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Objectives: To investigate cartilage tissue turnover in response to a supervised 12-week exercise-related joint loading training program followed by a 6-month period of unsupervised training in patients with knee osteoarthritis (OA). To study the difference in cartilage tissue turnover between high- and low-resistance training., Method: Patients with knee OA were randomized into either high-intensity or low-intensity resistance supervised training (two sessions per week) for 3 months and unsupervised training for 6 months. Blood samples were collected before and after the supervised training period and after the follow-up period. Biomarkers huARGS, C2M, and PRO-C2, quantifying cartilage tissue turnover, were measured by ELISA. Changes in biomarker levels over time within and between groups were analyzed using linear mixed models with baseline values as covariates., Results: huARGS and C2M levels increased after training and at follow-up in both low- and high-intensity exercise groups. No changes were found in PRO-C2. The huARGS level in the high-intensity resistance training group increased significantly compared to the low-intensity resistance training group after resistance training (p = 0.029) and at follow-up (p = 0.003)., Conclusion: Cartilage tissue turnover and cartilage degradation appear to increase in response to a 3-month exercise-related joint loading training program and at 6-month follow-up, with no evident difference in type II collagen formation. Aggrecan remodeling increased more with high-intensity resistance training than with low-intensity exercise. These exploratory biomarker results, indicating more cartilage degeneration in the high-intensity group, in combination with no clinical outcome differences of the VIDEX study, may argue against high-intensity training., (© 2023. The Author(s).)

Background: A stratified approach to exercise therapy may yield superior clinical and economic outcomes, given the large heterogeneity of individuals with knee osteoarthritis (OA)., Objective: To evaluate the cost-effectiveness during a 12-month follow-up of a model of stratified exercise therapy compared to usual exercise therapy in patients with knee OA, from a societal and healthcare perspective., Methods: An economic evaluation was conducted alongside a cluster-randomized controlled trial in patients with knee OA (n = 335), comparing subgroup-specific exercise therapy for a 'high muscle strength subgroup', 'low muscle strength subgroup', and 'obesity subgroup' supplemented by a dietary intervention for the 'obesity subgroup' (experimental group), with usual ('non-stratified') exercise therapy (control group). Clinical outcomes included quality-adjusted life years - QALYs (EuroQol-5D-5 L), knee pain (Numerical Rating Scale) and physical functioning (Knee Injury and Osteoarthritis Outcome Score in daily living). Costs were measured by self-reported questionnaires at 3, 6, 9 and 12-month follow-up. Missing data were imputed using multiple imputation. Data were analyzed through linear regression. Bootstrapping techniques were applied to estimate statistical uncertainty., Results: During 12-month follow-up, there were no significant between-group differences in clinical outcomes. The total societal costs of the experimental group were on average lower compared to the control group (mean [95% confidence interval]: € 405 [-1728, 918]), albeit with a high level of uncertainty. We found a negligible difference in QALYs between groups (mean [95% confidence interval]: 0.006 [-0.011, 0.023]). The probability of stratified exercise therapy being cost-effective compared to usual exercise therapy from the societal perspective was around 73%, regardless of the willingness-to-pay threshold. However, this probability decreased substantially to 50% (willingness-to-pay threshold of €20.000/QALY) when using the healthcare perspective. Similar results were found for knee pain and physical functioning., Conclusions: We found no clear evidence that stratified exercise therapy is likely to be cost-effective compared to usual exercise therapy in patients with knee OA. However, results should be interpreted with caution as the study power was lower than intended, due to the Coronavirus disease (COVID-19) pandemic., Competing Interests: Conflicts of interest All authors declare that they have no competing interests., (Copyright © 2022 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Muscle weakness is characteristic of knee osteoarthritis. Muscle steadiness may be an important adjunct to knee muscle strength in improving physical function in knee osteoarthritis. However, the role of muscle steadiness is uncertain., Aims: To determine the associations of knee extensor muscle steadiness with maximal voluntary torque and physical function in patients with knee osteoarthritis., Methods: Baseline data from 177 patients in a randomized clinical trial were used. Isokinetic knee extension torque was processed into maximal voluntary torque [Nm]. Muscle steadiness was expressed as the coefficient of variance [%] and as peak power frequency [Hz]. Physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index, the Get-Up-and-Go and Stair-climb tests. Associations were determined using regression analyses and adjusted for confounders., Findings: Lower muscle steadiness (i.e., higher coefficient of variance and peak power frequency) was associated with lower maximal voluntary torque (B = - 7.38, [-10.8, -3.95], R 2  = 0.10 and B = -14.71, [-28.29, -1.13], R 2  = 0.03, respectively). Higher coefficient of variance was associated with lower self-reported physical function (B = 1.14, [0.11,2.17], R 2  = 0.03) and remained significant after adjusting for potential confounders. Peak power frequency was not associated with physical function., Interpretation: Low muscle steadiness was weakly associated with low muscle strength and poorer self-reported physical function. Muscle steadiness and muscle strength seem to be different attributes of muscle function. There is no convincing evidence that muscle steadiness is an important adjunct in studying physical function in patients with knee osteoarthritis., Competing Interests: Declaration of Competing Interest None. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Most studies of knee osteoarthritis use isokinetic peak strength as a measure of muscle strength. However, estimated one-repetition maximum (1-RM) may have a stronger relationship than isokinetic peak strength with daily activities. The aim of this study was to test the following hypotheses: first, the estimated 1-RM is more strongly associated than isokinetic peak strength with daily activities; and secondly, the estimated 1-RM is most strongly associated with the 6-minute walk test (6MWT), followed by the Get Up and Go test (GUG test) and the stair-climb test., Methods: Data were used for 177 patients with knee osteoarthritis from a randomized controlled trial on improving muscle strength. The patients had a mean age of 67.6 ± 5.8 years. Isokinetic peak strength was measured using a dynamometer, 1-RM was estimated with the 10-RM test, and physical performance was measured with the 6-minute walk test (6MWT), get-up and go test (GUG) test and stair-climb test, at the start and end of 12 weeks of resistance training. Linear regression analyses provided standardized betas (β) that were comparable between the different associations between measures of muscle strength and daily activities., Results: Compared with the estimated 1-RM, isokinetic peak strength was more strongly associated with all performance-based measures. The associations between the estimated 1-RM and performance-based tests were not ranked in the order hypothesized (6MWT, GUG test, stair-climb test)., Conclusion: Contrary to the first hypothesis, isokinetic peak strength showed stronger associations with all daily activities than did estimated 1-RM. In addition, the second hypothesis regarding the activity-specific pattern for the 1-RM with regards walking, chair rising and stair climbing measurements was not confirmed.

Question: In people with knee osteoarthritis, how much more effective is stratified exercise therapy that distinguishes three subgroups (high muscle strength subgroup, low muscle strength subgroup, obesity subgroup) in reducing knee pain and improving physical function than usual exercise therapy?, Design: Pragmatic cluster randomised controlled trial in a primary care setting., Participants: A total of 335 people with knee osteoarthritis: 153 in an experimental arm and 182 in a control arm., Intervention: Physiotherapy practices were randomised into an experimental arm providing stratified exercise therapy (supplemented by a dietary intervention from a dietician for the obesity subgroup) or a control arm providing usual, non-stratified exercise therapy., Outcome Measures: Primary outcomes were knee pain severity (numerical rating scale for pain, 0 to 10) and physical function (Knee Injury and Osteoarthritis Outcome Score subscale activities of daily living, 0 to 100). Measurements were performed at baseline, 3 months (primary endpoint) and 6 and 12 months (follow-up). Intention-to-treat, multilevel, regression analysis was performed., Results: Negligible differences were found between the experimental and control groups in knee pain (mean adjusted difference 0.2, 95% CI -0.4 to 0.7) and physical function (-0.8, 95% CI -4.3 to 2.6) at 3 months. Similar effects between groups were also found for each subgroup separately, as well as at other time points and for nearly all secondary outcome measures., Conclusion: This pragmatic trial demonstrated no added value regarding clinical outcomes of the model of stratified exercise therapy compared with usual exercise therapy. This could be attributed to the experimental arm therapists facing difficulty in effectively applying the model (especially in the obesity subgroup) and to elements of stratified exercise therapy possibly being applied in the control arm., Registration: Netherlands National Trial Register NL7463., (Copyright © 2022 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess whether (i) high-intensity resistance training (RT) leads to increased muscle strength compared to low-intensity RT in patients with knee osteoarthritis (OA); and (ii) RT with vitamin D supplementation leads to increased muscle strength compared to placebo in a subgroup with vitamin D deficiency., Design: Randomized controlled trial., Setting: Outpatient rehabilitation centre., Subjects: Patients with knee OA., Interventions: 12 weeks of RT at high-intensity RT (70-80% of 1-repetition maximum (1-RM)) or low-intensity RT (40-50% of 1-RM) and 24 weeks of vitamin D (1200 International units vitamin D3 per day) or placebo supplementation., Main Measures: Primary outcome measure was isokinetic muscle strength. Other outcome measure for muscle strength was the estimated 1-RM. Secondary outcome measures were knee pain and physical functioning., Results: 177 participants with a mean age of 67.6 ± 5.8 years were included, of whom 50 had vitamin D deficiency. Isokinetic muscle strength (in Newton metre per kilogram bodyweight) at start, end and 24 weeks after the RT was 0.98 ± 0.40, 1.11 ± 0.40, 1.09 ± 0.42 in the high-intensity group and 1.02 ± 0.41, 1.15 ± 0.42, 1.12 ± 0.40 in the low-intensity group, respectively. No differences were found between the groups, except for the estimated 1-RM in favour of the high-intensity group. In the subgroup with vitamin D deficiency, no difference on isokinetic muscle strength was found between the vitamin D and placebo group., Conclusions: High-intensity RT did not result in greater improvements in isokinetic muscle strength, pain and physical functioning compared to low-intensity RT in knee OA, but was well tolerated. Therefore these results suggest that either intensity of resistance training could be utilised in exercise programmes for patients with knee osteoarthritis. No synergistic effect of vitamin D supplementation and RT was found, but this finding was based on underpowered data.

Background: Quadriceps weakness is assumed to be associated with compositional properties of the vastus medialis muscle in patients with knee osteoarthritis (OA)., Methods: The aim was to determine the association of non-contractile muscle tissue in the vastus medialis muscle, measured with routine MRI, with muscle extensor strength in patients with knee OA. Sagittal T1-weighted 3T MRI of 94 patients with knee OA, routinely acquired in clinical practice were used for analysis. Using the MRI's, the amount of non-contractile muscle tissue in the vastus medialis muscle was measured, expressed as a percentage of (non)-contractile tissue, dichotomized into a low and a high non-contractile percentage group. Muscle strength was assessed by isokinetic measurement of knee extensors and by conduction of the Get-Up and Go (GUG) test. In regression analyses, associations of percentage of non-contractile muscle tissue with muscle strength and GUG time were determined and controlled for sex, age, BMI and radiographic severity., Results: A high percentage of non-contractile muscle tissue (> 11.2%) was associated with lower muscle strength (B = -0.25, P = 0.006) and with longer GUG time (B = 1.09, P = 0.021). These associations were specifically confounded by sex and BMI, because these two variables decreased the regression coefficient (B) with > 10%., Conclusions: A high percentage of non-contractile muscle tissue in the vastus medialis muscle measured by clinical T1-weighted 3T MRI is associated with muscle weakness. The association is confounded by sex and BMI. Non-contractile muscle tissue seems to be an important compositional property of the vastus medialis muscle underlying quadriceps weakness., (© 2022. The Author(s).)

Background: We recently developed a model of stratified exercise therapy, consisting of (i) a stratification algorithm allocating patients with knee osteoarthritis (OA) into one of the three subgroups ('high muscle strength subgroup' representing a post-traumatic phenotype, 'low muscle strength subgroup' representing an age-induced phenotype, and 'obesity subgroup' representing a metabolic phenotype) and (ii) subgroup-specific exercise therapy. In the present study, we aimed to test the construct validity of this algorithm., Methods: Data from five studies (four exercise therapy trial cohorts and one cross-sectional cohort) were used to test the construct validity of our algorithm by 63 a priori formulated hypotheses regarding three research questions: (i) are the proportions of patients in each subgroup similar across cohorts? (15 hypotheses); (ii) are the characteristics of each of the subgroups in line with their proposed underlying phenotypes? (30 hypotheses); (iii) are the effects of usual exercise therapy in the 3 subgroups in line with the proposed effect sizes? (18 hypotheses)., Results: Baseline data from a total of 1211 patients with knee OA were analyzed for the first and second research question, and follow-up data from 584 patients who were part of an exercise therapy arm within a trial for the third research question. In total, the vast majority (73%) of the hypotheses were confirmed. Regarding our first research question, we found similar proportions in each of the three subgroups across cohorts, especially for three cohorts. Regarding our second research question, subgroup characteristics were almost completely in line with the proposed underlying phenotypes. Regarding our third research question, usual exercise therapy resulted in similar, medium to large effect sizes for knee pain and physical function for all three subgroups., Conclusion: We found mixed results regarding the construct validity of our stratification algorithm. On the one hand, it is a valid instrument to consistently allocate patients into subgroups that aligned our hypotheses. On the other hand, in contrast to our hypotheses, subgroups did not differ substantially in effects of usual exercise therapy. An ongoing trial will assess whether this algorithm accompanied by subgroup-specific exercise therapy improves clinical and economic outcomes., (© 2021. The Author(s).)

Objective: The objectives of the present study were to: (1) evaluate the effect of an educational course on competence (knowledge and clinical reasoning) of primary care physical therapists (PTs) in treating patients with knee osteoarthritis (KOA) and comorbidity according to the developed strategy; and (2) identify facilitators and barriers for usage., Method: The present research was an observational study with a pretest-posttest design using mixed methods. PTs were offered a postgraduate course consisting of e-learning and two workshops (blended education) on the application of a strategy for exercise prescription in patients with KOA and comorbidity. Competences were measured by questionnaire on knowledge (administered before and 2 weeks after the course), and a patient vignette to measure clinical reasoning (administered before the course and after a 6 month period of treating patients). Facilitators and barriers for using the strategy were assessed by a questionnaire and semi-structured interviews., Results: Thirty-four PTs were included. Competence (knowledge and clinical reasoning) improved significantly (p < 0.01). Fourteen out of 34 PTs had actually treated patients with KOA and comorbidity, during a 6-month period. The strategy was found to be feasible in daily practice. The main barriers included the limited number of (self-) referrals of patients, limited number of reimbursed treatment sessions by insurance companies and a suboptimal collaboration with (referring) physicians., Conclusion: A blended course on exercise therapy for patients with KOA and comorbidity seems to improve PTs' competence through increasing knowledge and clinical reasoning skills. Identified barriers should be solved before large-scale implementation of exercise therapy can take place in these complex patients., (© 2020 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Introduction: E-Exercise is an effective 12-week blended intervention consisting of around five face-to-face physiotherapy sessions and a web-based application for patients with hip/knee osteoarthritis. In order to facilitate effective implementation of e-Exercise, this study aims to identify physiotherapists' experiences and determinants related to the usage of e-Exercise. Methods : An explanatory sequential mixed methods design embedded in a randomized controlled trial comparing e-Exercise with usual physiotherapy in patients with hip/knee osteoarthritis. Usage of e-Exercise was based on recruitment rates of 123 physiotherapists allocated to e-Exercise and objective web-based application usage data. Experiences and determinants related to e-Exercise usage were investigated with a questionnaire and clarified with semi-structured interviews. Results : Of the 123 physiotherapists allocated to e-Exercise, 54 recruited more than one eligible patient, of whom 10 physiotherapists continued using e-Exercise after the study period. Physiotherapists had mixed experiences with e-Exercise. Determinants related to intervention usage were appropriateness, added value, time, workload, professional autonomy, environmental factors, and financial consequences. Physiotherapists recommended to improve the ability to tailor e-Exercise to the individual needs of the patient patients' individual needs. Discussion : Determinants related to the usage of e-Exercise provided valuable information for the implementation of e-Exercise on broader scale. Most importantly, the flexibility of e-Exercise needs to be improved. Next, there is a need for education on how to integrate an online program within physiotherapy.

Objectives: Knee osteoarthritis (OA) is characterized by its heterogeneity, with large differences in clinical characteristics between patients. Therefore, a stratified approach to exercise therapy, whereby patients are allocated to homogeneous subgroups and receive a stratified, subgroup-specific intervention, can be expected to optimize current clinical effects. Recently, we developed and pilot tested a model of stratified exercise therapy based on clinically relevant subgroups of knee OA patients that we previously identified. Based on the promising results, it is timely to evaluate the (cost-)effectiveness of stratified exercise therapy compared with usual, "nonstratified" exercise therapy., Methods: A pragmatic cluster randomized controlled trial including economic and process evaluation, comparing stratified exercise therapy with usual care by physical therapists (PTs) in primary care, in a total of 408 patients with clinically diagnosed knee OA. Eligible physical therapy practices are randomized in a 1:2 ratio to provide the experimental (in 204 patients) or control intervention (in 204 patients), respectively. The experimental intervention is a model of stratified exercise therapy consisting of (a) a stratification algorithm that allocates patients to a "high muscle strength subgroup," "low muscle strength subgroup," or "obesity subgroup" and (b) subgroup-specific, protocolized exercise therapy (with an additional dietary intervention from a dietician for the obesity subgroup only). The control intervention will be usual best practice by PTs (i.e., nonstratified exercise therapy). Our primary outcome measures are knee pain severity (Numeric Rating Scale) and physical functioning (Knee Injury and Osteoarthritis Outcome Score subscale daily living). Measurements will be performed at baseline, 3-month (primary endpoint), 6-month (questionnaires only), and 12-month follow-up, with an additional cost questionnaire at 9 months. Intention-to-treat, multilevel, regression analysis comparing stratified versus usual care will be performed., Conclusion: This study will demonstrate whether stratified care provided by primary care PTs is effective and cost-effective compared with usual best practice from PTs., (© 2019 The Authors. Physiotherapy Research International published by John Wiley & Sons Ltd.)

Objective: To evaluate whether improvement of proprioception, pain, or dynamic knee instability mediates the effect of wearing a soft knee brace on activity limitations in patients with knee osteoarthritis (OA)., Methods: We conducted an analysis of data for 44 patients with knee OA who were enrolled in a laboratory-based trial evaluating the effect of wearing a commercially available soft knee brace. Activity limitations were assessed with the 10-meter walk test and the Get Up and Go test. Knee joint proprioception was assessed by an active joint position sense test; pain was assessed on a numeric rating scale (NRS) (range 0-10); pressure pain threshold (PPT) was assessed with a hand-held pressure algometer; dynamic knee instability was expressed by the perturbation response, i.e., a measure reflecting a deviation in mean knee varus-valgus angle after a controlled mechanical perturbation on a treadmill, with respect to level walking. Mediation analysis was conducted using the product of coefficients approach. Confidence intervals were calculated with a bootstrap procedure., Results: A decrease in pain (scored on an NRS) and a decrease in dynamic knee instability mediated the effect of wearing a soft knee brace on the reduction of activity limitations (P < 0.05), while changes in proprioception and PPT did not mediate this effect (P > 0.05)., Conclusion: This study shows that decreased pain and reduced dynamic knee instability are pathways by which wearing a soft knee brace decreases activity limitations in patients with knee OA., (© 2018, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objectives: Wearing a soft knee brace has been shown to reduce self-reported knee instability in persons with knee OA. There is a need to assess whether a soft knee brace has a beneficial effect on objectively assessed dynamic knee instability as well. The aims of the study were to evaluate the effect of a soft knee brace on objectively assessed dynamic knee instability and to assess the difference in effect between a non-tight and a tight soft knee brace in persons with knee OA., Methods: Thirty-eight persons with knee OA and self-reported knee instability participated in a laboratory study. A within-subject design was used comparing no brace vs brace and comparing a non-tight vs a tight brace. The primary outcome measure was dynamic knee instability, expressed by the perturbation response (PR). The PR reflects deviation in the mean knee varus-valgus angle during level walking after a controlled mechanical perturbation. Linear mixed-effect model analysis was used to evaluate the effect of a brace on dynamic knee instability., Results: Wearing a brace significantly reduced the PR compared with not wearing a brace (B = -0.16, P = 0.01). There was no difference between a non-tight and a tight brace (B = -0.03, P = 0.60)., Conclusion: This study is the first to report that wearing a soft knee brace reduces objectively assessed dynamic knee instability in persons with knee OA. Wearing a soft brace results in an objective improvement of knee instability beyond subjectively reported improvement., Trial Registration: Nederlands Trial register (trialregister.nl) NTR6363.

Background: Blended physiotherapy, in which physiotherapy sessions and an online application are integrated, might support patients in taking an active role in the management of their chronic condition and may reduce disease related costs. The aim of this study was to evaluate the cost-effectiveness of a blended physiotherapy intervention (e-Exercise) compared to usual physiotherapy in patients with osteoarthritis of hip and/or knee, from the societal as well as the healthcare perspective., Methods: This economic evaluation was conducted alongside a 12-month cluster randomized controlled trial, in which 108 patients received e-Exercise, consisting of physiotherapy sessions and a web-application, and 99 patients received usual physiotherapy. Clinical outcome measures were quality-adjusted life years (QALYs) according to the EuroQol (EQ-5D-3 L), physical functioning (HOOS/KOOS) and physical activity (Actigraph Accelerometer). Costs were measured using self-reported questionnaires. Missing data were multiply imputed and bootstrapping was used to estimate statistical uncertainty., Results: Intervention costs and medication costs were significantly lower in e-Exercise compared to usual physiotherapy. Total societal costs and total healthcare costs did not significantly differ between groups. No significant differences in effectiveness were found between groups. For physical functioning and physical activity, the maximum probability of e-Exercise being cost-effective compared to usual physiotherapy was moderate (< 0.82) from both perspectives. For QALYs, the probability of e-Exercise being cost-effective compared to usual physiotherapy was 0.68/0.84 at a willingness to pay of 10,000 Euro and 0.70/0.80 at a willingness to pay of 80,000 Euro per gained QALY, from respectively the societal and the healthcare perspective., Conclusions: E-Exercise itself was significantly cheaper compared to usual physiotherapy in patients with hip and/or knee osteoarthritis, but not cost-effective from the societal- as well as healthcare perspective. The decision between both interventions can be based on the preferences of the patient and the physiotherapist., Trial Registration: NTR4224 (25 October 2013).

Background: To investigate (1) the association of specific biomechanical factors with knee osteoarthritis and knee osteoarthritis development, and (2) the impact of other relevant risk factors on this association., Methods: MEDLINE, EMBASE, CINAHL and SPORTDiscus were searched up until April 2017. Studies were included if they fulfilled the following criteria: the study 1) assessed the association of a biomechanical factor with knee osteoarthritis, or knee osteoarthritis development; 2) reported on skeletal malalignment, muscular dysfunction, impaired proprioception, laxity and abnormal loading during gait; 3) was a cohort study with participants developing knee osteoarthritis and participants not developing knee osteoarthritis, or a case-control or cross-sectional study with participants with knee osteoarthritis and without knee osteoarthritis. Risk of bias was assessed with the QUIPS tool and meta-analyses were performed using random effects models., Results: Of 6413 unique studies identified, 59 cross-sectional studies were eligible for meta-analyses (9825 participants, 5328 with knee osteoarthritis). No cohort studies fulfilled the inclusion criteria. Compared with healthy controls, patients with knee osteoarthritis have higher odds of having lower muscle strength, proprioception deficits, more medial varus-valgus laxity and less lateral varus-valgus laxity. Patients with medial knee osteoarthritis have higher odds of having a higher knee adduction moment than healthy controls. Level of evidence was graded as 'very low' to 'moderate' quality. Due to large between study differences moderation of other risk factors on biomechanical risk factors could not be evaluated., Conclusions: Patients with knee osteoarthritis are more likely to display a number of biomechanical characteristics. The causal relationship between specific biomechanical factors and the development of knee osteoarthritis could not be determined as no longitudinal studies were included. There is an urgent need for high quality, longitudinal studies to evaluate the impact of specific biomechanical factors on the development of knee osteoarthritis., Trial Registration: (PROSPERO ID: CRD42015025092 ).

Background: Integrating physical therapy sessions and an online application (e-Exercise) might support people with hip osteoarthritis (OA), knee OA, or both (hip/knee OA) in taking an active role in the management of their chronic condition and may reduce the number of physical therapy sessions., Objective: The objective of this study was to investigate the short- and long-term effectiveness of e-Exercise compared to usual physical therapy in people with hip/knee OA., Design: The design was a prospective, single-blind, multicenter, superiority, cluster- randomized controlled trial., Setting: The setting included 143 primary care physical therapist practices., Participants: The participants were 208 people who had hip/knee OA and were 40 to 80 years of age., Intervention: e-Exercise is a 3-month intervention in which about 5 face-to-face physical therapy sessions were integrated with an online application consisting of graded activity, exercise, and information modules. Usual physical therapy was conducted according to the Dutch physical therapy guidelines on hip and knee OA., Measurements: Primary outcomes, measured at baseline after 3 and 12 months, were physical functioning and free-living physical activity. Secondary outcome measures were pain, tiredness, quality of life, self-efficacy, and the number of physical therapy sessions., Results: The e-Exercise group (n = 109) received, on average, 5 face-to-face sessions; the usual physical therapy group (n = 99) received 12. No significant differences in primary outcomes between the e-Exercise group and the usual physical therapy group were found. Within-group analyses for both groups showed a significant improvement in physical functioning. After 3 months, participants in the e-Exercise group reported an increase in physical activity; however, no objectively measured differences in physical activity were found. With respect to secondary outcomes, after 12 months, sedentary behavior significantly increased in the e-Exercise group compared with the usual physical therapy group. In both groups, there were significant improvements for pain, tiredness, quality of life, and self-efficacy., Limitations: The response rate at 12 months was 65%., Conclusions: The blended intervention, e-Exercise, was not more effective than usual physical therapy in people with hip/knee OA.

Objective: Muscle weakness is common and strongly related to clinical outcome in patients with knee or hip osteoarthritis. To date, there is no clear overview of the information on factors associated with muscle strength in knee and hip osteoarthritis. The aim of this paper is to provide an overview of current knowledge on factors associated with upper leg muscle strength in this population., Design: The framework of a scoping review was chosen. MEDLINE database was searched systematically up to 22 April 2017. Studies that described a relationship between a factor and muscle strength in knee or hip osteoarthritis were included., Results: A total of 65 studies met the inclusion criteria. In studies of knee osteoarthritis, 4 factors were consistently found to be associated with lower muscle strength. Due to the low number of studies on hip osteoarthritis no conclusions could be drawn on associations., Conclusion: Lower muscle quality, physical inactivity, more severe joint degeneration, and higher pain are reported to be associated with lower strength in the upper leg muscles in knee osteoarthritis. Future research into knee osteoarthritis should focus on other potential determinants of muscle strength, such as muscle quantity, muscle activation, nutrition and vitamins, and inflammation. In hip osteoarthritis, more research is needed into all potential determinants.

Objectives: To determine whether systemic inflammation is associated with poor proprioception; to confirm that systemic inflammation is associated with muscle weakness; and to determine whether poor proprioception mediates the association between systemic inflammation and muscle weakness in knee osteoarthritis., Design: Cross-sectional study., Subjects: A total of 689 participants with knee osteoarthritis from the Amsterdam Osteoarthritis (AMS-OA) cohort., Methods: Systemic inflammation was assessed by erythrocyte sedimentation rate, knee proprioception by determining the joint motion detection threshold, and muscle strength with an isokinetic dynamometer. Linear regression models were used to estimate direct associations between systemic inflammation, proprioception and muscle strength, and the indirect association (mediation) between systemic inflammation and muscle strength via proprioception adjusted for potential confounders., Results: Higher erythrocyte sedimentation rates were associated with poor proprioception (p = 0.022). Poor proprioception (p < 0.001) and higher erythrocyte sedimentation rates (p < 0.001) were associated with muscle weakness. Poor proprio-ception mediated the association between systemic inflammation and muscle weakness (p = 0.035)., Conclusion: Results suggest that systemic inflammation is associated with poor proprioception in knee osteoarthritis. Poor proprioception may be a path-way through which systemic inflammation is associated with muscle weakness in patients with knee osteoarthritis.

Objectives: To systematically review and synthesize the effects of soft braces on pain and on self-reported and performance-based physical function in patients with knee osteoarthritis., Data Sources: The following electronic databases were searched from inception to April 20, 2016: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, SPORTDiscus, Web of Science, and PEDro., Study Selection: Randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs), such as controlled clinical trials, crossover studies, and case-control studies, were included. Two reviewers independently screened articles and determined inclusion through predefined criteria., Data Extraction: Data related to participant demographics, study design and methods, interventions, and outcomes, including numerical means and SDs, were extracted by 1 reviewer. Methodological quality assessment was independently performed by 2 reviewers., Data Synthesis: Eleven studies were identified, including 6 RCTs and 5 non-RCTs. The methodological quality of included RCTs was low. There was a moderate improvement in pain (standardized mean difference [SMD]=.52; 95% confidence interval [CI], .14-.89; P=.007; 284 participants) in favor of wearing a brace compared with not wearing a brace for the immediate, within-group comparison. There was a moderate improvement in pain (SMD=.61; 95% CI, .33-.89; P<.001; 206 participants) and a small to moderate improvement in self-reported physical function (SMD=.39; 95% CI, .11-.67; P=.006; 206 participants) in favor of patients receiving a soft brace versus standard care for the prolonged effect, between-group comparison., Conclusions: Currently available evidence indicates that soft braces have moderate effects on pain and small to moderate effects on self-reported physical function in knee osteoarthritis. These findings highlight the importance of soft braces as a technique to improve pain and physical function in both the short- and long-term. Additional high-quality studies are warranted to improve confidence in the findings., (Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Embedding Web-based interventions within physiotherapy has potential, but knowledge on patient adherence to these interventions is limited., Introduction: This study explores which patient-, intervention-, and environment-related factors are determinants of adherence to the online component of e-Exercise, a 12-week blended intervention for patients with hip and/or knee osteoarthritis., Methods: A convergent mixed methods study was performed, embedded within an ongoing trial. Quantitative data of 109 participants that received e-Exercise were used for negative binomial regression analysis. Adherence was defined as the number of online evaluated weeks. Next, semistructured interviews on factors related to adherence to the online component were analyzed., Results: Nineteen participants with missing outcome data because their program was not started were excluded. Of the 90 analyzed participants, 81.1% were evaluated for at least 8 weeks. Adherence was highest for participants with middle education, 1-5-year osteoarthritis duration, and participants who were physiotherapist recruited. The 10 analyzed interviews revealed that sufficient Internet skills, self-discipline, execution of the exercise plan, the intervention's usability, flexibility, persuasive design, added value, and acceptable required time, and research participation were linked to favorable adherence., Discussion: It is unknown if patients who adhered to the online component also adhered to their exercise plans. The relationship between adherence to the online component and clinical outcomes will be addressed in a future study., Conclusions: The majority of the participants adhered to the online component of e-Exercise, illustrating its applicability. The integration within the physiotherapy setting and intervention's persuasive design appear to have an important role in optimizing patient adherence.

Background: We aimed to (i) evaluate the immediate effect of a soft knee brace on pain, activity limitations, self-reported knee instability, and self-reported knee confidence, and (ii) to assess the difference in effect between a non-tight and a tight soft brace in patients with knee osteoarthritis (OA)., Methods: Forty-four patients with knee OA and self-reported knee instability participated in the single-session, laboratory, experimental study. A within-subject design was used, comparing a soft brace with no brace, and comparing a non-tight with a tight soft brace. The outcome measures were pain, self-reported knee instability and knee confidence during level and perturbed walking on the treadmill and activity limitations (10-m walk test and the get up and go (GUG) test). Linear mixed-effect model analysis for continuous outcomes and logistic generalized estimating equations for categorical outcomes were used to evaluate the effect of wearing a soft brace., Results: Wearing a soft brace significantly reduced pain during level walking (B - 0.60, P = 0.001) and perturbed walking (B - 0.80, P < 0.001), reduced the time to complete the 10-m walk (B - 0.23, P < 0.001) and the GUG tests (B - 0.23, P = 0.004), reduced self-reported knee instability during level walking (OR 0.41, P = 0.002) and perturbed walking (OR 0.36, P < 0.001), and reduced lack of confidence in the knees during level walking (OR 0.45, P < 0.001) and perturbed walking (OR 0.56, P < 0.001), compared with not wearing a soft brace. There was no difference in effects between a non-tight and tight brace, except for the 10-m walk test. Wearing a tight brace significantly reduced the time to complete the 10-m walk test in comparison with wearing a non-tight brace (B - 0.11, P = 0.03)., Conclusion: The results of this study indicate that a soft brace is an efficacious intervention targeting pain, activity limitations, self-reported knee instability, and knee confidence in the immediate term in patients with knee OA. Further studies are needed evaluating the mode of action based on exerted pressure, and on the generalization to functioning in daily life., Trial Registration: trialregister.nl, NTR6363 . Retrospectively registered on 15 May 2017.

Although analgesics are widely recommended in current guidelines, underuse and inadequate prescription of analgesics seem to result in suboptimal treatment effects in patients with knee and/or hip osteoarthritis (OA). This study aimed (i) to describe the use of analgesics; and (ii) to determine factors that are related to analgesic use in patients with knee and/or hip OA referred to an outpatient center. A cross-sectional study with data from 656 patients with knee and/or hip OA referred to an outpatient center (Amsterdam Osteoarthritis (AMS-OA) cohort) was conducted. Self-reported use of analgesic (yes/no) was administered and subdivided into acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs, including coxibs) and opioids. Logistic regression analyses were performed to analyze the association between analgesic use and disease-related, predisposing and enabling factors. Analgesic use was reported by 63% of the patients, with acetaminophen, NSAIDs and opioid use reported by 50, 30 and 12%, respectively. Factors related to analgesic use were higher pain severity, longer duration of symptoms, higher radiographic hip OA severity, overweight/obesity and psychological distress. These factors explained 21% of the variance of analgesic use. More than one-third of patients with established knee and/or hip OA referred to an outpatient center did not use any analgesics. Although multiple, mostly disease-related associated factors were found, analgesic use remained predominantly unexplained. Our study seems to indicate that prescription of analgesics should be guided more dominantly by clinical symptoms and needs, and preceded by a thorough shared decision-making process between patient and physician.

Background: To describe the prevalence of self-reported knee joint instability in patients with pre-surgery knee osteoarthritis (OA) and to explore the associations between self-reported knee joint instability and radiological features., Methods: A cross-sectional study including patients scheduled for primary Total Knee Arthroplasty (TKA). Self-reported knee instability was examined by questionnaire. Radiological features consisted of osteophyte formation and joint space narrowing (JSN), both scored on a 0 to three scale. Scores >1 are defined as substantial JSN or osteophyte formation. Regression analyses were provided to identify associations of radiological features with self-reported knee joint instability., Results: Two hundred and sixty-five patients (mean age 69years and 170 females) were included. Knee instability was reported by 192 patients (72%). Substantial osteophyte formation was present in 78 patients (41%) reporting and 33 patients (46%) not reporting knee joint instability. Substantial JSN was present in 137 (71%) and 53 patients (73%), respectively. Self-reported knee instability was not associated with JSN (relative to score 0, odds ratios (95% CI) of score 1, 2 and 3 were 0.87 (0.30-2.54), 0.98 (0.38-2.52), 0.68 (0.25-1.86), respectively) or osteophyte formation (relative to score 0, odds ratios (95% CI) of score 1, 2 and 3 were 0.77 (0.36-1.64), 0.69 (0.23-1.45), 0.89 (0.16-4.93), respectively). Stratified analysis for pain, age and BMI showed no associations between self-reported knee joint instability and radiological features., Conclusion: Self-reported knee joint instability is not associated with JSN or osteophyte formation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate whether relationships between upper leg muscle strength and activity limitations are non-linear in patients with knee osteoarthritis, and, if so, to determine muscle strength thresholds for limitations in daily activities., Design: Baseline data were used for 562 patients with knee osteoarthritis in the Amsterdam-Osteoarthritis cohort. Upper leg muscle strength (Nm/kg) was measured isokinetically. Activity limitations were measured with the timed Get Up and Go test and timed Stair Climb Test, subdivided into stair-ascent and stair-descent. Linear and non-linear relationships between muscle strength and activity limitations were evaluated, and thresholds were determined., Results: Non-linear models improved model fit compared with linear models. The improvement in percentage variance accounted for was 5.9, 8.2 and 5.2 percentage points for the timed Get Up and Go, stair-ascent and stair-descent times, respectively. Muscle strength thresholds were 0.93 Nm/kg (95% confidence interval (95% CI) 0.82-1.04), 0.89 Nm/kg (95% CI 0.77-1.02) and 0.97 Nm/kg (95% CI 0.85-1.11) for relationships with timed Get Up and Go, stair-ascent and stair-descent times, respectively., Conclusion: In patients with knee osteoarthritis, relationships between muscle strength and activity limitations are non-linear. Patients with muscle strength below the described thresholds might benefit more from muscle strength training to reduce limitations in daily activities than would patients with muscle strength above the thresholds. Further research is needed to assess the clinical value of the thresholds determined.

Objective: To evaluate the efficacy on physical functioning and safety of tailored exercise therapy in patients with knee osteoarthritis (OA) and comorbidities., Methods: In a randomized controlled trial, 126 participants were included with a clinical diagnosis of knee OA and at least 1 of the following target comorbidities: coronary disease, heart failure, type 2 diabetes mellitus, chronic obstructive pulmonary disease, or obesity (body mass index ≥30 kg/m 2 ), with severity score ≥2 on the Cumulative Illness Rating Scale. The intervention group received a 20-week, individualized, comorbidity-adapted exercise program consisting of aerobic and strength training and training of daily activities. The control group received their current medical care for knee OA and were placed on a waiting list for exercise therapy. Primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index, subscale physical functioning (WOMAC-pf), and the 6-minute walk test (6MWT). Measurements were performed at baseline, after 20 weeks (directly posttreatment), and at 3 months posttreatment., Results: Statistically significant physical functioning differences over time were found between the intervention and control group (WOMAC: B = -7.43 [95% confidence interval (95% CI) -9.99, -4.87], P < 0.001; and 6MWT: B = 34.16 [95% CI 17.68, 50.64], P < 0.001) in favor of the intervention group. At 3 months followup, the mean improvements in the intervention group were 33% on the WOMAC scale and 15% on the 6MWT. These improvements are of clinical relevance. No serious adverse events occurred during the intervention., Conclusion: This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and safe in patients with knee OA and severe comorbidities., (© 2016, American College of Rheumatology.)

Objective: We introduced a stepped-care strategy (SCS) for hip and knee osteoarthritis, focusing on delivery of high-quality stepped care. In this study, we aimed to identify factors associated with various steps of the SCS., Methods: We used data from a 2-year observational prospective cohort study, including 313 patients visiting their general practitioner (GP) with a new episode of hip/knee osteoarthritis. We used logistic multilevel analyses to identify factors at the level of the patient, the GP, and the general practice, related to treatment limited to primary care, referral to nonsurgical secondary care, or surgical procedures., Results: Patients whose treatment had been limited to primary care tended to function physically better (odds ratio [OR] 1.03). Furthermore, they less often received exercise therapy (OR 0.46), intraarticular injections (OR 0.08), and radiologic assessments (OR 0.06). Continuation of nonsurgical care after referral was more likely in employed patients (OR 2.90) and patients who had no exercise therapy (OR 0.19) or nonsteroidal antiinflammatory drugs (OR 0.35). Surgically treated patients more often received exercise therapy (OR 7.42). Referral and surgical treatment depended only to a limited extent on the GP or the general practice., Conclusion: After implementation of the SCS in primary care, the performance of exercise therapy, rather than disease severity or psychologic factors, seems to play a key role in the decision whether or not to refer for surgical or nonsurgical treatment in secondary care. To optimize patient-tailored treatment, future research should be adressed to determine the optimal moment of switching from primary to secondary care in patients with hip/knee osteoarthritis., (© 2016, American College of Rheumatology.)

Objective: To review the current literature regarding methods and effects of real-time biofeedback used as a method for gait retraining to reduce knee adduction moment (KAM), with intended application for patients with knee osteoarthritis (KOA)., Data Sources: Searches were conducted in MEDLINE, Embase, CINAHL, SPORTDiscus, Web of Science, and Cochrane Central Register of Controlled Trials with the keywords gait, feedback, and knee osteoarthritis from inception to May 2015., Study Selection: Titles and abstracts were screened by 1 individual for studies aiming to reduce KAM. Full-text articles were assessed by 2 individuals against predefined criteria., Data Extraction: Data were extracted by 1 individual according to a predefined list, including participant demographics and training methods and effects., Data Synthesis: Electronic searches resulted in 190 potentially eligible studies, from which 12 met all inclusion criteria. Within-group standardized mean differences (SMDs) for reduction of KAM in healthy controls ranged from .44 to 2.47 and from .29 to .37 in patients with KOA. In patients with KOA, improvements were reported in pain and function, with SMDs ranging from .55 to 1.16. Methods of implementation of biofeedback training varied between studies, but in healthy controls increased KAM reduction was noted with implicit, rather than explicit, instructions., Conclusions: This review suggests that biofeedback gait training is effective primarily for reducing KAM but also for reducing pain and improving function in patients with KOA. The review was limited by the small number of studies featuring patients with KOA and the lack of controlled studies. The results suggest there is value and a need in further researching biofeedback training for reducing KAM. Future studies should include larger cohorts of patients, long-term follow-up, and controlled trials., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

The aims of the study were to (i) determine the prevalence and course of self-reported knee instability at 2-year follow-up and (ii) identify factors predictive of retention of self-reported knee instability among patients with established knee osteoarthritis (OA). Among 201 patients from the Amsterdam Osteoarthritis (AMS-OA) cohort, demographic characteristics, self-reported knee instability, muscle strength, proprioception, pain, and physical function were assessed at baseline and at 2 years. Exercise over the past 2 years was assessed by evaluating the medical files. The course of self-reported knee instability was determined in patients reporting instability at baseline. Baseline predictors of self-reported knee instability were determined by uni- and multivariable logistic regression analyses. At baseline, 123 (61 %) patients reported knee instability, and of these, 85 (64 %) patients reported instability 2 years later, while 38 (29 %) reported no instability 2 years later. Poor proprioception and high pain assessed at baseline predicted retention of self-reported knee instability at 2 years among patients with self-reported instability at baseline. Knee instability is highly prevalent among patients with knee osteoarthritis. In patients with self-reported knee instability, the majority retained instability over 2 years. Poor proprioception and high pain predicted retention of self-reported knee instability over time.

Objective: To examine whether different groups of fatigue trajectories can be identified among patients with early symptomatic osteoarthritis (OA) of the knee or hip, to describe the level of fatigue severity within each of these fatigue groups, and to investigate the involvement of age, sex, use of medication, comorbidity, and OA severity in relation to group membership., Methods: Six years of followup data on fatigue (Medical Outcomes Study Short Form-36 Vitality scale) came from the Cohort Hip and Cohort Knee (CHECK) cohort. Growth mixture modeling was applied to identify distinct fatigue trajectories as well as to take into account the effects of the patient characteristics., Results: Three fatigue trajectories were identified: low fatigue, low-to-high fatigue, and high fatigue. Latter trajectories showed considerable overlap from years 2 to 6, but differed in some patient characteristics in comparison with each other and in comparison with the low fatigue group. Comorbidity, medication use, and sex were significantly associated with the identified trajectories. Women, individuals with a comorbid disease, and those who used medication were more likely to follow a high fatigue trajectory., Conclusion: These findings suggest heterogeneous development of fatigue in the early OA population associated with varying patient characteristics. Further, this study shows that a considerable number of patients with OA already experience elevated levels of fatigue at an early stage of OA. While these findings need to be replicated, the identification of these trajectories with differing patient characteristics may warrant tailored psychosocial interventions for patients with elevated levels of fatigue.

Objective: Vitamin D deficiency, which is common among elderly people, has been linked to muscle weakness. In patients with knee osteoarthritis (OA), the association between muscle strength and serum 25-hydroxy Vitamin D [25(OH)D] level has not been studied comprehensively. The aim of our study was to examine the association between serum 25(OH)D level and muscle strength in patients with knee OA., Methods: Data of the Amsterdam Osteoarthritis cohort from 319 participants with knee OA were used in a cross-sectional study. Serum 25(OH)D level (nmol/l) was measured by a competitive electrochemiluminescence method. Muscle strength (nm/kg) of the upper leg was measured isokinetically. Univariable and multivariable linear regression analyses were used to calculate the association between serum 25(OH)D level and muscle strength., Results: Serum 25(OH)D level was significantly associated with muscle strength (B = 0.036, 95% CI 0.017-0.054, p < 0.001), adjusted for season of blood collection. After adding body mass index (BMI) to the model, this association was no longer significant (B = 0.011, 95% CI -0.007 to 0.029, p = 0.214). Alcohol consumption, number of comorbidities, and sex were subsequently added and changed the model slightly. Without BMI, this model showed a significant association between serum 25(OH)D level and muscle strength (B = 0.029, 95% CI 0.014-0.043, p < 0.001)., Conclusion: The observed association between a low serum 25(OH)D level and muscle weakness in patients with knee OA is attenuated by BMI. Further studies are needed to explain the associations among Vitamin D level, muscle strength, and adiposity in patients with knee OA.

Introduction: Altered biomechanics, increased joint loading and tissue damage, might be related in a vicious cycle within the development of knee osteoarthritis (KOA). We have defined biomechanical factors as joint-related factors that interact with the forces, moments and kinematics in and around a synovial joint. Although a number of studies and systematic reviews have been performed to assess the association of various factors with the development of KOA, a comprehensive overview focusing on biomechanical factors that are associated with the development of KOA is not available. The aim of this review is (1) to identify biomechanical factors that are associated with (the development of) KOA and (2) to identify the impact of other relevant risk factors on this association., Methods and Analysis: Cohort, cross-sectional and case-control studies investigating the association of a biomechanical factor with (the development of) KOA will be included. MEDLINE, EMBASE, CINAHL and SPORTDiscus will be searched from their inception until August 2015. 2 reviewers will independently screen articles obtained by the search for eligibility, extract data and score risk of bias. Quality of evidence will be evaluated. Meta-analysis using random effects model will be applied in each of the biomechanical factors, if possible., Ethics and Dissemination: This systematic review and meta-analysis does not require ethical approval. The results of this systematic review and meta-analysis will be disseminated through publications in peer-reviewed journals and presentations at (inter)national conferences., Trial Registration Number: CRD42015025092., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: To compare the knee joint kinematics, kinetics and EMG activity patterns during a stepping-down task in patients with knee osteoarthritis (OA) with control subjects., Methods: 33 women with knee OA (early OA, n=14; established OA n=19) and 14 female control subjects performed a stepping-down task from a 20cm step. Knee joint kinematics, kinetics and EMG activity were recorded on the stepping-down leg during the loading phase., Results: During the stepping-down task patients with established knee OA showed greater normalized medial hamstrings activity (p=0.034) and greater vastus lateralis-medial hamstrings co-contraction (p=0.012) than controls. Greater vastus medialis-medial hamstrings co-contraction was found in patients with established OA compared to control subjects (p=0.040) and to patients with early OA (p=0.023). Self-reported knee instability was reported in 7% and 32% of the patients with early and established OA, respectively., Conclusions: The greater EMG co-activity found in established OA might suggest a less efficient use of knee muscles or an attempt to compensate for greater knee laxity usually present in patients with established OA. In the early stage of the disease, the biomechanical and neuromuscular control of stepping-down is not altered compared to healthy controls., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To systematically summarize the literature on the course of pain in patients with knee osteoarthritis (OA), prognostic factors that predict deterioration of pain, the course of physical functioning, and prognostic factors that predict deterioration of physical functioning in persons with knee OA., Methods: A search was conducted in PubMed, CINAHL, Embase, Psych-INFO, and SPORTDiscus up to January 2014. A meta-analysis and a qualitative data synthesis were performed., Results: Of the 58 studies included, 39 were of high quality. High heterogeneity across studies (I(2)  >90%) and within study populations (reflected by large SDs of change scores) was found. Therefore, the course of pain and physical functioning was interpreted to be indistinct. We found strong evidence for a number of prognostic factors predicting deterioration in pain (e.g., higher knee pain at baseline, bilateral knee symptoms, and depressive symptoms). We also found strong evidence for a number of prognostic factors predicting deterioration in physical functioning (e.g., worsening in radiographic OA, worsening of knee pain, lower knee extension muscle strength, lower walking speed, and higher comorbidity count)., Conclusion: Because of high heterogeneity across studies and within study populations, no conclusions can be drawn with regard to the course of pain and physical functioning. These findings support current research efforts to define subgroups or phenotypes within knee OA populations. Strong evidence was found for knee characteristics, clinical factors, and psychosocial factors as prognostics of deterioration of pain and physical functioning., (© 2016, American College of Rheumatology.)

Objective: Severe pain in patients with knee osteoarthritis (OA) hampers the ability to exercise. A protocol for the standardized optimization of analgesics in combination with exercise therapy was developed. The purpose of this protocol was to reduce pain, thereby allowing the patient to participate in exercise therapy. The objective of the present study was to evaluate the feasibility and outcome of the protocol., Methods: Forty-nine patients with knee OA and severe knee pain (numerical rating scale for pain ≥7) were included. Analgesics were prescribed following an incremental protocol. After 6 weeks, a 12-week exercise therapy program was added. Information about analgesic use and exercise therapy content was recorded. Knee pain and activity limitations were assessed at baseline, after 6 weeks, and after 18 weeks., Results: Statistically significant improvements in pain and activity limitations were found in intent-to-treat analysis after 6 weeks of analgesic use and after the intervention was completed. Mean improvements from baseline were 30% (P < 0.001) for pain and 17% (P < 0.001) for activity limitations after the intervention was completed. Seventy-eight percent of the patients were able to exercise according to the protocol. In these patients, exercise therapy following 6 weeks of analgesic use resulted in a further improvement of activity limitations of 10% (P = 0.004)., Conclusion: The combined intervention of standardized analgesic prescription and exercise therapy allows most patients with knee OA and severe pain to participate in exercise therapy, leading to reduction of pain and activity limitations. These promising results need to be confirmed in a randomized controlled trial., (© 2016, American College of Rheumatology.)

Objective: To investigate patterns of physical activity in older adults with knee osteoarthritis (OA) compared to older adults without knee OA across 6 European countries. We expect country-specific differences in the physical activity levels between persons with knee OA compared to persons without knee OA. A varying degree of physical activity levels across countries would express a facilitating or impeding influence of the social, environmental, and other contextual factors on a physically active lifestyle., Methods: Baseline cross-sectional data from the European Project on Osteoarthritis were analyzed. In total, 2,551 participants from 6 European countries (Germany, Italy, The Netherlands, Spain, Sweden, and the UK) were included., Results: Participants with knee OA were less likely to follow physical activity recommendations and had poorer overall physical activity profiles than those without knee OA (mean 62.9 versus 81.5 minutes/day, respectively; P = 0.015). The magnitude of this difference varied across countries. Detailed analysis showed that low physical activity levels in persons with knee OA could be attributed to less everyday walking time (odds ratio 1.31, 95% confidence interval 1.07-1.62)., Conclusion: This study highlighted the fact that having knee OA is associated with a varying degree of physical activity patterns in different countries. This national variation implies that low levels of physical activity among persons with knee OA cannot be explained exclusively by individual or disease-specific factors, but that social, environmental, and other contextual factors should also be taken into account., (© 2016, American College of Rheumatology.)

Objective: To examine the association between changes in knee muscle strength (extensor and flexor muscles separately, and mean values) and changes in activity limitations in patients with established knee osteoarthritis at 2 years., Methods: Data from 186 patients with knee osteoarthritis, part of the Amsterdam Osteoarthritis cohort, were gathered at baseline and at 2-year follow-up. Strength of the knee extensor and flexor muscles were assessed using an isokinetic dynamometer. Activity limitations were assessed using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) - Physical Function subscale, the Get Up and Go test (GUG), and the 12-steps stairs test. Univariate and multivariate linear regression analyses were used to assess the association between changes in muscle strength and changes in activity limitations, adjusting for relevant confounders and baseline activity limitations., Results: There was an overall 16% increase in mean knee muscle strength (p < 0.001), 19% increase in knee extensor muscle strength (p < 0.001), and 17% increase in knee flexor muscle strength (p < 0.001) at 2 years. Increased mean knee muscle strength and knee flexor muscle strength were associated with better self-reported physical function (WOMAC) (b = -5.7, p = 0.03 and b = -6.2, p = 0.05), decreased time on the GUG (b = -1.2, p = 0.003 and b = -1.4, p = 0.05) and decreased time on the stairs test (b = -4.4, p < 0.001 and b = -6.6, p < 0.001). Increased extensor muscle strength was associated only with decreased time on the stairs test (b = -2.7, p < 0.001)., Conclusion: Increased knee muscle strength, mainly in the knee flexors, was associated with decreased activity limitations in patients with knee osteoarthritis at 2 years. Thus, differences in muscle strength may partially explain the between-patients variability in activity limitations.

Objective: We aimed to evaluate the associations between knee muscle strength (MS) and falls, controlling for knee joint proprioception, varus-valgus knee joint laxity, and knee pain, among patients with knee osteoarthritis (OA) reporting knee instability., Methods: A sample of 301 subjects (203 women, 98 men, 35-82 yrs) with established knee OA and self-reported knee instability was studied. The occurrence of at least 1 fall in the previous 3 months was assessed by questionnaire. Maximum knee extension and flexion strength were measured isokinetically. Additionally, proprioception, varus-valgus laxity, and pain were assessed. Student t tests were used to assess differences between subgroups. The association of muscle strength and falls was calculated using univariate and multivariate logistic regression analysis., Results: Over 10% of the subjects (31 out of 301) reported a fall in the previous 3 months. High knee extension muscle strength (crude OR 0.3, 95% CI 0.1-0.8, p = 0.022) and high knee flexion muscle strength (crude OR 0.2, 95% CI 0.0-1.0, p = 0.048) were associated with a lower risk of falls. Proprioception and laxity did not confound this relationship. After adjusting for pain, extensor strength had an adjusted OR of 0.5 (95% CI 0.2-1.4, p = 0.212) for falls and flexor strength had an adjusted OR of 0.4 (95% CI 0.1-2.3, p = 0.312)., Conclusion: High knee extension and flexion muscle strength decreased the risk of falls in patients with knee OA and self-reported knee instability. After considering the effect of pain, there was insufficient statistical power to detect an association between muscle strength and falls, which might be because of the low number of subjects who fell (n = 31).

Background: A multidisciplinary, guideline-based Stepped-Care-Strategy (SCS), has recently been developed to improve the management of hip and knee osteoarthritis (OA). To date, it is unknown to what extent current Dutch OA care is consistent with the SCS, both with respect to the content of care as well as the sequence of care. Furthermore, there is a lack of clarity regarding the role of different health care providers in the performance of OA care according to the SCS. Therefore, the main purpose of this study is to describe the content of primary care in patients with hip/knee OA, including the compliance to the SCS and taking into account the introduction of patient self-referral to physical therapy., Methods: Data were used from NIVEL Primary Care Database. In total, 12.118 patients with hip/knee OA who visited their GP or physical therapist were selected. Descriptive statistics were used to compare the content of care in GP-referred and self-referred patients to physical therapy., Results: Content of care performed by GPs mostly concerned consultations, followed by NSAID prescriptions and referrals to secondary care. Both prescriptions of acetaminophen and referrals to physical therapy respectively dietary therapy were rarely mentioned. Nevertheless, still 65% of the patients in physical therapy practice were referred by their GP. Compared to GP-referred patients, self-referred patients more often presented recurrent complaints and were treated less often by activity-related exercise therapy. Education was rarely registered as singular intervention, neither in GP-referred nor in self-referred patients., Conclusion: In accordance with the SCS, less advanced interventions are more often applied than more advanced interventions. To optimize the adherence to the SCS, GPs could reconsider the frequent use of NSAIDs instead of analgesics and the low referral rate to allied health care. Self-referral to physical therapy partially distorts both the low referral rate in general practice and the low application rate of education as singular intervention in physical therapy practice. Further research is recommended to evaluate the effects of task-shifting in OA care, taking into account the content of the SCS.

Objective: It has been hypothesized that pain and low vitality lead to an increase in avoidance of activities in persons with early symptomatic knee osteoarthritis (OA), and that avoidance of activities leads to an increase in activity limitations. The present study aimed to evaluate these hypotheses., Methods: Baseline, 2-year, and 5-year followup data of 828 participants from the Cohort Hip and Cohort Knee Study with early symptomatic knee OA were used. Autoregressive generalized estimating equations and linear regression models were used to analyze the longitudinal and cross-sectional associations between self-reported knee pain, vitality, pain-related avoidance of activities, and activity limitations. The models were adjusted for the covariates age, sex, education level, body mass index, comorbidity, radiographic severity, and hip pain., Results: In longitudinal analyses, knee pain and vitality predicted a subsequent increase in avoidance of activities. Pain-related avoidance of activities predicted a subsequent increase in activity limitations; however, this relationship lost statistical significance (P = 0.089) after adjustment for covariates. Cross-sectional analyses showed strong relationships between knee pain, low vitality, pain-related avoidance of activities, and activity limitations at all time points., Conclusions: In persons with early symptomatic knee OA, knee pain and low vitality lead to a subsequent increase in avoidance of activities. Pain-related avoidance of activities is related to activity limitations at inception of symptoms, but also years later. Therefore, it can be recommended to monitor and target avoidance of activities at various stages of the disease., (Copyright © 2015 by the American College of Rheumatology.)

The avoidance model in patients with knee and hip osteoarthritis (OA) hypothesizes that pain and psychological distress lead to avoidance of activities, and thereby to muscle weakness and activity limitations. This paper systematically reviews the scientific evidence for the validity of this avoidance model. A qualitative data synthesis was used to identify levels of evidence. Sixty studies were included. In knee OA, strong evidence was found that avoidance of activities is associated with activity limitations via muscle weakness (mediation by muscle weakness), strong evidence was found for an association between muscle weakness and activity limitations, and weak evidence was found that pain and psychological distress are associated with muscle weakness via avoidance of activities (mediation by avoidance). In hip OA, weak evidence was found for mediation by muscle weakness; and strong evidence was found for an association between muscle weakness and activity limitations. More research is needed on the consecutive associations between pain or psychological distress, avoidance of activities and muscle weakness, and to confirm causal relationships.

Objective: To determine whether a decrease in muscle strength over 3 years is associated with an increase in activity limitations in persons with early symptomatic knee osteoarthritis (OA), and to examine whether the longitudinal association between muscle strength and activity limitations is moderated by knee joint proprioception and laxity., Design: A longitudinal cohort study with 3-year follow-up. Measurements were performed at the second (t0) and fifth (t1) year of the Cohort Hip and Cohort Knee (CHECK) study. Statistical analyses included paired t tests, chi-square tests, and regression analyses. In regression analyses, the association between muscle strength and activity limitations was adjusted for confounders., Setting: A rehabilitation and rheumatology center., Participants: Subjects (N=146) with early symptomatic knee OA from the CHECK study., Interventions: Not applicable., Main Outcome Measures: Muscle strength, proprioception, and laxity were assessed using specifically designed measurement devices. Self-reported and performance-based activity limitations were measured with the Western Ontario and McMaster Universities Osteoarthritis Index, the Get Up and Go test, the walk test, and the stair-climb test., Results: A total of 116 women (79.5%) and 30 men (20.5%), with a mean age ± SD of 58.4±4.9 years and a mean body mass index ± SD of 25.5±3.6, were included in the study. Overall, small 3-year changes in muscle strength and activity limitations were observed. At the group level, the average muscle strength increased by 10% (1.0±0.3 to 1.1±0.3Nm/kg) over the 3 years. The 3-year decrease in muscle strength was independently associated with an increase in performance-based activity limitations on all 3 measures (B=-1.12, B=-5.83, and B=-1.25, respectively). Proprioception and laxity did not moderate this association., Conclusions: In patients with early knee OA, decreased muscle strength is associated with an increase in activity limitations. Our results are a step toward understanding the role of muscle weakness in the development of activity limitations in knee OA. Further well-designed experimental studies are indicated to establish the causal role of muscle weakness in activity limitations., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Exercise therapy in patients with hip and/or knee osteoarthritis is effective in reducing pain, increasing physical activity and physical functioning, but costly and a burden for the health care budget. A web-based intervention is cheap in comparison to face-to-face exercise therapy and has the advantage of supporting in home exercises because of the 24/7 accessibility. However, the lack of face-to-face contact with a professional is a disadvantage of web-based interventions and is probably one of the reasons for low adherence rates. In order to combine the best of two worlds, we have developed the intervention e-Exercise. In this blended intervention face-to-face contacts with a physical therapist are partially replaced by a web-based exercise intervention. The aim of this study is to investigate the short- (3 months) and long-term (12 months) (cost)-effectiveness of e-Exercise compared to usual care physical therapy. Our hypothesis is that e-Exercise is more effective and cost-effective in increasing physical functioning and physical activity compared to usual care., Methods/design: This paper presents the protocol of a prospective, single-blinded, multicenter cluster randomized controlled trial. In total, 200 patients with OA of the hip and/or knee will be randomly allocated into either e-Exercise or usual care (physical therapy). E-Exercise is a 12-week intervention, consisting of maximum five face-to-face physical therapy contacts supplemented with a web-based program. The web-based program contains assignments to gradually increase patients' physical activity, strength and stability exercises and information about OA related topics. Primary outcomes are physical activity and physical functioning. Secondary outcomes are health related quality of life, self-perceived effect, pain, tiredness and self-efficacy. All measurements will be performed at baseline, 3 and 12 months after inclusion. Retrospective cost questionnaires will be sent at 3, 6, 9 and 12 months and used for the cost-effectiveness and cost-utility analysis., Discussion: This study is the first randomized controlled trial in the (cost)-effectiveness of a blended exercise intervention for patients with osteoarthritis of the hip and/or knee. The findings will help to improve the treatment of patients with osteoarthritis., Trial Registration: NTR4224.

Objective: To improve the management of hip or knee osteoarthritis (OA), a stepped care strategy (SCS) has been developed that presents the optimal sequence for care in three steps. This study evaluates the extent to which clinical practice is consistent with the strategy after implementation and identifies determinants of SCS-consistent care., Design: A 2-year observational prospective cohort study., Setting: General practices in the region of Nijmegen in the Netherlands., Participants: Three hundred and thirteen patients with hip or knee OA and their general practitioner (GP)., Interventions: Multifaceted interventions were developed to implement the strategy., Main Outcome Measures: Consistency between clinical practice and the strategy was examined regarding three aspects of care: (i) timing of radiological assessment, (ii) sequence of non-surgical treatment options and (iii) making follow-up appointments., Results: Out of the 212 patients who reported to have had an X-ray, 92 (44%) received it in line with the SCS. The sequence of treatment was inconsistent with the SCS in 58% of the patients, which was mainly caused by the underuse of lifestyle advice and dietary therapy. In 57% of the consultations, the patient reported to have been advised to make a follow-up appointment. No determinants that influenced all three aspects of care were identified., Conclusions: Consistency with the SCS was found in about half of the patients for each of the three aspects of care. Health care can be further optimized by encouraging GP s to use X-rays more appropriately and to make more use of lifestyle advice, dietary therapy and follow-up appointments., (© The Author 2014. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.)

Objectives: Knee osteoarthritis (OA) is a leading cause of activity limitations. The knee OA population is likely to consist of subgroups. The aim of the present study was to identify homogeneous subgroups with distinct trajectories of activity limitations in patients with early symptomatic knee OA and to describe characteristics of these subgroups., Methods: Follow-up data over a period of 5 years of 697 participants with early symptomatic knee OA from the Cohort Hip and Cohort Knee (CHECK) were used. Activity limitations were measured yearly with the Western Ontario and McMaster Universities Osteoarthritis Index. Latent class growth analyses identified homogeneous subgroups with distinct trajectories of activity limitations. Multivariable regression analyses examined differences in characteristics between the subgroups., Results: Three subgroups were identified. Participants in Subgroup 1 ('good outcome'; n=330) developed or displayed slight activity limitations over time. Participants in Subgroup 2 ('moderate outcome'; n=257) developed or displayed moderate activity limitations over time. Participants in subgroup 3 ('poor outcome'; n=110) developed or displayed severe activity limitations over time. Compared with the 'good outcome' subgroup, the 'moderate outcome' and 'poor outcome' subgroups were characterised by: younger age, higher body mass index, greater pain, bony tenderness, reduced knee flexion, hip pain, osteophytosis, ≥3 comorbidities, lower vitality or avoidance of activities., Conclusions: Based on the 5-year course of activity limitations, we identified homogeneous subgroups of knee OA patients with good, moderate or poor outcome. Characteristics of these subgroups were consistent with existing knowledge on prognostic factors regarding activity limitations, which supports the validity of this classification., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To test whether knee stabilization therapy, prior to strength/functional training, may have added value in reducing activity limitations only in patients with knee osteoarthritis who have knee instability and (i) low upper leg muscle strength, (ii) impaired knee proprioception, (iii) high knee laxity, or (iv) frequent episodes of knee instability., Design: Subgroup analyses in a randomized controlled trial comparing 2 exercise programmes (with/without knee stabilization therapy) (STABILITY; NTR1475)., Patients: Participants from the STABILITY-trial with clinical knee osteoarthritis and knee instability (n = 159)., Methods: Effect modification by upper leg muscle strength, knee proprioception, knee laxity, and patient-reported knee instability were determined using the interaction terms "treatment group subgroup factor", with the outcome measures WOMAC physical function (primary), numeric rating scale pain and the Get up and Go test (secondary)., Results: Effect modification by muscle strength was found for the primary outcome (p = 0.01), indicating that patients with greater muscle strength tend to benefit more from the experimental programme with additional knee stabilization training, while patients with lower muscle strength benefit more from the control programme., Conclusion: Knee stabilization therapy may have added value in patients with instability and strong muscles. Thus it may be beneficial if exercises target muscle strength prior to knee stabilization.

Introduction: The aim of this study was to examine the associations of elevated serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with change in muscle strength in patients with established knee osteoarthritis (OA), at 2 years., Methods: Data from 186 patients with knee OA were gathered at baseline and at 2-year follow-up. CRP (in milligrams per liter) and ESR (in millimeters per hour) were measured in serum from patients' blood. Strength of quadriceps and hamstrings muscles was assessed by using an isokinetic dynamometer. The association of inflammatory markers with change in knee muscle strength was analyzed by using uni- and multi-variate linear regression models., Results: Patients with elevated CRP values at both baseline and 2-year follow-up exhibited a lower increase in knee muscle strength for a period of 2 years (β = -0.22; P = 0.01) compared with the group with non-elevated levels at both times of assessment. The association persisted after adjustment for relevant confounders. Elevated ESR values at both times of assessment were not significantly associated with change in knee muscle strength (β = -0.05; P = 0.49)., Conclusions: Our results indicate that elevated CRP values are related to a lower gain in muscle strength over time in patients with established knee OA. Although the mechanism to explain this relationship is not fully elucidated, these results suggest inflammation as a relevant factor influencing muscle strength in this group of patients.

Objective: To enhance guideline-based nonsurgical management of osteoarthritis (OA), a multidisciplinary stepped-care strategy has been implemented in clinical practice. This study aimed to describe health care use after implementation of this strategy and to identify factors related to such use at multiple levels., Methods: For this 2-year observational prospective cohort, patients with symptomatic hip or knee OA were included by their general practitioner. Activities aligned with patients and health care providers were executed to implement the strategy. Health care use was described as the cumulative percentage of "users" for each modality recommended in the strategy. Determinants were identified at the level of the patient, general practitioner, and practice using backward stepwise logistic multilevel regression models., Results: Three hundred thirteen patients were included by 70 general practitioners of 38 practices. Their mean ± SD age was 64 ± 10 years and 120 (38%) were men. The most frequently used modalities were education, acetaminophen, lifestyle advice, and exercise therapy, which were used by 242 (82%), 250 (83%), 214 (73%), and 187 (63%) patients, respectively. Fourteen percent of the overweight patients reported being treated by a dietician. Being female, having an active coping style, using the booklet "Care for Osteoarthritis," and having limitations in functioning were recurrently identified as determinants of health care use., Conclusion: After implementation of the stepped-care strategy, most recommended nonsurgical modalities seem to be well used. Health care could be further improved by providing dietary therapy in overweight patients and making more efforts to encourage patients with a passive coping style to use nonsurgical modalities., (Copyright © 2014 by the American College of Rheumatology.)

Background: Exercise therapy is generally recommended for patients with osteoarthritis (OA) of the knee. Comorbidity, which is highly prevalent in OA, may interfere with exercise therapy. To date, there is no evidence-based protocol for the treatment of patients with knee OA and comorbidity. Special protocols adapted to the comorbidity may facilitate the application of exercise therapy in patients with knee OA and one or more comorbidities., Purpose: The purpose of this study was to develop comorbidity-adapted exercise protocols for patients with knee OA and comorbidity., Method: Several steps were undertaken to develop comorbidity-adapted protocols: selection of highly prevalent comorbidities in OA, a literature search to identify restrictions and contraindications for exercise therapy for the various comorbid diseases, consultation of experts on each comorbid disease, and field testing of the protocol in eleven patients with knee OA and comorbidity., Results: Based on literature and expert opinion, comorbidity-adapted protocols were developed for highly prevalent comorbidities in OA. Field testing showed that the protocols provided guidance in clinical decision making in both the diagnostic and the treatment phase. Because of overlap, the number of exercise protocols could be reduced to three: one for physiological adaptations (coronary disease, heart failure, hypertension, diabetes type 2, chronic obstructive pulmonary diseases, obesity), one for behavioral adaptations (chronic a-specific pain, nonspecific low back pain, depression), and one for environmental adaptations (visual or hearing impairments). Evaluation of patient outcome after treatment showed significant (P<0.05) and clinically relevant improvements in activity limitations and pain., Conclusion: Comorbidity-adapted exercise protocols for patients with knee OA were developed, providing guidance in clinical reasoning with regard to diagnostics and treatment. To evaluate the effectiveness of treatment in line with our protocols, a randomized clinical trial should be performed.