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Objective: To examine the association between weight change from young adulthood to midlife and the risk of incident arthritis., Methods: Using data from the National Health and Nutrition Examination Survey, we categorized participants into weight-change categories based on their recalled weight during young adulthood and midlife. We estimated the association of weight change and developing an arthritis condition over 10 years using adjusted Cox models. Findings were extrapolated to the US population to determine the proportion of incident arthritis cases that could be averted if the entire population maintained a normal body mass index (BMI) in young adulthood and midlife., Results: Among our sample of adults who were ages 40-69 years at their midlife weight measure (n = 13,669), 3,603 developed an arthritis condition. Compared with adults who maintained a normal-normal BMI, the normal-overweight, normal-obese, overweight-obese, and obese-obese groups had a significantly elevated risk of incident arthritis conditions. The obese-overweight group had a lower risk of incident arthritis conditions compared with the obese-obese group and a comparable risk to the overweight-overweight group. Nearly one-fourth of incident arthritis cases, corresponding to 2.7 million individuals, would have been averted under the hypothetical scenario where all individuals maintained normal weight from young adulthood to midlife., Conclusion: Weight loss from young adulthood to midlife was associated with a substantially reduced risk of developing an arthritis condition. We found no evidence of residual risk from having been heavier earlier in life. Our findings highlight the critical need to expand obesity treatment and prevention to achieve meaningful reductions in the burden of arthritis., (© 2020, American College of Rheumatology.)

Objective: To evaluate construct validity and scoring methods of the world health organization-health and work performance questionnaire (HPQ) for people with arthritis., Methods: Construct validity was examined through hypothesis testing using the recommended guidelines of the consensus-based standards for the selection of health measurement instruments (COSMIN)., Results: The HPQ using the absolute scoring method showed moderate construct validity as four of the seven hypotheses were met. The HPQ using the relative scoring method had weak construct validity as only one of the seven hypotheses were met., Conclusion: The absolute scoring method for the HPQ is superior in construct validity to the relative scoring method in assessing work performance among people with arthritis and related rheumatic conditions; however, more research is needed to further explore other psychometric properties of the HPQ.

Objective: To systematically rate the evidence on the measurement properties of work functioning instruments for people with arthritis and other rheumatologic conditions., Methods: A systematic review was conducted through a structured search to identify the quality of articles describing studies of assessment development and studies of their psychometric properties. The Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist was used to appraise the included studies. Finally, an evidence synthesis was performed to combine findings., Results: Nine arthritis-specific work outcome assessments were identified; 17 articles examining the psychometric properties of these instruments were identified and their quality was reviewed. Quality of studies was highly variable. The evidence synthesis showed that the Work Limitations Questionnaire had the strongest quality evidence of internal consistency and content validity (including structural validity and hypothesis testing), followed by the Work Instability Scale. None of the instruments had strong quality evidence of criterion validity or responsiveness., Conclusion: Considering the high variability and the low quality of the literature, we recommend that instrument developers integrate a full psychometric assessment of their instruments, including responsiveness and criterion validity, and consult guidelines (i.e., COSMIN) in reporting their findings., (© 2016, American College of Rheumatology.)

Background: People with arthritis are at risk of work disability. Job accommodation and educational programs delivered before imminent work loss can minimize work disability, yet are not currently being widely implemented. The Work-It Study is a randomized controlled trial testing the efficacy of a problem solving program delivered by physical and occupational therapy practitioners to prevent work loss over a two-year period among people with arthritis and rheumatological conditions., Objective: The purpose of this paper is to describe the protocol of the randomized controlled trial, and describe the baseline characteristics of the subjects and their work outcomes., Methods: 287 participants were recruited from the Boston area in Massachusetts, USA. Eligible participants were aged between 21-65, self-reported a physicians' diagnosis of arthritis, rheumatic condition, or chronic back pain, reported a concern about working now or in the near future due to your health, worked at least 15 hours a week, had plans to continue working, and worked or lived in Massachusetts. Subjects were recruited through community sources and rheumatology offices. Participants in the experimental group received a structured interview and an education and resource packet, while participants in the control received the resource packet only. The baseline characteristics and work related outcomes of the participants were analyzed., Conclusions: To our knowledge, the Work-It Study is the largest and most diverse randomized controlled trial to date aiming to identify and problem solve work-related barriers, promote advocacy, and foster work disability knowledge among people with chronic disabling musculoskeletal conditions. Despite advances in medical management of arthritis and other rheumatological and musculoskeletal conditions, many people still have concerns about their ability to remain employed and are seeking strategies to help them sustain employment.

Objective: Some reports suggest that education programs help arthritis patients better manage their symptoms and improve function. This review of the published literature was undertaken to assess the effect of such programs on pain and disability., Methods: Medline and HealthSTAR were searched for the period 1964-1998. The references of each article were then hand-searched for further publications. Studies were included in the meta-analysis if the intervention contained a self-management education component, a concurrent control group was included, and pain and/or disability were assessed as end points. Two authors reviewed each study. The methodologic attributes and efficacy of the interventions were assessed using a standardized abstraction tool, and the magnitude of the results was converted to a common measure, the effect size. Summary effect sizes were calculated separately for pain and disability., Results: The search strategy yielded 35 studies, of which 17 met inclusion criteria. The mean age of study participants was 61 years, and 69% were female. On average, 19% of patients did not complete followup (range 0-53%). The summary effect size was 0.12 for pain (95% confidence interval [95% CI] 0.00, 0.24) and 0.07 for disability (95% CI 0.00, 0.15). Funnel plots indicated no significant evidence of bias toward the publication of studies with findings that showed reductions in pain or disability., Conclusion: The summary effect sizes suggest that arthritis self-management education programs result in small reductions in pain and disability.

ObjectiveTo determine whether intraarticular glucocorticoid (GC) injections are associated with increased knee osteoarthritis (OA) progression compared to hyaluronic acid (HA) injections, which have been reported to delay OA progression and knee replacement.MethodsWe identified participants from 2 large cohort studies, the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study. Study visits were performed at regular intervals and included questionnaires about intraarticular GC or HA injection use in the previous 6 months and incident total knee replacement (TKR). Knee radiographs were obtained at each study visit and interpreted in a similar manner. Outcome measures were radiographic progression based on Kellgren/Lawrence (K/L) grade and joint space narrowing (JSN) for both cohorts and based on medial joint space width for OAI participants, and incident TKR. We compared preinjection and postinjection radiographs to generate rate ratios of progression comparing GC injection with HA injection. A Cox proportional hazards model was used to estimate the rate of TKR for both groups.ResultsWe studied 791 participants (980 knees) with knee OA, of whom 629 reported GC injection use and 162 HA injection use. Rate ratios of progression were similar between those receiving GCs and those receiving HA for JSN (1.00 [95% confidence interval (95% CI) 0.83-1.21]), K/L grade (1.03 [95% CI 0.83-1.29]), and medial joint space width (1.03 [95% CI 0.72-1.48]). Hazard of TKR was slightly lower for those receiving intraarticular GC compared to those receiving HA (hazard ratio 0.75 [95% CI 0.51-1.09]).ConclusionIntraarticular GC injections are not associated with an increased risk of knee OA progression compared to HA.

ObjectiveTo determine the relationship of patellofemoral osteoarthritis (PFOA) to changes in performance-based function over 7 years.MethodsThere were 2666 participants (62.2 ± 8.0 yrs, BMI 30.6 ± 5.9 kg/m2, 60% female) from the Multicenter Osteoarthritis Study with knee radiographs at baseline who completed repeated chair stands and a 20-meter walk test (20MWT) at baseline, 2.5, 5, and 7 years. Generalized linear models assessed the relation of radiographic PFOA and radiographic PFOA with frequent knee pain to longitudinal changes in performance-based function. Analyses were adjusted for age, sex, BMI, tibiofemoral OA, and injury/surgery.ResultsLinear models demonstrated a significant group-by-time interaction for the repeated chair stands (P = 0.04) and the 20MWT (P < 0.0001). Those with radiographic PFOA took 1.01 seconds longer on the repeated chair stands (P = 0.02) and 1.69 seconds longer on the 20MWT (P < 0.0001) at 7 years compared with baseline. When examining the relation of radiographic PFOA with frequent knee pain to performance-based function, there was a significant group-by-time interaction for repeated chair stands (P = 0.05) and the 20MWT (P < 0.0001). Those with radiographic PFOA with frequent knee pain increased their time on the repeated chair stands by 1.12 seconds (P = 0.04) and on the 20MWT by 1.91 seconds (P < 0.0001) over 7 years.ConclusionIndividuals with radiographic PFOA and those with radiographic PFOA with frequent knee pain have worsening of performance-based function over time. This knowledge may present opportunities to plan for early treatment strategies for PFOA to limit functional decline over time.

ObjectiveTo evaluate the association of fatty infiltration of the quadriceps and vastus medialis (VM) with an increase in knee cartilage, meniscus, or bone marrow lesions, using magnetic resonance imaging (MRI) in knee osteoarthritis (OA) over 3 years.MethodsParticipants (n = 69) with and without radiographic knee OA underwent MRI at baseline and 3 years later. Chemical shift-based water/fat MRI was used to quantify the intramuscular fat fraction and the lean anatomical cross-sectional area (ACSA) for the VM and entire quadriceps muscles. MRI images of the knee were analyzed using the semiquantitative modified whole-organ MRI score (mWORMS) grading to assess change in lesions in the articular cartilage, meniscus, and bone marrow. Logistic regression was used to assess whether baseline quadriceps and VM fat fraction and lean ACSA were associated with an increase in mWORMS scores. Odds ratios (ORs) were adjusted for age, sex, and body mass index.ResultsOverall, of the 69 subjects, 43 (62%) had an increase in cartilage lesions (26 of 43), meniscus lesions (19 of 43), or bone marrow lesions (22 of 43) scores. The quadriceps (OR 2.13 [95% confidence interval (95% CI) 1.09-4.15]) and VM (OR 2.05 [95% CI 1.25-3.36]) fat fraction were both associated with an increase in cartilage, meniscus, or bone marrow lesion scores over 3 years. The association of quadriceps or VM lean ACSA with the outcomes was not significant.ConclusionThese longitudinal findings using quantitative MRI methods for assessment of muscle adiposity highlight the role of quadriceps adiposity, specifically in the VM, in knee OA progression. However, studies in larger cohorts are needed to confirm these findings.

ObjectiveOsteoarthritis (OA) and pain are both made more severe by low-grade inflammation. This study was undertaken to examine whether visceral fat, a major source of inflammatory cytokines and adipokines, is associated with an increased risk of knee OA or musculoskeletal pain.MethodsSubjects in the Multicenter Osteoarthritis Study cohort, who were age 50-79 years and had or were at high risk of knee OA, underwent whole-body dual x-ray absorptiometry (DXA) at baseline. At baseline, 30 months, and 60 months radiographs and magnetic resonance images (MRIs) of the knees were obtained, and patients were asked to score the severity of their knee pain and to identify sites of joint pain using a body homunculus. Baseline DXA scans were used to measure total body fat and visceral and subcutaneous fat in the torso. The association of fat depot size with structural outcomes (incident radiographic OA and cartilage loss and synovitis on MRI) and with pain outcomes (worsening knee pain, number of painful joints, and widespread pain) was assessed. Regression analyses were adjusted for age, sex, race, education level, smoking status, physical activity, body mass index (BMI), and depressive symptoms.ResultsOf the 2,961 participants at baseline, 60.7% were women. The mean age was 62.5 years and mean BMI was 30.5 kg/m2 . After adjustment for covariates, no fat measures were associated with any structural outcomes. However, total and visceral, but not subcutaneous, fat were positively associated with worsening knee pain (P = 0.0005 for total fat and P = 0.007 for visceral fat) and widespread pain (P = 0.001 for total fat and P = 0.02 for visceral fat), and the amount of visceral fat was associated with the number of painful joints (P = 0.07).ConclusionOur findings indicate that visceral fat is associated with an increased risk of musculoskeletal and widespread pain.

ObjectiveTo investigate thresholds of strength below which individuals with knee osteoarthritis (OA) may have more difficulty carrying out physical functions of daily life. Individuals below such thresholds might benefit more from strengthening interventions than those with greater strength.MethodsWe studied individuals with symptomatic OA at baseline in the Multicenter Osteoarthritis Study who had knee extensor strength measured isokinetically at 60º/second. Participants underwent a 20-meter walk test and a sit-to-stand test and answered questions from the Western Ontario and McMaster Universities Osteoarthritis Index. Physical function results were plotted against measures of quadriceps strength (Nm) (and as strength:body weight) for the worst knee. Loess technique was used to examine inflection points. Nonlinear relationships were examined in piecewise linear regression models. Differences were tested using linear and logistic regression models.ResultsThe study had 834 participants (65.8% women). The mean ± SD age of the participants was 62.9 ± 7.9 years. In women, there were thresholds of strength below which the slope of strength versus function was steeper: walking speed (

ObjectiveParticipation restriction, common among people with knee osteoarthritis (OA), may be influenced by affect. We examined the risk of incident participation restriction over 84 months conferred by positive and negative affect among people with knee OA.MethodsParticipants were from the Multicenter Osteoarthritis Study and had or were at high risk of knee OA. Participation restriction was measured using the Instrumental Role Limitation subscale of the Late-Life Disability Index, and affect was measured using the positive affect and depressed mood subscales of the Center for Epidemiologic Studies Depression Scale. Robust Poisson regression was used to calculate the risk of incident participation restriction over 84 months conferred by combinations of low and high positive and negative affect, adjusting for covariates.ResultsOf 1,810 baseline participants (mean age 62.1 years, 56% female), 470 (26%) had incident participation restriction over 84 months. Participants with low positive affect had 20% greater risk of incident participation restriction than those with high positive affect; participants with high negative affect had 50% greater risk of incident participation restriction compared to those with low negative affect. Participants with both low positive and high negative affect had 80% greater risk of incident participation restriction compared to other combinations of positive and negative affect.ConclusionLow positive and high negative affect, both alone and in combination, increase the risk of participation restriction among adults with knee OA. Efforts aimed at preventing participation restriction in this population should consider these mood states.

ObjectiveOlder adults with knee osteoarthritis (OA) who live in environments with mobility barriers may be at greater risk of developing participation restrictions, defined as difficulties in engagement in life situations. We investigated the risk of participation restriction over 5 years due to self-reported environmental features among older adults with knee OA.MethodsParticipants from the Multicenter Osteoarthritis (MOST) Study self-reported participation at baseline, 30 months, and 60 months using the instrumental role subscale of the Late Life Disability Index (LLDI). Data on self-reported environmental features were from the Home and Community Environment questionnaire administered in the MOST Knee Pain and Disability study, an ancillary study of MOST. The relative risks (RRs) of developing participation restriction at 60 months, indicated by an LLDI score

ObjectiveMany persons with knee pain have joint pain outside the knee, but despite the impact and high frequency of this pain, its distribution and causes have not been studied. We undertook this study to test the hypothesis of those studying gait abnormalities who have suggested that knee pain causes pain in adjacent joints but that pain adaptation strategies are highly individualized.MethodsWe studied persons ages 50-79 years with or at high risk of knee osteoarthritis who were recruited from 2 community-based cohorts, the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative, and we followed them up for 5-7 years. We excluded those with knee pain at baseline and compared those who had developed knee pain at the first follow-up examination (the index visit) with those who had not. We examined pain on most days at joint regions outside the knee in examinations after the index visit. Logistic regression analyses examined the risk of joint-specific pain adjusted for age, sex, body mass index, and symptoms of depression, and we performed sensitivity analyses excluding those with widespread pain.ResultsIn the combined cohorts, 693 persons had knee pain at the index visit and 2,793 did not. A total of 79.6% of those with bilateral knee pain and 63.8% of those with unilateral knee pain had pain during follow-up in a joint region outside the knee, compared with 49.9% of those without knee pain. There was an increased risk of pain at most extremity joint sites, without a predilection for specific sites. Results were unchanged when those with widespread pain were excluded.ConclusionPersons with chronic knee pain are at increased risk of pain in multiple joints in no specific pattern.

ObjectivePain and functional decline are hallmarks of knee osteoarthritis (OA). Nevertheless, longitudinal studies unexpectedly reveal stable or improved physical function. The aim of this study was to impute missing and pre-total knee replacement (TKR) values to describe physical function over time among people with symptomatic knee OA.MethodsWe included participants from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) with incident symptomatic knee OA, observed during the first 30 months in MOST and 36 months in OAI. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function (WOMAC-PF), the 5-times sit-to-stand test, and the 20-meter-walk test were assessed at 4 and 5 years in MOST and at 6 years in OAI. We used a multiple imputation method for missing visits, and estimated pre-TKR values close to the time of TKR, using a fitted local regression smoothing curve. In mixed-effect models, we investigated the physical function change over time, using data before and after imputation and calculation of pre-TKR values.ResultsIn MOST, 225 (8%) had incident knee OA, with corresponding 577 (12.7%) in OAI. After adjusting for pre-TKR values and imputing missing values, we found that WOMAC-PF values remained stable or slightly declined over time, and the 20-meter-walk test results changed from stable in nonimputed analyses to worsening using imputed data.ConclusionData from MOST and OAI showed stable to worsening physical function over time in people with incident symptomatic knee OA after imputing missing values and adjusting pre-TKR values.

ObjectivePhysical activity is recommended to mitigate functional limitations associated with knee osteoarthritis (OA). However, it is unclear whether walking on its own protects against the development of functional limitation.MethodsWalking over 7 days was objectively measured as steps/day within a cohort of people with or at risk of knee OA from the Multicenter Osteoarthritis Study. Incident functional limitation over 2 years was defined by performance-based (gait speed 28 of 68) measures. We evaluated the association of steps/day at baseline with developing functional limitation 2 years later by calculating risk ratios adjusted for potential confounders. The number of steps/day that best distinguished risk for developing functional limitation was estimated from the maximum distance from chance on receiver operating characteristic curves.ResultsAmong 1,788 participants (mean age 67 years, mean body mass index 31 kg/m(2) , 60% women), each additional 1,000 steps/day was associated with a 16% and 18% reduction in incident functional limitation by performance-based and self-report measures, respectively. Walking 6,000 steps/day provides a preliminary estimate of the level of walking activity to protect against developing functional limitation in people with or at risk of knee OA.

ObjectiveWhile depressive symptoms and knee pain are independently known to impede daily walking in older adults, it is unknown whether positive affect promotes daily walking. This study investigated this association among adults with knee osteoarthritis (OA) and examined whether knee pain modified this association.MethodsThis study is a cross-sectional analysis of the Multicenter Osteoarthritis Study. We included 1,018 participants (mean ± SD age 63.1 ± 7.8 years, 60% women) who had radiographic knee OA and had worn a StepWatch monitor to record their number of steps per day. High and low positive affect and depressive symptoms were based on the Center for Epidemiologic Studies Depression Scale. Knee pain was categorized as present in respondents who reported pain on most days at both a clinic visit and a telephone screening.ResultsCompared to respondents with low positive affect (27% of all respondents), those with high positive affect (63%) walked a similar number of steps per day, while those with depressive symptoms (10%) walked less (adjusted β -32.6 [95% confidence interval (95% CI) -458.9, 393.8] and -579.1 [95% CI -1,274.9, 116.7], respectively). There was a statistically significant interaction of positive affect by knee pain (P = 0.0045). Among the respondents with knee pain (39%), those with high positive affect walked significantly more steps per day (adjusted β 711.0 [95% CI 55.1, 1,366.9]) than those with low positive affect.ConclusionHigh positive affect was associated with more daily walking among adults with painful knee OA. Positive affect may be an important psychological factor to consider for promoting physical activity among people with painful knee OA.

IntroductionOur objective was to determine whether markers of bone resorption and formation could serve as markers for the presence of bone marrow lesions (BMLs).MethodsWe conducted an analysis of data from the Boston Osteoarthritis of the Knee Study (BOKS). Knee magnetic resonance images were scored for BMLs using a semiquantitative grading scheme. In addition, a subset of persons with BMLs underwent quantitative volume measurement of their BML, using a proprietary software method. Within the BOKS population, 80 people with BMLs and 80 without BMLs were selected for the purposes of this case-control study. Bone biomarkers assayed included type I collagen N-telopeptide (NTx) corrected for urinary creatinine, bone-specific alkaline phosphatase, and osteocalcin. The same methods were used and applied to a nested case-control sample from the Framingham study, in which BMD assessments allowed evaluation of this as a covariate. Logistic regression models were fit using BML as the outcome and biomarkers, age, sex, and body mass index as predictors. An receiver operating characteristic curve was generated for each model and the area under the curve assessed.ResultsA total of 151 subjects from BOKS with knee OA were assessed. The mean (standard deviation) age was 67 (9) years and 60% were male. Sixty-nine per cent had maximum BML score above 0, and 48% had maximum BML score above 1. The only model that reached statistical significance used maximum score of BML above 0 as the outcome. Ln-NTx (Ln is the natural log) exhibited a significant association with BMLs, with the odds of a BML being present increasing by 1.4-fold (95% confidence interval = 1.0-fold to 2.0-fold) per 1 standard deviation increase in the LnNTx, and with a small partial R2 of 3.05. We also evaluated 144 participants in the Framingham Osteoarthritis Study, whose mean age was 68 years and body mass index was 29 kg/m2, and of whom 40% were male. Of these participants 55% had a maximum BML score above 0. The relationship between NTx and maximum score of BML above 0 revealed a significant association, with an odds ratio fo 1.7 (95% confidence interval = 1.1 to 2.7) after adjusting for age, sex, and body mass index.ConclusionsSerum NTx was weakly associated with the presence of BMLs in both study samples. This relationship was not strong and we would not advocate the use of NTx as a marker of the presence of BMLs.

We used data from a longitudinal observation study to determine whether markers of cartilage turnover could serve as predictors of cartilage loss on magnetic resonance imaging (MRI). We conducted a study of data from the Boston Osteoarthritis of the Knee Study (BOKS), a completed natural history study of knee osteoarthritis (OA). All subjects in the study met American College of Rheumatology criteria for knee OA. Baseline and follow-up knee magnetic resonance images were scored for cartilage loss by means of the WORMS (Whole Organ Magnetic Resonance Imaging Score) semiquantitative grading scheme. Within the BOKS population, 80 subjects who experienced cartilage loss and 80 subjects who did not were selected for the purposes of this nested case control study. We assessed the baseline levels of cartilage degradation and synthesis products by means of assays for type I and II cleavage by collagenases (Col2:3/4C(short) or C1,2C), type II cleavage only with Col2:3/4C(longmono) (C2C), type II synthesis (C-propeptide), the C-telopeptide of type II (Col2CTx), aggrecan 846 epitope, and cartilage oligomeric matrix protein (COMP). We performed a logistic regression to examine the relation of levels of each biomarker to the risk of cartilage loss in any knee. All analyses were adjusted for gender, age, and body mass index (BMI); results stratified by gender gave similar results. One hundred thirty-seven patients with symptomatic knee OA were assessed. At baseline, the mean (standard deviation) age was 67 (9) years and 54% were male. Seventy-six percent of the subjects had radiographic tibiofemoral OA (Kellgren & Lawrence grade of greater than or equal to 2) and the remainder had patellofemoral OA. With the exception of COMP, none of the other biomarkers was a statistically significant predictor of cartilage loss. For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times (95% confidence interval [CI] 1.34 to 27.67). After the analysis of COMP was adjusted for age, gender, and BMI, the risk for cartilage loss was 6.35 (95% CI 1.36 to 29.65). Among subjects with symptomatic knee OA, a single measurement of increased COMP predicted subsequent cartilage loss on MRI. The other biochemical markers of cartilage synthesis and degradation do not facilitate prediction of cartilage loss. With the exception of COMP, if changes in cartilage turnover in patients with symptomatic knee OA are associated with cartilage loss, they do not appear to affect systemic biomarker levels.

Objective: Studies suggest that parenteral MTX may be more efficacious than the oral form at equivalent doses for the treatment of rheumatoid arthritis. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in RA. Methods: PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed following PRISMA 2009 guidelines, by two independent reviewers. To be included, trials had to study adults with RA randomized to the same dose of either oral or parenteral MTX. The primary endpoint was ACR20 at 6 months. Intention-to-treat analysis results were used when possible. Data from direct comparisons between oral and parenteral methotrexate quantitatively analyzed using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as an odds ratio [OR] (OR>1 indicated a benefit for parenteral therapy). Results: The search yielded 357 papers or abstracts. After review of titles or abstracts and full text papers, we found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at 15mg/week and increased up to 25mg/week. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 3.02 (95% CI 1.41, 6.46), with no significant difference in the risk for all adverse events. Conclusion: Parenteral MTX therapy had significantly higher odds than oral MTX of achieving reduction in disease activity. We propose that parenteral MTX is more effective than weekly oral MTX; its widespread use may lead to better control of disease and a decrease in demand for biologic agents. [ABSTRACT FROM AUTHOR]

The article identifies factors that explain heterogeneity in trials of glucosamine. The study found that heterogeneity among trials of glucosamine is larger than would be expected by chance. It also found that effect sizes were consistently higher among trials with industry involvement. Explanations for the difference include different glucosamine preparations, inadequate allocation concealment, and industry bias.

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. [ABSTRACT FROM AUTHOR]