The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU) in this population. This study investigated the impact of exacerbations on COPD-related HCU. METHODS: This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001-2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe). RESULTS: The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations). Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation (p < 0.01) for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (p < 0.001). CONCLUSIONS: Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.

Differences in self-monitored, blood glucose test strip utilization by therapy for type 2 diabetes mellitus.

AIMS: To determine whether blood glucose test strip (BGTS) utilization in patients with type 2 diabetes (T2D) is associated with the type of diabetes therapy, classified according to hypoglycemic risk. METHODS: A retrospective, longitudinal (2006-2012) study of Canadian private drug plans (PDP) and Ontario Public Drug Programs (OPDP) prescription claims was conducted. Analyses were restricted to patients with T2D with or without a claim for BGTS. Daily BGTS utilization (TS/patient/day) was evaluated by diabetes therapy classified by hypoglycemic risk. Multivariate analyses were conducted to identify determinants of BGTS utilization. RESULTS: The T2D cohort comprised 5,759,591 observations from 1,949,129 claimants. Mean BGTS utilization was 0.84 TS/patient/day and differed between PDP and OPDP (0.66 vs. 1.00). Daily utilization was greatest in patients receiving therapy associated with a pre-defined high risk of hypoglycemia [insulin: basal + bolus (2.16), premixed (1.65), basal (1.16), other insulin regimens (2.13), and sulfonylureas (0.74)] versus non-sulfonylurea non-insulin-based regimens (0.52). For non-insulin therapy, BGTS utilization was greater for patients on multiple non-insulin therapies versus monotherapy (0.74 vs. 0.53 TS/patient/day). In multivariate analyses, drivers for BGTS utilization included insulin use, previous BGTS use, and female gender. Previous diabetes therapy and duration of therapy were negatively correlated with BGTS utilization. CONCLUSIONS: BGTS utilization varies depending on the type of therapy used to treat T2D according to hypoglycemic risk. Decision making regarding BGTS needs to account for robust analyses of current utilization and its value in those settings, including in patients not receiving diabetes therapy and the prevalence of circumstances conducive to more intensive monitoring.

Cost-utility of albiglutide versus insulin lispro, insulin glargine, and sitagliptin for the treatment of type 2 diabetes in the US.

Objective To compare the cost-utility of the glucagon-like peptide-1 receptor agonist albiglutide with those of insulin lispro (both in combination with insulin glargine), insulin glargine, and the dipeptidyl peptidase-4 inhibitor sitagliptin, representing treatments along the type 2 diabetes treatment continuum. Methods The Centre for Outcomes Research and Effectiveness (CORE) Diabetes Model was used for the cost-utility analysis. Data from three Phase 3 clinical trials (HARMONY 6, HARMONY 4, and HARMONY 3) evaluating albiglutide for the treatment of patients with type 2 diabetes were used for the baseline characteristics and treatment effects. Utilities and costs were derived from published sources. Results Albiglutide treatment was associated with an improvement in mean quality-adjusted life expectancy of 0.099, 0.033, and 0.101 years when compared with insulin lispro, insulin glargine, and sitagliptin, respectively. Over the 50-year time horizon, mean total costs in the albiglutide arm were $4332, $2597, and $2223 more than in the other respective treatments. These costs resulted in an incremental cost-utility ratio of $43,541, $79,166, and $22,094 per quality-adjusted life-year (QALY) gained for albiglutide vs insulin lispro, insulin glargine, and sitagliptin, respectively. At a willingness-to-pay threshold of $50,000 per QALY gained, there was a 53.0%, 41.5%, and 67.5% probability of albiglutide being cost-effective compared with the other respective treatments. Limitations This analysis was an extrapolation over a 50-year time horizon based on relatively short-term data obtained during clinical trials. It does not take into account potential differences between the respective treatments in adherence and persistence that can influence both effects and costs. Conclusions Albiglutide represents a reasonable treatment option for patients with type 2 diabetes based on its cost-utility, relative to insulin lispro, insulin glargine, and sitagliptin.

Assessing the Reliability of a Semiautomated Segmentation Algorithm for Quantifying Erosions in the Metacarpophalangeal Joints of Patients with Rheumatoid Arthritis.

OBJECTIVE: Assess the reliability of early erosions in rheumatoid arthritis (EERA) software for quantifying erosive damage to the metacarpophalangeal joints of patients with rheumatoid arthritis (RA). METHODS: One hundred magnetic resonance image sets from 68 patients with early referral RA were evaluated. Reliability was assessed using 95% limits of agreement and intraclass correlation coefficient (ICC) with 95% CI. RESULTS: Limits of agreement linearly depended on erosion volume: 0.44× between readers and 0.19× within readers. Interrater ICC was 0.976 (95% CI 0.965-0.984) and intrarater ICC was 0.996 (95% CI 0.994-0.997). CONCLUSION: EERA is highly reproducible for quantifying erosions in patients with early RA.

A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial.

BACKGROUND: Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA. METHODS: A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of 186 (62 per group) patients will be required to determine a 36% difference in pharmacological treatment escalation between the three groups with intermediate dispersion of data with 90% power at a 5% level of significance. DISCUSSION: This study will determine if monitoring RA and undifferentiated inflammatory arthritis patients using MRI and X-ray every 6 months over 2 years provides incremental evidence over standard of care to influence pharmacotherapeutic decision-making and ultimately hinder disease progression. TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008).

A parallel group cohort to determine the measurement properties of an early inflammatory arthritis detection tool.

OBJECTIVES: To determine the comprehensibility, internal consistency, test-retest reliability and discriminative properties of an early inflammatory arthritis (IA) detection tool. METHODS: Four groups were recruited from outpatient clinics at two tertiary care hospitals: early IA, established IA, non-IA musculoskeletal conditions (MSK) and non-MSK. Participants attended a study visit where they completed the 11-item tool with binary yes/no response options. Comprehensibility was assessed for each tool item on a 5-point Likert scale. For test-retest assessment, the tool was mailed to participants following a 2-week recall washout interval. Two items were randomly selected to test internal consistency. Discriminative properties compared tool item responses with blinded rheumatologist clinical assessments. A previously developed rheumatology triage algorithm was externally validated. RESULTS: A total of 170 participants were enrolled in the study. Comprehensibility approached unity for all tool items. The internal consistency Kuder-Richardson Formula 20 was 0.985 (P < 0.0001). The mean test-retest reliability kappa (S.D.) was 0.81 (0.02). The intraclass correlation coefficient (ICC) (95% CI) for summed yes responses between test and retest phases was 0.94 (0.93, 0.95) and for algorithm scores was 0.97 (0.96, 0.98). Patient responses were significantly associated with the corresponding clinical evaluations (P < 0.0001, respectively). The sum of yes responses and rheumatology triage algorithm scores both differentiated early IA from each of the other three groups (P < 0.004, respectively). The scoring algorithm receiver operating characteristic plot area under the curve (S.E.) was 0.829 (0.003). CONCLUSION: The tool has favourable measurement and discriminative properties. The discriminative properties of the rheumatology triage scoring algorithm were externally validated.

Validation of a self-administered inflammatory arthritis detection tool for rheumatology triage.

OBJECTIVE: The benefits of early intensive treatment of inflammatory arthritis (IA) are dependent on timely and accurate case identification. In our study, a scoring algorithm for a self-administered IA detection tool was developed and validated for the rheumatology triage clinical setting. METHODS: A total of 143 consecutive consenting adults, newly referred to 2 outpatient rheumatology practices, completed the tool. A scoring algorithm was derived from the best-fit logistic regression model using age, sex, and responses to the 12 tool items as candidate predictors of the rheumatologists' blinded classification of IA. Bootstrapping was used to internally validate and refine the model. RESULTS: The 30 IA cases were younger than the 113 non-cases (p < 0.0001) and included clinical diagnoses of early IA (n = 10), rheumatoid arthritis (n = 9), and spondyloarthropathies (n = 11). Non-cases included osteoarthritis (n = 46), pain syndromes (n = 19), systemic lupus erythematosus (n = 5), and miscellaneous, noninflammatory musculoskeletal complaints (n = 43). The best-fit model included younger age, male sex, "trouble making a fist," "morning stiffness," "ever told you have RA," and "psoriasis diagnosis." The overall predictive performance (standard error, SE) of the derivation model was 0.91 (0.03). Internal validation of the derivation model across 200 bootstrap samples resulted in a mean predictive performance (SE) of 0.904 (0.002). The refined tool had a mean predictive performance (SE) of 0.915 (0.002), a sensitivity of 0.855 (0.005), and specificity of 0.873 (0.003). CONCLUSION: A simple, self-administered tool was developed and internally validated for the sensitive and specific detection of IA in a rheumatology waiting list sample. The tool may be used to triage IA from rheumatology referrals.

Time to disease-modifying antirheumatic drug treatment in rheumatoid arthritis and its predictors: a national, multicenter, retrospective cohort.

OBJECTIVE: To determine the proportion of patients with rheumatoid arthritis (RA) under rheumatologic care treated with disease-modifying antirheumatic drugs (DMARD) within 6 months from symptom onset and the components of time to treatment and its predictors. METHODS: A historical inception cohort of 339 patients with RA randomly selected from 18 rheumatology practices was audited. The proportion that initiated DMARD treatment within 6 months from symptom onset was estimated using Kaplan-Meier analysis. Time to each component of the care pathway was estimated. Multivariable modeling was used to determine predictors of early treatment using 12 preselected variables available in the clinical charts. Bootstrapping was used to validate the model. RESULTS: Within 6 months from symptom onset, 41% (95% CI 36%-46%) of patients were treated with DMARD. The median time to treatment was 8.4 (interquartile range 3.8-24) months. Events preceding rheumatology referral accounted for 78.1% of the time to treatment. The most prominent predictor of increased time to treatment was a concomitant musculoskeletal condition, such as osteoarthritis or fibromyalgia. The significance of other variables was less consistent across the models investigated. Included variables accounted for 0.69 ± 0.03 of the variability in the model. CONCLUSION: Fewer than 50% of patients with RA are treated with DMARD within 6 months from symptom onset. Time to referral to rheumatology represents the greatest component delay to treatment. Concomitant musculoskeletal condition was the most prominent predictor of delayed initiation of DMARD. Implications of these and other findings warrant further investigation.

Early management of newly diagnosed rheumatoid arthritis by Canadian rheumatologists: a national, multicenter, retrospective cohort.

OBJECTIVE: To describe early rheumatologic management for newly diagnosed rheumatoid arthritis (RA) in Canada. METHODS: A retrospective cohort of 339 randomly selected patients with RA diagnosed from 2001-2003 from 18 rheumatology practices was audited between 2005-2007. RESULTS: The most frequent initial disease-modifying antirheumatic drugs (DMARD) included hydroxychloroquine (55.5%) and methotrexate (40.1%). Initial therapy with multiple DMARD (15.6%) or single DMARD and corticosteroid combinations (30.7%) was infrequent. Formal assessment measures were noted infrequently, including the Health Assessment Questionnaire (34.6%) and Disease Activity Score for 28 joints (8.9%). CONCLUSION: Initial pharmacotherapy is consistent with guidelines from the period. The infrequent reporting of multiple DMARD combinations and formal assessment measures has implications for current clinical management and warrants contemporary reassessment.

Classification of rheumatologic opinion on early inflammatory arthritis: harmonization of a heterogeneous standard.

OBJECTIVE: Interrater variability limits rheumatologic opinion as a reference standard for early inflammatory arthritis (IA) classification. The study objectives were to determine whether rheumatologic opinion is associated with potential early IA classification methods despite high interrater variability, and to compare the relative strengths of those associations. METHODS: Eighteen rheumatologists independently classified 30 initial rheumatology presentation summaries as early IA or not and recommended a pharmacotherapy. Case fulfillment of the following classification methods was independently determined: early referral to rheumatology recommendation for rheumatoid arthritis (ERRR), common early IA cohort inclusion criteria (CEAC), and prevalent IA classification criteria (American College of Rheumatology [ACR]/European Spondylarthropathy Study Group [ESSG]). Associations between rheumatologic opinion, disease-modifying antirheumatic drug (DMARD) recommendation, and each classification method were determined. RESULTS: Participating rheumatologists published on early IA and represented 3 continents. The median case was age 43 (interquartile range [IQR] 30-53) years, had 40 (IQR 24-104) weeks of symptoms, 60 (IQR 18-120) minutes of morning stiffness, a swollen joint count of 6 (IQR 1-13), and an erythrocyte sedimentation rate of 25 (IQR 10-51) mm/hour. The mean ± SD multiple-rater kappa for rheumatologic opinion on early IA was 0.16 ± 0.02. The common odds ratios for associations between rheumatologic opinion and ERRR, CEAC, and ACR/ESSG were 10.3 (95% confidence interval [95% CI] 4.6-23.2), 4.4 (95% CI 2.5-7.7), and 0.7 (95% CI 0.4-1.1), respectively. Odds ratios for associations between DMARD recommendation and ERRR, rheumatologic opinion, CEAC, and ACR/ESSG were 18.7 (95% CI 8.1-43.2), 10.6 (95% CI 6.0-18.8), 2.8 (95% CI 1.7-4.6), and 0.5 (95% CI 0.3-0.7), respectively. CONCLUSION: Classification methods can be used to harmonize rheumatologic opinion of early IA despite high interrater variability. The ERRR is very strongly associated with both rheumatologic opinions of early IA and DMARD treatment recommendations.

Development of a self-administered early inflammatory arthritis detection tool.

BACKGROUND: Barriers to care limit the potential benefits of pharmacological intervention for inflammatory arthritis. A self-administered questionnaire for early inflammatory arthritis (EIA) detection may complement contemporary triage interventions to further reduce delays to rheumatologic care. The objective of this study was to develop a self-administered EIA detection tool for implementation in pre-primary care settings. METHODS: A core set of dimensions and constructs for EIA detection were systematically derived from the literature and augmented by investigative team arbitration. Identified constructs were formulated into lay language questions suitable for self-administration. A three-round Delphi consensus panel of EIA experts and stakeholders evaluated the relevance of each question to EIA detection and suggested additional items. Questions accepted by less than 70% of respondents in rounds one or two were eliminated. In round three, questions accepted by at least 80% of the panel were selected for the tool. RESULTS: Of 584 citations identified, data were extracted from 47 eligible articles. Upon arbitration of the literature synthesis, 30 constructs encompassing 13 dimensions were formulated into lay language questions and posed to the Delphi panel. A total of 181 EIA experts and stakeholders participated on the Delphi panel: round one, 60; round two, 59; and, round three, 169; 48 participated in all three rounds. The panel evaluated the 30 questions derived from the literature synthesis, suggested five additional items, and eliminated a total of 24. The eleven-question instrument developed captured dimensions of articular pain, swelling, and stiffness, distribution of joint involvement, function, and diagnostic and family history. CONCLUSIONS: An eleven-question, EIA detection tool suitable for self-administration was developed to screen subjects with six to 52 weeks of musculoskeletal complaints. Psychometric and performance property testing of the tool is ongoing.