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2.  An administrative data validation study of the accuracy of algorithms for identifying rheumatoid arthritis: the influence of the reference standard on algorithm performance 
We have previously validated administrative data algorithms to identify patients with rheumatoid arthritis (RA) using rheumatology clinic records as the reference standard. Here we reassessed the accuracy of the algorithms using primary care records as the reference standard.
We performed a retrospective chart abstraction study using a random sample of 7500 adult patients under the care of 83 family physicians contributing to the Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Using physician-reported diagnoses as the reference standard, we computed and compared the sensitivity, specificity, and predictive values for over 100 administrative data algorithms for RA case ascertainment.
We identified 69 patients with RA for a lifetime RA prevalence of 0.9%. All algorithms had excellent specificity (>97%). However, sensitivity varied (75-90%) among physician billing algorithms. Despite the low prevalence of RA, most algorithms had adequate positive predictive value (PPV; 51-83%). The algorithm of “[1 hospitalization RA diagnosis code] or [3 physician RA diagnosis codes with ≥1 by a specialist over 2 years]” had a sensitivity of 78% (95% CI 69–88), specificity of 100% (95% CI 100–100), PPV of 78% (95% CI 69–88) and NPV of 100% (95% CI 100–100).
Administrative data algorithms for detecting RA patients achieved a high degree of accuracy amongst the general population. However, results varied slightly from our previous report, which can be attributed to differences in the reference standards with respect to disease prevalence, spectrum of disease, and type of comparator group.
PMCID: PMC4078363  PMID: 24956925
Rheumatoid arthritis; Health administrative databases; Validation study; Sensitivity and specificity; Predictive values; Diagnostic test
3.  Access to rheumatologists among patients with newly diagnosed rheumatoid arthritis in a Canadian universal public healthcare system 
BMJ Open  2014;4(1):e003888.
Our objective was to estimate the percentage of patients with incident rheumatoid arthritis (RA) who were seen by a rheumatologist within 3, 6 and 12 months of suspected diagnosis by a family physician, and assess what factors may influence the time frame with which patients are seen.
Ontario, Canada.
Over 2000–2009, we studied patients with incident RA who were initially diagnosed by a family physician.
Primary and secondary outcome measures
We assessed secular trends in rheumatology encounters and differences between patients who received versus did not receive rheumatology care. We performed hierarchical logistic regression analyses to determine whether receipt of rheumatology care was associated with patient, primary care physician and geographical factors.
Among 19 760 patients with incident RA, 59%, 75% and 84% of patients were seen by a rheumatologist within 3, 6 and 12 months, respectively. The prevalence of initial consultations within 3 months did not increase over time; however, access within 6 and 12 months increased over time. Factors positively associated with timely consultations included higher regional rheumatology supply (adjusted OR (aOR) 1.35 (95% CI 1.13 to 1.60)) and higher patient socioeconomic status (aOR 1.18 (95% CI 1.07 to 1.30)). Conversely, factors inversely associated with timely consultations included remote patient residence (aOR 0.51 (95% CI 0.41 to 0.64)) and male family physicians (aOR 0.88 (95% CI 0.81 to 0.95)).
Increasing access to rheumatologists within 6 and 12 months occurred over time; however, consultations within 3 months did not change over time. Measures of poor access (such as proximity to and density of rheumatologists) were negatively associated with timely consultations. Additional factors that contributed to disparities in access included patient socioeconomic status and physician sex.
PMCID: PMC3913026  PMID: 24486677
4.  Investigating clinical heterogeneity in systematic reviews: a methodologic review of guidance in the literature 
While there is some consensus on methods for investigating statistical and methodological heterogeneity, little attention has been paid to clinical aspects of heterogeneity. The objective of this study is to summarize and collate suggested methods for investigating clinical heterogeneity in systematic reviews.
We searched databases (Medline, EMBASE, CINAHL, Cochrane Library, and CONSORT, to December 2010) and reference lists and contacted experts to identify resources providing suggestions for investigating clinical heterogeneity between controlled clinical trials included in systematic reviews. We extracted recommendations, assessed resources for risk of bias, and collated the recommendations.
One hundred and one resources were collected, including narrative reviews, methodological reviews, statistical methods papers, and textbooks. These resources generally had a low risk of bias, but there was minimal consensus among them. Resources suggested that planned investigations of clinical heterogeneity should be made explicit in the protocol of the review; clinical experts should be included on the review team; a set of clinical covariates should be chosen considering variables from the participant level, intervention level, outcome level, research setting, or others unique to the research question; covariates should have a clear scientific rationale; there should be a sufficient number of trials per covariate; and results of any such investigations should be interpreted with caution.
Though the consensus was minimal, there were many recommendations in the literature for investigating clinical heterogeneity in systematic reviews. Formal recommendations for investigating clinical heterogeneity in systematic reviews of controlled trials are required.
PMCID: PMC3564789  PMID: 22846171
6.  Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative 
Rheumatology (Oxford, England)  2012;51(8):1416-1425.
Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA).
Methods. A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008–09 European League Against Rheumatism (EULAR)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical practice.
Results. A total of 49 242 references were identified, from which 167 studies were included in the systematic reviews. One clinical question regarding different comorbidities was divided into two separate reviews, resulting in 11 recommendations in total. Oxford levels of evidence were applied to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty per cent of rheumatologists reported that the algorithm would change their practice, and 75% felt the algorithm was in accordance with their current practice.
Conclusions. Eleven evidence-based recommendations on the management of pain by pharmacotherapy in IA were developed. They are supported by a large panel of rheumatologists from 17 countries, thus enhancing their utility in clinical practice.
PMCID: PMC3397467  PMID: 22447886
arthritis; evidence-based medicine; analgesics
7.  An empirical study using permutation-based resampling in meta-regression 
Systematic Reviews  2012;1:18.
In meta-regression, as the number of trials in the analyses decreases, the risk of false positives or false negatives increases. This is partly due to the assumption of normality that may not hold in small samples. Creation of a distribution from the observed trials using permutation methods to calculate P values may allow for less spurious findings. Permutation has not been empirically tested in meta-regression. The objective of this study was to perform an empirical investigation to explore the differences in results for meta-analyses on a small number of trials using standard large sample approaches verses permutation-based methods for meta-regression.
We isolated a sample of randomized controlled clinical trials (RCTs) for interventions that have a small number of trials (herbal medicine trials). Trials were then grouped by herbal species and condition and assessed for methodological quality using the Jadad scale, and data were extracted for each outcome. Finally, we performed meta-analyses on the primary outcome of each group of trials and meta-regression for methodological quality subgroups within each meta-analysis. We used large sample methods and permutation methods in our meta-regression modeling. We then compared final models and final P values between methods.
We collected 110 trials across 5 intervention/outcome pairings and 5 to 10 trials per covariate. When applying large sample methods and permutation-based methods in our backwards stepwise regression the covariates in the final models were identical in all cases. The P values for the covariates in the final model were larger in 78% (7/9) of the cases for permutation and identical for 22% (2/9) of the cases.
We present empirical evidence that permutation-based resampling may not change final models when using backwards stepwise regression, but may increase P values in meta-regression of multiple covariates for relatively small amount of trials.
PMCID: PMC3351721  PMID: 22587815
8.  Minimal clinically important improvement and patient acceptable symptom state for subjective outcome measures in rheumatic disorders 
The Journal of Rheumatology  2007;34(5):1188-1193.
The concepts of minimal clinically important improvement (MCII) and patient acceptable symptomatic state (PASS) could help in interpreting results of trials involving patient-reported outcomes by translating the response at the group level (change in mean scores) into more clinically meaningful information by addressing the patient level as “therapeutic success (yes/no)”. The aims of the special-interest group (SIG) at OMERACT 8 were to discuss specific issues concerning the MCII and PASS concepts, especially the wording of the external anchor questions used to determine the MCII and PASS estimates and to move towards a consensus for the cut-off values to use as the MCII and PASS in the different outcome criteria. The purpose of this SIG at OMERACT 8 was to inform participants of the MCII and PASS concepts and to agree on MCII and PASS values for pain, patient global assessment and functional impairment.
PMCID: PMC2760122  PMID: 17477485
Health Status; Humans; Outcome Assessment (Health Care); Patient Satisfaction; Remission Induction; Rheumatic Diseases; diagnosis; physiopathology; therapy; Severity of Illness Index; Treatment Outcome; Minimal clinically important difference; Patient acceptable symptomatic state; Response to therapy; Outcome criteria; Patient's persepctive
9.  Identifying the Best Treatment Among Common Nonsurgical Neck Pain Treatments 
European Spine Journal  2008;17(Suppl 1):184-191.
Study Design
Decision analysis.
To identify the best treatment for nonspecific neck pain.
Summary of Background Data
In Canada and the United States, the most commonly prescribed neck pain treatments are nonsteroidal anti-inflammatory drugs (NSAIDs), exercise, and manual therapy. Deciding which treatment is best is difficult because of the trade-offs between beneficial and harmful effects, and because of the uncertainty of these effects.
(Quality-adjusted) life expectancy associated with standard NSAIDs, Cox-2 NSAIDs, exercise, mobilization, and manipulation were compared in a decision-analytic model. Estimates of the course of neck pain, background risk of adverse events in the general population, treatment effectiveness and risk, and patient-preferences were input into the model. Assuming equal effectiveness, we conducted a baseline analysis using risk of harm only. We assessed the stability of the baseline results by conducting a second analysis that incorporated effectiveness data from a high-quality randomized trial.
There were no important differences across treatments. The difference between the highest and lowest ranked treatments predicted by the baseline model was 4.5 days of life expectancy and 3.4 quality-adjusted life-days. The difference between the highest and lowest ranked treatments predicted by the second model was 7.3 quality-adjusted life-days.
When the objective is to maximize life expectancy and quality-adjusted life expectancy, none of the treatments in our analysis were clearly superior.
PMCID: PMC2271109
decision analysis; exercise; quality-of-life; neck pain; nonsteroidal anti-inflammatory drug; manual therapy; effectiveness; treatment risk
10.  A critical appraisal of clinical practice guidelines for the treatment of lower-limb osteoarthritis 
Arthritis Research  2001;4(1):36-44.
Clinical practice guidelines are important tools to assist clinical decision-making. Recently, several guidelines addressing the management of osteoarthritis (OA) have been published. Clinicians treating patients with OA must ensure that these guidelines are developed with consistency and methodological rigour. We undertook a qualitative summary and critical appraisal of six medical treatment guidelines for the management of lower-limb OA published in the medical literature within the past 5 years. A review of these six guidelines revealed that each possesses strengths and weakness. While most described the scope and intended patient populations, the guidelines varied considerably in the rigour of their development, coverage of implementation issues, and disclosure of conflicts of interest.
PMCID: PMC128916  PMID: 11879536
clinical practice guidelines; osteoarthritis
11.  Multidisciplinary rehabilitation for chronic low back pain: systematic review 
BMJ : British Medical Journal  2001;322(7301):1511-1516.
To assess the effect of multidisciplinary biopsychosocial rehabilitation on clinically relevant outcomes in patients with chronic low back pain.
Systematic literature review of randomised controlled trials.
A total of 1964 patients with disabling low back pain for more than three months.
Main outcome measures
Pain, function, employment, quality of life, and global assessments.
Ten trials reported on a total of 12 randomised comparisons of multidisciplinary treatment and a control condition. There was strong evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration improves function when compared with inpatient or outpatient non-multidisciplinary treatments. There was moderate evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration reduces pain when compared with outpatient non-multidisciplinary rehabilitation or usual care. There was contradictory evidence regarding vocational outcomes of intensive multidisciplinary biopsychosocial intervention. Some trials reported improvements in work readiness, but others showed no significant reduction in sickness leaves. Less intensive outpatient psychophysical treatments did not improve pain, function, or vocational outcomes when compared with non-multidisciplinary outpatient therapy or usual care. Few trials reported effects on quality of life or global assessments.
The reviewed trials provide evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration reduces pain and improves function in patients with chronic low back pain. Less intensive interventions did not show improvements in clinically relevant outcomes.
What is already known on this topicDisabling chronic pain is regarded as the result of interrelating physical, psychological, and social or occupational factors requiring multidisciplinary interventionTwo previous systematic reviews of multidisciplinary rehabilitation for chronic pain were open to bias and did not include any of the randomised controlled trials now availableWhat this study addsIntensive, daily biopsychosocial rehabilitation with a functional restoration approach improves pain and function in chronic low back painLess intensive interventions did not show improvements in clinically relevant outcomesIt is unclear whether the improvements are worth the cost of these intensive treatments
PMCID: PMC33389  PMID: 11420271
12.  Multinational evidence-based recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative 
Annals of the Rheumatic Diseases  2013;73(2):328-335.
We aimed to develop evidence-based multinational recommendations for the diagnosis and management of gout. Using a formal voting process, a panel of 78 international rheumatologists developed 10 key clinical questions pertinent to the diagnosis and management of gout. Each question was investigated with a systematic literature review. Medline, Embase, Cochrane CENTRAL and abstracts from 2010–2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, rheumatologists from 14 countries (Europe, South America and Australasia) developed national recommendations. After rounds of discussion and voting, multinational recommendations were formulated. Each recommendation was graded according to the level of evidence. Agreement and potential impact on clinical practice were assessed. Combining evidence and clinical expertise, 10 recommendations were produced. One recommendation referred to the diagnosis of gout, two referred to cardiovascular and renal comorbidities, six focused on different aspects of the management of gout (including drug treatment and monitoring), and the last recommendation referred to the management of asymptomatic hyperuricaemia. The level of agreement with the recommendations ranged from 8.1 to 9.2 (mean 8.7) on a 1–10 scale, with 10 representing full agreement. Ten recommendations on the diagnosis and management of gout were established. They are evidence-based and supported by a large panel of rheumatologists from 14 countries, enhancing their utility in clinical practice.
PMCID: PMC3913257  PMID: 23868909
Gout; Treatment; Synovial fluid

Results 1-12 (12)