Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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12209484 | Long-term outcome in rheumatoid arthritis: a simple algorithm of baseline parameters can p | 2002 Aug | OBJECTIVES: To predict the long-term outcome of rheumatoid arthritis (RA) with respect to radiographic damage, disability, and disease course using baseline variables, and to construct decision trees identifying patients on an individual level at the extremes of the outcome spectrum of these 3 dimensions. METHODS: The 12-year outcome of 112 female RA patients from a prospective inception cohort was assessed by measuring the tertiles of radiographic damage (measured by the modified Sharp/van der Heijde method, SHS), disability (measured by the Health Assessment Questionnaire, HAQ), and severe disease course as defined by patients with either the 33% highest cumulative disease activity (area under the curve of all observed disease activity scores) or the highest tertile of radiographic damage. Patients in the lowest (mild) and highest tertile (severe) of each outcome measure were identified. All baseline parameters known to be associated with each outcome (demographic and socioeconomic parameters; disease duration; disease activity measures; laboratory measures including rheumatoid factor, HLA typing, percentage agalactosyl IgG, functional and radiographic measures) were entered into cross-validated stepwise logistic regression models to find the best predictive combination of baseline parameters for each of the outcomes. Using the results of the logistic regression models, simple decision trees were constructed to categorize patients at an individual level in a particular prognostic group. RESULTS: After 12 years, the lowest and highest tertiles were, respectively, 42.3 and 189 for the SHS and 0.37 and 1.25 for the HAQ. Fifty-five patients had a severe disease course. Mild and severe radiographic damage could be predicted with an accuracy of 90% and 85%, respectively. Mild and severe HAQ could be predicted with an accuracy of 90% and 84%, respectively, and severe disease course with an accuracy of 81%. The baseline variables found to be predictive of all 3 outcome measures were very similar and consisted of combinations of the following baseline parameters: swollen joint count (SJC), Ritchie score, rheumatoid factor (RF), the presence of erosions, and the HAQ score. Additional knowledge of the HLA typing hardly improved the accuracy of the prediction. To predict outcome at the individual level, simple decision trees were constructed using the RF, HAQ, SJC, and presence of erosions at baseline. CONCLUSION: The present study shows that prediction of outcome in long-term RA is possible and can be done using widely available baseline parameters. | |
15188327 | Survey of the use and effect of assistive devices in patients with early rheumatoid arthri | 2004 Jun 15 | OBJECTIVE: To identify activity limitation in early rheumatoid arthritis (RA) to detect patients needing assistive devices. To evaluate the effects of assistive devices. METHODS: A multicenter cohort of 284 early RA patients was examined using the Evaluation of Daily Activity Questionnaire 12 and 24 months after diagnosis. RESULTS: The extent of activity limitation was stable over time for both women and men. Most limitations concerned eating and drinking. Women reported more difficulties than did men. The use of assistive devices was related to subgroups with severe disease and more disability. Use of assistive devices reduced difficulties significantly. For both women and men, assistive devices were mostly used in activities related to eating and drinking. CONCLUSION: Already 1 year after diagnosis, RA patients reported activity limitation that remained stable over time. Use of assistive devices was related to more severe disease and more pronounced disability. Use of devices reduced difficulties significantly. | |
12852013 | [Characteristics of rehabilitation in patients with rheumatic diseases]. | 2003 May | The paper deals with problems of rehabilitation of patients with rheumatoid arthritis, osteoarthrosis and systemic lupus erythematosus. These problems are rather topical in view of high prevalence of rheumatic diseases, their severe course and a high rate of invalidization at the most productive age. Relevant multifactorial therapeutic measures should be staged, aimed at lowering and stabilization of the disease activity. The role of updated medication, joint surgery, diet therapy, etc. is shown. | |
12794369 | [Changes of bone mineral density in rheumatoid arthritis]. | 2003 | The aim of the study was to evaluate changes of bone mineral density in rheumatoid arthritis (RA) patients in one-year period and to establish the possible relation with the clinical and laboratory symptoms of inflammation and radiological signs of structural damage of the joints. Forty-one RA patient was investigated. Clinical activity of rheumatoid arthritis was assessed by the duration of morning stiffness, counts of tender and swollen joints, and general evaluation of the disease activity by the patient and investigator. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used as laboratory markers of activity of inflammation. X-ray progression was evaluated by the appearance of new erosions and worsening of the joint spaces on the hands X-ray. Bone mineral density was measured by DEXA method (QDR 4500W Elite Hologic, USA) in the 1-4 lumbar vertebral bodies, and in the proximal part of the hip. It was established that systemic bone mineral density lossin all investigated locations was characteristic for active rheumatoid arthritis. Bone mineral density diminishing in the hip was in close correlation with the and symptoms of disease activity and radiological progression. This correlation was not characteristic for the lumbar vertebral bodies. Above-mentioned clinical, laboratory and radiological features of the disease had minimal influence on bone mineral density for the patients with long-standing rheumatoid arthritis. | |
12794791 | Vertebral deformities in 229 female patients with rheumatoid arthritis: associations with | 2003 Jun 15 | OBJECTIVE: To examine the occurrence of vertebral deformities in female patients with rheumatoid arthritis (RA), and the relationship between vertebral deformities and bone mineral density (BMD) and between vertebral deformities and clinical variables. METHODS: Lateral radiographs of the spine were obtained in 229 female patients with RA (mean age 63.4 years, range 51.4-73.6 years) recruited from a county RA register. Vertebral deformities were measured semiquantitatively by an experienced radiologist. A clinical examination including core measurements of disease activity and severity was performed, and BMD was measured at the spine (L2-L4) and hip. RESULTS: According to the statistical analysis, 49 patients were considered to have relevant vertebral deformities. The occurrence of vertebral deformities was independently associated with age, long-term corticosteroid use, and previous nonvertebral fracture, as well as reduced BMD. Our results failed to show any independent relationship between vertebral deformities and the activity or severity of disease. CONCLUSION: Corticosteroid use is an important marker of established osteoporosis in patients with RA. Additionally, there seems to be a consistent relationship between BMD and vertebral deformities in this patient group. | |
15053449 | Progressive and nonprogressive rheumatoid arthritis over a 10-year period in Japan. | 2004 Mar | We followed 207 patients with rheumatoid arthritis who were registered at our hospital over a 10-year period from between 1989 and 1990. The number of patients who were still treated at our hospital in 2001 was 87. Sixty patients had died, 39 had changed hospitals, 11 had interrupted treatment, and 10 had not had further followup. The patients at our hospital in 2001 were divided into 2 groups: progressive and nonprogressive disease. We compared clinical and laboratory data obtained for the 2 groups from the initial examination against data obtained from the final examination. The progressive group had a greater number of operations, used a greater variety of disease modifying antirheumatic drugs, and received higher dosages of steroids than the nonprogressive group. In the progressive group the levels of C-reactive protein, erythrocyte sedimentation rate, and IgG were significantly higher, while the levels of hemoglobin were lower at final laboratory examination. However, the initial laboratory examination revealed no significant differences between these groups that could be used to predict the likely progression of disease. | |
15188319 | Development and validation of Cedars-Sinai Health-Related Quality of Life in Rheumatoid Ar | 2004 Jun 15 | OBJECTIVE: To develop an abridged version of the 33-item Cedars-Sinai Health-Related Quality of Life in Rheumatoid Arthritis instrument (CSHQ-RA) and test the validity and reliability of the abridged instrument. METHODS: Items from the original 33-item, 5-domain CSHQ-RA were assessed using psychometric and regression analyses of survey responses from 274 patients with rheumatoid arthritis. Items were retained in the final instrument based on statistical analysis and evaluation by an expert panel. Test-retest reliability, internal consistency, convergent and discriminant validity, and ceiling and floor effects were examined for the shortened CSHQ-RA. RESULTS: Statistical analysis and expert assessment yielded an 11-item instrument including questions in 4 domains. Test-retest reliability and internal consistency were high and the instrument showed good convergent and discriminant validity. CONCLUSION: The abridged CSHQ-RA short form is a valid and reliable instrument that can be used to examine the impact of RA on patients' health-related quality of life. Prospective validation in clinical trial settings is warranted. | |
12563672 | Interleukin 1 receptor antagonist anakinra improves functional status in patients with rhe | 2003 Feb | OBJECTIVE: This study evaluated the benefit of anakinra, a human recombinant form of interleukin 1 receptor antagonist, on the functional status of patients with active rheumatoid arthritis (RA) despite taking maximally tolerated doses of methotrexate (MTX). METHODS: Patients (n = 419) were randomized to receive, in addition to MTX (15 to 25 mg/wk), placebo or anakinra doses of 0.04, 0.1, 0.4, 1, or 2 mg/kg once daily for 24 weeks. Functional status measured on 8 scales (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities) was evaluated at baseline and every 4 weeks with the Health Assessment Questionnaire (HAQ). A weighted sum of the scale scores is the HAQ disability index (HAQ-DI). Primary analysis of the HAQ-DI was based on an omnibus test for a positive dose-response relationship between anakinra treatment and change in HAQ-DI from baseline to week 24. RESULTS: Patients receiving anakinra experienced rapid and sizeable improvements in their HAQ-DI scores in a dose-related fashion. For patients receiving either of the 2 highest doses of anakinra, improvements in the HAQ-DI occurred by week 4 that were of a magnitude considered clinically important and statistically significantly superior to placebo. CONCLUSION: In patients with persistence of RA despite MTX therapy, treatment with anakinra results in a rapid improvement in functional status as measured by the HAQ-DI. | |
12366812 | Relationship between histological findings and clinical findings in rheumatoid arthritis. | 2002 Aug | The aim of the present study was to compare histological findings and clinical symptoms of patients with advanced stages of rheumatoid arthritis (RA). Synovial tissue specimens were obtained during reconstructive knee surgery from 93 RA patients (18 men; 75 women). The histological assessments of specimens were evaluated using two histological scoring systems reported by Rooney and Koizumi. Clinical symptoms (duration of morning stiffness, joint score, grip strength), laboratory data (erythrocyte sedimentation ratio, C-reactive protein (CRP), rheumatoid factor), X-ray findings (Larsen score) and drug usage were assessed before surgery. Significant statistical correlations between both histological scoring systems were observed; however, there was no significant correlation between the clinical findings and the histological scoring systems. A statistically significant correlation was found between the levels of CRP and Koizumi's scoring system. In addition, Koizumi score correlated significantly to X-ray findings. Rooney's scoring system had an inverse correlation to methotrexate history. Histological findings do not correlate to simultaneous clinical symptoms in advanced RA patients. However, our data indicate that observed histological changes reflect X-ray damage. | |
12028539 | Relationship of polymorphisms of the Interleukin-1 gene cluster to occurrence and severity | 2002 Feb | Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). We investigated whether IotaL-1 gene locus polymorphisms are associated with susceptibility to or severity of RA. Genotyping for IL-1alpha, IL-1beta and IL-1Ra single nucleotide polymorphisms (SNPs) performed in a cross-sectional group of 312 consecutive RA patients (RA-group 1) and a cohort of 94 incident female RA patients (RA-group 2) revealed that the rare IL-1RN + 2017 C allele was significantly increased in RA compared to controls (n = 245). A retrospective analysis in RA-group 1 showed no significant associations between IL-1 genotypes and disease severity. A prospective study in RA-group 2 demonstrated that the extent of joint destruction over 12 years was higher in patients genotyped heterozygous for the IL-1 A + 4845, IL-1B + 3953 and IL-1RN + 5111 SNPs compared to homozygous wildtype patients, although differences did not reach statistical significance. These data indicate that the IL-1RN + 2017 polymorphism is associated with susceptibility to RA. | |
15170920 | High sensitivity C-reactive protein as a disease activity marker in rheumatoid arthritis. | 2004 Jun | OBJECTIVE: To elucidate the potential contribution of high sensitivity C-reactive protein (hs-CRP) testing in the assessment of disease activity in rheumatoid arthritis (RA). METHODS: We recorded clinical and psychological variables, the hs-CRP, and erythrocyte sedimentation rate (ESR) in 146 consecutive patients with RA. We analyzed the associations between the ESR and hs-CRP versus the other recorded variables. RESULTS: The median (interquartile range) ESR (mm/h) and hs-CRP (mg/l) were 15 (7-36) and 5 (2.3-13.9), respectively. Thirty-two (22%) patients had an hs-CRP < 2 mg/l, 61 (42%) an hs-CRP of 2-8 mg/l and 53 (36%) an hs-CRP > 8 mg/l. In patients with an hs-CRP of 2-8 mg/l, the swollen joint counts and the physician disease activity scales were higher, and remission rates were lower than in patients with an hs-CRP of < 2 mg/l. The hs-CRP was consistently more closely associated with disease activity, depression, and helplessness than was the ESR. CONCLUSION: High sensitivity CRP testing reveals systemic inflammation that is generally not detectable with routine CRP assays and that is associated with disease activity in RA. | |
12540080 | The influence of rheumatoid chemotherapy, age, and presence of rheumatoid nodules on posto | 2003 Jan | The records of 104 patients who underwent reconstructive foot and ankle surgery for deformities secondary to rheumatoid arthritis were reviewed. The use of rheumatoid chemotherapeutic agents, age, sex, rheumatoid nodule status, and the number of concurrent surgical procedures performed was analyzed to determine any association with the postoperative outcome for wound healing and infectious complications. The 104 patients, ranging in age from 23 to 83 years, underwent 725 operative procedures. An overall 32% complication rate was recorded. Analysis of five specific rheumatoid chemotherapeutic agents (NSAIDs, steroids, methotrexate, hydroxychloroquine, gold), age, sex, number of operative procedures performed, and presence of rheumatoid nodules, either alone or in combination, failed to prove a statistical association with either a healing or infectious postoperative complication. | |
15586840 | A comparison of four indirect methods of assessing utility values in rheumatoid arthritis. | 2004 Nov | OBJECTIVES: Utility scores can be assessed indirectly using preference-based instruments and used as weightings for quality-adjusted life years in economic analyses. It is not clear whether available instruments yield similar results or what domains of health are contributing to the overall score in a sample of patients with rheumatoid arthritis (RA). SUBJECTS: Our study included 313 individuals with rheumatologist-confirmed RA. MEASURES: A self-completed survey that permitted scoring of 4 indirect utility instruments (the Health Utilities Index Mark 2 and 3 (HUI-2 and HUI-3), the EuroQoL (EQ-5D), and the Short Form 6D (SF-6D) was the basis of our study. RESULTS: Mean (standard deviation) global utility scores were 0.63 (0.24) for the SF-6D, 0.66 (0.13) for the EQ-5D, 0.71 (0.19) for the HUI-2, and 0.53 (0.29) for the HUI-3 (P = 0.02 by repeated-measures analysis of variance). The intraclass correlation across all the indices was 0.67 (95% confidence interval 0.62-0.71). Bland-Altman plots revealed that agreement among instruments was poor at lower utility values. In this elderly RA sample, all of the global utilities mostly measured functional ability and pain. CONCLUSIONS: There are significant differences in utilities obtained from different indirect methods. Agreement among the instruments was moderate but poorer at lower utilities. It is unlikely that these utility values, if used as the weightings for quality-adjusted life years, would result in comparable estimates. | |
15478164 | Are there more than cross-sectional relationships of social support and support networks w | 2004 Oct 15 | OBJECTIVE: To investigate whether greater social support and support network are cross-sectionally associated with less functional limitations and psychological distress in patients with early rheumatoid arthritis (RA); whether this association is constant over time; and whether increases in social support or support network are associated with less functional limitations and psychological distress. METHODS: Subjects were from the European Research on Incapacitating Diseases and Social Support cohort and had early RA. Social support, support network, functional limitations (Health Assessment Questionnaire), and psychological distress (General Health Questionnaire) were assessed annually. Variance and covariance analyses with repeated measures were performed. RESULTS: A total of 542 subjects were assessed for 3 years. On average, patients with a greater amount of specific social support or a stronger specific support network experienced less functional limitation and less psychological distress. Changes in a given subject's functional limitations and psychological distress did not depend on his or her baseline social support or support network. Neither social support nor support network change over time. CONCLUSION: There may be a cross-sectional link between specific social support or support network and functional limitations and psychological distress, but no longitudinal association could be evidenced. | |
15083883 | Early rheumatoid arthritis: does gender influence disease expression? | 2004 Mar | OBJECTIVE: To investigate whether gender is an independent factor associated with disease expression in early rheumatoid arthritis (RA) patients. METHODS: 438 patients with early RA (disease duration less than one year) were studied. They all were patients with early RA who presented at the Rheumatology Clinic of the University Hospital of Ioannina during the period 1991-2000. All patients fulfilled the American College of Rheumatology criteria for RA. The demographic, clinical, laboratory, radiological and therapeutic characteristics of the disease at diagnosis, and at the last follow-up were analyzed according to gender. RESULTS: We studied 312 women and 126 men with early RA. The female to male ratio was 2.5:1 and the mean age at diagnosis was 49.4 +/- 14.9 years for women and 55.3 +/-15.6 years for men (P < 0.0003). Women had a longer duration of follow-up (P < 0.0003). There were no differences between genders in the general symptoms or the simmetricity of joint involvement at at disease onset. However at disease onset women had a higher erythrocyte sedimentation rate (ESR) (> 30 mm/1st hour), although there were no significant differences between the two groups concerninig the rest of the clinical, laboratory and radiological findings. At the last follow-up women still had a higher ESR (>30 min/1st hour), but no significant differences were found between the two groups concerning the rest of the parameters investigated independently of the follow-up duration. Finally, women and men showed the same degree of radiological changes and functional ability and were treated similarly except for the more frequent use of hydroxychloroquine in women. CONCLUSION: It seems that gender does not signficantly influence the expression of RA. | |
15850338 | [Hydrogen sulfide water balneum effect on erythrocyte superoxide dismutase activity in pat | 2004 | The aim of the study was to investigate, in vitro, hydrogen sulphide water balneum effect on erythrocyte superoxide dismutase activity in patients with rheumatoid arthritis. Erythrocytes from 29 consecutive patients with rheumatoid arthritis (11 men, 18 women) aged 54 years were obtained. The control group comprised of 30 healthy subjects with a mean age of about 40 years. Patients with rheumatoid arthritis were subdivided into two groups: with active disease (18 patients) and in remission (11 patients), and secondly into patients receiving (21 subjects) and not receiving (8 subjects) non-steroidal anti-inflammatory drugs. For erythrocyte superoxide dismutase activity evaluation, with method of Misra i Fridovich was used. Superoxide dismutase activity was assessed after 5, 10, 15, and 20 minutes erythrocytes incubation with hydrogen sulphide water. The mean baseline erythrocyte superoxide dismutase activity (T0) was in rheumatoid arthritis patients 1589.95+/-208.41 U/gHb and was 1622.12+/-321+/-321.58 U/gHb in the control group (ns). After 5 and 10 minutes of incubation with hydrogen sulphide water T0-T5 i T5-T10 erythrocyte superoxide dismutase activity increased significantly (p<0.05) in rheumatoid arthritis patients. In rheumatoid arthritis patients erythrocyte superoxide dismutase activity was higher and increased significantly when compared with control group. It seems that hydrogen sulphide water balneum produces an antioxidant effect on erythrocyte status in patients with rheumatoid arthritis. | |
15466895 | Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial | 2005 Jan | OBJECTIVES: Peptidylarginine deiminases (PADIs) convert peptidylarginine into citrulline via post-translational modification. Anti-citrullinated peptide antibodies are highly specific for rheumatoid arthritis (RA). Our genome-wide case-control study of single-nucleotide polymorphisms found that the PADI4 gene polymorphism is closely associated with RA. Here, we localized the expression of PADI4 and the citrullinated protein product in synovial RA tissue. METHODS: We used immunohistochemistry, double immunofluorescent labelling and western blotting. RESULTS: We found that PADI4 is extensively expressed in T cells, B cells, macrophages, neutrophils, fibroblast-like cells and endothelial cells in the lining and sublining areas of the RA synovium. We also found extracellular and intracellular expression of PADI4 in fibrin deposits with loose tissue structures where apoptosis was widespread. Unlike PADI4, citrullinated protein generally appeared in fibrin deposits that were abundant in the RA synovium. The citrullinated fibrin aggregate was immunoreactive against immunoglobulin (Ig) A and IgM, but not IgG and IgE. Although a little PADI4 was expressed in osteoarthritic and normal synovial tissues, significant citrullination was undetectable. CONCLUSIONS: The results showed that PADI4 is mainly distributed in cells of various haematopoietic lineages and expressed at high levels in the inflamed RA synovium. The co-localization of PADI4, citrullinated protein and apoptotic cells in fibrin deposits suggests that PADI4 is responsible for fibrin citrullination and is involved in apoptosis. The immunoreactivity of citrullinated fibrin with IgA and IgM in the RA synovium supports the notion that citrullinated fibrin is a potential antigen of RA autoimmunity. | |
14726212 | A pattern of protein expression in peripheral blood mononuclear cells distinguishes rheuma | 2004 Jan 14 | We compared the expression levels of proteins in peripheral blood mononuclear cells (PBMCs) of healthy control individuals to those of patients diagnosed with rheumatoid arthritis (RA) using a proteomics approach. Using two-dimensional electrophoresis we identified 18 proteins that were 2-fold or more highly expressed in patients than in controls, and 11 proteins that were 2-fold or more highly expressed in controls than in patients. Some of these differentially expressed proteins, identified by MALDI-TOF spectrometry, have previously been shown to play a potential role in the pathogenesis of RA. Hierarchical cluster analyses of the data segregated the samples into two groups, one which contained only controls and the other which contained only patients, and was used to compare the expression pattern of these 29 proteins in individual samples with the median expression pattern determined in the healthy control and in the RA patient groups. This analyses was able to predict whether a sample was derived from a rheumatoid arthritis patient or from a healthy individual, suggesting that a comparison of such protein expression patterns may be of diagnostic value. | |
12379523 | The influence of negative illness cognitions and neuroticism on subjective symptoms and mo | 2002 Nov | BACKGROUND: It was hypothesised that negative RA related illness cognitions are strongly related to the neuroticism trait and act as a common factor behind other self reported subjective symptoms (pain and ADL status), mood, and positive RA related illness cognitions; but are unrelated to objective indices of impairment (disease duration, C reactive protein (CRP), and joint stiffness). OBJECTIVE: To examine the relative influence of negative illness cognitions and neuroticism versus degree of impairment on subjective symptoms, positive illness cognitions, and mood in rheumatoid arthritis (RA). METHODS: Structural equation modelling analyses (LISREL) were performed on two independent samples of patients with RA consisting of 212 outpatients and 105 inpatients, respectively. RESULTS: The hypotheses were largely confirmed. Firstly, negative RA cognitions were found to be dependent on neuroticism. Secondly, negative RA cognitions had a strong and dominating influence on all other self reported data. Subjective symptoms were equally well explained by negative RA cognitions as by degree of impairment. No relations were found between negative RA cognitions (or neuroticism) and degree of impairment. CONCLUSIONS: The findings suggest that neuroticism, recognised as a relatively stable personality trait, strongly influences self rated symptoms and wellbeing in RA. This has important clinical implications concerning the use of standardised self rating questionnaires commonly used to assess illness status in RA and the long term effectiveness of psychological interventions and patient training courses in RA rehabilitation. | |
12234022 | Health-related quality of life measurements and studies in rheumatoid arthritis. | 2002 Sep | BACKGROUND: Rheumatoid arthritis (RA) is a major cause of disability and impairment of health-related quality of life (HRQOL) in the United States. Increasingly, HRQOL assessments are becoming part of a package of materials reviewed by managed care providers in making formulary and reimbursement decisions. OBJECTIVE: To help managed care administrators understand how to interpret and apply the results of HRQOL assessment scales. METHODS: Several patient-reported instruments in common use in RA were reviewed, including the Health Assessment Questionnaire (HAQ), Modified HAQ, Arthritis Impact Measurement Scale, and the 36-item Short-Form Health Survey. RESULTS: These self-assessment scales help improve patient/physician communication and thus enable better treatment decision-making. The scales can also aid managed care administrators in evaluating the efficacy and the financial benefits of therapies. The HAQ was one scale that stood out as being short, easy to administer, and disease-specific for RA. CONCLUSIONS: Self-assessment reports, such as the HAQ, provide key data on disability and HRQOL from the patient's perspective. The information so gained enables the clinician to select the most cost-effective therapies and interventions that slow disease progression, maintain functional status, and improve HRQOL. |