Tai Chi for treating knee osteoarthritis: Designing a long-term follow up randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Knee Osteoarthritis (KOA) is a major cause of pain and functional impairment among elders. Currently, there are neither feasible preventive intervention strategies nor effective medical remedies for the management of KOA. Tai Chi, an ancient Chinese mind-body exercise that is reported to enhance muscle function, balance and flexibility, and to reduce pain, depression and anxiety, may safely and effectively be used to treat KOA. However, current evidence is inconclusive. Our study examines the effects of a 12-week Tai Chi program compared with an attention control (wellness education and stretching) on pain, functional capacity, psychosocial variables, joint proprioception and health status in elderly people with KOA. The study will be completed by July 2009.</p> <p>Methods/Design</p> <p>Forty eligible patients, age > 55 yr, BMI ≤ 40 kg/m²with tibiofemoral osteoarthritis (American College of Rheumatology criteria) are identified and randomly allocated to either Tai Chi (10 modified forms from classical Yang style Tai Chi) or attention control (wellness education and stretching). The 60-minute intervention sessions take place twice weekly for 12 weeks. The study is conducted at an urban tertiary medical center in Boston, Massachusetts. The primary outcome measure is the Western Ontario and McMaster Universities (WOMAC) pain subscale at 12 weeks. Secondary outcomes include weekly WOMAC pain, function and stiffness scores, patient and physician global assessments, lower-extremity function, knee proprioception, depression, self-efficacy, social support, health-related quality of life, adherence and occurrence of adverse events after 12, 24 and 48 weeks.</p> <p>Discussion</p> <p>In this article, we present the challenges of designing a randomized controlled trial with long-term follow up. The challenges encountered in this design are: strategies for recruitment, avoidance of selection bias, the actual practice of Tai Chi, and the maximization of adherence/follow-up while conducting the clinical trial for the evaluation of the effectiveness of Tai Chi on KOA.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: NCT00362453</p

Early change in proteinuria as a surrogate end point for kidney disease progression: an individual patient meta-analysis.

BACKGROUND: It is controversial whether proteinuria is a valid surrogate end point for randomized trials in chronic kidney disease. STUDY DESIGN: Meta-analysis of individual patient-level data. SETTING & POPULATION: Individual patient data for 9,008 patients from 32 randomized trials evaluating 5 intervention types. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of kidney disease progression until 2007 with measurements of proteinuria both at baseline and during the first year of follow-up, with at least 1 further year of follow-up for the clinical outcome. PREDICTOR: Early change in proteinuria. OUTCOMES: Doubling of serum creatinine level, end-stage renal disease, or death. RESULTS: Early decline in proteinuria was associated with lower risk of the clinical outcome (pooled HR, 0.74 per 50% reduction in proteinuria); this association was stronger at higher levels of baseline proteinuria. Pooled estimates for the proportion of treatment effect on the clinical outcome explained by early decline in proteinuria ranged from -7.0% (95%CI, -40.6% to 26.7%) to 43.9% (95%CI, 25.3% to 62.6%) across 5 intervention types. The direction of the pooled treatment effects on early change in proteinuria agreed with the direction of the treatment effect on the clinical outcome for all 5 intervention types, with the magnitudes of the pooled treatment effects on the 2 end points agreeing for 4 of the 5 intervention types. The pooled treatment effects on both end points were simultaneously stronger at higher levels of proteinuria. However, statistical power was insufficient to determine whether differences in treatment effects on the clinical outcome corresponded to differences in treatment effects on proteinuria between individual studies. LIMITATIONS: Limited variety of interventions tested and low statistical power for many chronic kidney disease clinical trials. CONCLUSIONS: These results provide new evidence supporting the use of an early reduction in proteinuria as a surrogate end point, but do not provide sufficient evidence to establish its validity in all settings

Performance of glomerular filtration rate estimating equations in a community-based sample of Blacks and Whites: the multiethnic study of atherosclerosis.

BackgroundThe Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are recommended for glomerular filtration rate (GFR) estimation in the general population. They have not been evaluated in community-based populations, including Blacks at higher levels of GFR, but are commonly applied in such populations.MethodsIn an ancillary study of Multi-Ethnic Study of Atherosclerosis conducted at one site, we evaluated the performance of the CKD-EPI equations for creatinine (eGFRcr), cystatin C (eGFRcys) or the combination (eGFRcr-cys) compared with GFR measured as plasma clearance of iohexol.ResultsAmong 294 participants, the mean age was 71 (SD 9) years, 47% were Black, 48% were women and the mean measured GFR (mGFR) was 72.6 (SD 18.8) mL/min/1.73 m2. The CKD-EPI equations overestimated mGFR with a larger median bias for eGFRcr and eGFRcr-cys than eGFRcys [-8.3 (95% confidence interval -9.7, -6.5), -7.8 (-9.2, -6.2) and -3.7 (-5.0, -1.8) mL/min/1.73 m2, respectively], with smaller bias for those with lower compared with higher eGFR and by race compared with sex.ConclusionThe small differential bias of the CKD-EPI equation between races suggests that they can be used in Blacks as well as Whites in older community-based adults. The large differential bias in women versus men in all equations is in contrast to other studies and is unexplained. Further studies are required in multiracial and multiethnic community-based cohorts, taking into account differences in GFR measurement methods

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney.

To access publisher's full text version of this article click on the hyperlink belowStudies in chronic kidney disease populations suggest that the non-glomerular filtration rate (GFR) determinants of serum levels of the low-molecular-weight protein filtration markers cystatin C, β2-microglobulin (B2M), and beta-trace protein (BTP) are less affected by age, sex, and ethnicity than those of creatinine.Cross-sectional study.Predominantly elderly participants selected from the Age, Gene/Environment Susceptibility Kidney Study (AGES-Kidney; N=683; mean [SD] age, 79 [4] years; GFR, 62 [17]mL/min/1.73 m(2)) and from the Multi-Ethnic Study of Atherosclerosis Kidney Study (MESA-Kidney; N=273; mean [SD] age, 70.5 [9] years; GFR, 73 [19]mL/min/1.73 m(2)).Demographic and clinical factors hypothesized to be associated with conditions affecting non-GFR determinants of the filtration markers.Measured GFRs and estimated GFRs (eGFRs) based on creatinine, cystatin C, B2M, and BTP levels (eGFRcr, eGFRcys, eGFRB2M, and eGFRBTP, respectively). Residual associations of factors with eGFR after accounting for measured GFR as the parameter of interest.eGFRcys, eGFRB2M, and eGFRBTP had significantly less strong residual associations with age and sex than eGFRcr in both AGES-Kidney and MESA-Kidney and were not associated with ethnicity (black vs white) in MESA-Kidney. After adjusting for age, sex, and ethnicity, residual associations with most clinical factors were smaller than observed with age and sex. eGFRcys and eGFRB2M, but not eGFRBTP, had significant residual associations with C-reactive protein levels in both studies.Small sample size may limit power to detect associations. Participants may be healthier than the general population.Similar to previous studies in chronic kidney disease, in community-dwelling elders, cystatin C, B2M, and BTP levels are less affected than creatinine level by age and sex and are not affected by ethnicity. Both cystatin C and B2M levels may be affected by inflammation. These findings are important for the development and use of GFR estimating equations based on low-molecular-weight serum proteins throughout the range in GFRs.NIH, National Kidney Foundation Gilead Sciences Siemens Novartis NIH Amgen Pharmalink A

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney.

To access publisher's full text version of this article click on the hyperlink belowStudies in chronic kidney disease populations suggest that the non-glomerular filtration rate (GFR) determinants of serum levels of the low-molecular-weight protein filtration markers cystatin C, β2-microglobulin (B2M), and beta-trace protein (BTP) are less affected by age, sex, and ethnicity than those of creatinine.Cross-sectional study.Predominantly elderly participants selected from the Age, Gene/Environment Susceptibility Kidney Study (AGES-Kidney; N=683; mean [SD] age, 79 [4] years; GFR, 62 [17]mL/min/1.73 m(2)) and from the Multi-Ethnic Study of Atherosclerosis Kidney Study (MESA-Kidney; N=273; mean [SD] age, 70.5 [9] years; GFR, 73 [19]mL/min/1.73 m(2)).Demographic and clinical factors hypothesized to be associated with conditions affecting non-GFR determinants of the filtration markers.Measured GFRs and estimated GFRs (eGFRs) based on creatinine, cystatin C, B2M, and BTP levels (eGFRcr, eGFRcys, eGFRB2M, and eGFRBTP, respectively). Residual associations of factors with eGFR after accounting for measured GFR as the parameter of interest.eGFRcys, eGFRB2M, and eGFRBTP had significantly less strong residual associations with age and sex than eGFRcr in both AGES-Kidney and MESA-Kidney and were not associated with ethnicity (black vs white) in MESA-Kidney. After adjusting for age, sex, and ethnicity, residual associations with most clinical factors were smaller than observed with age and sex. eGFRcys and eGFRB2M, but not eGFRBTP, had significant residual associations with C-reactive protein levels in both studies.Small sample size may limit power to detect associations. Participants may be healthier than the general population.Similar to previous studies in chronic kidney disease, in community-dwelling elders, cystatin C, B2M, and BTP levels are less affected than creatinine level by age and sex and are not affected by ethnicity. Both cystatin C and B2M levels may be affected by inflammation. These findings are important for the development and use of GFR estimating equations based on low-molecular-weight serum proteins throughout the range in GFRs.NIH, National Kidney Foundation Gilead Sciences Siemens Novartis NIH Amgen Pharmalink A

Midlife Blood Pressure and Late-Life GFR and Albuminuria: An Elderly General Population Cohort.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageChronic kidney disease (CKD) is common in the elderly, but the cause is often not identifiable. Some posit that age-related reductions in glomerular filtration rate (GFR) and increases in albuminuria are normal, whereas others suggest that they are a consequence of vascular disease.Cross-sectional analysis of a substudy of a prospective cohort.AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study.Exposure to higher blood pressure in midlife.Measured GFR using plasma clearance of iohexol and urine albumin-creatinine ratio.GFR was measured in 805 participants with mean age in midlife and late life of 51.0±5.8 and 80.8±4.0 (SD) years, respectively. Mean measured GFR was 62.4±16.5mL/min/1.73m(2) and median albuminuria was 8.0 (IQR, 5.4-16.5) mg/g. Higher midlife systolic and diastolic blood pressures were associated with lower later-life GFRs. Associations persisted after adjustment. Higher midlife systolic and diastolic blood pressures were also associated with higher albumin-creatinine ratios, and associations remained significant even after adjustment.This is a study of survivors, and people who agreed to participate in this study were healthier than those who refused. Blood pressure may encompass effects of the other risk factors. Results may not be generalizable to populations of other races. We were not able to adjust for measured GFR or albuminuria at the midlife visit.Factors other than advanced age may account for the high prevalence of CKD in the elderly. Midlife factors are potential contributing factors to late-life kidney disease. Further studies are needed to identify and treat midlife modifiable factors to prevent the development of CKD