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Association Between Sedentary Time and Quality of Life From the Osteoarthritis Initiative: Who Might Benefit Most From Treatment?
Pinto, D, Song, J, Lee, J, Chang, RW, Semanik, PA, Ehrlich-Jones, LS, Pellegrini, CA, Dunlop, DD
Archives of physical medicine and rehabilitation. 2017;(12):2485-2490
Abstract
OBJECTIVE To investigate the relationship between sedentary behavior and quality-adjusted life years (QALYs) among participants in the Osteoarthritis Initiative. DESIGN Longitudinal, observational design. SETTING Osteoarthritis Initiative cohort. PARTICIPANTS Individuals (N=1794) from a prospective, multicenter longitudinal cohort were classified into quantile groups based on average daily sedentary time (most sedentary, quartile 1 [Q1] ≥11.6h; 10.7h≤ Q2 <11.6h; 9.7h≤ Q3 <10.7h; least sedentary, Q4 <9.7h). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Individual QALYs were estimated over 2 years from the area under the curve of health-related utility scores derived from the Medical Outcomes Study 12-Item Short-Form Health Survey versus time. The relationship between baseline sedentary behavior and median 2-year QALYs was estimated using quantile regression adjusted for socioeconomic factors and body mass index. RESULTS Lower QALYs over 2 years were more frequently found among the most sedentary (Q1, median 1.59), and QALYs increased as time spent in baseline sedentary behavior decreased (median QALYs for Q2, 1.64; Q3, 1.65; Q4, 1.65). The relationship of sedentary time and median QALY change was only significant for the most sedentary Q1 group, where an additional hour of sedentary behavior significantly reduced QALYs by -.072 (95% confidence interval, -.121 to -.020). CONCLUSIONS Our findings suggest that individuals with the most extreme sedentary profiles may be vulnerable to additional losses of quality of life if they become more sedentary. Targeting these individuals to decrease sedentary behavior has the potential to be cost-effective.
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Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial.
Zhuang, Q, Bian, Y, Wang, W, Jiang, J, Feng, B, Sun, T, Lin, J, Zhang, M, Yan, S, Shen, B, et al
BMJ open. 2016;(9):e011732
Abstract
INTRODUCTION Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. METHODS AND ANALYSIS This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. ETHICS AND DISSEMINATION Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. TRIAL REGISTRATION NUMBER NCT02198924.
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Impact of concomitant low-dose aspirin on the safety and tolerability of naproxen and esomeprazole magnesium delayed-release tablets in patients requiring chronic nonsteroidal anti-inflammatory drug therapy: an analysis from 5 Phase III studies.
Angiolillo, DJ, Datto, C, Raines, S, Yeomans, ND
Journal of thrombosis and thrombolysis. 2014;(1):11-23
Abstract
Patients receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) and concomitant low-dose aspirin (LDA) are at increased risk of gastrointestinal (GI) toxicity. A fixed-dose combination of enteric-coated (EC) naproxen and immediate-release esomeprazole magnesium (NAP/ESO) has been designed to deliver a proton-pump inhibitor followed by an NSAID in a single tablet. To examine safety data from 5 Phase III studies of NAP/ESO in LDA users (≤ 325 mg daily, administered at any time during the study), and LDA non-users, data were analyzed from 6-month studies assessing NAP/ESO versus EC naproxen in patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis (n = 2), 3-month studies assessing NAP/ESO vs celecoxib or placebo in patients with knee osteoarthritis (n = 2), and a 12-month, open-label, safety study of NAP/ESO (n = 1). In an analysis of two studies, incidences of endoscopically confirmed gastric ulcers (GUs) and duodenal ulcers (DUs) were summarized by LDA subgroups. In the pooled analysis from all five studies, incidences of treatment-emergent adverse events (AEs) (including prespecified NSAID-associated upper GI AEs and cardiovascular AEs), serious AEs, and AE-related discontinuations were stratified by LDA subgroups. Overall, 2,317 patients received treatment; 1,157 patients received NAP/ESO and, of these, 298 received LDA. The cumulative incidence of GUs and DUs in the two studies with 6-month follow-up was lower for NAP/ESO vs EC naproxen in both LDA subgroups [GUs: 3.0 vs 27.9%, respectively, for LDA users, 6.4 vs 22.4%, respectively, for LDA non-users (both P < 0.001); DUs: 1.0 vs 5.8% for LDA users, 0.6 vs 5.3% for LDA non-users]. The incidence of erosive gastritis was lower in NAP/ESO- vs EC naproxen-treated patients for both LDA users [18.2 vs 36.5%, respectively (P = 0.004)] and LDA non-users [19.8 vs 38.5%, respectively (P < 0.001)]. Among LDA users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 16.1%; EC naproxen, 31.7%; celecoxib, 22.1%; placebo, 23.2%. Among LDA non-users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 20. %; EC naproxen, 36.6%; celecoxib, 18.5%; placebo, 18.9%. For LDA users, incidences of cardiovascular AEs were: NAP/ESO, 3.0%; EC naproxen, 1.0%; celecoxib, 0%; placebo, 0%. For LDA non-users, incidences of cardiovascular AEs were: NAP/ESO, 1.0%; EC naproxen, 0.6%; celecoxib, 0.3%; placebo, 0%. NAP/ESO appears to be well-tolerated in patients receiving concomitant LDA. For LDA users, AE incidence was less than that observed for EC naproxen. For most AE categories, incidences were similar among NAP/ESO, celecoxib and placebo groups. The safety of NAP/ESO appeared similar regardless of LDA use.
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A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain.
Conrozier, T, Mathieu, P, Bonjean, M, Marc, JF, Renevier, JL, Balblanc, JC
Alternative therapies in health and medicine. 2014;:32-7
Abstract
BACKGROUND Devil's claw (Harpagophytum procumbens), turmeric (Curcuma longa), and bromelain are nutraceuticals that have demonstrated anti-inflammatory and analgesic properties and may be potential solutions in the treatment of acute or chronic joint pain. Their analgesic effect, however, is generally considered mild to moderate, and the relevance of their clinical use remains subject to discussion. OBJECTIVES The aim of the study was to evaluate the clinical relevance of the efficacy of a marketed complex of 3 plant extracts-H procumbens, C longa, and bromelain (AINAT, 650 mg)-in the treatment of degenerative joint pain. METHODS A multicenter, observational, prospective, open-label survey was conducted in 8 rheumatology centers. The study included 2 groups, 1 group with participants suffering from chronic osteoarthritis (OA) pain and 1 group suffering from acute OA pain. SETTING The research team carried out the study under daily practice conditions. PARTICIPANTS A total of 42 patients (36 women; mean age = 67 y) suffering from acute or chronic, degenerative spine or joint pain participated. INTERVENTION Two 650-mg capsules of AINAT were administered 3 ×/d to patients with acute pain and 2 ×/d to patients with chronic pain. OUTCOME MEASURES At baseline, and during a follow-up visit at 15 d for the acute pain group and 60 d for the chronic pain group, the research team obtained each participant's global assessment (PGA) and each rheumatologist's global assessment (RGA), as well as each participant's pain score, using for each of them a 100-mm visual analogue scale (VAS). The clinical relevance of the efficacy was evaluated by comparing the outcome measures at endpoint to the values defining the patient acceptable symptom state (PASS) and by comparing the variations (in mm and %) between baseline and endpoint to those defining the minimal clinically important improvement (MCII). Tolerance was also assessed by collecting adverse events at each visit and by using a 4-point scale (very good to bad) at the endpoint. RESULTS At baseline, the VAS pain score (standard deviation) was 69.1 mm (15.4) and 68.0 mm (18.2) for patients with acute and chronic pain, respectively. At the endpoint, the scores decreased to 42.1 mm (21.1) and 37.8 mm (25.9), respectively. This reduction of pain, as a percentage as well as an absolute value, corresponds to the required definition of MCII, particularly in patients with chronic joint pain. At the endpoint, most of the patients in both groups reached the level of pain defined as the PASS. No withdrawals occurred due to treatment side effects. CONCLUSION The improvement of joint pain was clinically relevant in patients treated with AINAT for both acute and chronic OA pain. Considering its excellent tolerance profile, the tested complex of 3 plant extracts with antiinflammatory properties may be a valuable and safe alternative to NSAIDs in patients suffering from degenerative joint diseases.
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Willow bark extract STW 33-I in the long-term treatment of outpatients with rheumatic pain mainly osteoarthritis or back pain.
Uehleke, B, Müller, J, Stange, R, Kelber, O, Melzer, J
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2013;(11):980-4
Abstract
STUDY OBJECTIVE Efficacy and safety of willow bark extract for pain reduction in patients suffering from musculoskeletal disorders (MSD) has been shown in clinical short term trials. Therefore this observational study over 6 months should evaluate patterns of treatments like mono- or combinations therapy, dosage and safety during long-term treatment under pragmatic conditions with the aqueous willow bark extract STW 33-I, (Proaktiv(®); drug-extract-ratio 16-23:1). PATIENTS AND METHODS The patients were treated with STW 33-I; comedication with other NSAIDs and opioids was allowed. An extensive case report form including pain questionnaires and patient diary was used for outcome evaluation. RESULTS Four hundred and thirty-six patients with rheumatic pain mainly due to osteoarthritis (56.2%) and back pain (59.9%) were included. During the study the mean reductions from baseline value 58.4±22.6-31.8±22.5 after 24 weeks in the pain intensity scale (VAS 0-100mm) were significant even after 3 weeks with a reduction by 26 mm (45.6% of the baseline value) at the end of the study. The relative reductions of the weekly means of the daily patient self-rated scores of the pain (6-point Likert-scales) were between 33% and 44% of the baseline values during the course of the study. We present results of subgroups according their analgetic/antiphlogistic comedication. The distribution and specification of the main adverse events and the ratings of the treatment showed a good tolerability. No relevant drug interactions were reported. CONCLUSION These data suggest that STW 33-I can be used as a basic treatment in the long-term therapy of painful musculoskeletal disorders and that it can be combined with NSAIDs and opioids if necessary.
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Sodium hyaluronate for the treatment of chronic shoulder pain associated with glenohumeral osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled trial.
Kwon, YW, Eisenberg, G, Zuckerman, JD
Journal of shoulder and elbow surgery. 2013;(5):584-94
Abstract
BACKGROUND Nonoperative treatments for glenohumeral osteoarthritis (GH-OA) are limited. Intra-articular therapy with sodium hyaluronate (HA) has been effective in treating OA of the knee. Therefore, we sought to evaluate the efficacy and safety of HA in treating chronic pain associated with GH-OA. METHODS This double-blind, randomized, controlled multicenter trial enrolled 300 patients with GH-OA: 150 received HA and 150 received phosphate-buffered saline (PBS) in 3 weekly injections and were evaluated over 26 weeks. Primary and secondary outcome measurements were visual analog scale (VAS) for pain and the percentage of Outcome Measures in Rheumatoid Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) high responders. RESULTS In HA and PBS intent-to-treat (ITT) patients, there was a mean improvement from baseline in VAS of 19.88 mm and 16.29 mm at week 26, respectively. Similarly, the percentage of OMERACT-OARSI high responders in the HA group was higher (40.8% vs 34.9%); however, neither difference was statistically significant (P = .1121 and P = .0690, respectively). In a subset of patients without concomitant shoulder pathologies, the differences of VAS and OMERACT-OARSI high-responder rates between groups were 4.0 mm and 8.37%, respectively, which reached statistical significance. Safety analyses showed comparable rates of adverse events between groups, and neither group reported serious treatment-related adverse events. CONCLUSIONS A numeric advantage, but without statistical significance, was found for HA ITT patients with GH-OA. Although data for a subset of HA patients without concomitant pathologies reached statistical significance, additional randomized trials are needed to confirm the clinical implication of this outcome.
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Long-term safety of naproxen and esomeprazole magnesium fixed-dose combination: phase III study in patients at risk for NSAID-associated gastric ulcers.
Sostek, MB, Fort, JG, Estborn, L, Vikman, K
Current medical research and opinion. 2011;(4):847-54
Abstract
OBJECTIVE To evaluate long-term safety of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg fixed-dose combination (FDC) in patients at risk of NSAID-associated upper gastrointestinal (UGI) ulcers. RESEARCH DESIGN AND METHODS In this open-label, multicenter, phase III study, Helicobacter pylori-negative patients aged ≥50 years or 18-49 years with history of uncomplicated ulcer within the past 5 years, who had osteoarthritis, rheumatoid arthritis, or other condition requiring daily NSAIDs for ≥12 months received naproxen/esomeprazole twice daily for 12 months. CLINICAL TRIAL REGISTRATION NCT00527904. MAIN OUTCOME MEASURES Adverse events (AEs), vital signs, physical examination, and laboratory tests. Subgroup analyses included age and low-dose aspirin (LDA) use. Predefined NSAID-associated UGI and cardiovascular AEs were analyzed. RESULTS Of 239 patients treated (safety population), 135 completed ≥348 treatment days (12-month completers). AE incidence was approximately 70%; dyspepsia, constipation, upper respiratory tract infection, nausea, back pain, and contusion were most frequent (≥5% patients, either population). Treatment-related AEs occurred in 28.0% and 23.7% of patients in the safety and 12-month completer populations, respectively; 18.8% of patients withdrew due to AEs (safety population). Few serious AEs and no deaths occurred. In the safety population, AE incidence was 71.4% and 76.9% in patients aged <65 years (n = 161) and ≥65 years (n = 78), respectively, and 67.6% and 75.8% in LDA users (n = 74) and non-users (n = 165), respectively. Predefined UGI and cardiovascular AEs were observed in 18.8% and 6.3% of patients, respectively, in the safety population, and 16.3% and 5.2%, respectively, in 12-month completers. Dyspepsia and hypertension were most common. Additional assessments showed no unexpected findings. CONCLUSIONS Based on these outcome measures, long-term treatment with FDC naproxen/esomeprazole is not associated with any new safety issues, including predefined UGI and cardiovascular AEs, in patients requiring NSAID therapy who are at risk of UGI complications.
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Clinical trial: the incidence of NSAID-associated endoscopic gastric ulcers in patients treated with PN 400 (naproxen plus esomeprazole magnesium) vs. enteric-coated naproxen alone.
Goldstein, JL, Hochberg, MC, Fort, JG, Zhang, Y, Hwang, C, Sostek, M
Alimentary pharmacology & therapeutics. 2010;(3):401-13
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Abstract
BACKGROUND Gastroprotective co-therapy may reduce the risk of nonsteroidal anti-inflammatory drug (NSAID)-associated gastric ulcers, but adherence is suboptimal. AIM: To compare the incidence of gastric ulcers with PN 400 [enteric-coated (EC) naproxen 500 mg and immediate-release esomeprazole 20 mg], or EC naproxen. METHODS Two randomized, double-blind, multicentre studies (PN400-301, PN400-302). Patients [stratified by low-dose aspirin (< or =325 mg) use] aged > or =50 years or 18-49 years with a history of ulcer, received PN 400 BID (301, n = 218; 302, n = 210) or EC naproxen 500 mg BID (301, n = 216; 302, n = 210) for 6 months. The primary endpoint was the cumulative incidence of endoscopic gastric ulcers. RESULTS The cumulative incidence of gastric ulcers was significantly lower with PN 400 vs. EC naproxen (301: 4.1% vs. 23.1%, P < 0.001; 302: 7.1% vs. 24.3%, P < 0.001). PN 400 was associated with a lower combined incidence of gastric ulcers vs. EC naproxen in low-dose aspirin users (n = 201) (3.0% vs. 28.4%, P < 0.001) and non-users (n = 653) (6.4% vs. 22.2%, P < 0.001). The incidence of, and discontinuations due to, upper gastrointestinal (UGI) AEs was significantly lower with PN 400 relative to EC naproxen (P < 0.01, both studies). CONCLUSIONS PN 400 significantly reduces the incidence of gastric ulcers, regardless of low-dose aspirin use, in at-risk patients, and is associated with improved UGI tolerability relative to EC naproxen (ClinicalTrials.gov, NCT00527782).
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A randomised controlled trial of subcutaneous sodium salicylate therapy for osteoarthritis of the thumb.
Smith, AS, Doré, CJ, Dennis, L, Julius, A, Mackworth-Young, CG
Postgraduate medical journal. 2010;(1016):341-5
Abstract
BACKGROUND Current treatment for osteoarthritis (OA) is limited. Many patients with OA of the hand have areas of tender subcutaneous thickening in the forearm and upper scapular region. A pilot study showed an improvement in pain from OA at the first carpometacarpal joint after injection of such areas with 0.5% sodium salicylate or saline, an inexpensive treatment that can be administered by general practitioners and nurses. The study indicated that a randomised, sham-controlled trial was justified. METHODS 40 patients with OA of the first carpometacarpal joint were randomised to receive either injections of sodium salicylate into tender, thickened areas of subcutaneous tissue on the forearm (baseline) and upper scapular region (week 1) or sham injections consisting of pressure without skin penetration. Blinded assessments were made at weeks 3, 7 and 13 after baseline. RESULTS Pain and tenderness during follow-up were both significantly lower in the active treatment group compared with the sham group: 19% and 14% greater reduction in mean visual analogue scale (VAS) score, respectively (p=0.007 and 0.02, baseline mean 5.65 and 5.35 cm, average difference in change from baseline VAS 1.9 and 1.4 cm, 95% CI 0.6 to 3.2 and 0.2 to 2.5). Active and sham injections were painful, the former significantly more so; however, there was no significant correlation between the pain of active injections and response. CONCLUSION The data show that subcutaneous sodium salicylate injections are an effective symptomatic treatment for OA of the thumb. The results provide a basis for further physiological and therapeutic research in this area.
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Comparative efficacy and tolerability of two sustained-release formulations of diclofenac: results of a double-blind, randomised study in patients with osteoarthritis and a reappraisal of diclofenac's use in this patient population.
Wagenitz, A, Mueller, EA, Frentzel, A, Cambon, N
Current medical research and opinion. 2007;(8):1957-66
Abstract
OBJECTIVE To compare the analgesic efficacy and tolerability of a sustained-release pellet formulation of diclofenac (Olfen-100 SR Depocaps, SR-CAP, Mepha Ltd, Aesch, Switzerland) with the standard reference formulation (Voltaren retard 100, SR-TAB, Novartis Pharma AG, Basel, Switzerland), both containing 100 mg diclofenac sodium, in patients with osteoarthritis (OA) of the knee and/or hip. In addition, diclofenac's current place in the symptomatic therapy of OA is briefly reviewed. METHODS In this 2-week double-blind, active-controlled, non-inferiority trial, 210 OA patients were randomised to receive either SR-CAP once daily or SR-TAB once daily (n = 105 for both groups). The primary efficacy endpoint was the change in visual analogue scale (VAS) pain score (0-100 mm) at rest at Day 14 compared with baseline. Secondary variables included the change in VAS pain score on movement and global assessments of efficacy and tolerability using verbal rating scales (VRS). RESULTS Between baseline and Day 14, mean +/- SD VAS pain score at rest decreased by 44.4 +/- 18.5 mm in the SR-CAP group (n = 89) compared with 41.2 +/- 19.8 mm in the SR-TAB group (n = 82) based on the per protocol population. Comparable changes were observed in the intention-to-treat population. The lower bound of the 1-sided 97.5% confidence interval was -2.7 mm and greater than the prespecified non-inferiority limit of -10 mm. There was a trend towards a better tolerability with SR-CAP compared with SR-TAB based on mean +/- SD VRS scores (SR-CAP, 0.6 +/- 0.68; SR-TAB, 0.9 +/- 1.0 for assessment by patients; p = 0.063). CONCLUSION SR-CAP is as effective as and possibly better tolerated than SR-TAB in patients suffering from painful OA.