Osteoarthritis (OA) is typically associated with pain, but many patients are not treated.
This point in time study explored factors associated with treatment status, using logistic regression of data ...from the Adelphi OA Disease Specific Programme conducted in the United States. Patients' treatment status was based on physician-reported, current: 1) prescription medication for OA vs. none; and 2) physician treatment (prescription medication and/or recommendation for specified nonpharmacologic treatment for OA physical or occupational therapy, acupuncture, transcutaneous electrical nerve stimulation, or cognitive behavior therapy/psychotherapy) vs. self-management (no prescription medication or specified nonpharmacologic treatment).
The 841 patients (including 57.0% knee OA, 31.9% hip OA) reported mild (45.4%) or moderate or severe (54.6%) average pain intensity over the last week. The majority were prescribed medication and/or recommended specified nonpharmacologic treatment; 218 were not prescription-medicated and 122 were self-managed. Bivariate analyses showed less severe patient-reported pain intensity and physician-rated OA severity, fewer joints affected by OA, lower proportion of joints affected by knee OA, better health status, lower body mass index, and lower ratings for cardiovascular and gastrointestinal risks, for those not prescribed medication (vs. prescription-medicated). Multivariate analyses confirmed factors significantly (p < 0.05) associated with prescription medication included (odds ratio): physician-rated current moderate OA severity (vs. mild, 2.03), patient-reported moderate OA severity 6 months ago (vs. mild, 1.71), knee OA (vs. not, 1.81), physician-recommended (0.28) and patient-reported (0.43) over-the-counter medication use (vs. not), prior surgery for OA (vs. not, 0.37); uncertain income was also significant. Factors significantly (p < 0.05) associated with physician treatment included (odds ratio): physician-recommended nonpharmacologic therapy requiring no/minimal medical supervision (vs. not, 2.21), physician-rated current moderate OA severity (vs. mild, 2.04), patient-reported over-the-counter medication use (vs. not, 0.26); uncertain time since diagnosis was also significant. Patient-reported pain intensity and most demographic factors were not significant in either model.
Approximately 1 in 4 patients were not prescribed medication and 1 in 7 were self-managed, although many were using over-the-counter medications or nonpharmacologic therapies requiring no/minimal medical supervision. Multiple factors were significantly associated with treatment status, including OA severity and over-the-counter medication, but not pain intensity or most demographics.
Abstract Individuals with spinal cord injury experience a rapid loss of bone mineral below the neurological lesion. The clinical consequence of this bone loss is a high rate of fracture around ...regions of the knee. The ability to predict the mechanical competence of bones at this location may serve as an important clinical tool to assess fracture risk in the spinal cord injury population. The purpose of this study was to develop, and statistically compare, non-invasive methods to predict torsional stiffness ( K ) and strength ( Tult ) of the proximal tibia. Twenty-two human tibiae were assigned to either a “training set” or a “test set” (11 specimens each) and mechanically loaded to failure. The training set was used to develop subject-specific finite element (FE) models, and statistical models based on dual energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT), to predict K and Tult ; the test set was used for cross-validation. Mechanical testing produced clinically relevant spiral fractures in all specimens. All methods were accurate and reliable predictors of K (cross-validation r2 ≥0.91; error≤13%), however FE models explained an additional 15% of the variance in measured Tult and illustrated 12–16% less error than DXA and QCT models. Given the strong correlations between measured and FE predicted K (cross-validation r2 =0.95; error=10%) and Tult (cross-validation r2 =0.91; error=9%), we believe the FE modeling procedure has reached a level of accuracy necessary to answer clinically relevant questions.
Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and ...safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention.
All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up.
Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio HR 0.43; 95% confidence interval CI, 0.22-0.85; P = .02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P = .05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P = .27).
PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.
Patients often take opioids to relieve osteoarthritis (OA) pain despite limited benefits and potential harms. This study aimed to compare cross-sectional perspectives of patients that were taking ...prescription opioid (N = 471) or nonopioid medications (N = 185) for OA in terms of satisfaction, expectations of effectiveness, and concerns. Patients prescribed opioids (>7 days) reported more prior treatments (2.47 vs. 1.74), greater mean pain intensity (5.47 vs. 4.11), and worse quality of life (EQ-5D-5L index value mean 0.45 vs. 0.71) than patients prescribed nonopioid medications (all
< 0.0001). Based on linear regression models adjusting for demographics and pain intensity, patients prescribed opioids were less satisfied with overall regimen (3.40 vs. 3.67,
= 0.0322), had less belief that medications were meeting effectiveness expectations (2.72 vs. 3.13,
< 0.0001), and had more concerns about treatments being "not very good" (3.66 vs. 3.22,
= 0.0026) and addiction (3.30 vs. 2.65,
< 0.0001) than patients prescribed nonopioid regimens. When the models were replicated for subgroups with ≥30 days' medication regimen duration, the findings were consistent with the main analyses. Patients have concerns about the risk of opioid addiction, but those with greater disease burden and more prior treatments continue taking opioid regimens.
Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs, but evidence is limited, and the possibility that ...these inhibitors increase cardiovascular events has been raised. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen.
18 325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) for 52 weeks, in two substudies of identical design (lumiracoxib
vs ibuprofen or naproxen). Randomisation was stratified for low-dose aspirin use and age. The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications (bleeding, perforation, or obstruction); analysis was by modified intention to treat. The principle measure of adverse cardiovascular events was the Antiplatelet Trialists' Collaboration endpoint (myocardial infarction, stroke, or cardiovascular death); this analysis was intention to treat.
81 (0·44%) patients did not start treatment and 7120 (39%) did not complete the study. In patients not taking aspirin, the cumulative 1-year incidence of ulcer complications was 1·09% (95% CI 0·82–1·36) with non-steroidal anti-inflammatory drugs (64 events) versus 0·25% (95% CI 0·12–0·39) with lumiracoxib (14 events; hazard ratio 0·21 95% CI 0·12–0·37, p<0·0001). Reductions in ulcer complications were also significant in the overall population (0·34 0·22–0·52, p<0·0001) but not in those taking aspirin (0·79 0·40–1·55, p=0·4876). In the overall population, 0·55% (50/9127) of those on non-steroidal anti-inflammatory drugs and 0·65% (59/9117) of those on lumiracoxib reached the cardiovascular endpoint (1·14 0·78–1·66, p=0·5074).
Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events, suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis.
To determine whether sex influences the analgesic efficacy of systemic pharmacological treatment in patients with knee osteoarthritis.
A systematic review, guided by Cochrane methods, sourced studies ...from Medline, Cochrane Library, Embase, and CINAHL Plus with Full Text as of October 10, 2022. Eligible studies were double-blind RCTs evaluating systemic pharmacological treatments for knee osteoarthritis in adults, with minimum 30-day treatment duration, reporting sex-specific results or mentioning sex subgroup analysis for analgesic efficacy. The risk of bias was assessed using the Cochrane Risk of Bias tool version 2 (RoB 2).
9 studies (5201 participants) met inclusion criteria, analyzing drugs including duloxetine, etoricoxib, tapentadol, naproxcinod, lutikizumab, and rofecoxib. Only one study reported sex-specific results. Review findings suggested no significant sex-based differences in treatment efficacy, however, data were limited due to a lack of sex-specific reporting or inclusion of sex in subgroup analyses.
Current evidence does not support the existence of sex differences in the analgesic efficacy of systemic knee osteoarthritis treatments. However, this conclusion is substantially limited by the paucity of sex-specific reporting of results or subgroup analyses in most primary studies, emphasizing the need for future research to report on sex-stratified data to allow for comprehensive, personalized treatment strategies.
Chronic musculoskeletal pain is a major - and growing - burden on today's ageing populations. Professional organisations including the American College of Rheumatology (ACR), American Pain Society ...(APS) and European League Against Rheumatism (EULAR) have published treatment guidelines within the past 5 years to assist clinicians achieve effective pain management. Safety is a core concern in all these guidelines, especially for chronic conditions such as osteoarthritis that require long-term treatment. Hence, there is a consensus among recommendations that paracetamol should be the first-line analgesic agent due to its favourable side effect and safety profile, despite being somewhat less effective in pain relief than anti-inflammatory drugs. Cyclooxygenase-2 (COX-2)-selective anti-inflammatory drugs were developed with the goal of delivering effective pain relief without the serious gastrointestinal (GI) side effects linked with traditional non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Clinical trial evidence supported these benefits, and COX-2 inhibitors were widely adopted, both in clinical practice and in official guidelines. Recently, accumulating data have linked COX-2 inhibitors with serious cardiovascular and/or cardiorenal effects and/or serious cutaneous adverse reactions (SCARs), particularly at anti-inflammatory doses or when used long term. Regulatory authorities in both Europe and the USA have responded to these data with the withdrawal of rofecoxib and valdecoxib, and the strengthening of prescribing advice on all anti-inflammatory drugs. COX-2 inhibitors and non-selective NSAIDs should now be used with increased caution in patients at increased cardiovascular and/or cardiorenal risk, e.g., patients with congestive heart failure, hypertension, etc. Regulatory advice and good clinical practice are to use anti-inflammatory drugs at the lowest effective dose and for the shortest possible time. There are as yet no updated official guidelines that incorporate these new data and regulatory advice. An international multidisciplinary panel, the Working Group on Pain Management, has generated new recommendations for the treatment of moderate-to-severe musculoskeletal pain. These guidelines, formulated in response to recent developments concerning COX-2 inhibitors and other NSAIDs, focus on paracetamol as the baseline drug for chronic pain management; when greater analgesia is desired, the addition of weak opioids is recommended based on a preferable GI and cardiovascular profile, compared with non-steroidal anti-inflammatory drugs.
Abstract Chronic pain is a hallmark of osteoarthritis (OA), yet little is known about its properties and representation in the brain. Here we use fMRI combined with psychophysics to study knee pain ...in fourteen OA patients and nine healthy controls. Mechanical painful pressure stimuli were applied to the knee in both groups and ratings of evoked pain and related brain activity examined. We observe that psychophysical properties and brain activation patterns of evoked pain are essentially the same between OA patients and healthy subjects, and between worse and better OA knees. In OA patients, stimulus-related brain activity could be distinguished from brain activity associated with spontaneous pain. The former activated brain regions commonly observed for acute painful stimuli in healthy subjects, while the spontaneous pain of OA engaged prefrontal-limbic regions closely corresponding to areas observed for spontaneous pain in other chronic pain conditions, such as chronic back pain and post-herpetic neuralgia. Arthritis-related clinical characteristics of knee OA also mapped to prefrontal-limbic regions. In a subgroup of patients ( n = 6) we examined brain activity changes for a 2-week, repeat measure, cyclooxygenase-2 inhibitor (valdecoxib) therapy. Treatment decreased spontaneous pain for the worse knee and clinical characteristics of OA, and increased blood and csf levels of the drug which correlated positively with prefrontal-limbic brain activity. These findings indicate dissociation between mechanically induced and spontaneous OA knee pain, the latter engaging brain regions involved in emotional assessment of the self, and challenge the standard clinical view regarding the nature of OA pain.
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