Delayed timing of physical therapy initiation increases the risk of future opioid use in individuals with knee osteoarthritis: a real-world cohort study.

OBJECTIVE: We assessed whether late versus early initiation of physical therapy (PT) was related to greater risk of future opioid use in people with knee osteoarthritis (OA) who receive PT. METHODS: We used Commercial and Medicare Advantage claims data from 1999 to 2018 from American adults with incident knee OA referred for PT within 1 year of diagnosis. We categorised people as opioid naïve or opioid experienced based on prior prescriptions. We examined the association of timing of PT initiation with any and chronic opioid use over 1 year. RESULTS: Of the 67 245 individuals with incident knee OA, 35 899 were opioid naïve and 31 346 were opioid experienced. In the opioid naïve group, compared with PT within 1 month, PT 1 to <3, 3 to <6, 6 to <9, 9-12 months from diagnosis was associated with adjusted risk ratio (aRR (95% CIs)) for any opioid use of 1.18 (1.10 to 1.28), 1.49 (1.37 to 1.61), 1.73 (1.58 to 1.89) and 1.93 (1.76 to 2.12), respectively; aRRs (95% CIs) for chronic opioid use were 1.25 (1.01 to 1.54), 1.83 (1.48 to 2.26), 2.29 (1.82 to 2.89) and 2.50 (1.96 to 3.19). Results were similar among opioid experienced; aRRs (95% CIs) for any opioid use were 1.19 (1.14 to 1.24), 1.32 (1.26 to 1.37), 1.39 (1.32 to 1.45) and 1.54 (1.46 to 1.61); aRRs (95% CIs) for chronic opioid use were 1.25 (1.17 to1.34), 1.43 (1.33 to 1.54), 1.53 (1.41 to 1.66) and 1.65 (1.51 to 1.80). CONCLUSION: Compared with PT initiation within 1 month, delayed PT initiation was associated with higher risk of opioid use in people with incident knee OA. The longer the delay in PT initiation, the greater was the risk.

Cost-Effectiveness of Weight-Loss Interventions Prior to Total Knee Replacement for Patients With Class III Obesity.

OBJECTIVE: Class III obesity (body mass index >40 kg/m2 ) is associated with higher complications following total knee replacement (TKR), and weight loss is recommended. We aimed to establish the cost-effectiveness of Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and lifestyle nonsurgical weight loss (LNSWL) interventions in knee osteoarthritis patients with class III obesity considering TKR. METHODS: Using the Osteoarthritis Policy model and data from published literature to derive model inputs for RYGB, LSG, LNSWL, and TKR, we assessed the long-term clinical benefits, costs, and cost-effectiveness of weight-loss interventions for patients with class III obesity considering TKR. We assessed the following strategies with a health care sector perspective: 1) no weight loss/no TKR, 2) immediate TKR, 3) LNSWL, 4) LSG, and 5) RYGB. Each weight-loss strategy was followed by annual TKR reevaluation. Primary outcomes were cost, quality-adjusted life expectancy (QALE), and incremental cost-effectiveness ratios (ICERs), discounted at 3% per year. We conducted deterministic and probabilistic sensitivity analyses to examine the robustness of conclusions to input uncertainty. RESULTS: LSG increased QALE by 1.64 quality-adjusted life-years (QALYs) and lifetime medical costs by $17,347 compared to no intervention, leading to an ICER of $10,600/QALY. RYGB increased QALE by 0.22 and costs by $4,607 beyond LSG, resulting in an ICER of $20,500/QALY. Relative to immediate TKR, LSG and RYGB delayed and decreased TKR utilization. In the probabilistic sensitivity analysis, RYGB was cost-effective in 67% of iterations at a willingness-to-pay threshold of $50,000/QALY. CONCLUSION: For patients with class III obesity considering TKR, RYGB provides good value while immediate TKR without weight loss is not economically efficient.

Cost-Effectiveness of Surgical Weight-Loss Interventions for Patients With Knee Osteoarthritis and Class III Obesity.

OBJECTIVE: Class III obesity (body mass index [BMI] ≥40 kg/m2 ) is associated with worse knee pain and total knee replacement (TKR) outcomes. Because bariatric surgery yields sustainable weight loss for individuals with BMI ≥40 kg/m2 , our objective was to establish the value of Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) in conjunction with usual care for knee osteoarthritis (OA) patients with BMI ≥40 kg/m2 . METHODS: We used the Osteoarthritis Policy model to assess long-term clinical benefits, costs, and cost-effectiveness of RYGB and LSG. We derived model inputs for efficacy, costs, and complications associated with these treatments from published data. Primary outcomes included quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs), all discounted at 3%/year. This analysis was conducted from a health care sector perspective. We performed sensitivity analyses to evaluate uncertainty in input parameters. RESULTS: The usual care + RYGB strategy increased the quality-adjusted life expectancy by 1.35 years and lifetime costs by $7,209, compared to usual care alone (ICER = $5,300/QALY). The usual care + LSG strategy yielded less benefit than usual care + RYGB and was dominated. Relative to usual care alone, both usual care + RYGB and usual care + LSG reduced opioid use from 13% to 4%, and increased TKR usage from 30% to 50% and 41%, respectively. For cohorts with BMI between 38 and 41 kg/m2 , usual care + LSG dominated usual care + RYGB. In the probabilistic sensitivity analysis, at a willingness-to-pay threshold of $50,000/QALY, usual care + RYGB and usual care + LSG were cost-effective in 70% and 30% of iterations, respectively. CONCLUSION: RYGB offers good value among knee OA patients with BMI ≥40 kg/m2 , while LSG may provide good value among those with BMI between 35 and 41 kg/m2 .

Cost-Effectiveness of Arthroscopic Partial Meniscectomy and Physical Therapy for Degenerative Meniscal Tear.

OBJECTIVE: We examined the cost-effectiveness of treatment strategies for concomitant meniscal tear and knee osteoarthritis (OA) involving arthroscopic partial meniscectomy surgery and physical therapy (PT). METHODS: We used the Osteoarthritis Policy Model, a validated Monte Carlo microsimulation, to compare three strategies, 1) PT-only, 2) immediate surgery, and 3) PT + optional surgery, for participants whose pain persists following initial PT. We modeled a cohort with baseline meniscal tear, OA, and demographics from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial of arthroscopic partial meniscectomy versus PT. We estimated risks and costs of arthroscopic partial meniscectomy complications and accounted for heightened OA progression post surgery using published data. We estimated surgery use rates and treatment efficacies using MeTeOR data. We considered a 5-year time horizon, discounted costs, and quality-adjusted life-years (QALYs) 3% per year and conducted sensitivity analyses. We report incremental cost-effectiveness ratios. RESULTS: Relative to PT-only, PT + optional surgery added 0.0651 QALY and $2,010 over 5 years (incremental cost-effectiveness ratio = $30,900 per QALY). Relative to PT + optional surgery, immediate surgery added 0.0065 QALY and $3080 (incremental cost-effectiveness ratio = $473,800 per QALY). Incremental cost-effectiveness ratios were sensitive to optional surgery efficacy in the PT + optional surgery strategy. In the probabilistic sensitivity analysis, PT + optional surgery was cost-effective in 51% of simulations at willingness-to-pay thresholds of both $50,000 per QALY and $100,000 per QALY. CONCLUSION: First-line arthroscopic partial meniscectomy has a prohibitively high incremental cost-effectiveness ratio. Under base case assumptions, second-line arthroscopic partial meniscectomy offered to participants with persistent pain following initial PT is cost-effective at willingness-to-pay thresholds between $31,000 and $473,000 per QALY. Our analyses suggest that arthroscopic partial meniscectomy can be a high-value treatment option for patients with meniscal tear and OA when performed following an initial PT course and should remain a covered treatment option.

FDA/Arthritis Foundation osteoarthritis drug development workshop recap: Assessment of long-term benefit.

OBJECTIVE: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market. DESIGN: Summary of the one-day workshop held virtually on June 22nd, 2021. RESULTS: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit. CONCLUSIONS: Demonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.

Does Screening for Depressive Symptoms Help Optimize Duloxetine Use in Knee Osteoarthritis Patients With Moderate Pain? A Cost-Effectiveness Analysis.

OBJECTIVE: Duloxetine is a treatment approved by the US Food and Drug Administration for both osteoarthritis (OA) pain and depression, though uptake of duloxetine in knee OA management varies. We examined the cost-effectiveness of adding duloxetine to knee OA care in the absence or presence of depression screening. METHODS: We used the Osteoarthritis Policy Model, a validated computer microsimulation of knee OA, to examine the value of duloxetine for patients with knee OA who have moderate pain by comparing 3 strategies: 1) usual care, 2) usual care plus duloxetine for patients who screen positive for depression on the Patient Health Questionnaire 9 (PHQ-9), and 3) usual care plus universal duloxetine. Outcome measures included quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. Model inputs, drawn from the published literature and national databases, included annual cost of duloxetine ($721-937); average pain reduction for duloxetine (17.5 points on the Western Ontario and McMaster Universities Osteoarthritis Index pain scale [0-100]), and likelihood of depression remission with duloxetine (27.4%). We considered 2 willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY. We varied parameters related to the PHQ-9 and the cost of duloxetine, efficacy, and toxicities to address uncertainty in model inputs. RESULTS: The screening strategy led to an additional 17 QALYs per 1,000 subjects and increased costs by $289/subject (ICER = $17,000/QALY). Universal duloxetine led to an additional 31 QALYs per 1,000 subjects and $1,205 per subject (ICER = $39,300/QALY). Under the majority of sensitivity analyses, universal duloxetine was cost-effective at the $100,000/QALY threshold. CONCLUSION: The addition of duloxetine to usual care for knee OA patients with moderate pain, regardless of depressive symptoms, is cost-effective at frequently used WTP thresholds.

Societal Cost of Opioid Use in Symptomatic Knee Osteoarthritis Patients in the United States.

OBJECTIVE: Symptomatic knee osteoarthritis (SKOA) is a chronic, disabling condition, requiring long-term pain management; over 800,000 SKOA patients in the US use opioids on a prolonged basis. We aimed to characterize the societal economic burden of opioid use in this population. METHODS: We used the Osteoarthritis Policy Model, a validated computer simulation of SKOA, to estimate the opioid-related lifetime and annual cost generated by the US SKOA population. We included direct medical, lost productivity, criminal justice, and diversion costs. We modeled the SKOA cohort with a mean ± SD age of 54 ± 14 years and Western Ontario and McMaster Universities Osteoarthritis Index pain score of 29 ± 17 (0-100, 100 = worst). We estimated annual costs of strong ($1,381) and weak ($671) opioid regimens using Medicare fee schedules, Red Book, the Federal Supply Schedule, and published literature. The annual lost productivity and criminal justice costs of opioid use disorder (OUD), obtained from published literature, were $11,387 and $4,264, per-person, respectively. The 2015-2016 Medicare Current Beneficiary Survey provided OUD prevalence. We conducted sensitivity analyses to examine the robustness of our estimates to uncertainty in input parameters. RESULTS: Assuming 5.1% prevalence of prolonged strong opioid use, the total lifetime opioid-related cost generated by the US SKOA population was estimated at $14.0 billion, of which only $7.45 billion (53%) were direct medical costs. CONCLUSION: Lost productivity, diversion, and criminal justice costs comprise approximately half of opioid-related costs generated by the US SKOA population. Reducing prolonged opioid use may lead to a meaningful reduction in societal costs that can be used for other public health causes.

The Value of Total Knee Replacement in Patients With Knee Osteoarthritis and a Body Mass Index of 40 kg/m2 or Greater : A Cost-Effectiveness Analysis.

BACKGROUND: Total knee replacement (TKR) is an effective and cost-effective strategy for treating end-stage knee osteoarthritis. Greater risk for complications among TKR recipients with a body mass index (BMI) of 40 kg/m2 or greater has raised concerns about the value of TKR in this population. OBJECTIVE: To assess the value of TKR in recipients with a BMI of 40 kg/m2 or greater using a cost-effectiveness analysis. DESIGN: Osteoarthritis Policy Model to assess long-term clinical benefits, costs, and cost-effectiveness of TKR in patients with a BMI of 40 kg/m2 or greater. DATA SOURCES: Total knee replacement parameters from longitudinal studies and published literature, and costs from Medicare Physician Fee Schedules, the Healthcare Cost and Utilization Project, and published data. TARGET POPULATION: Recipients of TKR with a BMI of 40 kg/m2 or greater in the United States. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: Total knee replacement. OUTCOME MEASURES: Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. RESULTS OF BASE-CASE ANALYSIS: Total knee replacement increased QALYs by 0.71 year and lifetime medical costs by $25 200 among patients aged 50 to 65 years with a BMI of 40 kg/m2 or greater, resulting in an ICER of $35 200. Total knee replacement in patients older than 65 years with a BMI of 40 kg/m2 or greater increased QALYs by 0.39 year and costs by $21 100, resulting in an ICER of $54 100. RESULTS OF SENSITIVITY ANALYSIS: In TKR recipients with a BMI of 40 kg/m2 or greater and diabetes and cardiovascular disease, ICERs were below $75 000 per QALY. Results were most sensitive to complication rates and preoperative pain levels. In the probabilistic sensitivity analysis, at a $55 000-per-QALY willingness-to-pay threshold, TKR had a 100% and 90% likelihood of being a cost-effective strategy for patients aged 50 to 65 years and patients older than 65 years, respectively. LIMITATION: Data are derived from several sources. CONCLUSION: From a cost-effectiveness perspective, TKR offers good value in patients with a BMI of 40 kg/m2 or greater, including those with multiple comorbidities. PRIMARY FUNDING SOURCE: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.

Relation of NSAIDs, DMARDs, and TNF Inhibitors for Ankylosing Spondylitis and Psoriatic Arthritis to Risk of Total Hip and Knee Arthroplasty.

OBJECTIVE: Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) often affect the hip and/or knee. If effective, treatments might reduce risk of total hip or total knee arthroplasty (THA/TKA). We evaluated risk of THA/TKA related to use of medical therapies in AS/PsA. METHODS: We conducted a nested case-control study using 1994-2018 data from the OptumLabs Data Warehouse, which includes deidentified medical and pharmacy claims, laboratory results, and enrollment records for commercial and Medicare Advantage enrollees. Among those with AS/PsA, THA/TKA cases were matched up to 4 controls by sex, age, AS/PsA diagnosis, diagnosis year, insurance type, obesity, and prior THA/TKA. We assessed AS/PsA treatment 6 months prior to THA/TKA, including disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibitors (TNFi), alone or in combination, stratified by nonsteroidal antiinflammatory drug (NSAID) use. We evaluated the relation of treatment to risk of THA/TKA using conditional logistical regression with adjustment for confounders. RESULTS: Among 16,748 adults with AS, there were 444 THA/TKA cases and 1613 matched controls. Among 34,512 adults with PsA, there were 1003 cases and 3793 controls. Adjusted ORs for treatment category and THA/TKA ranged from 0.60 to 1.92; however, none were statistically significant. Results were similarly null in several sensitivity analyses. CONCLUSION: Odds of THA/TKA were not reduced with any combinations of NSAIDs, DMARDs, or TNFi among persons with AS or PsA. Given current utilization patterns in this population of US adults with AS and PsA, these medical therapies did not appear to be associated with less end-stage peripheral joint damage.

Flare Rate Thresholds for Patient Assessment of Disease Activity States in Gout.

OBJECTIVE: To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS). METHODS: Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare. A distribution-based approach and extended Youden index identified possible flare count thresholds for each state. RESULTS: Investigators from 17 countries recruited 512 participants. Remission was associated with a median recalled flare count of zero over both 6 and 12 months. Each recalled flare reduced the likelihood of self-perceived remission compared with being in higher disease activity than LDA/PASS, by 52% for 6 months and 23% for 12 months, and the likelihood of self-perceived LDA/PASS by 15% and 5% for 6 and 12 months, respectively. A threshold of 0 flares in preceding 6 and 12 months was associated with correct classification of self-perceived remission in 58% and 56% of cases, respectively. CONCLUSION: Flares are significantly associated with perceptions of disease activity in gout, and no flares over the prior 6 or 12 months is necessary for most people to self-categorize as being in remission. However, recalled flare counts alone do not correctly classify all patients into self-categorized disease activity states, suggesting that other factors may also contribute to self-perceived gout disease activity.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.

OBJECTIVE: To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. METHODS: We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. RESULTS: Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Assessment of Cardiovascular Risk in Older Patients With Gout Initiating Febuxostat Versus Allopurinol: Population-Based Cohort Study.

BACKGROUND: Hyperuricemia and gout are associated with an increased risk of cardiovascular disease. Xanthine oxidase inhibitors, allopurinol and febuxostat, are the mainstay of urate-lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout. METHODS: Using US Medicare claims data (2008-2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among patients with gout ≥65 years of age. The primary outcome was a composite end point of hospitalization for myocardial infarction or stroke. Secondary outcomes were individual end points of hospitalization for myocardial infarction, stroke, coronary revascularization, new and recurrent heart failure, and all-cause mortality. We used propensity score matching with a ratio of 1:3 to control for confounding. We estimated incidence rates and hazard ratios for primary and secondary outcomes in the propensity score-matched cohorts of febuxostat and allopurinol initiators. RESULTS: We included 24 936 febuxostat initiators propensity score-matched to 74 808 allopurinol initiators. The median age was 76 years, 52% were male, and 12% had cardiovascular disease at baseline. The incidence rate per 100 person-years for the primary outcome was 3.43 in febuxostat and 3.36 in allopurinol initiators. The hazard ratio for the primary outcome was 1.01 (95% CI, 0.94-1.08) in the febuxostat group compared with the allopurinol group. Risk of secondary outcomes including all-cause mortality was similar in both groups, except for a modestly decreased risk of heart failure exacerbation (hazard ratio, 0.94; 95% CI, 0.91-0.99) in febuxostat initiators. The hazard ratio for all-cause mortality associated with long-term use of febuxostat (>3 years) was 1.25 (95% CI, 0.56-2.80) versus allopurinol. Subgroup and sensitivity analyses consistently showed similar cardiovascular risk in both groups. CONCLUSIONS: Among a cohort of 99 744 older Medicare patients with gout, overall there was no difference in the risk of myocardial infarction, stroke, new-onset heart failure, coronary revascularization, or all-cause mortality between patients initiating febuxostat compared with allopurinol. However, there seemed to be a trend toward an increased, albeit not statistically significant, risk for all-cause mortality in patients who used febuxostat for >3 years versus allopurinol for >3 years. The risk of heart failure exacerbation was slightly lower in febuxostat initiators.

Review: Unmet Needs and the Path Forward in Joint Disease Associated With Calcium Pyrophosphate Crystal Deposition.

Calcium pyrophosphate (CPP) crystal deposition (CPPD) is prevalent and can be associated with synovitis and joint damage. The population of elderly persons predominantly affected by CPPD is growing rapidly. Since shortfalls exist in many aspects of CPPD, we conducted an anonymous survey of CPPD unmet needs, prioritized by experts from the Gout, Hyperuricemia and Crystal-Associated Disease Network. We provide our perspectives on the survey results, and we propose several CPPD basic and clinical translational research pathways. Chondrocyte and cartilage culture systems for generating CPP crystals in vitro and transgenic small animal CPPD models are needed to better define CPPD mechanism paradigms and help guide new therapies. CPPD recognition, clinical research, and care would be improved by international consensus on CPPD nomenclature and disease phenotype classification, better exploitation of advanced imaging, and pragmatic new point-of-care crystal analytic approaches for detecting CPP crystals. Clinical impacts of CPP crystals in osteoarthritis and in asymptomatic joints in elderly persons remain major unanswered questions that are rendered more difficult by current inability to therapeutically limit or dissolve the crystal deposits and assess the consequent clinical outcome. Going forward, CPPD clinical research studies should define clinical settings in which articular CPPD does substantial harm and should include analyses of diverse clinical phenotypes and populations. Clinical trials should identify the best therapeutic targets to limit CPP crystal deposition and associated inflammation and should include assessment of intraarticular agents. Our perspective is that such advances in basic and clinical science in CPPD are now within reach and can lead to better treatments for this disorder.

Cardiovascular Risks of Probenecid Versus Allopurinol in Older Patients With Gout.

BACKGROUND: Patients with gout are at an increased risk of cardiovascular (CV) disease including myocardial infarction (MI), stroke, and heart failure (HF). OBJECTIVES: The authors conducted a cohort study to examine comparative CV safety of the 2 gout treatments-probenecid and allopurinol-in patients with gout. METHODS: Among gout patients ≥65 years of age and enrolled in Medicare (2008 to 2013), those who initiated probenecid or allopurinol were identified. The primary outcome was a composite CV endpoint of hospitalization for MI or stroke. MI, stroke, coronary revascularization, HF, and mortality were assessed separately as secondary outcomes. The authors estimated the incidence rate and hazard ratio of the primary and secondary outcomes in the 1:3 propensity score-matched cohort of probenecid and allopurinol initiators. RESULTS: A total of 9,722 probenecid initiators propensity score-matched to 29,166 allopurinol initiators with mean age of 76 ± 7 years, and 54% males were included. The incidence rate of the primary composite endpoint of MI or stroke per 100 person-years was 2.36 in probenecid and 2.83 in allopurinol initiators with a hazard ratio of 0.80 (95% confidence interval: 0.69 to 0.93). In the secondary analyses, probenecid was associated with a decreased risk of MI, stroke, HF exacerbation, and mortality versus allopurinol. These results were consistent in the subgroup analyses of patients without baseline CV disease or those without baseline chronic kidney disease. CONCLUSIONS: In this large cohort of 38,888 elderly gout patients, treatment with probenecid appears to be associated with a modestly decreased risk of CV events including MI, stroke, and HF exacerbation compared with allopurinol.

Trends in Emergency Department Visits and Charges for Gout in the United States between 2006 and 2012.

OBJECTIVE: To examine temporal trends in the rate of gout emergency department (ED) visits and charges in the United States between 2006 and 2012. METHODS: A serial cross-sectional analysis of the Nationwide Emergency Department Sample. RESULTS: The rate of ED visits for gout in adults overall increased from 75.0 to 85.4 per 100,000 persons over the study period (14% increase, p < 0.001), and increased 29% for those aged 45-54 years. Nationwide ED charges increased from $156 million to $281 million (80% increase, p < 0.001). CONCLUSION: Between 2006 and 2012, the rate of gout ED visits increased among US adults, most notably in those aged 45-54 years.

Assessment of the item selection and weighting in the Birmingham vasculitis activity score for Wegener's granulomatosis.

OBJECTIVE: To assess the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) with respect to its selection and weighting of items. METHODS: This study used the BVAS/WG data from the Wegener's Granulomatosis Etanercept Trial. The scoring frequencies of the 34 predefined items and any "other" items added by clinicians were calculated. Using linear regression with generalized estimating equations in which the physician global assessment (PGA) of disease activity was the dependent variable, we computed weights for all predefined items. We also created variables for clinical manifestations frequently added as other items, and computed weights for these as well. We searched for the model that included the items and their generated weights yielding an activity score with the highest R(2) to predict the PGA. RESULTS: We analyzed 2,044 BVAS/WG assessments from 180 patients; 734 assessments were scored during active disease. The highest R(2) with the PGA was obtained by scoring WG activity based on the following items: the 25 predefined items rated on >or=5 visits, the 2 newly created fatigue and weight loss variables, the remaining minor other and major other items, and a variable that signified whether new or worse items were present at a specific visit. The weights assigned to the items ranged from 1 to 21. Compared with the original BVAS/WG, this modified score correlated significantly more strongly with the PGA. CONCLUSION: This study suggests possibilities to enhance the item selection and weighting of the BVAS/WG. These changes may increase this instrument's ability to capture the continuum of disease activity in WG.

The future of damage assessment in vasculitis.

Damage denotes the aspects of chronic disease that do not reverse with therapy. This concept is particularly important for the primary systemic vasculitides, since the careful differentiation between activity and damage may help avoid unnecessary exposure to cytotoxic medications. Damage significantly influences both longterm prognosis and quality of life. Because the primary systemic vasculitides have diverse manifestations, the use of a damage assessment instrument is crucial to ensure reproducibility. The Vasculitis Damage Index (VDI) is the only validated measure for damage assessment in vasculitis. Use of the VDI in recent clinical trials has shown that it may not adequately determine the full spectrum of damage experienced by patients with vasculitis of small- and medium-size vessels. We propose reexamining the way in which damage is assessed, focusing on vasculitides of small- and medium-size vessels, and outline an initiative to create a substantially revised and improved damage assessment instrument using data-driven approaches. This initiative is part of a larger international effort to create a unified approach to disease assessment for the primary systemic vasculitides.