Improvement In WOMAC Pain Research Articles

Identifying subgroups of patients that may benefit from robotic arm-assisted total knee arthroplasty: Secondary analysis of data from a randomised controlled trial

BackgroundThe aims were to assess whether a specific subgroup(s) of patients had a clinically significant benefit in their knee specific outcome or health-related quality of life (HRQoL) when undergoing robotic total knee arthroplasty (rTKA) when compared to manually performed TKA (mTKA). MethodsOne hundred patients were randomised to either rTKA or mTKA, 50 to each group, of which 46 and 41 were available for functional review at 6-months, respectively. Subgroup analysis was undertaken for sex, age (<67-years versus ≥ 67-years), preoperative WOMAC score (<40 versus ≥ 40) and EQ-5D utility (<0.604 versus ≥ 0.604). ResultsMale patients undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (mean difference (MD) 16.3, p = 0.011) at 2-months, function (MD 12.6, p = 0.032) and total score (MD 12.7, p = 0.030), and OKS (MD 6.0, p = 0.030) at 6-months. Patients < 67-years old undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 10.3, p = 0.039) at 2-months, and function (MD 12.9, p = 0.040) and total (MD 13.1, p = 0.038) scores at 6-months. Patients with a preoperative WOMAC total score of < 40 points undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 14.6, p = 0.044) at 6-months. Patients with a preoperative EQ-5D utility of <0.604 undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 15.5, p = 0.011) at 2-months. ConclusionPatients of male sex, younger age, worse preoperative knee specific function and HRQoL had a clinically significantly better early functional outcome with rTKA when compared to mTKA.

Ultrasound guided injection with Collagen-based Medical Device: real-life evaluation of efficacy and safety in hip osteoarthritis.

Data regarding the treatment of hip osteoarthritis (OA) with collagen-based extracellular bio-scaffolds are lacking. We evaluated the treatment of hip OA with ultrasound guided intraarticular injections of Collagen-based Medical Device(CMD). Forty-four patients with Kellgren-Lawrence grade (KLG) I or II were selected, and 20/44randomly selected patients (CMD group), were treated with 2 weekly consecutive ultrasound guided intraarticular injections ofCMD (MD-HIP, Guna S.p.a. Milan, Italy). An additional 24/44 patients were treated with oral non-steroidal anti-inflammatorydrugs (NSAIDs) daily (NSAIDs group). Clinical assessment, X-rays and ultrasound evaluation were performed at baseline,and after 1 month in both groups, and after 3 months in the CMD group. Outcome measures were general pain VAS (0-10), thewhole WOMAC score, and the WOMAC specific subscores. CMD and NSAIDs group were homogenous for age,gender, VAS pain and WOMAC scores. The CMD group had significant improvement of the VAS pain (p<0.0001), globalWOMAC score (p<0.0001) and WOMAC function (p<0.0001) from baseline to the 1st month, with further improvementfrom the 1st to the 3rd month (p<0,001; p<0.01; p<0.03, respectively). Significant improvement in WOMAC pain (p<0.0001)and WOMAC stiffness (p<0.0001) was detected at 1st month, with no significant change at 3rd month. In the NSAIDs groupsignificant improvement in WOMAC function was detected after 1 month (p=0.021) only. No adverse events were recorded inthe CMD and NSAIDs group. The ultrasound guided intraarticular hip injections of CMD resulted in significantimprovement in VAS pain and WOMAC scores compared to treatment with oral NSAIDs.

JOINT REPAIR EVALUATED ON RADIOGRAPHS IS ASSOCIATED WITH PAIN AND SYNOVIAL FLUID MARKER CHANGES AFTER KNEE JOINT DISTRACTION TREATMENT

Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. The objective was to analyse structural changes after KJD in patients using this AI-based measurement method, and relate these changes to clinical outcome and SF markers.20 knee OA patients (&lt;65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ~one year after treatment. Radiographs were analysed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria), and 10 pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analysed and linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers.After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64;p=0.020). A greater increase in MCP1 (β=0.67;p=0.033) and lower increase in TGFβ1 (β=-0.787;p=0.007) were associated with JSW improvement.Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome.

Observed efficacy and clinically important improvements in participants with osteoarthritis treated with subcutaneous tanezumab: results from a 56-week randomized NSAID-controlled study

BackgroundA recent phase 3 study demonstrated that treatment with tanezumab, a nerve growth factor inhibitor, or nonsteroidal anti-inflammatory drugs (NSAIDs) improves pain and physical function in participants with moderate-to-severe osteoarthritis (OA) of the hip or knee. Here, we evaluated the time course and clinical importance of these initial efficacy findings using a mixture of primary, secondary, and post hoc endpoints.MethodsParticipants on stable NSAID therapy and with a history of inadequate response to other standard OA analgesics were enrolled in an 80-week (56-week treatment/24-week safety follow-up), randomized, NSAID-controlled, phase 3 study primarily designed to assess the safety of tanezumab for moderate-to-severe OA of the knee or hip. Participants received oral NSAID (twice daily naproxen, celecoxib, or diclofenac) or subcutaneous tanezumab (2.5mg or 5mg every 8 weeks). Non-responders were discontinued at week 16. Changes from baseline in WOMAC Pain and Physical Function, Patient’s Global Assessment of Osteoarthritis (PGA-OA), and average pain in the index joint were compared between tanezumab and NSAID groups over the 56-week treatment period. Clinically meaningful response (e.g., ≥30% and ≥50% improvement in WOMAC Pain and Physical Function), rescue medication use, and safety were also assessed.ResultsAll groups improved WOMAC Pain, WOMAC Physical Function, PGA-OA, and average pain in the index joint over the 56-week treatment period relative to baseline. Across all groups, improvements generally occurred from the time of first assessment (week 1 or 2) to week 16 and then slightly decreased from week 16 to 24 before stabilizing from weeks 24 to 56. The magnitude of improvement and the proportion of participants achieving ≥30% and ≥50% improvement in these measures was greater (unadjusted p≤0.05) with tanezumab than with NSAID at some timepoints on or before week 16. Adverse events of abnormal peripheral sensation, prespecified joint safety events, and total joint replacement surgery occurred more frequently with tanezumab than with NSAID.ConclusionsTanezumab and NSAID both provided early and sustained (up to 56 weeks) efficacy relative to baseline. Improvements in pain and function were clinically meaningful in a substantial proportion of participants. Adverse events of abnormal peripheral sensation and joint safety events occurred more frequently with tanezumab than with NSAID.Trial registrationClinicalTrials.govNCT02528188. Registered on 19 July 2015.

JOINT REPAIR EVALUATED AUTOMATICALLY ON RADIOGRAPHS IS ASSOCIATED WITH PAIN AND SYNOVIAL FLUID MARKER CHANGES AFTER KNEE JOINT DISTRACTION TREATMENT

Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. To 1) analyze structural changes after KJD in patients using this AI-based measurement method, and relate these changes to 2) clinical outcome and 3) SF markers. 20 knee OA patients (<65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6-7 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ∼one year after treatment. Radiographs were analyzed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria) to obtain whole-joint KL grade, medial and lateral joint space narrowing (JSN) scores, compartmental continuous minimum and standardized JSW, and osteophytes and sclerosis scores of the medial and lateral tibia and femur. 10 Pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analyzed using Wilcoxon Signed Rank tests for categorical and paired t-test for continuous variables. Linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers. After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. Radiographic changes were not statistically significant (p>0.1), except for the medial JSW (p<0.05). A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64; p=0.020). A greater increase in MCP1 (β=0.67; p=0.033) and lower increase in TGFβ1 (β=-0.787; p=0.007) were associated with JSW improvement. Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome. Versus Arthritis project grant (20783), Centre for OA Pathogenesis Versus Arthritis (grants 20205 and 21621), the Kennedy Trust for Rheumatology Research, and ReumaNederland (ISP14-3-301/16-1-404). CS, EB, MD: ImageBiopsyLab GmbH. NA CORRESPONDENCE ADDRESS: m.p.jansen-36@umcutrecht.nl

Single and Composite Endpoints of Within-Patient Improvement in Symptoms: Pooled Tanezumab Data in Patients with Osteoarthritis.

IntroductionCombining measures of key core domains (especially pain and function) into a composite endpoint that requires each patient to meet a threshold of improvement for each domain provides information on multiple aspects of osteoarthritis within individual patients. This pooled analysis of two phase 3 studies (NCT02697773, NCT02709486) explored single and composite endpoints for assessing within-patient improvement in knee or hip osteoarthritis symptoms following subcutaneous administration of tanezumab or placebo.MethodsEndpoints at week 16 included proportions of responders (≥ 30% improvement) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function, WOMAC Pain/Function composite, and weekly average pain; and patient acceptable symptom state (PASS) composite responders, minimal clinically important improvement (MCII) composite responders, Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders, and sustained weekly average pain responders.ResultsPooled population comprised 1545 patients. Of patients who had a ≥ 30% improvement in WOMAC Pain and/or WOMAC Physical Function, 88.5% were WOMAC Pain/Function composite responders, 7.0% were WOMAC Pain (but not Function) responders, and 4.4% were WOMAC Function (but not Pain) responders. Of weekly average pain responders, 43.1% were PASS composite responders. Odds ratios (tanezumab 2.5 mg and 5 mg groups, respectively, vs placebo) were 1.75 and 1.86 (WOMAC Pain/Function composite responders), 1.41 and 1.65 (weekly average pain responders), 1.60 and 1.73 (PASS composite responders), 1.52 and 1.68 (MCII composite responders), 1.75 and 1.88 (OMERACT-OARSI responders), and 1.85 and 1.48 (sustained weekly average pain responders). Subgroup analyses suggested a greater magnitude of effect for patients with a knee index joint compared with hip on some endpoints.ConclusionResponders on single pain endpoints were in many cases also responders on function or composite endpoints. Separation of tanezumab from placebo was similar and consistent across single and composite endpoints.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00372-2.

Physical Therapy Use, Costs, and Value for Latent Classes of Good vs Poor Outcome in Patients Who Catastrophize About Their Pain Prior to Knee Arthroplasty

ObjectiveTo examine use, costs, and value of physical therapy (PT) among subgroups. DesignWe conducted an observational study of data from a randomized trial of a pain coping skills intervention. Good and poor outcome subgroups were determined based on Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain and Physical Function scores. The use and costs of PT care as well as changes in WOMAC Pain and Physical Function scores over 4 time periods during a 1-year follow-up were reported. We compared the number of PT visits, total PT costs, and cost per 1-unit improvement in WOMAC scores for the 2 latent subgroups. SettingFive academic medical centers. ParticipantsPatients who catastrophized about their pain prior to knee arthroplasty (N=384). InterventionsPain coping skills training, arthritis education, and usual care. Main Outcome MeasuresThe WOMAC Pain Scale was the primary outcome. ResultsThe value of PT was lower and the cost of PT was higher for poor vs good outcome subgroups beginning 2 months after knee arthroplasty. For example, during the 2- to 6-month period, participants in the poor outcome subgroup incurred a PT cost of $5181.22 per 1-unit improvement in WOMAC Pain compared with $437.87 per 1-unit improvement in WOMAC Pain for the good outcome subgroup (P<.001). From the 6- to 12-month period, WOMAC scores worsened for the poor outcome subgroup, indicating no benefit from PT. ConclusionsPatients in 2 latent classes demonstrated clinically important differences in value of PT. Future research should identify rehabilitation-based interventions that reduce utilization and enhance effectiveness for patients at high risk for poor outcome.

Bioavailable turmeric extract for knee osteoarthritis: a randomized, non-inferiority trial versus paracetamol

BackgroundTo compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA).MethodsIn this randomized, non-inferiority, controlled clinical study, patients of knee OA were randomized to receive bioavailable turmeric extract (BCM-95®) 500 mg capsule two times daily or paracetamol 650 mg tablet three times daily for 6 weeks. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The secondary outcome measures were WOMAC total, WOMAC stiffness, and WOMAC physical function scores. Responder analysis of individual patients at different levels (≥ 20%, ≥ 50%, and ≥ 70%) for WOMAC score was calculated. TNF alpha and CRP levels were evaluated and adverse events (AE) were also recorded.ResultsSeventy-one and seventy-three knee OA patients, respectively in bioavailable turmeric extract and paracetamol groups, completed the study. Non-inferiority (equivalence) test showed that WOMAC scores were equivalent in both the groups (p value < 0.05) in all the domains within the equivalence limit defined by effect size (Cohen’s d) of 0.5 whereas CRP and TNF-α were better reduced with turmeric extract than paracetamol. After 6 weeks of treatment, WOMAC total score, pain, stiffness, and function scores got a significant improvement of 23.59, 32.09, 28.5, and 20.25% respectively with turmeric extract. In the turmeric extract group, 18% of patients got more than 50% improvement and 3% of patients got more than 70% improvement in WOMAC pain and function/stiffness score and none of the patients in the paracetamol group met the criteria. CRP and TNF-α got significantly reduced (37.21 and 74.81% respectively) in the turmeric extract group. Adverse events reported were mild and comparatively less in the turmeric extract group (5.48%) than in the paracetamol group (12.68%).ConclusionThe results of the study suggest that bioavailable turmeric extract is as effective as paracetamol in reducing pain and other symptoms of knee osteoarthritis and found to be safe and more effective in reducing CRP and TNF-α.Trial registrationClinical Trials Registry – India CTRI/2017/02/007962. Registered on 27 February 2017

What Are the Early Outcomes of True Reverse Periacetabular Osteotomy for Symptomatic Hip Overcoverage?

What Are the Early Outcomes of True Reverse Periacetabular Osteotomy for Symptomatic Hip Overcoverage?

Autologous Protein Solution Injections for the Treatment of Knee Osteoarthritis: 3-Year Results

Background: Blood derivative injections have been recently proposed to address osteoarthritis (OA) with overall positive results, although long-term data on their efficacy are lacking. A novel blood derivative has been developed to concentrate growth factors and antagonists of inflammatory cytokines and shown promising early findings. Purpose: To investigate if the positive effects of a single intra-articular injection of autologous protein solution (APS) in patients affected by knee OA—previously documented at 1 year in a multicenter double-blind randomized saline-controlled trial—last up to 3 years. Study Design: Case series; Level of evidence, 4. Methods: A total of 46 patients with Kellgren-Lawrence 2 or 3 knee OA were randomized into 2 groups: 1 ultrasound-guided APS injection (n = 31) or 1 saline injection (n = 15). At 1 year, the saline group was allowed to cross over. Patients were re-evaluated at 24 and 36 months through the visual analog scale for pain (VAS), Western Ontario and McMaster Universities Osteoarthritis Index Likert 3.1 (WOMAC LK 3.1), Knee injury and Osteoarthritis Outcome Score (KOOS), 36-Item Short Form Health Survey (SF-36), and Outcome Measures in Rheumatology–Osteoarthritis Research Society International (OMERACT-OARSI) responder rate. Magnetic resonance imaging evaluation was performed with the MRI Osteoarthritis Knee Score (MOAKS) before and at 24 months after treatment, and radiographs were assessed per Kellgren-Lawrence before and annually after treatment. Results: In the APS cohort, WOMAC pain improved from 11.5 ± 2.4 (mean ± SD) to 4.3 ± 4.0 at 1 year and to 5.7 ± 5.0 at 3 years (P < .0001 vs baseline). The APS cohort also showed a statistically significant improvement in its KOOS pain score from 39.4 ± 13.1 to 70.6 ± 21.5 at 1 year and to 64.1 ± 24.6 at 3 years (P < .0001 vs baseline) and VAS pain scores from 5.5 ± 2.2 to 2.6 ± 2.5 at 1 year and to 3.4 ± 2.9 at 3 years (P = .0184 vs baseline). VAS pain score significantly worsened from 12 to 36 months (P = .0411). All patients in the saline group decided to cross over to APS, and their final scores were better than baseline, although not significantly better than at the crossover point. Overall, 7 of 26 (26.9%) APS cases and 4 of 14 (28.6%) crossover cases were considered failures as patients underwent further injective treatments or surgical procedures between the 12- and 36-month follow-up. MOAKS findings showed no statistically significant differences. Patients with better cartilage had greater WOMAC pain improvement when their baseline scores were worse, whereas the trend was reversed for patients with cartilage loss at baseline. Conclusion: Intra-articular use of APS for mild to moderate knee OA was safe, and significant pain improvement was documented 3 years after a single injection. Patients with better cartilage status seem to respond better than patients with more cartilage loss, with more clinical improvement even when starting from more painful conditions. Registration: NCT02138890 (ClinicalTrials.gov identifier).

Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period

ObjectiveTanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up.MethodsThis double-blind, randomised, phase III...

Onset and maintenance of efficacy of subcutaneous tanezumab in patients with moderate to severe osteoarthritis of the knee or hip: A 16-week dose-titration study

ObjectiveTo examine the onset and maintenance of efficacy of subcutaneous tanezumab for pain relief and functional improvement in difficult-to-treat patients with moderate-to-severe osteoarthritis (OA) in a 16-week dose-titration study (NCT02697773). MethodsPatients were randomized to placebo (placebo group) or tanezumab 2.5 mg at baseline and week 8 (tanezumab 2.5 mg group), or tanezumab 2.5 mg at baseline and tanezumab 5 mg at week 8 (tanezumab 2.5/5 mg group). Analyses included change from baseline in average daily index joint pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and treatment responses (WOMAC Pain improvement criteria and Outcome Measures in Rheumatology-Osteoarthritis Research Society International [OMERACT-OARSI] criteria). ResultsThe 696 patients received placebo (n = 232), tanezumab 2.5 mg (n = 231), or tanezumab 2.5/5 mg (n = 233). Average daily index joint pain was statistically significantly improved within the first week (day 3–5) with tanezumab 2.5 mg compared with placebo. On first post-randomization WOMAC measurement (week 2), both tanezumab groups had statistically significant improvements compared with placebo in WOMAC Pain and Physical Function, and more tanezumab-treated patients achieved treatment response criteria (≥30%, ≥50%, or ≥70% reduction in WOMAC Pain or OMERACT-OARSI response). Efficacy was generally maintained throughout the 16-week treatment period. ConclusionSubcutaneous tanezumab provided statistically significant improvements compared with placebo in average daily index joint pain within the first week and WOMAC Pain and Physical Function (week 2) that were generally maintained throughout the 16-week treatment period. Tanezumab 5 mg provided only modest additional efficacy over tanezumab 2.5 mg.

Asynchronous Bilateral Total Knee Arthroplasty: Predictors of the Functional Outcome and Patient Satisfaction for the Second Knee Replacement

BackgroundThe primary aim of this study is to identify independent preoperative predictors of outcome and patient satisfaction for the second total knee arthroplasty (TKA). MethodsA retrospective cohort of 454 patients undergoing an asynchronous (6 weeks or more apart) bilateral primary TKA were identified from an arthroplasty database. Patient demographics, comorbidities, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form-12 scores were collected preoperatively and 1 year postoperatively. Overall patient satisfaction was assessed at 1 year. ResultsThe 1 year WOMAC pain score (P = .01), and improvement in WOMAC pain (P < .001) and functional (P = .002) scores were significantly lower for the second TKA. Worse preoperative WOMAC pain, function, and stiffness scores were demonstrated to be independent predictors of improvement in the WOMAC pain, function, and stiffness scores, respectively, for both the first and second TKA. The overall rate of satisfaction with the first TKA was 94.0% and 94.7% for the second TKA (P = .67). The rate of satisfaction for the second TKA was 77.8% for patients that were dissatisfied with their first TKA, which was an independent predictor of dissatisfaction (P = .02). ConclusionImprovement in pain and function is less with the second TKA, but the satisfaction rate remains similar. There are common independent predictors for change in the WOMAC score for the first and second TKA; however, the predictors of satisfaction were different with no common factors. Patients that were dissatisfied with their first TKA were more likely to be dissatisfied with their second TKA. Level of Evidence IIPrognostic retrospective cohort study.

Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip.

PurposeA pooled analysis was conducted to evaluate tanezumab efficacy and safety in patients with osteoarthritis (OA), including subgroup analyses of at-risk patients with diabetes, severe OA symptoms, and those aged ≥65 years.Patients and methodsData from phase III placebo-controlled clinical trials of patients with moderate-to-severe OA of the knee or hip were pooled to evaluate tanezumab efficacy (four trials) and safety (nine trials). Patients received intravenous tanezumab, tanezumab plus an oral NSAID (naproxen, celecoxib, or diclofenac), active comparator (naproxen, celecoxib, diclofenac, or oxycodone), or placebo. Efficacy assessments included change from baseline to week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores, Patient’s Global Assessment (PGA) of OA, and percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement in WOMAC pain. Safety assessments included adverse event (AE) documentation and physical and neurologic examinations.ResultsTanezumab significantly improved all efficacy end points in the overall population. Efficacy in at-risk patient subgroups was similar to the overall population. Incidence of AEs was highest in the tanezumab plus NSAID group and lowest in the placebo group. Incidence of AEs in the tanezumab monotherapy and active comparator groups was similar. Overall incidence of AEs was similar across subgroups. AEs of abnormal peripheral sensation were more frequently reported in tanezumab-treated patients compared with placebo or active comparator. Patients receiving active comparator had a slightly higher incidence of AEs suggestive of postganglionic sympathetic dysfunction.ConclusionTanezumab consistently provided significant improvement of pain, physical function, and PGA in individuals with OA, including patients with diabetes, severe OA symptoms, or aged ≥65 years. No increased safety risk was observed in at-risk patient subgroups.Trial registrationNCT00733902, NCT00744471, NCT00830063, NCT00863304, NCT00809354, NCT00864097, NCT00863772, NCT01089725, NCT00985621.

A 15 to 17-year follow-up of the Kinemax total knee replacement

BackgroundThere is a paucity of long-term data concerning the pre- and postoperative patient reported function of total knee replacement. The aim of this study was to determine the mortality, implant survivorship, patient reported function and satisfaction in a cohort of 114 patients, from a single centre, who received a Kinemax total knee replacement more than 15 years ago. MethodsPatients completed a questionnaire incorporating validated disease- and joint-specific scores, patient satisfaction and overall health preoperatively, at three months, one year, two years and a minimum of 15 years following surgery. NHS National Strategic Tracing Service, hospital and primary care records were used to establish mortality and for implant survivorship in deceased patients. ResultsForty five patients were alive at final follow-up. The survivorship of the cohort with revision of the TKR as the endpoint was 84%. Four cases were revised for wear, three for loosening and one for peri-prosthetic fracture. There was a significant improvement in WOMAC Pain, Function and Stiffness Scores, Oxford Knee Score and Self-Administered Patient Satisfaction Scale between pre-operative and all post-operative time points, although patient satisfaction had decreased significantly by the time of final follow-up. ConclusionIn this cohort, the Kinemax TKR showed survivorship of 84% at 16.3 years with functional scores demonstrating a high level of patient satisfaction at all follow-up time points. Level of evidence2 — Prospective Cohort Study

Achieving important improvement in womac pain and function by three months post-surgery influences satisfaction 1 year following total knee replacement

Purpose: Our prior work showed that achieving important improvement (II) in function by one year post total knee replacement (TKR) was directly associated with satisfaction with outcome. However, understanding the impact of the time of achievement of II has the potential to further our understanding of outcomes and inform care pathways. The objective of this work was to determine if the timing to achieve II in WOMAC pain and function and higher demand function as measured by the Late Life Disability (LLDI) was associated with satisfaction. Methods: We followed 354 patients from pre- to 1-year post-TKR. Pre-surgery, participants completed demographic and health questionnaires, the WOMAC pain and function and LLDI limitation subscales and identified outcome expectations for pain, other symptoms, mobility/activities of daily living (ADL), and participation in social roles/instrumental activities of daily living (IADL). The WOMAC and LLDI questionnaires also were completed at 3, 6, and 12 months post surgery. Satisfaction was completed at 12 months. All were scored 0-100 with higher scores indicating better outcome. Using II values for WOMAC pain, function and high demand activities generated from a separate cohort, we derived an ordinal variable of achieved II by 3, 6 or 12 months post-surgery or not achieved for each outcome. Based on sensitivity analysis, we categorized those who had baseline scores precluding achievement of II who reached the measure ceiling as achieving the II. We used a Bayesian path model with non-informative priors to evaluate if time to II achievement was associated with outcome satisfaction, adjusting for age, sex, education, obesity, depression (Hospital Anxiety and Depression Scale), comorbidity count and self-rated health. Expectations were modeled as individual predictors. As the Bayesian model (model 1) provided only a single estimator for our ordinal II variables, we also fit a generalized linear model to understand which time(s) of II achievement was associated with satisfaction (model 2). Results: Sample mean age was 65 years; 65% were female; and, 66% had >high school education. The mean comorbidity count was 1.6 (sd = 1.3) and depression was 5.3 (sd = 3.5). 40% rated their overall health as very good/excellent. The mean pre-surgery pain, function and high demand activities scores were 47.8 (sd = 17.8), 50.3 (sd = 18.5) and 59.2 (sd = 11.0) respectively. Mean satisfaction was 80.7 (sd = 21.9). Those who achieved II in pain, function and high demand activities by 3 months had satisfaction scores 87.8−89.3 compared to lower scores for all others; range 64.7−69.8 for those who did not achieve II. Fifty-seven, 47, 57 and 15% expected improvement in pain, other symptoms, mobility/ADL and social roles/IADL respectively. In model 1 (Fig. 1), earlier II achievement in pain (estimate −0.191) and function (estimate −0.389) was directly associated with higher satisfaction and higher expectation for mobility/ADL improvements (−0.106) was directly associated with lower satisfaction. Earlier achievement of II in function was associated with higher demand II achievement (0.628) but II in higher demand activities was not associated with satisfaction. All other significant effects were indirect. Model 2 showed that achievement of II in each of pain, function and high demand activities by 3 months was significantly associated with higher satisfaction as compared to achievement by 6 or 12 months (2–5 fold impact) or not achieving II (12–17 fold impact). Conclusions: People who achieve important improvement in pain, and function by 3 months post TKR are more satisfied with their outcome. Efforts to minimize recovery time should be tested to determine if more people recover more quickly and are satisfied with their outcomes.

Efficacy and safety of twice daily sustained-release paracetamol formulation for osteoarthritis pain of the knee or hip: a randomized, double-blind, placebo-controlled, twelve-week study

Objective: Evaluate efficacy and safety of an investigational, twice daily sustained-release (SR) paracetamol formulation in subjects with knee or hip osteoarthritis (OA).Methods: In this multicenter, double-blind, parallel study (NCT02311881), subjects with hip or knee OA were randomly assigned to SR paracetamol 2 × 1000 mg BID, extended-release (ER) paracetamol 2 × 665 mg TID or placebo for 12 weeks. Primary endpoint was mean change from baseline through 12 weeks in WOMAC Osteoarthritis Index pain. Secondary efficacy endpoints included other WOMAC categories, Global Patient Assessment of Osteoarthritis (GPAOA), Patient Global Assessment of Response to Therapy (PGART) and responder rate.Results: A total of 676 subjects were included in the analysis population (mITT). Mean change from baseline in WOMAC pain subscale was not significantly greater with SR paracetamol BID versus placebo (LS mean [SE]: −28.25 [1.697] vs. −25.74 [1.713]; p = .163). Reduction in WOMAC physical function and stiffness subscales with SR paracetamol BID was not significantly greater than with placebo (p = .089 and .054, respectively). Significant improvement over placebo was observed for GPAOA (p = .043), PGART (p = .012), and proportion of high-improvement responders (p = .015). Safety and tolerability were consistent with the known profile of paracetamol.Conclusions: Improvement in WOMAC pain, physical function and stiffness subscales from treatment with SR paracetamol BID versus placebo in subjects with knee or hip OA was not significant. SR paracetamol BID demonstrated significant improvements in GPAOA, PGART, and high-responder rate. High placebo response may have contributed to lack of statistical separation on some outcomes. All interventions were generally well tolerated.

An Autologous Anti-Inflammatory Protein Solution Yielded a Favorable Safety Profile and Significant Pain Relief in an Open-Label Pilot Study of Patients with Osteoarthritis.

Osteoarthritis (OA) is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS) Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient's own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs) were experienced by seven subjects (63.6%). There was one serious AE (diverticulitis) unrelated to the device or procedure. One subject experienced AEs that were judged “likely” to be procedure related (arthralgia/musculoskeletal discomfort) and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores improved significantly over time (ANOVA, p < 0.0001, 12.0 ± 1.2 preinjection, 3.3 ± 2.9 one year postinjection, and 72.5% WOMAC pain improvement). There was significant positive correlation between white blood cell concentration in APS and improvement in WOMAC pain scores.

A randomized trial of a motivational interviewing intervention to increase lifestyle physical activity and improve self-reported function in adults with arthritis.

Arthritis is a leading cause of chronic pain and functional limitations. Exercise is beneficial for improving strength and function and decreasing pain. We evaluated the effect of a motivational interviewing-based lifestyle physical activity intervention on self-reported physical function in adults with knee osteoarthritis (KOA) or rheumatoid arthritis (RA). Participants were randomized to intervention or control. Control participants received a brief physician recommendation to increase physical activity to meet national guidelines. Intervention participants received the same brief baseline physician recommendation in addition to motivational interviewing sessions at baseline, 3, 6, and 12 months. These sessions focused on facilitating individualized lifestyle physical activity goal setting. The primary outcome was change in self-reported physical function. Secondary outcomes were self-reported pain and accelerometer-measured physical activity. Self-reported KOA outcomes were evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for KOA (WOMAC scores range from 0 to 68 for function and 0 to 20 for pain) and the Health Assessment Questionnaire (HAQ) for RA. Outcomes were measured at baseline, 3, 6, 12, and 24 months. Multiple regression accounting for repeated measures was used to evaluate the overall intervention effect on outcomes controlling for baseline values. Participants included 155 adults with KOA (76 intervention and 79 control) and 185 adults with RA (93 intervention and 92 control). Among KOA participants, WOMAC physical function improvement was greater in the intervention group compared to the control group [difference = 2.21 (95% CI: 0.01, 4.41)]. WOMAC pain improvement was greater in the intervention group compared to the control group [difference = 0.70 (95% CI: -0.004, 1.41)]. There were no significant changes in physical activity. Among RA participants, no significant intervention effects were found. Participants with KOA receiving the lifestyle intervention experienced modest improvement in self-reported function and a trend toward improved pain compared to controls. There was no intervention effect for RA participants. Further refinement of this intervention is needed for more robust improvement in function, pain, and physical activity.

Achieving Important Improvement in Womac Pain and Function Impacts Satisfaction 1 Year Following Total Knee Replacement

Achieving Important Improvement in Womac Pain and Function Impacts Satisfaction 1 Year Following Total Knee Replacement