Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. DESIGN: Systematic review and network meta-analysis of randomised trials. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656

Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study

<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) is over-expressed in 70–75% of colorectal adenocarcinomas (CRC). The anti-EGFR monoclonal antibody cetuximab has been approved for the treatment of metastatic CRC, however tumor response to cetuximab has not been found to be associated with EGFR over-expression by immunohistochemistry (IHC). The aim of this study was to explore EGFR and the downstream effector phosphatase and tensin homologue deleted on chromosome 10 (PTEN) as potential predictors of response to cetuximab.</p> <p>Methods</p> <p>CRC patients treated with cetuximab by the Hellenic Cooperative Oncology group, whose formalin-fixed paraffin-embedded tumor tissue was available, were included. Tissue was tested for EGFR and PTEN by IHC and fluorescence in situ hybridization (FISH).</p> <p>Results</p> <p>Eighty-eight patients were identified and 72 were included based on the availability of tissue blocks with adequate material for analysis on them. All patients, except one, received cetuximab in combination with chemotherapy. Median follow-up was 53 months from diagnosis and 17 months from cetuximab initiation. At the time of the analysis 53% of the patients had died. Best response was complete response in one and partial response in 23 patients. In 16 patients disease stabilized. Lack of PTEN gene amplification was associated with more responses to cetuximab and longer time to progression (p = 0.042).</p> <p>Conclusion</p> <p>PTEN could be one of the molecular determinants of cetuximab response. Due to the heterogeneity of the population and the retrospective nature of the study, our results are hypothesis generating and should be approached with caution. Further prospective studies are needed to validate this finding.</p

Joint protection programmes for people with osteoarthritis and rheumatoid arthritis of the hand: An overview of systematic reviews

© 2021, University of Toronto Press. All rights reserved. Purpose: Joint protection has been introduced as a self-management strategy for people with rheumatoid arthritis (RA) and osteoarthritis (OA) of the hand. The purpose of this study was to conduct an overview of systematic reviews (SRs) and critically appraise the evidence to establish the current effectiveness of joint protection for people with hand RA and OA. Method: A comprehensive search was conducted of six databases from January 2008 to May 2018. SRs that evaluated the effectiveness of joint protection for people with hand arthritis were eligible for inclusion. The A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 checklist was used to assess the methodological quality of each SR. Results: Nine SRs were included: two were rated as high quality, and seven were rated as low quality. Seven of the nine did not take into account risk of bias when interpreting or discussing their findings, six did not assess publication bias, and five did not register their protocol. The high-quality reviews found no clinically important benefit of joint protection for pain, hand function, and grip strength levels. The low-quality reviews reported improvements in function, pain, grip strength, fatigue, depression, self-efficacy, joint protection behaviours, and disease symptoms in people with RA. Conclusions: High-quality evidence from high-quality reviews found a lack of any clinically important benefit of joint protection programmes for pain, hand function, and grip strength outcomes, whereas low-quality evidence from low-quality reviews found improvements in these outcomes

Evaluation of the content validity index of the Australian/Canadian osteoarthritis hand index, the patient-rated wrist/hand evaluation and the thumb disability exam in people with hand arthritis

Background: The Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Patient-Rated Wrist/Hand Evaluation (PRWHE) and the Thumb Disability Exam (TDX) are patient-reported outcome measures (PROM) designed to assess pain and hand function in patients with hand arthritis, hand pain and disability, or thumb pathology respectively. This study evaluated the content validity of AUSCAN, PRWHE and TDX in people with hand arthritis. Methods: This study enrolled participants with hand arthritis to rate the items of all 3 PROM in terms of relevance and clarity. The Content Validity Index (CVI) was computed for each item in each scale (I-CVI) as well as for the overall scale (S-CVI). Kappa was used to determine the inter-rater agreement among the raters. Results: Overall, 64 individuals with hand arthritis (27% with OA, 67% with rheumatoid arthritis and 6% with psoriatic arthritis) participated in the study. The I-CVI for all items and all scales were very high (I-CVI &gt; 0.76) and the modified Kappa agreement among the raters demonstrated excellent agreement (k &gt; 0.76). The S-CVI for all PROMs was very high for relevance (AUSCAN = 0.92, 95% CI 0.90 to 0.94; PRWHE = 0.85, 95% CI 0.82 to 0.88 and TDX = 0.87, 95% CI 0.85 to 0.89) and for clarity (AUSCAN = 0.99, 95% CI 0.98 to 1.00; PRWHE = 0.95, 95% CI 0.93 to 0.97 and TDX = 0.91, 95% CI 0.89 to 0.94), respectively. Conclusions: This study demonstrated very high content validity indices for the AUSCAN, PRWHE and TDX; with strong consensus across raters. This augments prior studies demonstrating appropriate statistical measurement properties, to provide confidence that all three measures assess important patient concepts of pain and disability. © 2020 The Author(s)

Patient-reported outcome measures used for neck disorders: An overview of systematic reviews

Copyright © 2018 Journal of Orthopaedic & Sports Physical Therapy®. BACKGROUND: The evaluation of patient-reported outcome measures for the neck from multiple systematic reviews will provide a broader view of, and may identify potential conflicting or consistent results for, their psychometric properties. OBJECTIVES: The purpose of this study was to conduct an overview of systematic reviews and synthesize evidence to establish the current state of knowledge on psychometric properties of patient-reported outcome measures for patients with neck disorders. METHODS: In this overview of systematic reviews, an electronic search of 6 databases (MED-LINE, Embase, CINAHL, ILC, the Cochrane Central Register of Controlled Trials, and LILACS) was conducted to identify reviews that addressed at least one measurement property of outcome measures for people with neck pain. Only systematic reviews with patient-reported outcome measures were included in the analysis. Risk of bias was assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR). Data on measurement properties were extracted from each systematic review. RESULTS: From 13 systematic reviews, 8 patient-reported outcome measures were evaluated in 2 or more reviews. Risk-of-bias scores ranged from moderate (5-7) to high (4 and lower). Findings on internal consistency, test-retest reliability, construct validity, responsiveness to change, and content and structural validity were synthesized for the Neck Disability Index (NDI) in 11 systematic reviews; the Northwick Park Neck Pain Questionnaire and Neck Pain and Disability scale (NPDS) in 6 systematic reviews; the Copenhagen Neck Functional Disability Scale in 5 systematic reviews; the Neck Bournemouth Questionnaire in 4 systematic reviews; the Core Neck Pain Questionnaire and Patient-Specific Functional Scale in 3 systematic reviews, and the Whiplash Disability Questionnaire in 2 systematic reviews. CONCLUSION: High-quality evidence was found of good to excellent internal consistency and moderate to excellent test-retest reliability for the NDI. Moderate-quality evidence was found of good to excellent internal consistency and good test-retest reliability for the Northwick Park Neck Pain Questionnaire. High-quality evidence was found of excellent test-retest reliability and good to strong construct validity with pain scales for the Copenhagen Neck Functional Disability Scale. Moderate-quality evidence was found of unclear to excellent internal consistency and moderate to strong concurrent associations with the NDI and global assessment of change for the Neck Pain and Disability scale. Moderate-quality evidence was found of excellent internal consistency for the Whiplash Disability Questionnaire and of high test-retest reliability for the Patient-Specific Functional Scale

Barriers, facilitators, preferences and expectations of joint protection programmes for patients with hand arthritis: A cross-sectional survey

Objectives The objective of this survey was to investigate the barriers, facilitators, expectations and patient preferences regarding joint protection (JP) programmes in people with hand arthritis. Design Cross-sectional survey. Setting Tertiary clinic. Participants Patients with hand arthritis: Osteoarthritis, rheumatoid arthritis, psoriatic arthritis and other forms of arthritis. Primary and secondary outcome measures This study used a survey among people with hand arthritis. Descriptive statistics and percentages were reported for all the data about the barriers, facilitators and preferences around JP. Results A total of 192 patients consented to participate. Most of the patients (82%) were unaware of JP. Factors that may act as barriers to participation and were regarded as â a very big concern&apos; were: Cost of the programme (44%), time of offering the programme (39%), work commitments (36%) and having a centre/clinic close to the house (28%). Factors that may act as facilitators and rated as â extremely helpful&apos; were: Research that shows that JP works (26%) and having the centre/clinic close to the house (25%). An online format for JP was the most preferred option (54%). Half (46%) preferred a timeframe of 1 hour, three times per week and 44% preferred a 2-hour programme, for three times per week. Conclusions Awareness of the potential benefits of JP, and prior experience with JP programme were very low. Common potentially modifiable patient-reported barriers to participate in future JP interventions, included: Cost, work commitments, distance from home to clinic and times that the intervention were provided. These barriers might be addressed with free and accessible forms of delivery of JP, which may lead to better uptake and participation in JP programmes. © Author(s) (or their employer(s)) 2021