Long-term nonsteroidal anti-inflammatory drug (NSAID) use was protective against Alzheimer disease. Findings were clearest for ibuprofen. A beta (1-42)-suppressing NSAIDs did not differ from others.

ABSTRACT

Objective. Investigators in trials of glucosamine report a range of estimates for efficacy, making conclusions difficult. We undertook this study to identify factors that explain heterogeneity in trials of glucosamine.Methods. We searched for reports of trial results in Ovid Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and proceedings of scientific conferences. We selected reports of randomized, double-blind, placebocontrolled trials of glucosamine for pain from osteoarthritis of the knee or hip. We extracted data regarding features of design, subjects, and markers of industry involvement, including industry funding, whether a drug was supplied by industry, industry participation, and industry-affiliated authorship. We examined which factors best accounted for differences in the effect sizes of studies grouped by these characteristics, and we examined changes in I 2 , a measure of heterogeneity. Results. Fifteen trials met our inclusion criteria. The summary effect size was 0.35 (95% confidence interval 0.14, 0.56). I 2 was 0.80. Except for allocation concealment, no feature of study design explained this substantial heterogeneity. Summary effect sizes ranged from 0.05 to 0.16 in trials without industry involvement, but the range was 0.47-0.55 in trials with industry involvement. The effect size was 0.06 for trials using glucosamine hydrochloride and 0.44 for trials using glucosamine sulfate. Trials using Rottapharm products had an effect size of 0.55, compared with 0.11 for the rest.Conclusion. Heterogeneity among trials of glucosamine is larger than would be expected by chance. Glucosamine hydrochloride is not effective. Among trials with industry involvement, effect sizes were consistently higher. Potential explanations include different glucosamine preparations, inadequate allocation concealment, and industry bias.Osteoarthritis (OA) is one of the most common chronic diseases affecting Americans and is a major source of disability in elderly persons (1). Pharmacologic therapy for pain relief is widely perceived to be the backbone of effective management. Unfortunately, many of the most effective pain relievers, especially nonsteroidal antiinflammatory drugs, have well-known side effects that limit their use.Glucosamine, which is classified as a "dietary supplement" in the US and is available over the counter, appears to be safe and is widely marketed for pain relief in OA. However, its efficacy is uncertain. While several trials have suggested that glucosamine has a marginal, if any, effect compared with placebo, others report robust efficacy.In a series of trials using similar methods and subjects, we would expect random variation in the estimate of the true effect of an intervention. If the observed variation in outcomes from trial to trial is consistent with chance variation, then the trials are said to be homogeneous (i.e., the trials are all evaluating the same effect and their conclusions are similar). If the observed variation in outcomes is...

Objective. To identify classification criteria for the rheumatic diseases and to evaluate their measurement properties and methodologic rigor using current measurement standards. Methods. We performed a systematic review of published literature and evaluated criteria sets for stated purpose, derivation and validation sample characteristics, methods of criteria generation and reduction, and consideration of validity, and reliability. Results. We identified 47 classification criteria sets encompassing 13 conditions. Approximately 50% of the criteria sets were developed based on expert opinion rather than patient data. Of the 47 criteria sets, control samples were derived from patients with rheumatic disease in 15 (32%) sets, from patients with nonrheumatic diseases in 4 (9%) sets, and from healthy participants in 2 (4%) sets. Where patient data were used, the number of cases ranged from 20 -588 and the number of controls from 50 -787. In only 1 (2%) criteria set was there a distinct separation between investigators who derived the criteria set and clinicians who provided cases and controls. Authors commented on the need for individual criterion to be reliable in 5 (11%) sets, precise in 5 (11%) sets; authors noted the importance of content validity in 12 (26%) sets, and construct validity in 12 (26%) sets. Conclusion. The variation in methodologic rigor used in sample selection affects the validity and reliability of the criteria sets in different clinical and research settings. Despite potential deficiencies in the methods used for some criteria development, the sensitivity and specificity of many criteria sets is moderate to strong. KEY WORDS. Classification criteria; Methodologic properties; Rheumatic disease. INTRODUCTIONClassification criteria for the rheumatic diseases are the basis for much research in clinical rheumatology. Classification criteria serve to define disease groups for clinical and epidemiologic studies. If they are not valid, participants without disease may be included in disease groups in studies, and participants with clear-cut disease may be excluded. Thus, the validity of classification criteria is Standards for the development and validation of classification criteria have changed substantially over time. Recommendations for the development and validation of criteria sets have been proposed based on the current standards of measurement science (1,2). The classification criteria currently in use have been published over several decades, and many of them precede our current understanding of how to develop valid criteria; therefore there is likely to be variation in the methodologies used in the development, validation, and performance characteristics of classification criteria. Furthermore, advances in our understanding of the pathophysiology of disease, diagnostic tests, patient populations, and treatments during the past 20 years suggest that some criteria sets need to be updated. Therefore, the methodology of the development and the subsequent validity and reliability of classification...

Study question Is there concordance between hip pain and radiographic hip osteoarthritis? Methods In this diagnostic test study, pelvic radiographs were assessed for hip osteoarthritis in two cohorts: the Framingham Osteoarthritis Study (community of Framingham, Massachusetts) and the Osteoarthritis Initiative (a multicenter longitudinal cohort study of osteoarthritis in the United States). Using visual representation of the hip joint, participants reported whether they had hip pain on most days and the location of the pain: anterior, groin, lateral, buttocks, or low back. In the Framingham study, participants with hip pain were also examined for hip pain with internal rotation. The authors analysed the agreement between radiographic hip osteoarthritis and hip pain, and for those with hip pain suggestive of hip osteoarthritis they calculated the sensitivity, specificity, positive predictive value, and negative predictive value of radiographs as the diagnostic test. Study answer and limitations In the Framingham study (n=946), only 15.6% of hips in patients with frequent hip pain showed radiographic evidence of hip osteoarthritis, and 20.7% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of radiographic hip osteoarthritis for hip pain localised to the groin was 36.7%, specificity 90.5%, positive predictive value 6.0%, and negative predictive value 98.9%. Results did not differ much for hip pain at other locations or for painful internal rotation. In the Osteoarthritis Initiative study (n=4366), only 9.1% of hips in patients with frequent pain showed radiographic hip osteoarthritis, and 23.8% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of definite radiographic hip osteoarthritis for hip pain localised to the groin was 16.5%, specificity 94.0%, positive predictive value 7.1%, and negative predictive value 97.6%. Results also did not differ much for hip pain at other locations. What this study adds Hip pain was not present in many hips with radiographic osteoarthritis, and many hips with pain did not show radiographic hip osteoarthritis. Most older participants with a high suspicion for clinical hip osteoarthritis (groin or anterior pain and/or painful internal rotation) did not have radiographic hip osteoarthritis, suggesting that in many cases, hip osteoarthritis might be missed if diagnosticians relied solely on hip radiographs. Funding, competing interests, data sharing See the full paper on thebmj.com for funding. The authors have no competing interests. Additional data are available from bevochan@bu.edu .

Objectives The last prevalence survey encompassing urban populations was part of the nationwide Health and Nutrition examination survey (NHANES I) in the 1970's. We carried out a prevalence survey for hip osteoarthritis (OA) in the Framingham Study Community cohort. Methods Persons age 50 and older living in Framingham in 2002 – 2005 were recruited by random digit dialing without respect to joint pain or arthritis. Anteroposterior standing long-limb radiographs of the lower extremities including the pelvis were obtained and read for radiographic hip OA (ROA) by two trained physicians with all possible cases of ROA confirmed by an experienced musculoskeletal radiologist. ROA was defined as Kellgren-Lawrence score ≥ 2. Using a homunculus in which the hip joint was depicted, participants were asked whether they had hip pain on most days. Those who said ‘yes’ were defined as having hip pain. Symptomatic hip OA (SxOA) was defined as radiographic OA with ipsilateral hip pain. We defined a person as having hip OA if at least one of their hip joints was affected. Results Of 978 subjects studied (mean age 63.5 years; 56% women), age-standardized prevalence of ROA was 19.6% (95% CI 16.7%-23.0%) and SxOA was 4.2% (95% CI 2.9%-6.1%%). Overall, we found that men had higher prevalence of ROA (p<0.0001) compared to women, but men did not have a higher prevalence of SxOA compared to women (5.2% vs 3%, p=0.08). Conclusion In conclusion, hip osteoarthritis is a common condition in middle aged and older persons in urban and suburban U.S.

Results. Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. Conclusion. These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Objective. Due to advances in rheumatoid arthritis (RA) therapies over the last few years, an increasing proportion of patients are able to achieve a state of remission. However, the definition of remission is unclear. Currently, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient's disease state. The need for a uniform definition of remission is vital for research findings to be correctly interpreted. Methods. The American College of Rheumatology (ACR) constituted a committee that included international clinical researchers, trialists, and clinical epidemiologists in order to redefine remission in RA. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of remission, and develop a research agenda that would inform future work in the development of an ACR definition of remission. Results. In its first meeting, the committee preferred to develop a strict definition, implying no or very low disease activity. Such a definition would need to be validated against long-term outcome, e.g., physical function and damage. Conclusion. The committee decided to consider both a definition for trials and a modified version for clinical practice. Since the first meeting, the ACR and the European League Against Rheumatism (EULAR) have decided to sponsor this initiative as an official ACR/EULAR collaboration.