Beyond the joint:Measurement and treatment of sensitisation in patients undergoing total knee of hip arthroplasty

Osteoarthritis is one of the most common causes of pain. Why and how osteoarthritis leads to so much pain in some people is still not fully understood. In a number of people, the pain does not even go away after a hip or knee replacement. This kind pain is a complicated process involving many different factors, including increased pain sensitivity of the nerves and brain. This is called sensitization. The aim of this thesis was to investigate the measurement of signs of sensitization in people with hip or knee osteoarthritis. For this we have created a Dutch version of a reliable and representative questionnaire for signs of sensitization, specifically for patients with hip or knee osteoarthritis. In addition, we investigated whether targeted treatment of sensitization reduces the pain after a hip or knee replacement. The treatment consisted of duloxetine, a pain reliever that works on the brain's processing of pain. Osteoarthritis patients from the Medical Center Leeuwarden, the Martini Hospital and the UMCG participated. No effect of duloxetine treatment was found on the amount of pain remaining in patients after total hip or knee replacement. We did find that the questionnaire used to measure pain after hip or knee replacement was good at measuring change over time. We also found that after a hip or knee replacement, patients' perception of pain changes, as if their internal pain measure is being reset. This is important to consider in future studies examining pain after hip or knee replacement

Responsiveness and interpretability of the pain subscale of the Knee and Hip Osteoarthritis Outcome Scale (KOOS and HOOS) in osteoarthritis patients according to COSMIN guidelines

BACKGROUND: The pain subscales of the Knee and Hip Osteoarthritis Outcome Scores (KOOS and HOOS) are among the most frequently applied, patient reported outcomes to assess pain in osteoarthritis patients and evaluation of the results after Total Knee Arthroplasty (TKA) and Total Hip Arthroplasty (THA). For the evaluation of change over time it is essential to know the responsiveness and interpretability of these measurement instruments. Aim of this study is to investigate responsiveness and interpretability of the KOOS and HOOS pain subscales in patients with knee or hip OA and patients after TKA and THA as recommended by COSMIN guidelines. COSMIN stands for COnsensus based Standards for the selection of health Measurement Instruments. COSMIN recommends methods for assessing responsiveness similar to those assessing validity, using extensive hypothesis testing to assess criterion validity and construct validity of the change score.DESIGN: This clinimetric study was conducted using data obtained from the Duloxetine in OsteoArthritis (DOA) trial. Primary knee or hip osteoarthritis patients were included. During the study, half of the participants received pre-operative targeted treatment with duloxetine, and all participants received TKA or THA. Patients filled out a set of patient-reported outcomes at several time points.METHODS: Using the criterion validity approach the change scores of the KOOS and HOOS pain subscales directly after duloxetine treatment but before TKA and THA were correlated to the Patient Global Improvement anchor-question (PGI-I). Receiver Operating Characteristic curves (ROC curves) were obtained. Using the construct validity approach, hypothesis testing was conducted investigating the correlation between change scores in the KOOS and HOOS pain subscale with change scores in other questionnaires six months after TKA and THA. For interpretability, an anchor-based approach was used to consider the Minimally Important Change (MIC) of the KOOS and HOOS pain subscale. We compared the outcomes after duloxetine treatment and six months after TKA and THA in order to investigate any response shift.RESULTS: Ninety-three participants (53 knee patients and 41 hip patients) were included. Mean change was 4.3 and 4.6 points after conservative treatment for knee and hip OA patients respectively and 31.7 and 48.8 points after TKA and THA respectively. The KOOS and HOOS pain subscales both showed a gradual increase in change scores over the different categories of improvement on the PGI-I, with an Area Under the Curve of 0.72 (95% CI 0.527-0.921) and 0.79 (95% CI 0.588-0.983) respectively. Of the predefined hypotheses, 69% were confirmed for both subscales. The MICs were between 12.2 to 37.9 for the KOOS pain subscale, and between 11.8 to 48.6 for the HOOS pain subscale, depending on whether the PGI-I was administered after conservative treatment, or six months after TKA and THA.CONCLUSIONS: This study endorses the responsiveness of the KOOS and HOOS pain subscales in patients with knee or hip OA and patients after TKA and THA based on construct and criterion validity approaches. The KOOS pain subscale might be able to detect the MIC at an individual level after arthroplasty, but both the KOOS and HOOS pain subscales were not able to do so after conservative treatment. This study is the first to report a considerable response shift in MIC of the KOOS and HOOS pain subscales. This should be taken into consideration when evaluating MIC of the KOOS and HOOS pain subscale after conservative versus operative treatment. Future research should present more reference data regarding MIC scores after different treatments.</p

Validity of the Dutch modified painDETECT questionnaire for patients with hip or knee osteoarthritis

BACKGROUND: The modified painDETECT questionnaire (PDQ) is a self-reported questionnaire to discriminate between nociceptive and neuropathic-like pain in patients with knee/hip osteoarthritis (OA). This study aims to assess the structural and construct validity of this questionnaire. METHODS: Confirmatory factor analysis and hypothesis-testing was used. For 168 patients, predefined hypotheses were formulated on the correlation between the modified painDETECT and several other questionnaires, and in a subsample of 46 with pain pressure thresholds (PPTs). RESULTS: Two principal components were confirmed. The pain pattern item did not load on any component. Eighty per cent of the hypotheses on the correlation between modified PDQ and the questionnaires were met, as were 50% concerning PPTs measurements. CONCLUSIONS: This study is the first to assess structural and construct validity of the modified PDQ knee/hip by using factor analysis and hypothesis-testing. This questionnaire seems to reflect neuropathic-like pain symptoms experienced by hip/knee OA-patients with adequate validity. The item on pain pattern might not reflect the construct. More than 75% of the predefined hypotheses regarding the modified PDQ and the other questionnaires were met. Only 50% of the hypotheses on PPTs measurements were met, probably due to heterogeneity and limited size of this subsample. Implications for rehabilitation Pain in osteoarthritis (OA) is partly caused by modification of pain transmission in the peripheral and central nervous system, leading to sensitisation. This process seems particularly significant in a subgroup of OA patients. Sensitisation in OA is associated with more disability in daily life, lower quality of life and more widespread pain, as well as poorer outcome of total joint surgery. Screening for sensitisation can help to identify the subgroup of patients who could benefit from multidisciplinary treatment options focussing on desensitisation, cognitive- and behavioural therapy and reducing chronification of widespread pain. Therefore, being particularly important in the field of rehabilitation. The Dutch modified PainDETECT-questionnaire is very useful for rehabilitation professionals as it is one of the first questionnaires specifically validated to assess neuropathic-like symptoms (indicating sensitisation) in patients with knee or hip osteoarthritis

Neuropathic-like symptoms and the association with joint-specific function and quality of life in patients with hip and knee osteoarthritis

Objective There is an association between osteoarthritis-related pain severity and function, yet clear evidence about the sole influence of neuropathic-like symptoms on joint function and health-related quality of life (HRQoL) is lacking. Previous studies among knee OA patients show an association between neuropathic-like symptoms, lower functional status and lower quality of life, however analyses were unadjusted or had limited adjustment for influential covariates like pain intensity. The aim of this study was therefore to determine the influence of neuropathic-like symptoms-adjusted for multiple influential covariates-on joint-specific function and HRQoL in hip and knee OA patients. Methods In this observational study 255 patients (117 with hip OA and 138 with knee OA) completed the modified painDETECT questionnaire (mPDQ) to identify subjects with neuropathic-like symptoms (mPDQ score>12, possible neuropathic pain [NP] phenotype). The WOMAC and the RAND-36 were used to asses respectively function and HRQoL. Results were adjusted stepwise for age, sex and BMI (Model 1); back disorder, painful body regions, comorbidities and previous surgery (Model 2); and pain intensity and analgesic usage (Model 3). Results A possible NP phenotype was experienced by 37% of hip and 46% of knee OA patients. Final model 3 analysis revealed that hip OA patients with neuropathic-like symptoms scored significantly lower on pain-related aspects of HRQoL (GRAND-36 bodily pain: 6.8 points, p = 0.047) compared to patients with the unlikely NP phenotype. In knee OA patients, a possible NP phenotype was associated with diminished joint function (AWOMAC domains ranging 7.1 to 10.5 points, p Conclusion Neuropathic-like symptoms deteriorate the subjective rating of pain-related quality of life in hip OA patients and significantly influence function in knee OA patients

Effect of preoperative duloxetine treatment on postoperative chronic residual pain after total hip or knee arthroplasty:a randomised controlled trial

OBJECTIVES: A key predictor for developing chronic residual pain after total knee or hip arthroplasty (TKA/THA) is sensitisation. Sensitisation can be defined as an ‘increased responsiveness of nociceptive neurons in the nervous system’. Aim of this study is to investigate the effects of preoperative treatment with duloxetine in sensitised knee and hip osteoarthritis (OA) patients on postoperative chronic residual pain up to 1 year after arthroplasty. SETTING: A multicentre, pragmatic, prospective, randomised clinical trial was conducted in three secondary care hospitals in the Netherlands. PARTICIPANTS: Patients with primary knee/hip OA who were planned for TKA/THA were screened using the modified painDETECT Questionnaire. Patients whose painDETECT score indicated that sensitisation may be present were eligible for participation. 111 participants were included and randomly assigned 1:1 to an intervention or control group. The intervention group received additional duloxetine treatment, the control group did not receive any additional treatment but was allowed to continue with any pain medication they were already taking. INTERVENTIONS: Preoperative oral treatment for 7 weeks with 60 mg/day of duloxetine was compared with usual care. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was pain at 6 months after arthroplasty, assessed with the Pain Subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip disability and Osteoarthritis Outcome Score (HOOS) with a 0–100 scale. Secondary outcome measures were Visual Analogue Scale (VAS), and neuropathic-like pain measured using the modified PainDETECT Questionnaire. Longitudinal data collection included time points directly after duloxetine treatment, 1-day preoperatively, and 6 weeks, 6 months and 12 months postoperatively. RESULTS: Mean improvement in the KOOS/HOOS pain subscale at 6 months postoperatively was 37 (SD 28.1) in the intervention group and 43 (SD 26.5) in the control group. No statistically significant difference was found in change score 6 months postoperatively between the two groups (p=0.280). 12 patients from the intervention group (21%) discontinued duloxetine due to adverse effects. CONCLUSIONS: Preoperative targeted treatment with duloxetine in end-stage knee and hip OA patients with sensitisation does not influence postoperative chronic residual pain after TKA/THA. TRIAL REGISTRATION NUMBER: NTR4744

Clinical outcome, survival and polyethylene wear of an uncemented total hip arthroplasty:a 10- to 12-year follow-up study of 81 hips

A complete 10- to 12-year follow-up of an uncemented total hip arthroplasty (THA) was performed regarding survival, clinical outcome, polyethylene wear and influencing factors on wear. Seventy-two patients (75 Mallory Head uncemented THA) with primary osteoarthritis operated on in 1999 or 2000 were included in the survival study. Mean age at the time of operation was 57.9 years (range 37-70). The survival rate after 11.9 years was 96% (95% Cl 0.89-1.01). In three cases the acetabular component was revised because of extensive polyethylene wear. Fifty-four patients with 57 THAs were available for clinical and radiological analysis. At a mean follow-up time of 10.7 years (range 10-12) the clinical outcome can be considered comparable to other uncemented THA. Mean polyethylene wear was 1.8 mm (range 0.4-3.8) with an annual wear rate of 0.15 mm/y. There was a significant correlation between polyethylene wear and inclination of the cup as well as male gender. (C) 2013 Elsevier Inc. All rights reserved

Duloxetine in OsteoArthritis (DOA) study: effects of duloxetine on pain and function in end-stage hip and knee OA - a pragmatic enriched randomized controlled trial

BACKGROUND: Some osteoarthritis (OA) patients experience inadequate pain relief from analgesics like acetaminophen and nonsteroidal anti-inflammatory drugs. This could be the result of experienced non-nociceptive centralized pain. Placebo-controlled randomized trials (RCT) have proven the effectiveness of duloxetine for OA and several chronic pain conditions where central sensitization (CS) is one of the key underlying pain mechanisms. OBJECTIVES: Assess the efficacy of an 8-week duloxetine treatment compared to usual care in end-stage knee and hip OA patients with a level of centralized pain. DESIGN: Pragmatic, enriched, open-label RCT. METHODS: Patients were randomized to duloxetine or to care-as-usual. Primary outcome was pain in the index joint, measured with the pain domain of the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip disability and Osteoarthritis Outcome Score (HOOS). The intention-to-treat principle was used, with mixed-model repeated measures to analyze the effect. RESULTS: One hundred eleven patients were randomized. Nearly 44% felt much to very much better after duloxetine usage compared to 0% in the care-as-usual group (p < 0.001). The duloxetine group scored 11.3 points (95%CI: 5.8, 16.8) better on the pain domain of the KOOS/HOOS (p < 0.001). Knee patients improved significantly more than hip patients (18.7 [95%CI: 11.3, 26.1] versus 6.0 [95%CI: - 2.6, 14.5] points better). CONCLUSIONS: Adding duloxetine treatment seems to be beneficial for end-stage knee OA patients with neuropathic-like symptoms (at risk of CS). End stage Hip OA patients seem to be nonresponsive to duloxetine. TRIAL REGISTRATION: Dutch Trial Registry with number NTR 4744 (15/08/2014) and in the EudraCT database with number 2013-004313-41

Study recruitment diagram (flowchart).

<p>Study recruitment diagram (flowchart).</p

Neuropathic-like symptoms and the association with joint-specific function and quality of life in patients with hip and knee osteoarthritis

<div><p>Objective</p><p>There is an association between osteoarthritis-related pain severity and function, yet clear evidence about the sole influence of neuropathic-like symptoms on joint function and health-related quality of life (HRQoL) is lacking. Previous studies among knee OA patients show an association between neuropathic-like symptoms, lower functional status and lower quality of life, however analyses were unadjusted or had limited adjustment for influential covariates like pain intensity. The aim of this study was therefore to determine the influence of neuropathic-like symptoms—adjusted for multiple influential covariates—on joint-specific function and HRQoL in hip and knee OA patients.</p><p>Methods</p><p>In this observational study 255 patients (117 with hip OA and 138 with knee OA) completed the modified painDETECT questionnaire (mPDQ) to identify subjects with neuropathic-like symptoms (mPDQ score>12, possible neuropathic pain [NP] phenotype). The WOMAC and the RAND-36 were used to asses respectively function and HRQoL. Results were adjusted stepwise for age, sex and BMI (Model 1); back disorder, painful body regions, comorbidities and previous surgery (Model 2); and pain intensity and analgesic usage (Model 3).</p><p>Results</p><p>A possible NP phenotype was experienced by 37% of hip and 46% of knee OA patients. Final model 3 analysis revealed that hip OA patients with neuropathic-like symptoms scored significantly lower on pain-related aspects of HRQoL (ΔRAND-36 bodily pain: 6.8 points, p = 0.047) compared to patients with the unlikely NP phenotype. In knee OA patients, a possible NP phenotype was associated with diminished joint function (ΔWOMAC domains ranging 7.1 to 10.5 points, p<0.05) and more deficits on the physical functional aspect of HRQoL (ΔRAND-36 physical functioning: 6.8 points, p = 0.016).</p><p>Conclusion</p><p>Neuropathic-like symptoms deteriorate the subjective rating of pain-related quality of life in hip OA patients and significantly influence function in knee OA patients.</p></div