Changes in alcohol intake and serum urate changes: longitudinal analyses of annual medical examination database.

INTRODUCTION: Despite the established cross-sectional association between alcohol intake and serum urate (SU), its longitudinal association remains unknown. This study aimed to determine whether changes in alcohol intake have a clinically relevant association with SU change. METHOD: We conducted retrospective analyses using systematically collected annual medical examination data from October 2012 to October 2022 in a Japanese preventive medicine centre. The exposure was changes in alcohol intake between two consecutive visits. The association of SU changes with alcohol intake changes was estimated by mixed-effect linear regression with adjustment for relevant covariates. RESULTS: We analysed 63 486 participants (median age, 47.0 years; 55% women; 58.6% regular alcohol drinkers with a median of 1.4 drinks/day) with 370 572 visits. The median SU level was 5.3 mg/dL, and 506 (0.8%) participants had diagnoses of gout or hyperuricemia without medication use during the study period. Decreasing one daily alcohol intake had a clinically small association with SU changes (-0.019 (95% CI: -0.021 to -0.017) mg/dL). Beer had the largest association with SU (-0.036 (95% CI: -0.039 to -0.032) mg/dL for one beer decrease). Complete discontinuation of any alcohol from a mean of 0.8 drinks/day was associated with -0.056 mg/dL (95% CI: -0.068 to -0.043) decrease in SU; the association became larger in hyperuricemic participants (-0.110 mg/dL (95% CI: -0.154 to -0.066) for alcohol discontinuation from a mean of 1.0 drinks/day). CONCLUSIONS: This study revealed changes in alcohol intake had small associations with SU change at the general Japanese population level. Complete discontinuation of alcohol in hyperuricemic participants had only modest improvement in SU.

Prevalence and Characteristics of Adults with Difficult-to-Treat Rheumatoid Arthritis in a Large Patient Registry.

OBJECTIVES: An estimated 5-20% of patients with rheumatoid arthritis (RA) fail multiple treatments and are considered "difficult-to-treat" (D2T), posing a substantial clinical challenge for rheumatologists. A European Alliance of Associations for Rheumatology (EULAR) task force proposed a definition of D2T-RA in 2021. We applied EULAR's D2T definition in a cohort of patients with established RA to assess prevalence and we compared clinical characteristics of participants with D2T-RA with matched comparisons. METHODS: Data from the longitudinal Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry was used. Participants were classified as D2T if they met EULAR's definition. A comparison group of non-D2T RA patients were matched 2:1 to every D2T patient, and differences in characteristics were evaluated in descriptive analyses. Prevalence rates of D2T were estimated using Poisson regression. RESULTS: We estimated the prevalence of D2T-RA to be 14.4 (95% CI: 12.8-16.3 per 100 persons) among 1,581 participants with RA, and 22.3 (95% CI: 19.9-25.0 per 100 persons) among 1,021 who were biologic/targeted synthetic DMARD experienced. We observed several differences in demographics, comorbidities, and RA disease activity between D2T-RA and non-D2T RA comparisons. Varying EULAR sub-criteria among all participants in BRASS resulted in a range of D2T-RA prevalence rates, from 0.6-17.5 per 100 persons. CONCLUSION: EULAR's proposed definition of D2T-RA identifies patients with RA who have not achieved treatment targets. Future research should explore heterogeneity in these patients and evaluate outcomes to inform the design of future studies aimed at developing more effective RA management protocols.

Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial.

OBJECTIVES: Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable treatment on the risk of disease activity flares in patients with RA in remission ≥1 year. METHODS: This randomised, open-label, non-inferiority trial was undertaken at nine Norwegian rheumatology departments. Patients with RA in remission ≥12 months on stable TNFi therapy were allocated by computer-based block-randomisation to tapering to discontinuation of TNFi or stable TNFi. Conventional synthetic disease-modifying antirheumatic co-medication was unchanged. The primary endpoint was disease flare during the 12-month study period (non-inferiority margin 20%), assessed in the per-protocol population. RESULTS: Between June 2013 and January 2019, 99 patients were enrolled and 92 received the allocated treatment strategy. Eighty-four patients were included in the per-protocol population. In the tapering TNFi group, 27/43 (63%) experienced a flare during 12 months, compared with 2/41 (5%) in the stable TNFi group; risk difference (95% CI) 58% (42% to 74%). The tapering strategy was not non-inferior to continued stable treatment. The number of total/serious adverse events was 49/3 in the tapering group, 57/2 in the stable group. CONCLUSION: In patients with RA in remission for more than 1 year while using TNFi, an increase in flare rate was reported in those who tapered TNFi to discontinuation. However, most regained remission after reinstatement of full-dose treatment. TRIAL REGISTRATION NUMBERS: EudraCT: 2012-005275-14 and clinicaltrials.gov: NCT01881308.

Examining the potential direct cardiovascular benefit of tumor-necrosis factor inhibitor in rheumatoid arthritis: Natural and controlled direct effect analyses.

BACKGROUND/PURPOSE: Tumor necrosis factor inhibitors (TNFi) may have a direct benefit on cardiovascular (CV) disease beyond reducing rheumatoid arthritis (RA) disease activity measured by the Clinical Disease Activity Index (CDAI). METHODS: We compared TNFi initiators and methotrexate (MTX) monotherapy initiators from the CorEvitas RA registry. Two approaches to the "direct effect" of TNFi beyond CDAI were used. In the natural direct effect (NDE) analysis, the potential CV benefit of TNFi was partitioned into NDE and the natural indirect effect (NIE) mediated by CDAI during the first 6 months. We also estimated the controlled direct effects (CDE), corresponding to the direct benefit of TNFi when CDAI trajectories were hypothetically equalized between the initiators of TNFi and MTX monotherapy at a constant value. Estimates were given on the hazard ratio scale. RESULTS: We identified 5764 initiators of TNFi and 3588 initiators of MTX monotherapy. TNFi initiators were younger (58 vs. 64 years) with a shorter disease duration. Our total effect estimates (TNFi vs. MTX [reference]) were protective in direction (0.76-0.91). The NDE estimate was 0.76 [95% confidence interval (CI) 0.59, 0.98], whereas the NIE estimate was 1.00 [95%CI 1.00, 1.00]. In the CDE analyses accounting for longitudinal CDAI, the CDE estimates was 1.27 [95%CI 0.60, 2.69]. CONCLUSIONS: We could not convincingly demonstrate a direct benefit of TNFi outside its impact on CDAI. At present, the emphasis should be on the stringent control of RA disease activity, a known important CV risk factor, regardless of medication choice.

Discontinuation of Conventional Synthetic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis and Excellent Disease Control.

This open-label randomized clinical trial assessed the 12-month risk of disease activity flares after discontinuation of conventional synthetic DMARDs (csDMARDs) compared with continuing half-dose csDMARDs in adult Norwegian patients with rheumatoid arthritis and excellent disease control.

Impact of RA treatment strategies on lipids and vascular inflammation in rheumatoid arthritis: a secondary analysis of the TARGET randomized active comparator trial.

BACKGROUND: Treatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk. METHODS: In this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR. RESULTS: We studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms. CONCLUSIONS: Both treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02374021.

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial.

BACKGROUND: Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. METHODS: In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. FINDINGS: Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). INTERPRETATION: Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. FUNDING: Research Council of Norway and South-Eastern Norway Regional Health Authority.

A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.

A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.

Implementing a Treat-to-Target Approach for Rheumatoid Arthritis During the COVID-19 Pandemic: Results of a Virtual Learning Collaborative Program.

OBJECTIVE: A treat-to-target (TTT) approach improves outcomes in rheumatoid arthritis (RA). In prior work, we found that a learning collaborative (LC) program improved implementation of TTT. We conducted a shorter virtual LC to assess the feasibility and effectiveness of this model for quality improvement and to assess TTT during virtual visits. METHODS: We tested a 6-month virtual LC in ambulatory care. The LC was conducted during the 2020-2021 COVID-19 pandemic when many patient visits were conducted virtually. All LC meetings used videoconferencing and a website to share data. The LC comprised a 6-hour kickoff session and 6 monthly webinars. The LC discussed TTT in RA, its rationale, and rapid cycle improvement as a method for implementing TTT. Practices provided de-identified patient visit data. Monthly webinars reinforced topics and demonstrated data on TTT adherence. This was measured as the percentage of TTT processes completed. We compared TTT adherence between in-person visits versus virtual visits. RESULTS: Eighteen sites participated in the LC, representing 45 rheumatology clinicians. Sites inputted data on 1,826 patient visits, 78% of which were conducted in-person and 22% of which were held in a virtual setting. Adherence with TTT improved from a mean of 51% at baseline to 84% at month 6 (P for trend < 0.001). Each aspect of TTT also improved. Adherence with TTT during virtual visits was lower (65%) than during in-person visits (79%) (P < 0.0001). CONCLUSION: Implementation of TTT for RA can be improved through a relatively low-cost virtual LC. This improvement in TTT implementation was observed despite the COVID-19 pandemic, but we did observe differences in TTT adherence between in-person visits and virtual visits.

Routinely measuring and reporting pneumococcal vaccination among immunosuppressed rheumatology outpatients: the first step in improving quality.

OBJECTIVE: The Centers for Disease Control (CDC) recommends pneumococcal vaccination for immunocompromised patients. Data suggest that rates of vaccination in this population are not optimal. To support continuous quality improvement efforts, we electronically measured vaccination status among rheumatology outpatients over time. METHODS: Using data from administrative (billing) and electronic health record sources, we identified rheumatology clinic patients seen between 1 February 2008 and 31 January 2010 and prescribed an immunosuppressive medication. CDC recommendations for pneumococcal vaccination were applied. We calculated the proportion of eligible patients who were up-to-date with pneumococcal vaccination: (i) while on an immunosuppressive medication and (ii) before newly starting an immunosuppressive medication in the last 12 months. RESULTS: We identified 2763 rheumatology clinic patients on immunosuppressive medications, with 568 initiated in the last 12 months. The mean age was 57 years, 75% were female and 77% were Caucasian. The most frequent disease was RA (50%) and the most common immunosuppressive medication was MTX (59%). Of patients on immunosuppressive medications, 1491/2763 (54%) were up to date with pneumococcal vaccination. Among new initiators of immunosuppressive medications, 258/568 (45%) were vaccinated before starting the immunosuppressive medication. Patients treated by rheumatologists in practice for ≤10 years were more likely to be up to date with pneumococcal vaccination (72%) than those with providers in practice >10 years (52%, P < 0.001). CONCLUSION: The proportion of patients who are up to date with documented pneumococcal vaccination was suboptimal in our rheumatology practice. The ability to continuously repeat electronic measurement permits us to initiate continuous quality improvement efforts.

Designing a Strategy Trial for the Management of Gout: The Use of a Modified Delphi Panel.

OBJECTIVE: Disagreement exists between rheumatology and primary care societies regarding gout management. This paper describes a formal process for gathering input from stakeholders in the planning of a trial to compare gout management strategies. METHODS: We recruited patients, nurses, physician assistants, primary care clinicians, and rheumatologists to participate in a modified Delphi panel (mDP) to provide input on design of a trial focused on optimal management for primary care patients with gout. The 16 panelists received a plain-language briefing document that discussed the rationale for the trial, key clinical issues in gout, and aspects of trial design. The panelists also received information and considerations on nine voting questions (VQs), judged to be the key design questions. Cognitive interviews with panelists ensured that the VQs were understood by the range of panelists involved in the mDP. Panelists were asked to score all VQs from 1 (definitely no) to 9 (definitely yes). Two voting rounds were conducted-round 1 by email and round 2 by video conference. RESULTS: The VQs were modified through the cognitive interviews. The round 1 voting resulted in consensus on eight items, with consensus defined as median voting score in the same tercile (1-3, 4-6 or 7-9). Re-voting at the meeting (round 2) reached consensus on the remaining item. CONCLUSION: An mDP with various stakeholders facilitated consensus on the design of a trial of different management strategies for chronic gout. This method may be useful for designing trials of clinical questions with substantial disagreement across stakeholders.

Rationale and design of the Study Assessing the Effect of Cardiovascular Medications Provided as Low-cost, Evidence-based Generic Samples (SAMPLES) trial.

BACKGROUND: Highly effective generic cardiovascular medications are frequently underused, leading to greater overall drug costs and cost-related nonadherence. OBJECTIVE: We sought to assess an intervention to stimulate appropriate generic cardiovascular drug use without creating administrative or financial barriers that may impede essential medication use. TRIAL DESIGN: The SAMPLES (Study Assessing the Effect of Cardiovascular Medications Provided as Low-cost, Evidence-based Generic Samples) trial is a clustered, randomized controlled trial of the effect of providing physicians with free generic samples of hydrochlorothiazide for hypertensive patients and simvastatin for patients with hyperlipidemia. We will randomize 660 primary care physicians in Pennsylvania, clustered by physician practice, to receive free samples for both conditions or to receive no samples. We will use data on filled prescriptions obtained from a state-sponsored prescription drug assistance program to perform an intention-to-treat evaluation of the impact of the intervention on physician prescribing behavior (proportion of prescriptions that are generic) and patient adherence. Secondary outcomes will include physician adherence to established guidelines and overall prescription drug costs. CONCLUSION: This trial will define the potential role of an innovative approach to stimulate clinically appropriate cost-effective prescribing. We will determine whether free generic samples can reduce overall drug costs as well as out-of-pocket costs to the patient without sacrificing efficacy and whether this approach results in improved adherence to essential cardiovascular medications. This intervention may also improve adherence to practice guidelines and improve the quality of care received. If effective, this strategy could be used broadly by private insurers or government payers aiming to stimulate more cost-effective and higher-quality care.

Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease-Modifying Antirheumatic Drugs: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess hepatitis B virus (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving disease-modifying antirheumatic drugs (DMARDs) and with or without antiviral prophylaxis. METHODS: We conducted a systematic review and meta-analysis. Electronic searches were conducted in PubMed, Medline, and Embase using Ovid through December 31, 2015. A search strategy was developed for each database using the following inclusion criteria: for participants, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and resolved or chronic HBV infection; for intervention, tumor necrosis factor (TNF) inhibitors or non-TNF biologic or nonbiologic DMARDs; and for outcome, HBV reactivation. Four reviewers independently extracted study data and assessed study quality using the Newcastle-Ottawa Scale. To determine the pooled HBV reactivation rate, the variances of the raw proportions were stabilized using a Freeman-Tukey-type arcsine square root transformation, using a random-effects model. RESULTS: Twenty-five studies met the inclusion criteria. The overall pooled rate of HBV reactivation was 1.6% (95% confidence interval [95% CI] 0.8-2.6) in patients with resolved HBV. Similar rates were observed in resolved patients taking TNF inhibitors (1.4% [95% CI 0.5-2.6]), non-TNF biologics (6.1% [95% CI 0.0-16.6]), and nonbiologic DMARDs (1.7% [95% CI 0.2-4.2]). We also found that the reactivation rate was lower in patients with chronic HBV infection who received antiviral prophylaxis (9.0% [95% CI 4.1-15.5]) than in those who did not (14.6% [95% CI 4.3-29.0]). CONCLUSION: We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis.

Osteoporosis improvement: a large-scale randomized controlled trial of patient and primary care physician education.

UNLABELLED: We conducted a randomized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries. Primary care physicians and their patients were randomized to usual care, patient intervention only, physician intervention only, or both interventions. There was no difference in the probability of the primary composite endpoint (BMD test or osteoporosis medication) or in either of its components comparing the combined intervention group with usual care (risk ratio = 1.04; 95% CI, 0.85-1.26). INTRODUCTION: Fractures from osteoporosis are associated with substantial morbidity, mortality, and cost. However, only a minority of at-risk older adults receives screening and/or treatment for this condition. We evaluated the effect of educational interventions for osteoporosis targeting at-risk patients, primary care physicians, or both. MATERIALS AND METHODS: We conducted a randomized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries. Primary care physicians and their patients were randomized to usual care, patient intervention only, physician intervention only, or both interventions. The at-risk patients were women >or=65 yr of age, men and women >or=65 yr of age with a prior fracture, and men and women >or=65 yr of age who used oral glucocorticoids. The primary outcome studied was a composite of either undergoing a BMD test or initiating a medication used for osteoporosis. The secondary outcome was a hip, humerus, spine, or wrist fracture. RESULTS: We randomized 828 primary care physicians and their 13,455 eligible at-risk patients into four study arms. Physician and patient characteristics were very similar across all four groups. Across all four groups, the rate of the composite outcome was 10.3 per 100 person-years and did not differ between the usual care and the combined intervention groups (p = 0.5). In adjusted Cox proportional hazards models, there was no difference in the probability of the primary composite endpoint comparing the combined intervention group with usual care (risk ratio = 1.04; 95% CI, 0.85-1.26). There was also no difference in either of the components of the composite endpoint. The probability of fracture during follow-up was 4.2 per 100 person-years and did not differ by treatment assignment (p = 0.9). CONCLUSIONS: In this trial, a relatively brief program of patient and/or physician education did not work to improve the management of osteoporosis. More intensive efforts should be considered for future quality improvement programs for osteoporosis.

Medicaid prior-authorization programs and the use of cyclooxygenase-2 inhibitors.

BACKGROUND: Over the past five years, selective cyclooxygenase-2 inhibitors (coxibs) have accounted for a growing proportion of prescriptions for nonsteroidal antiinflammatory drugs (NSAIDs). To control these expenses, many state Medicaid programs have implemented prior-authorization requirements before coxibs can be prescribed. We evaluated the effect of such programs on the use of coxibs by Medicaid beneficiaries. METHODS: We surveyed state Medicaid agencies to determine whether prescription of coxibs required prior authorization and, if so, the criteria for authorization. For each program, we compared these criteria with evidence-based recommendations for prescribing of coxibs. Using data for all filled prescriptions in 50 state Medicaid programs from 1999 through the end of 2003, we calculated the proportion of defined daily doses of NSAIDs accounted for by coxibs. Time-series analyses were used to measure the changes in prescription patterns after the implementation of each prior-authorization program. RESULTS: By 2001, coxibs accounted for half of all NSAID doses covered by Medicaid. This proportion varied widely according to the state in 2003, from a low of 11 percent to a high of 70 percent of all NSAID doses. Twenty-two states implemented prior-authorization programs for coxibs during the study period. Overall, the implementation of such programs reduced the proportion of NSAID doses made up by coxibs by 15.0 percent (95 percent confidence interval, 10.9 to 19.2 percent), corresponding to a decrease of 10.28 dollars (95 percent confidence interval, 7.56 dollars to 13.00 dollars) in spending per NSAID prescription. The effect of such programs was not influenced by the degree to which a prior-authorization program incorporated evidence-based prescribing recommendations. CONCLUSIONS: The use of coxibs and spending on NSAIDs varies widely by state and declined substantially after the implementation of prior-authorization programs. Determining whether these reductions are clinically appropriate will have important implications for the development of rational drug-reimbursement policies.

Self-management education programs in chronic disease: a systematic review and methodological critique of the literature.

BACKGROUND: Self-management programs have been widely reported to help patients manage symptoms and contain utilization of health care resources for several chronic conditions, but to date no systematic review across multiple chronic diseases has been reported. We evaluated the efficacy of patient self-management educational programs for chronic diseases and critically reviewed their methodology. METHODS: We searched MEDLINE and HealthSTAR for the period January 1, 1964, through January 31, 1999, then hand searched the reference section of each article for other relevant publications. We included studies if a self-management education intervention for a chronic disease was reported, a concurrent control group was included, and clinical outcomes were evaluated. Two authors reviewed each study and extracted the data on clinical outcomes. RESULTS: We included 71 trials of self-management education. Trial methods varied substantially and were suboptimal. Diabetic patients involved with self-management education programs demonstrated reductions in glycosylated hemoglobin levels (summary effect size, 0.45; 95% confidence interval [CI], 0.17-0.74); diabetic patients had improvement in systolic blood pressure (summary effect size, 0.20; 95% CI, 0.01-0.39); and asthmatic patients experienced fewer attacks (log rate ratio, 0.59; 95% CI, 0.35-0.83). Although we found a trend toward a small benefit, arthritis self-management education programs were not associated with statistically significant effects. Evidence of publication bias existed. CONCLUSIONS: Self-management education programs resulted in small to moderate effects for selected chronic diseases. In light of evidence of publication bias, further trials that adhere to a standard methodology would help clarify whether self-management education is worthwhile.