Søren Thorgaard Skou

A Randomized, Controlled Trial of Total Knee Replacement

BACKGROUND More than 670,000 total knee replacements are performed annually in the United States; however, high-quality evidence to support the effectiveness of the procedure, as compared with nonsurgical interventions, is lacking. METHODS In this randomized, controlled trial, we enrolled 100 patients with moderate-to-severe knee osteoarthritis who were eligible for unilateral total knee replacement. Patients were randomly assigned to undergo total knee replacement followed by 12 weeks of nonsurgical treatment (total-knee-replacement group) or to receive only the 12 weeks of nonsurgical treatment (nonsurgical-treatment group), which was delivered by physiotherapists and dietitians and consisted of exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the change from baseline to 12 months in the mean score on four Knee Injury and Osteoarthritis Outcome Score subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4); scores range from 0 (worst) to 100 (best). RESULTS A total of 95 patients completed the 12-month follow-up assessment. In the nonsurgical-treatment group, 13 patients (26%) underwent total knee replacement before the 12-month follow-up; in the total-knee-replacement group, 1 patient (2%) received only nonsurgical treatment. In the intention-to-treat analysis, the total-knee-replacement group had greater improvement in the KOOS4 score than did the nonsurgical-treatment group (32.5 vs. 16.0; adjusted mean difference, 15.8 [95% confidence interval, 10.0 to 21.5]). The total-knee-replacement group had a higher number of serious adverse events than did the nonsurgical-treatment group (24 vs. 6, P=0.005). CONCLUSIONS In patients with knee osteoarthritis who were eligible for unilateral total knee replacement, treatment with total knee replacement followed by nonsurgical treatment resulted in greater pain relief and functional improvement after 12 months than did nonsurgical treatment alone. However, total knee replacement was associated with a higher number of serious adverse events than was nonsurgical treatment, and most patients who were assigned to receive nonsurgical treatment alone did not undergo total knee replacement before the 12-month follow-up. (Funded by the Obel Family Foundation and others; MEDIC ClinicalTrials.gov number, NCT01410409.).

Widespread sensitization in patients with chronic pain after revision total knee arthroplasty.

Summary Widespread sensitization is predominant in patients with pain after revision total knee arthroplasty. This is important when considering revision arthroplasty in the treatment of knee osteoarthritis. ABSTRACT Pain and sensitization are major issues in patients with osteoarthritis both before and after total knee arthroplasty (TKA) and revision TKA (re‐TKA). The aim of this study was to assess sensitization in patients with and without chronic pain after re‐TKAs. Twenty patients with chronic knee pain and 20 patients without pain after re‐TKA participated. Spreading of pain was evaluated as the number of pain sites using a region‐divided body chart. The pressure pain threshold (PPT) and pressure pain tolerance (PTT) were assessed by cuff algometry at the lower leg. Temporal summation of pain was assessed by recordings of the pain intensity on a visual analog scale (VAS) during repeated cuff pressure stimulations. Conditioning pain modulation (CPM) was recorded by experimental tonic arm pain by cuff pressure stimulation and assessment of PPTs on the knee, leg, and forearm using handheld pressure algometry. Participants with pain after re‐TKA compared to participants without pain demonstrated: (1) significantly more pain sites (P = .004), (2) decreased cuff PPTs and PTTs at the lower leg (P < .001), (3) facilitated temporal summation (P < .001), and (4) impaired CPM (P < .001). Additionally, significant correlations between knee pain intensity and cuff PPTs, temporal summation, and CPM and between total duration of knee pain and temporal summation were found (P < .05). This study demonstrated widespread sensitization in patients with pain after re‐TKA and highlighted the importance of ongoing nociceptive input for the chronification process. This has important implications for future revisions, and precautions should be taken if patients have widespread sensitization.

OARSI Clinical Trials Recommendations: Design, conduct, and reporting of clinical trials for knee osteoarthritis

The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After the members voted we calculated the median score among the nine members of the working group who completed the score. The document includes 25 recommendations regarding randomization, blocking and stratification, blinding, enhancing accuracy of patient-reported outcomes (PRO), selecting a study population and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials that target symptom or structure modification among individuals with knee OA. These updated recommendations incorporate novel technologies (e.g., magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of knee OA.

Facilitation of pain sensitization in knee osteoarthritis and persistent post-operative pain: A cross-sectional study

Around 20% of patients with osteoarthritis (OA) have chronic post‐operative pain after total knee arthroplasty (TKA) and often undergo revision surgery with unfavourable pain outcome. This study compared sensitization in pain patients with knee OA and after revision TKA (re‐TKA).

Altered Central Sensitization and Pain Modulation in the CNS in Chronic Joint Pain

Musculoskeletal pain disorders are the second largest contributor to global disability underlining the significance of effective treatments. However, treating chronic musculoskeletal pain, and chronic joint pain (osteoarthritis (OA)) in particular, is challenging as the underlying peripheral and central pain mechanisms are not fully understood, and safe and efficient analgesic drugs are not available. The pain associated with joint pain is highly individual, and features from radiological imaging have not demonstrated robust associations with the pain manifestations. In recent years, a variety of human quantitative pain assessment tools (quantitative sensory testing (QST)) have been developed providing new opportunities for profiling patients and reaching a greater understanding of the mechanisms involved in chronic joint pain. As joint pain is a complex interaction between many different pain mechanisms, available tools are important for patent profiling and providing the basic knowledge for development of new drugs and for developing pain management regimes.

Relating clinical measures of pain with experimentally assessed pain mechanisms in patients with knee osteoarthritis

ABSTRACT Background Peripheral and central sensitisation is prominent in knee osteoarthritis (KOA) and could be important for the reduced efficacy in some cases after as well surgery as pharmacological interventions. Although sensitisation is important in KOA it is not known to what degree it contributes to the overall clinical pain problem. The aim was therefore to investigate how much a combination of quantitative pain measures assessing various pain mechanisms (local and spreading hyperalgesia, temporal and spatial summation, descending inhibition) could predict peak pain intensity in patients with KOA. Methods While resting in a comfortable recumbent position the pressure pain thresholds (PPT) in the peripatellar region (eight locations) and at the tibialis anterior muscle (TA) were assessed by handheld pressure algometry, computer-controlled pressure algometry and cuff-algometry in the affected leg of 17 KOA patients without pain or sensory dysfunctions in other regions than the knee. Cuff-algometry was used to detect spatial pain summation of the lower leg. Temporal pain summation was assessed by repeated pressure stimulation on the TA muscle. The conditioning pain modulation (CPM) was evaluated by conditioning tonic arm pain and by PPT from the peripatellar region. The participants rated their peak pain intensity in the previous 24 h using on a 10 cm visual analogue scale. Results A multiple-regression model based on TA pressure pain sensitivity (spreading sensitisation) and temporal pain summation on the lower leg accounted for 55% of the variance in peak pain intensity experienced by the patients (P=0.001). Significant correlations (P< 0.05) were found between PPTs assessed by handheld pressure algometry in the peripatellar region and at TA (R = 0.94), PPTs assessed by computer-controlled pressure algometry and handheld pressure algometry in the peripatellar region (R = 0.71), PPTs assessed by computer-controlled pressure algometry in the peripatellar region and handheld pressure algometry at TA (R = 0.71) and temporal summation at the knee and at TA (R = 0.73). Conclusion Based on the multiple regression model 55% variance of the perceived maximal pain intensity in painful KOA could be explained by the quantitative experimental pain measures reflecting central pain mechanisms (spreading sensitisation, temporal summation). The lack of other correlations between the methods used in assessing pain mechanisms in this study highlights the importance of applying different tests and different pain modalities when assessing the sensitised pain system as different methods add complementary information. Implications Clinical pain intensity can be explained by influences of different central pain mechanisms in KOA. This has implications for pain management in KOA where treatment addressing central pain components may be more important than previously acknowledged.

The efficacy of 12 weeks non-surgical treatment for patients not eligible for total knee replacement: a randomized controlled trial with 1-year follow-up

OBJECTIVE To compare the efficacy of a 12-week non-surgical treatment program with usual care in patients with knee osteoarthritis (OA) not eligible for total knee replacement (TKR). METHOD This two-arm parallel group assessor-blinded randomized controlled trial (RCT) included 100 adults from secondary care with knee OA, confirmed by radiography (Kellgren-Lawrence grade ≥1), but not eligible for a TKR. The 12-week non-surgical treatment program consisted of individualized progressed neuromuscular exercise, patient education, insoles, dietary advice and prescription of pain medication if indicated, while usual care comprised two leaflets with information and advice on knee OA and recommended treatments. The primary outcome was the change from baseline to 12 months in the Knee injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the KOOS subscales of pain, symptoms, activities of daily living (ADL), and quality of life (QOL). RESULTS 91% of the patients completed the 12 months follow-up on the primary outcome. Compared with usual care, patients undergoing the treatment program improved more in KOOS4 (adjusted mean difference (95% CI) of 9.6 (4.4-14.8)) with no serious treatment-related adverse events (AE). The number needed to treat (NNT), defined as the number of patients needed to treat for one person to improve 15% was 7.2. Secondary outcomes supported the primary findings. CONCLUSION In patients with mostly moderate to severe knee OA not eligible for TKR, a 12-week individualized, non-surgical treatment program is more efficacious at 12 months compared with usual care and has few treatment-related AE. TRIAL REGISTRATION ClinicalTrials.gov (NCT01535001).

Osteoarthritis: Models for appropriate care across the disease continuum

Osteoarthritis (OA) is a leading cause of pain and disability worldwide. Despite the existence of evidence-based treatments and guidelines, substantial gaps remain in the quality of OA management. There is underutilization of behavioral and rehabilitative strategies to prevent and treat OA as well as a lack of processes to tailor treatment selection according to patient characteristics and preferences. There are emerging efforts in multiple countries to implement models of OA care, particularly focused on improving nonsurgical management. Although these programs vary in content and setting, key lessons learned include the importance of support from all stakeholders, consistent program delivery and tools, a coherent team to run the program, and a defined plan for outcome assessment. Efforts are still needed to develop, deliver, and evaluate models of care across the spectrum of OA, from prevention through end-stage disease, in order to improve care for this highly prevalent global condition.

Association of knee confidence with pain, knee instability, muscle strength, and dynamic varus-valgus joint motion in knee osteoarthritis

To investigate associations between self‐reported knee confidence and pain, self‐reported knee instability, muscle strength, and dynamic varus–valgus joint motion during walking.

Influence of biomechanical characteristics on pain and function outcomes from exercise in medial knee osteoarthritis and varus malalignment: Exploratory analyses from a randomized controlled trial

To investigate whether selected biomechanical characteristics influence changes in pain and physical function with exercise in people with medial knee osteoarthritis (OA) and varus malalignment.