screen” (HPRSS) to assess the impact of HQOL on outcomes in newly dx patients with MM. Methods:We retrospectively reviewed charts of 453 patients with newly dx MM seen at Mayo Clinic, Rochester from 2009 to 2014. All patients who visit Mayo clinic hematology clinic complete a 3-point questionnaire (HPRSS) on pain, fatigue and quality of life (QOL) (scored on a scale of 0-10; with 0 being the least fatigue or pain and 10 being the best QOL). Pain, fatigue and QOL scores documented at the time of dx and at 6 months were collected. JMP version 10 was used for the data analysis. Results: The median age at diagnosis was 67 years (range, 33-95); 60% were male. The estimated median OS for the cohort was 21 m (95% CI19, 23); 387 (85%) of the patients were alive at last follow up and the median OS for the population was not reached. The median (IQR) scores for pain, fatigue and QOL were 4 (2, 6), 3 (1, 5), and 7 (5, 9), respectively. First, we examined the relationship between each of the scores (dichotomized at the median) and the baseline characteristics. Higher fatigue scores were associated with lower Hb and serum albumin and higher beta 2 microglobulin, LDH and marrow plasmacytosis. Higher pain scores were seen in female patients, and associated with higher B2M, serum calcium and lytic bone lesions. Lower QOL scores were associated with lower absolute lymphocyte count and serum albumin levels. Next, we examined the relationship between the scores and the OS from diagnosis. The overall survival was inferior for patients with higher pain scores, fatigue scores and lower QOL scores (Figure). In a multivariable analysis, fatigue scores were most strongly associated with survival outcome. Patients with adverse scores in two or more of pain, fatigue and QOL had significantly inferior outcomes (Figure). In univariate analysis, age, B2M, LDH, FISH high risk and the presence of two or more adverse scores were all significantly associated with poorer OS. In a multivariable analysis, age, LDH and the presence >=2 adverse scores were all associated with shorter OS. Of the 453 patients included in the study, 222 patients had pain, fatigue and QOL scores at 6 month from diagnosis. At 6 months, the median (IQR) scores for pain, fatigue and QOL were 2 (1, 5), 4 (2, 5), and 7 (5, 9), respectively; suggesting improved pain, worsened fatigue and static QOL scores. Improvement in the scores by at least one point was seen in 50%, 49% and 38% for the fatigue, pain and QOL scores. While the pain and fatigue scores at 6 months correlated inversely with OS, improvements in the scores in any of the three were not associated with any improved outcomes. Conclusion: A simple, patient reported scoring system for pain, fatigue, and overall perceived QOL at the time of diagnosis is a powerful predictor of survival outcomes in patients with newly diagnosed MM and should be considered routinely in clinical practice. The results of these patient reported measures can be utilized to develop risk-adapted trials in patients with MM. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Indirect Costs of Rheumatoid Arthritis Depending on Type of Treatment—A Systematic Literature Review

2019 ◽  
Vol 16 (16) ◽  
pp. 2966 ◽  
Author(s):  
Batko ◽  
Rolska-Wójcik ◽  
Władysiuk
Keyword(s):  
Rheumatoid Arthritis ◽  
Productivity Loss ◽  
Indirect Costs ◽  
Course Of Disease ◽  
Biological Dmards ◽  
Medline Search ◽  
Full Text Review ◽  
Economic Analyses ◽  
The Relationship

The economic burden of rheumatoid arthritis (RA) on society is high. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstone of therapy. Biological DMARDs are reported to prevent disability and improve quality of life, thus reducing indirect RA costs. We systematically reviewed studies on the relationship between RA and indirect costs comparing biological treatment with standard care. Studies, economic analyses, and systematic reviews published until October 2018 through a MEDLINE search were included. A total of 153 non-duplicate citations were identified, 92 (60%) were excluded as they did not meet pre-defined inclusion criteria. Sixty-one articles were included, 17 of them (28%) were reviews. After full-text review, 28 articles were included, 11 of them were reviews. Costs associated with productivity loss are substantial; in several cases, they may represent over 50% of the total. The most common method of estimation is the Human Capital method. However, certain heterogeneity is observed in the method of estimating, as well as in the resultant figures. Data from included trials indicate that biological therapy is associated with improved labor force participation despite an illness, in which the natural course of disease is defined by progressive work impairment. Use of biological DMARDs may lead to significant indirect cost benefits to society.

The relationship between quality of life and aerobic fitness in patients with rheumatoid arthritis

2009 ◽  
Vol 28 (6) ◽  
pp. 685-691 ◽  
Author(s):  
Chia-Ling Chang ◽  
Cheng-Ming Chiu ◽  
Su-Ying Hung ◽  
Si-Huei Lee ◽  
Chang-Shun Lee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Aerobic Fitness ◽  
The Relationship

scholarly journals Metabolite Shifts Induced by Marathon Race Competition Differ between Athletes Based on Level of Fitness and Performance: A Substudy of the Enzy-MagIC Study

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 87 ◽  
Author(s):  
Jana F. Schader ◽  
Mark Haid ◽  
Alexander Cecil ◽  
Julia Schoenfeld ◽  
Martin Halle ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Mitochondrial Enzyme ◽  
Protein Catabolism ◽  
Targeted Metabolomics ◽  
Entire Cohort ◽  
Marathon Race ◽  
Top Performers ◽  
Metabolite Concentrations ◽  
And Performance ◽  
Plasma Metabolite

This study compared metabolite shifts induced by training for, participation in, and recovery from a marathon race competition among athletes divided into three groups based on fitness (relative maximum oxygen uptake (VO2max)) and performance levels (net running time). Plasma samples from 76 male runners participating in the Munich Marathon were analyzed for metabolite shifts using a targeted metabolomics panel. For the entire cohort of runners, pronounced increases were measured immediately after the race for plasma concentrations of acylcarnitines (AC), the ratio (palmitoylcarnitine + stearoylcarnitine)/free carnitine that is used as a proxy for the activity of the mitochondrial enzyme carnitine palmitoyltransferase, and arginine-related metabolites, with decreases in most amino acids (AA) and phospholipids. Plasma levels of AA and phospholipids were strongly increased 24 and 72 h post-race. Post-race plasma concentrations of AC and arginine-related metabolites were higher in the low compared to top performers, indicating an accumulation of fatty acids and a reliance on protein catabolism to provide energy after the marathon event. This study showed that marathon race competition is associated with an extensive and prolonged perturbation in plasma metabolite concentrations with a strong AC signature that is greater in the slower, less aerobically fit runners. Furthermore, changes in the arginine-related metabolites were observed.

The Relationship Between Anxiety, Depression, Suicidal Ideation and Quality of Life in Patients with Rheumatoid Arthritis

2019 ◽  
Vol 91 (1) ◽  
pp. 53-64 ◽  
Author(s):  
Aslı Beşirli ◽  
Jülide Öncü Alptekin ◽  
Derya Kaymak ◽  
Ömer Akil Özer
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Suicidal Ideation ◽  
Anxiety Depression ◽  
The Relationship

Sleep quality and endometriosis: A group comparison study

2020 ◽  
Vol 12 (2) ◽  
pp. 94-100
Author(s):  
Stacey Davie ◽  
Yasu Hamilton ◽  
Lachlan Webb ◽  
Akwasi A Amoako
Keyword(s):  
Quality Of Life ◽  
Sleep Quality ◽  
Statistical Significance ◽  
Reproductive Age ◽  
Control Group ◽  
Poor Sleep ◽  
Online Questionnaire ◽  
Pain Scores ◽  
The Relationship

Introduction: Endometriosis affects around 10% of women of reproductive age with symptoms of pelvic pain, dysmenorrhoea, dyspareunia, dyschezia, and infertility. Current research highlights a possible relationship between endometriosis and poor sleep quality. The aim of this study was to assess the relationship between sleep quality and endometriosis. Outcomes measured included sleep quality and quality of life and pain score. Methods: Thirty women with a histological diagnosis of endometriosis and 30 control patients completed an online questionnaire that assessed sleep quality (Pittsburgh Sleep Quality Index) and quality of life (WHO-QOL-BREF). Pain scores within the endometriosis group were evaluated using a visual analogue scale. Results: Women with endometriosis had significantly poorer sleep quality (80% vs 50%, p = 0.015) and lower quality of life scores when compared to the control group. Within the endometriosis group, there were trends between poor sleep, a reduced quality of life, and higher pain scores; however, these did not reach statistical significance. Discussion: Sleep quality and quality of life were significantly reduced in women with endometriosis when compared to controls.

scholarly journals Effect of Diet Composition on Plasma Metabolite Profiles in a Migratory Songbird

The Condor ◽  
2007 ◽  
Vol 109 (1) ◽  
pp. 48-58 ◽  
Author(s):  
Susan B Smith ◽  
Scott R McWILLIAMS ◽  
Christopher G Guglielmo
Keyword(s):  
Uric Acid ◽  
Physiological State ◽  
Plasma Concentrations ◽  
Plasma Metabolites ◽  
Macronutrient Composition ◽  
Nonesterified Fatty Acids ◽  
High Carbohydrate ◽  
Low Protein ◽  
Metabolite Concentrations ◽  
Plasma Metabolite

Abstract Abstract Plasma metabolites provide information about the physiological state and fuel use of birds, and have been used for predicting refueling rates of birds during migratory stopovers. However, little is known about the effect of diet on metabolite concentrations in small songbirds. We investigated the effect of dietary macronutrient composition on lipid and protein metabolites in captive White-throated Sparrows (Zonotrichia albicollis). Birds fed a high-protein, low-carbohydrate insect diet had lower plasma triglyceride concentrations and higher plasma B-hydroxybutyrate concentrations than birds fed a high-carbohydrate, low-protein grain diet during feeding. The insect-fed birds also had higher plasma uric acid concentrations than grain-fed birds and birds fed a low-protein, high-fat, and high-carbohydrate fruit diet. Diet did not significantly influence plasma concentrations of glycerol or nonesterified fatty acids. After subsequent overnight fasting, birds in all three diet groups had similar concentrations of lipid metabolites, but uric acid was marginally elevated in insect-fed birds. Given that dietary macronutrient composition affected certain plasma metabolite concentrations in sparrows, investigators should consider such diet effects when using these metabolites to estimate refueling rates of free-living migratory songbirds, particularly in species that exhibit dietary plasticity during migration.

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