[Show abstract][Hide abstract] ABSTRACT: Objective:
Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout.
An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set.
The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively).
The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.
Arthritis and Rheumatology 09/2015; 67(10):2557-2568. DOI:10.1002/art.39254
[Show abstract][Hide abstract] ABSTRACT: Validation of claims-based algorithms to identify serious hypersensitivity reactions and osteonecrosis of the jaw has not been performed in large osteoporosis populations. The objective of this project is to estimate the positive predictive value of the claims-based algorithms in older women with osteoporosis enrolled in Medicare. Using the 2006-2008 Medicare 5% sample data, we identified potential hypersensitivity and osteonecrosis of the jaw cases based on ICD-9 diagnosis codes. Potential hypersensitivity cases had a 995.0, 995.2, or 995.3 diagnosis code on emergency department or inpatient claims. Potential osteonecrosis of the jaw cases had ≥1 inpatient or outpatient physician claim with a 522.7, 526.4, 526.5, or 733.45 diagnosis code or ≥2 claims of any type with a 526.9 diagnosis code. All retrieved records were redacted and reviewed by experts to determine case status: confirmed, not confirmed, or insufficient information. We calculated the positive predictive value as the number of confirmed cases divided by the total number of retrieved records with sufficient information. We requested 412 potential hypersensitivity and 304 potential osteonecrosis of the jaw records and received 174 (42%) and 84 (28%) records respectively. Of 84 potential osteonecrosis of the jaw cases, 6 were confirmed, resulting in a positive predictive value (95% CI) of 7.1% (2.7, 14.9). Of 174 retrieved potential hypersensitivity records, 95 were confirmed. After exclusion of 25 records with insufficient information for case determination, the overall positive predictive value (95% CI) for hypersensitivity reactions was 76.0% (67.5, 83.2). In a random sample of Medicare data, a claim-based algorithm to identify serious hypersensitivity reactions performed well. An algorithm for osteonecrosis of the jaw did not, partly due to the inclusion of diagnosis codes that are not specific for osteoporosis of the jaw.
PLoS ONE 07/2015; 10(7):e0131601. DOI:10.1371/journal.pone.0131601 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To address the low prevention and treatment rates for those at risk of glucocorticoid-induced osteoporosis (GIOP), we evaluated the influence of a direct-to-patient, Internet-based educational video intervention using "storytelling" on rates of antiosteoporosis medication use among chronic glucocorticoid users who were members of an online pharmacy refill service.
We identified members who refilled ≥ 5 mg/day of prednisone (or equivalent) for 90 contiguous days and had no GIOP therapy for ≥ 12 months. Using patient stories, we developed an online video addressing risk factors and treatment options, and delivered it to members refilling a glucocorticoid prescription. The intervention consisted of two 45-day "Video ON" periods, during which the video automatically appeared at the time of refill, and two 45-day "Video OFF" periods, during which there was no video. Members could also "self-initiate" watching the video by going to the video link. We used an interrupted time series design to evaluate the effectiveness of this intervention on GIOP prescription therapies over 6 months.
Among 3017 members (64.8%) exposed to the intervention, 59% had measurable video viewing time, of which 3% "self-initiated" the video. The GIOP prescription rate in the "Video ON" group was 2.9% versus 2.7% for the "Video OFF" group. There was a nonsignificant trend toward greater GIOP prescription in members who self-initiated the video versus automated viewing (5.7% vs 2.9%, p = 0.1).
Among adults at high risk of GIOP, prescription rates were not significantly affected by an online educational video presented at the time of glucocorticoid refill. ClinicalTrials.gov Identifier: NCT01378689.
The Journal of Rheumatology 07/2015; 42(8). DOI:10.3899/jrheum.141238 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Older and disabled rheumatoid arthritis (RA) patients are often not present in large numbers in clinical trials or registries. A novel, claims-based clinical effectiveness algorithm provides the potential to compare the effectiveness of different biologics among this population using large administrative databases.
Using Medicare 2006-2010 data for 100% of patients with RA, we identified biologic naïve users of abatacept, adalimumab, etanercept, and infliximab, defined as no biologic use during the 12 months before the biologic initiation. The effectiveness was evaluated at 365 days after biologic initiation, determined using a validated claims-based algorithm. We compared the proportion meeting effectiveness criteria for each biologic using robust Poisson regression to compute risk ratios (RRs) adjusted for potential confounders. One-year cost per effectively treated patient was calculated by different biologics.
The study included biologic naïve users of abatacept (n = 2129), adalimumab (n = 2944), etanercept (n = 3517) and infliximab (n = 5654). The algorithm classified the medications as 26% effective for abatacept, 24% for adalimumab, 28% for etanercept, and 23% for infliximab, indicating comparable effectiveness However, after adjustment and compared to infliximab, the RRs for effectiveness were 1.17 (95% CI: 1.06-1.30) for abatacept, 1.11 (95% CI: 1.02-1.23) for adalimumab, and 1.27 (95% CI: 1.17-1.39) for etanercept. Older patients had a higher effectiveness than patients who were disabled (RR = 1.18, CI: 1.08-1.28). Infliximab had highest cost per effectively treated patient.
Abatacept, adalimumab, and etanercept are more effective than infliximab among RA patients initiating biologics. Effectiveness was significantly higher among older patients compared disabled RA Medicare patients.
This article is protected by copyright. All rights reserved.
British Journal of Clinical Pharmacology 06/2015; DOI:10.1111/bcp.12709 · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During the use of glucocorticoids (GCs), both vertebral and nonvertebral fracture risk are increased, due to the direct and indirect negative effects of GCs on bone, muscles, and the activity of the underlying inflammatory diseases. Inhibition of bone formation and increased apoptosis of osteocytes play a consistent and crucial role in the pathogenesis of glucocorticoid-induced osteoporosis (GIO), while changes in bone resorption during GC-use are variable. To prevent fractures, important general measures include using the lowest possible dose of GCs, treating the underlying disease adequately, a healthy life style, adequate calcium and vitamin D supplementation, and regular exercise. Although it has been shown that bisphosphonates reduce vertebral fractures during the first 2 years of GC-treatment, there are no data on long-term use of bisphosphonates during GC-treatment. Of some concern in GIO, bisphosphonates reduce bone turnover, including bone formation, which is already downregulated by GCs. In contrast, the use of the anabolic agent teriparatide is more effective in reducing vertebral fractures than alendronate. In summary, bisphosphonates remain the first choice in the first two years of treatment in GC-treated patients with high fracture risk, but their long-term effects on bone quality and fracture risk reduction remain uncertain.
[Show abstract][Hide abstract] ABSTRACT: Background
Denosumab 60mg is a biologic used to treat osteoporosis. Its safety profile given concurrently with biologics for rheumatoid arthritis [RA] has not been well studiedObjective
We evaluated hospitalized infections among patients treated with RA biologics who initiated denosumab or zoledronic acid[ZA], a parenteral bisphosphonate without known associations with infection. We hypothesized that the rate of hospitalized infection on denosumab would be non-inferior to ZA.Methods
We identified RA patients enrolled in Medicare in 2006-2012 treated with biologics who initiated Dmab or ZA. Cox proportional hazards models compared the risk for hospitalized infection, comparing denosumab to ZA users and adjusting for potentially confounding factors . A non-inferiority margin was specified a-priori to demonstrate that denosumab had no greater infection risk than ZA if the upper bound of the 95% CI of the hazard ratio (HR) was less than 1.5.ResultsEligible RA patients receiving biologics initiated denosumab (n=1,354) or ZA (n=4,460). Characteristics of the denosumab users: mean (SD) age 73.0(8.9), 98.2% women, with a majority receiving infliximab (35.7%) or abatacept (18.6%). Denosumab users had a higher prevalence of prior infections (11.5% hospitalized, 48.3% outpatient) and infection-related risk factors. The crude rate of hospitalized infection for Dmab (14.9/100py; 95% CI 12.2-18.1) was comparable to ZA (13.9/100py; 95% CI 12.5-15.4). After adjustment, the HR of hospitalized infection for denosumab users was non-inferior to ZA (HR=0.89, 95% CI 0.69 - 1.15)Conclusion
The rate of hospitalized infection among RA patients receiving denosumab concurrently with biologics for RA was not increased compared to zoledronate. This article is protected by copyright. All rights reserved.
Arthritis and Rheumatology 02/2015; 67(6). DOI:10.1002/art.39075
[Show abstract][Hide abstract] ABSTRACT: Context. Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired. Objective. To improve model discrimination by developing a 5-yr composite fracture prediction model for fracture sites that display similar risk profiles. Design. Prospective, observational cohort study. Setting. Primary care practices in 10 countries. Patients. Women aged ≥55 years. Intervention. Self-administered questionnaires collected data on patient characteristics, fracture risk factors and previous fractures. Main Outcome Measure. Main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age. Results. Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index 0.75, 47,066 women), and lowest for FRAX major fracture and a 10-site model (c indices 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 yr of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 yr of age from a 10% decrease to a 60% increase. Conclusions. After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.
The Journal of Clinical Endocrinology and Metabolism 12/2014; 99(3):jc20133468. DOI:10.1210/jc.2013-3468 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify modifiable patient and provider factors associated with allopurinol adherence and the achievement of a serum urate acid (SUA) goal in gout.
We identified a retrospective cohort of patients with gout, newly treated with allopurinol. All patient data came from administrative datasets at a large integrated health delivery system. Patients were ≥ 18 years old at time of initial allopurinol dispensing, and had 12 months or more of membership and drug eligibility prior to the index date. Allopurinol adherence was defined as a proportion of days covered ≥ 0.80, evaluated during the first 12 months of observation after the initial dispensing. Multivariable logistic regression was used to examine factors associated with allopurinol nonadherence and attaining an SUA concentration < 6.0 mg/dl.
We identified 13,341 patients with gout with incident allopurinol use (mean age 60 yrs, 78% men). Of these, 9581 patients (72%) had SUA measured both at baseline and during followup. Only 3078 patients (32%) attained an SUA target of < 6.0 mg/dl during followup. Potentially modifiable factors associated with treatment adherence and obtaining the SUA goal in the multivariable analysis included concomitant diuretic use, prescriber specialty, and allopurinol dosing practices. Adherent patients were 2.5-fold more likely than nonadherent patients to achieve an SUA < 6.0 mg/dl during observation.
Among patients with gout initiating allopurinol in our study, 68% did not reach the SUA goal and 57% of patients were nonadherent. Modifiable factors, including allopurinol dose escalation, treatment adherence, rheumatology referral, and concomitant medication use, could be important factors to consider in efforts aimed at optimizing gout treatment outcomes.
The Journal of Rheumatology 12/2014; 42(3). DOI:10.3899/jrheum.140588 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine patients' preferences for, and understanding of, FRAX® fracture risk conveyed through illustrations.
Drawing on examples from published studies, four illustrations of fracture risk were designed and tested for patient preference, ease of understanding, and perceived risk. We enrolled a convenience sample of adults aged 50 and older at two medical clinics located in the Midwestern and Southern United States. In-person structured interviews were conducted to elicit patient ranking of preference, ease of understanding, and perceived risk for each illustration.
Most subjects (n = 142) were female (64%), Caucasian (76%) and college educated (78%). Of the four risk depictions, a plurality of participants (37%) listed a bar graph as most preferred. Subjects felt this illustration used the stoplight color system to display risk levels well and was the most "clear," "clean," and "easy to read". The majority of subjects (52%) rated the pictogram as the most difficult to understand as this format does not allow people to quickly ascertain their individual risk category.
Communicating risk to patients with illustrations can be done effectively with clearly designed illustrations responsive to patient preference.
ClinicalTrials.gov Identifier: NCT01507662.
BMC Medical Informatics and Decision Making 11/2014; 14(1):101. DOI:10.1186/s12911-014-0101-y · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To examine whether concomitant methotrexate (MTX) use is associated with better biologic persistence and whether self-administered anti-tumor necrosis factor (anti-TNF) therapies are used at reduced doses in real-world clinical care settings, not just clinical trials.
We conducted a retrospective cohort study among rheumatoid arthritis (RA) patients using Medicare claims data from 2006 to 2012. Subjects were new initiators of etanercept, infliximab, adalimumab, abatacept, and tocilizumab with at least 12 months of continuous medical and pharmacy coverage after treatment initiation. We examined the association between concomitant MTX use and persistence on biologic agents using Cox proportional hazards regression, adjusting for demographics and baseline comorbidities. We further identified a subgroup of patients who initiated and were adherent on etanercept or adalimumab for at least 12 months and examined the proportion of patients who subsequently used these therapies at reduced doses continuously for an additional 12, 18, and 24 months.
Of 26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall, patients who initiated biologic monotherapy were 1.4 (95% confidence interval [95% CI] 1.3-1.5) times more likely to discontinue at 1 year compared to those who initiated combination therapy, and 1.8 (95% CI 1.7-2.0) times more likely if starting infliximab monotherapy. Approximately 10-20% of patients who initiated and adhered to etanercept and adalimumab for ≥12 months subsequently received reduced-dose therapy for an 12 additional months and beyond.
In real-world practice, concomitant MTX was associated with improved persistence on biologic therapy, especially for infliximab users; reduced-dose injectable anti-TNF therapy was used by a substantial proportion of RA patients.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To examine the patterns of methotrexate (MTX) use among rheumatoid arthritis (RA) patients.
Using data from RA patients enrolled in a US commercial health plan and the US Medicare program, we identified RA patients initiating oral MTX. Persistence with MTX (oral or subcutaneous [SC]) was defined as no gap for ≥90 days.
New oral MTX users in Medicare (n = 20,431) were 76.9% women, had a mean ± SD age of 69.7 ± 11.7 years, and contributed a median followup of 2.6 years (interquartile range 1.7-3.5 years). Only 38% received dosages ≥20 mg/week at any time. Approximately 50% of patients discontinued MTX at 1 year, although more than one-third of patients subsequently restarted. New commercially insured oral MTX users (n = 4,048) were similar to Medicare patients, except for age. Among Medicare patients, 19% starting oral MTX subsequently initiated a biologic agent, mostly anti-tumor necrosis factor (85%). Of these, only 50% received MTX at a dosage of ≥20 mg/week, and only 21% of individuals switched to SC MTX (4%) or received hydroxychloroquine (8%), sulfasalazine (5%), or leflunomide (8%) prior to biologic agents. In commercially insured patients, 35% initiated a biologic agent, mostly anti-tumor necrosis factor therapies (90%). Of these, 43% never received MTX ≥20 mg/week.
Titration to a higher-dose oral MTX and use of SC MTX among RA patients were infrequent and may have been underutilized. Further work to optimize MTX dosing before patients are switched to a biologic agent may be warranted.
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study was to evaluate screening questions for estimating nonsteroidal anti-inflammatory drug (NSAID) risk knowledge.
Cross-sectional data from a telephone interview of NSAID users 50 years or older from 39 physician practices in Alabama were used. Patient-reported awareness of prescription NSAID risk and health literacy were the independent variables, and a cumulative index score of objectively tested knowledge of 4 prominent NSAID risks was the dependent variable. General linearized latent and mixed model ordered logistic regression was used to estimate associations among the independent variables, covariates, and objectively tested NSAID risk knowledge. Population-averaged probabilities for levels of objectively tested NSAID risk knowledge were subsequently estimated.
Subjective awareness of any prescription NSAID risk (adjusted odds ratio [AOR], 2.40; 95% confidence interval [CI], 1.55-3.74), adequate health literacy (AOR, 1.71; 95% CI, 1.04-2.83), and physician counseling about 1 or more NSAID risks (AOR, 1.69; 95% CI, 1.09-2.61) were significantly and positively associated with NSAID risk knowledge. The probability of correctly answering at least 1 of the 4 NSAID risk knowledge questions was 70% in the absence of any subjective risk awareness and in less than adequate health literacy. Whereas the probability of correctly answering at least 1 of the 4 NSAID risk knowledge questions increased to 86% in the presence of subjective awareness of any prescription NSAID risk and adequate health literacy.
Screening questions for subjective NSAID risk awareness and health literacy are predictive of objectively tested NSAID knowledge and can be used to triage patients as well as subsequently initiate and direct a conversation about NSAID risk.
Journal of Patient Safety 10/2014; Publish Ahead of Print. DOI:10.1097/PTS.0000000000000143 · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Subtrochanteric femoral shaft fractures after little or no trauma have been reported in long-term users of bisphosphonates, but risks relative to hip fracture protective effects and among men are not clear. We examined associations between bisphosphonate use and nontraumatic subtrochanteric (NTST) femoral fractures and hip fractures in the Veterans Health Administration.
This retrospective cohort study was conducted using 1998-2007 Veterans Health Administration electronic medical records data on 78,155 individuals who had a fragility fracture at age 45 years or older. Time-to-event analysis examined associations of bisphosphonates with risk of NTST femoral fracture and, separately, hip fracture, controlling for sociodemographics, medications, and comorbid medical conditions.
The cohort had a mean age 66.5 years (32.5% were ≥75 years old) at the time of their first fracture, and 69.3% were observed for 6 or more years; only 11.8% were prescribed bisphosphonates during observation. During follow-up, 408 had an NTST femoral second fracture, and 1584 had a hip second fracture. Compared with those never on bisphosphonates, the adjusted hazard ratio for NTST femoral second fracture among patients on 4 years of therapy or longer was 0.40 (95% confidence interval, 0.16-0.97) and for hip second fracture was 0.38 (95% confidence interval, 0.24-0.61).
Bisphosphonate treatment in this high-risk cohort was infrequent with few long-term users, limiting power to assess long-term effects. Nontraumatic subtrochanteric femoral fractures were uncommon, and longer bisphosphonate use was associated with lower (not higher) risk. In men, risks of NTST femoral fractures associated with bisphosphonate treatment may be low in contrast to substantial protective benefits for hip fracture.