Obesity and body mass index: Past and future considerations in osteoarthritis research.

Obesity is an important topic for the osteoarthritis (OA) scientific community. However, the predominant use of body mass index (BMI) to define obesity in OA research is associated with uncertainties and limitations. These include an inability to discern fat and muscle mass, account for sex-differences in fat distribution, or identify adiposity-related health impairments. A focus on BMI in OA research may influence weight bias in clinical practice and impact disparities in access to effective OA treatments. To ensure that our understanding and approaches to improve health outcomes for individuals with or at risk for OA continues to advance in the next decade, future research will need to consider alternative measures beyond BMI for obesity identification and align with evolving obesity science. OA researchers must be aware of issues associated with weight stigma and work to minimize negative generalizations based on BMI.

Intracluster correlation coefficients in osteoarthritis cluster randomized trials: A systematic review.

OBJECTIVES: The design, analysis, and interpretation of cluster randomized clinical trials (RCTs) require accounting for potential correlation of observations on individuals within the same cluster. Reporting of observed intracluster correlation coefficients (ICCs) in cluster RCTs, as recommended by Consolidated Standards of Reporting Trials (CONSORT), facilitates sample size calculation of future cluster RCTs and understanding of the trial statistical power. Our objective was to summarize observed ICCs in osteoarthritis (OA) cluster RCTs. DESIGN: Systematic review of knee/hip OA cluster RCTs. We searched Cochrane Central Register of Controlled Trials for trials published from 2012, when CONSORT cluster RCTs extension was published, to September 2022. We calculated the proportion of cluster RCTs that reported observed ICCs. Of those that did, we extracted observed ICCs. PROSPERO: CRD42022365660. RESULTS: We screened 1121 references and included 20 cluster RCTs. Only 5 trials (25%) reported the observed ICC for at least one outcome variable. ICC values for pain outcomes were: 0, 0.01, 0.18; for physical function outcomes were: 0, 0.06, 0.13 (knee)/0.27 (hip); Western Ontario and McMaster Universities Arthritis Index (WOMAC) total: 0.02, 0.02; symptoms of anxiety/depression: 0.22; disability: 0; and global change: 0. One out of four (25%) trials reported an ICC that was larger than the ICC used for sample size calculation and thus was underpowered. CONCLUSIONS: Despite CONSORT statement recommendations for reporting cluster RCTs, few OA trials reported the observed ICC. Given the importance of the ICC to interpretation of trial results and future trial design, this reporting gap warrants attention.

Patient appropriateness for total knee arthroplasty and predicted probability of a good outcome.

OBJECTIVES: One-fifth of total knee arthroplasty (TKA) recipients experience a suboptimal outcome. Incorporation of patients' preferences in TKA assessment may improve outcomes. We determined the discriminant ability of preoperative measures of TKA need, readiness/willingness and expectations for a good TKA outcome. METHODS: In patients with knee osteoarthritis (OA) undergoing primary TKA, we preoperatively assessed TKA need (Western Ontario-McMaster Universities OA Index (WOMAC) Pain Score and Knee injury and Osteoarthritis Outcome Score (KOOS) function, arthritis coping), health status, readiness (Patient Acceptable Symptom State, depressive symptoms), willingness (definitely yes-yes/no) and expectations (outcomes deemed 'very important'). A good outcome was defined as symptom improvement (met Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria) and satisfaction with results 1 year post TKA. Using logistic regression, we assessed independent outcome predictors, model discrimination (area under the receiver operating characteristic curve, AUC) and the predicted probability of a good outcome for different need, readiness/willingness and expectations scenarios. RESULTS: Of 1,053 TKA recipients (mean age 66.9 years (SD 8.8); 58.6% women), 78.1% achieved a good outcome. With TKA need alone (WOMAC pain subscale, KOOS physical function short-form), model discrimination was good (AUC 0.67, 95% CI 0.63 to 0.71). Inclusion of readiness/willingness, depressive symptoms and expectations regarding kneeling, stair climbing, well-being and performing recreational activities improved discrimination (p=0.01; optimism corrected AUC 0.70, 0.66-0.74). The predicted probability of a good outcome ranged from 44.4% (33.9-55.5) to 92.4% (88.4-95.1) depending on level of TKA need, readiness/willingness, depressive symptoms and surgical expectations. CONCLUSIONS: Although external validation is required, our findings suggest that incorporation of patients' TKA readiness, willingness and expectations in TKA decision-making may improve the proportion of recipients that experience a good outcome.

Improving diagnosis and treatment of knee osteoarthritis in persons with type 2 diabetes: development of a complex intervention.

BACKGROUND: Symptomatic knee osteoarthritis (OA) commonly co-occurs in people with type 2 diabetes (T2DM) and increases the risk for diabetes complications, yet uptake of evidence-based treatment is low. We combined theory, stakeholder involvement and existing evidence to develop a multifaceted intervention to improve OA care in persons with T2DM. This was done in partnership with Arthritis Society Canada to leverage the existing infrastructure and provincial funding for community arthritis care. METHODS: Each step was informed by a User Advisory Panel of stakeholder representatives, including persons with lived experience. First, we identified the target groups and behaviours through consulting stakeholders and current literature. Second, we interviewed persons living with T2DM and knee OA (n = 18), health professionals (HPs) who treat people with T2DM (n = 18) and arthritis therapists (ATs, n = 18) to identify the determinants of seeking and engaging in OA care (patients), assessing and treating OA (HPs) and considering T2DM in OA treatment (ATs), using the Theoretical Domains Framework (TDF). We mapped the content to behavioural change techniques (BCTs) to identify the potential intervention components. Third, we conducted stakeholder meetings to ascertain the acceptability and feasibility of intervention components, including content and modes of delivery. Fourth, we selected intervention components informed by prior steps and constructed a programme theory to inform the implementation of the intervention and its evaluation. RESULTS: We identified the barriers and enablers to target behaviours across a number of TDF domains. All stakeholders identified insufficient access to resources to support OA care in people with T2DM. Core intervention components, incorporating a range of BCTs at the patient, HP and AT level, sought to identify persons with knee OA within T2DM care and refer to Arthritis Society Canada for delivery of evidence-based longitudinal OA management. Diverse stakeholder input throughout development allowed the co-creation of an intervention that appears feasible and acceptable to target users. CONCLUSIONS: We integrated theory, evidence and stakeholder involvement to develop a multifaceted intervention to increase the identification of knee OA in persons with T2DM within diabetes care and improve the uptake and engagement in evidence-based OA management. Our partnership with Arthritis Society Canada supports future spread, scalability and sustainability. We will formally assess the intervention feasibility in a randomized pilot trial.

The Effects of Continuity of Rheumatology Care on Emergency Department Utilization and Hospitalizations for Individuals With Early Rheumatoid Arthritis: A Population-Based Study.

OBJECTIVE: To determine if continuity of rheumatology care influences rates of emergency department (ED) visits and hospitalizations in patients with rheumatoid arthritis (RA). METHODS: A closed inception cohort of patients with RA diagnosed between 2000 and 2009 were followed until December 31, 2019. During the first 5 years following diagnosis, we categorized patients into 3 rheumatology care continuity groups (high, intermediate, and not retained in rheumatology care). Using a landmark analysis, we compared rates of ED visits and hospitalizations during follow-up. Multivariable Poisson regression models were used to estimate rate ratios (RRs), adjusting for demographics, comorbidities, and health services access and supply measures. RESULTS: The cohort included 38,528 patients, of which 57.7% (n = 22,221) were classified in the high rheumatology continuity group, 17.2% (n = 6636) were in the intermediate group, and 25.1% (n = 9671) were not retained in rheumatology care. Relative to the high continuity group, both the intermediate and nonretention groups had higher ED rates (RR 1.14, 95% CI 1.08-1.20, and RR 1.12, 95% CI 1.08-1.16, respectively). The intermediate group also experienced higher adjusted hospitalization rates (207.4, 95% CI 203.0-211.8 per 1000 person-years [PY]) than the high continuity group (193.5, 95% CI 191.4-195.6 per 1000 PY). CONCLUSION: Patients with RA with higher continuity of rheumatology care had lower rates of ED visits and hospitalizations compared to those who did not receive continuous rheumatology care during the first 5 years of follow-up. These findings provide evidence to support the value of early and continuous rheumatology care for reducing hospitalizations and ED visits.

Barriers and enablers to health care providers assessment and treatment of knee osteoarthritis in persons with type 2 diabetes mellitus: A qualitative study using the Theoretical Domains Framework.

Objectives: Symptomatic knee osteoarthritis (OA) commonly co-exists in persons with Type 2 diabetes (T2DM) and may impede diabetes self-management. Yet, OA is often underdiagnosed and undertreated due to competing health care demands. We sought to determine healthcare providers' (HCPs') perceptions of the barriers and enablers to assessing and treating knee OA in persons with T2DM. Design: We conducted 18 semi-structured telephone interviews with HCPs who manage persons with T2DM (family physicians, endocrinologists, diabetes educators). Interviews were analyzed deductively using Theoretical Domains Framework (TDF), a framework developed to comprehensively identify behavioural determinants. Within relevant domains, data were thematically analyzed to generate belief statements, and these were compared across the different HCP disciplines. Results: Six TDF domains influenced HCPs behaviour to assess and treat knee OA in persons with T2DM. For all HCPs, important barriers included not seeing assessment/treatment of joint pain as a priority for their patients (intention), and insufficient access to required resources such as physiotherapy to treat OA (environmental context and resources). Endocrinologists and diabetes educators perceived having insufficient knowledge and skills to identify and manage OA (knowledge, skills), did not consider it within their professional role to do so (professional role and identity), and perceived other physicians would not want to receive a referral for OA care (social influences). Conclusions: We identified barriers and enablers encountered by diabetes HCPs to assessing and treating knee OA in persons with T2DM involving multiple domains of the TDF. These will help inform development of a complex intervention to improve health outcomes.

Understanding the behavioural determinants of seeking and engaging in care for knee osteoarthritis in persons with type 2 diabetes mellitus: A qualitative study using the theoretical domains framework.

Objectives: Symptomatic knee osteoarthritis (OA) frequently co-occurs in individuals with type 2 diabetes mellitus (T2DM). In the context of T2DM, OA is often underdiagnosed and undertreated. To elucidate strategies to improve OA care in persons with T2DM, we assessed their perceptions of the barriers and enablers to seeking and engaging in OA care. Design: We conducted semi-structured interviews with 18 individuals with T2DM and symptomatic knee OA in Ontario, Canada. Transcripts were deductively coded using the Theoretical Domains Framework (TDF), an implementation science framework that incorporates theoretical domains of behaviour determinants, which can be linked to behaviour change techniques. Within each of the relevant domains, data were thematically analyzed to generate belief statements. Results: Seven of the TDF domains prominently influenced the behaviour to seek and engage in OA care. Participants described insufficient receipt of OA knowledge to fully engage in care (knowledge), feeling incapable of participating in physical activity due to joint pain (beliefs about capabilities), uncertainty about effectiveness of therapies (optimism) and lack of guidance from health care providers and insufficient access to community programs/supports (environmental context and resources). Key enablers were strong social support (social influences), sources of accountability (behavioural regulation) and experiencing benefit from treatment (reinforcement). Participants did not see concomitant T2DM as limiting the desire to seek OA care. Conclusions: Among individuals with symptomatic knee OA and T2DM, we identified behavioural determinants of seeking and engaging in OA care. These will be mapped to behavioural change techniques to inform development of a complex intervention.

Formulating Knee Osteoarthritis Management Plans Taking Type 2 Diabetes Into Account: Qualitative Study of Arthritis Therapists Using Theoretical Domains Framework.

OBJECTIVE: Delivering person-centered care in individuals with knee osteoarthritis (OA) necessitates consideration of other chronic conditions that frequently co-occur. We sought to understand the extent to which arthritis therapists consider type 2 diabetes mellitus (T2DM) when treating persons with knee OA and concomitant T2DM, and barriers to doing so. METHODS: We conducted 18 semistructured telephone interviews with arthritis therapists working within a provincially funded arthritis care program (Arthritis Society Canada) in Ontario, Canada. We first analyzed interviews deductively using the Theoretical Domains Framework (TDF) to comprehensively identify barriers and enablers to health behaviors. Then, within TDF domains, we inductively developed themes. RESULTS: We identified 5 TDF domains as prominently influencing the behavior of arthritis therapists considering concomitant T2DM when developing a knee OA management plan. These were as follows: therapists' perceived lack of specific knowledge around comorbidities including diabetes; the lack of breadth in skills in behavioral change techniques to help patients set and reach their goals, particularly when it came to physical activity; variable intention to factor a patient's comorbidity profile to influence their treatment recommendations; the perception of their professional role and identity as joint focused; and the environmental context with lack of formalized follow-up structure of the current Arthritis Society Canada program that limited sufficient patient monitoring and follow-up. CONCLUSION: Within the context of a Canadian arthritis program, we identified several barriers to arthritis therapists considering T2DM in their management plan for persons with knee OA and T2DM. These results can help inform strategies to improve person-centered OA care and overall health outcomes.

Effect of Physical Therapy vs Arthroscopic Partial Meniscectomy in People With Degenerative Meniscal Tears: Five-Year Follow-up of the ESCAPE Randomized Clinical Trial.

Importance: There is a paucity of high-quality evidence about the long-term effects (ie, 3-5 years and beyond) of arthroscopic partial meniscectomy vs exercise-based physical therapy for patients with degenerative meniscal tears. Objectives: To compare the 5-year effectiveness of arthroscopic partial meniscectomy and exercise-based physical therapy on patient-reported knee function and progression of knee osteoarthritis in patients with a degenerative meniscal tear. Design, Setting, and Participants: A noninferiority, multicenter randomized clinical trial was conducted in the orthopedic departments of 9 hospitals in the Netherlands. A total of 321 patients aged 45 to 70 years with a degenerative meniscal tear participated. Data collection took place between July 12, 2013, and December 4, 2020. Interventions: Patients were randomly allocated to arthroscopic partial meniscectomy or 16 sessions of exercise-based physical therapy. Main Outcomes and Measures: The primary outcome was patient-reported knee function (International Knee Documentation Committee Subjective Knee Form (range, 0 [worst] to 100 [best]) during 5 years of follow-up based on the intention-to-treat principle, with a noninferiority threshold of 11 points. The secondary outcome was progression in knee osteoarthritis shown on radiographic images in both treatment groups. Results: Of 321 patients (mean [SD] age, 58 [6.6] years; 161 women [50.2%]), 278 patients (87.1%) completed the 5-year follow-up with a mean follow-up time of 61.8 months (range, 58.8-69.5 months). From baseline to 5-year follow-up, the mean (SD) improvement was 29.6 (18.7) points in the surgery group and 25.1 (17.8) points in the physical therapy group. The crude between-group difference was 3.5 points (95% CI, 0.7-6.3 points; P < .001 for noninferiority). The 95% CI did not exceed the noninferiority threshold of 11 points. Comparable rates of progression of radiographic-demonstrated knee osteoarthritis were noted between both treatments. Conclusions and Relevance: In this noninferiority randomized clinical trial after 5 years, exercise-based physical therapy remained noninferior to arthroscopic partial meniscectomy for patient-reported knee function. Physical therapy should therefore be the preferred treatment over surgery for degenerative meniscal tears. These results can assist in the development and updating of current guideline recommendations about treatment for patients with a degenerative meniscal tear. Trial Registration: ClinicalTrials.gov Identifier: NCT01850719.

Minimal clinically important difference for improvement in six-minute walk test in persons with knee osteoarthritis after total knee arthroplasty.

BACKGROUND: The interpretability of the six-minute walk test (6MWT) in individuals with knee osteoarthritis (OA) is unclear. We aimed to determine the minimal clinically important difference (MCID) for improvement in 6MWT in persons with knee OA at 12 months after total knee arthroplasty (TKA), and if it differed by baseline walking ability. METHODS: Participants with knee OA were assessed 1 month pre- and 12 months post-TKA, including completion of 6MWT. At 12 months, participant-perceived change in walking ability was assessed on an 8-point Likert scale ranging from "extremely worse" to "extremely better". Using logistic regression, ROC curves examined the ability of change in 6MWT distance to discriminate those who perceived walking was improved. MCID was selected overall and then by quartile of baseline 6MWT distance using the Youden method. RESULTS: Two hundred seventy-eight participants were included: mean age 67 years (SD 8.5), 65.5% female, mean pre-TKA 6MWT distance 323.1 (SD 104.7) m, and mean 12-mo 6MWT distance 396.0 (SD 111.9) m. The overall MCID was 74.3 m (AUC 0.65). Acceptable model discrimination (AUC > 0.70) was achieved for individuals in the lowest quartiles of baseline 6MWT distance: Quartile 1: MCID 88.63 m (AUC 0.73); Quartile 2: MCID 84.47 m (AUC 0.72). CONCLUSIONS: In persons with knee OA 12 months post-TKA, 6MWT MCID is dependent on baseline walking ability. Poor model discrimination for those in the highest (best) quartiles of baseline walking ability raise questions about 6MWT use across the full spectrum of walking ability. Further research is needed to better understand use of 6MWT as a performance-based measure of physical function for persons with knee OA.

The Burden of Osteoarthritis in Older Adults.

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability among older people. One in 3 people over age 65, and disproportionately more women than men, are living with OA. The prevalence of OA is rising related to an increasing prevalence of OA risk factors, including aging and obesity. In older adults, OA frequently exists alongside other common chronic conditions and may increase the risk for worse outcomes from these conditions. Given the growing burden and impact of OA, enhanced effort is required to deliver effective and safe treatments to those living with the disease.

The Effect of Patient Age and Surgical Appropriateness and Their Influence on Surgeon Recommendations for Primary TKA: A Cross-Sectional Study of 2,037 Patients.

BACKGROUND: Rising total knee arthroplasty (TKA) rates in younger patients raises concern about appropriateness. We asked: are younger individuals who seek consultation for TKA less likely to be appropriate for and, controlling for appropriateness, more likely to be recommended for surgery? METHODS: This cross-sectional study was nested within a prospective cohort study of knee osteoarthritis (OA) patients referred for TKA from 2014 to 2016 to centralized arthroplasty centers in Alberta, Canada. Pre-consultation, questionnaires assessed patients' TKA appropriateness (need, based on knee symptoms and prior treatment; readiness/willingness to undergo TKA; health status; and expectations) and contextual factors (for example, employment). Post-consultation, surgeons confirmed study eligibility and reported their TKA recommendation. Using generalized estimating equations to control for clustering by surgeon, we assessed relationships between patient age (<50, 50 to 59, ≥60 years) and TKA appropriateness and receipt of a surgeon TKA recommendation. RESULTS: Of 2,037 participants, 3.3% and 22.7% were <50 and 50 to 59 years of age, respectively, 58.7% were female, and 35.5% were employed. Compared with older participants, younger participants reported significantly worse knee symptoms, higher use of OA therapies, higher TKA readiness, and similar willingness, but had higher body mass index and were more likely to smoke and to consider the ability to participate in vigorous activities, for example, sports, as very important TKA outcomes. TKA was offered to 1,500 individuals (73.6% overall; 52.2%, 71.0%, and 75.4% of those <50, 50 to 59, and ≥60 years, respectively). In multivariate analyses, the odds of receiving a TKA recommendation were higher with greater TKA need and willingness, in nonsmokers, and in those who indicated that improved ability to go upstairs and to straighten the leg were very important TKA outcomes. Controlling for TKA appropriateness, patient age was not associated with surgeons' TKA recommendations. CONCLUSIONS: Younger individuals with knee OA referred for TKA had similar or greater TKA need, readiness, and willingness than older individuals. Incorporation of TKA appropriateness criteria into TKA decision-making may facilitate consideration of TKA benefits and risks in a growing population of young, obese individuals with knee OA. CLINICAL RELEVANCE: Younger people seeking TKA for knee OA had significant OA pain and disability despite recommended OA therapies, suggesting appropriateness for surgical consideration. However, they were significantly more likely to have morbid obesity, to smoke, and to consider return to vigorous activities, like sport, as important TKA outcomes. Whether the short- and longer-term risks of TKA are outweighed by the benefits is unclear and warrants additional research.

Effect of race, gender identity, and their intersection on career satisfaction: A cross-sectional survey of academic physicians.

PURPOSE: Ensuring a representative workforce is a matter of equity and social justice and has implications for patient care and population health. We examined the relationship of the binary gender identity and race of physicians who felt comfortable to self-identify, with workplace experiences and career satisfaction in academic medicine. METHODS: The outcome of interest of a cross-sectional survey of full-time clinical faculty members within the Department of Medicine, University of Toronto, was physician's self-reported career satisfaction. Using logistic regression, we examined relationships of binary gender identity (female/male) and race [under-represented minority (URM) versus over-represented in medicine (ORM)] to: workplace experiences (respectful interactions, perception of having to work harder, exclusion from social networks, witnessing/experiencing unprofessionalism, and confidence in taking action to address incivility without reprisal); and career satisfaction, controlling for age, rank, protected time, and workplace experiences. RESULTS: Female gender and URM status were associated with younger age, lower rank, and less positive workplace experiences. 132 respondents (44.4%) strongly agreed they had career satisfaction. Compared with ORM men, career satisfaction was significantly lower for URM and ORM female physicians (OR 0.30, 95% CI 0.14-0.65, and 0.48, 95% CI 0.27-0.85, respectively) and non-significantly lower for URM male physicians (OR 0.62, 95% CI 0.32-1.19). Adjustment for academic rank and workplace experiences fully attenuated these relationships. CONCLUSIONS: URM female academic physicians had lower career satisfaction than their ORM male counterparts, largely explained by systematic differences in workplace experiences, particularly perceptions of exclusion from social networks and having to work harder to be perceived as legitimate scholars. This suggests a role for institutions and leaders to build inclusive, anti-racist, and anti-oppressive cultures to support the flourishing of all faculty.

Relationship Between Patient-Reported Readiness for Total Knee Arthroplasty and Likelihood of a Good Outcome at One-Year Follow-Up.

OBJECTIVE: To determine the relationship between patients' preoperative readiness for total knee arthroplasty (TKA) and surgical outcome at 1 year post-TKA. METHODS: This prospective cohort study recruited patients with knee osteoarthritis (OA) who were ≥30 years and were referred for TKA at 2 hip/knee surgery centers in Alberta, Canada. Those who underwent primary unilateral TKA completed questionnaires prior to TKA to assess pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), physical disability using the Knee Injury and Osteoarthritis Outcome Score physical function short form, perceived arthritis coping efficacy, general self-efficacy, depressed mood using the Patient Health Questionnaire 8, body mass index, comorbidities, and TKA readiness (patient acceptable symptom state; willingness to undergo TKA); these same individuals also completed the above questionnaires 1 year post-TKA to assess surgical outcomes. A good TKA outcome was defined as an individual having improved knee symptoms, measured using the Osteoarthritis Research Society International-Outcome Measures in Rheumatology responder criteria, and overall satisfaction with results of the TKA. Poisson regression with robust error estimation was used to estimate the relative risk (RR) of a good outcome for exposures, before and after controlling for covariates. RESULTS: Of 1,272 TKA recipients assessed at 1 year post-TKA, 1,053 with data for the outcome assessed in the study were included (mean ± SD age 66.9 ± 8.8 years; 58.6% female). Most patients (87.8%) were definitely willing to undergo TKA and had "unacceptable" knee symptoms (79.7%). Among patients who underwent TKA, 78.1% achieved a good outcome. Controlling for pre-TKA OA-related disability, arthritis coping efficacy, comorbid hip symptoms, and depressed mood, definite willingness to undergo TKA and unacceptable knee symptoms were associated with a greater likelihood of a good TKA outcome, with adjusted RRs of 1.18 (95% confidence interval [95% CI] 1.04-1.35) and 1.14 (95% CI 1.02-1.27), respectively. CONCLUSION: Among patients who underwent TKA for knee OA, patients' psychological readiness for TKA and willingness to undergo TKA were associated with a greater likelihood of a good outcome. Incorporation of these factors in TKA decision-making may enhance patient outcomes and appropriate the use of TKA.

Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. DESIGN: Systematic review and network meta-analysis of randomised trials. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656.

Allopurinol adherence, persistence and patterns of use in individuals with diabetes and gout: A retrospective, population-based cohort analysis.

OBJECTIVE: There has been growing interest in the potential role for allopurinol to reduce cardiovascular events in people with diabetes. While adherence to allopurinol is poor in those with gout, our aim was to characterize persistence, patterns of use, and predictors of allopurinol use in a population-based cohort of individuals with diabetes and gout. METHODS: Individuals with diabetes older than 66 (thus eligible for prescription medication coverage) and newly prescribed allopurinol were followed for up to three years in a retrospective cohort study. Allopurinol use patterns were categorized as adherer (used continuously throughout follow-up), interrupter (non-persistent but subsequently resumed), or discontinuer (non-persistent with no subsequent resumption). Main outcomes were allopurinol non-persistence (no subsequent prescription accounting for a grace period), and indicators of gout severity throughout follow-up (prescriptions for prednisone or colchicine, outpatient gout visits, hospitalization/emergency department visits for gout). Outcome frequencies were determined, a multivariable Cox proportional hazards model evaluated associations between predictors and non-persistence, and zero-inflated negative binomial (ZINB) models evaluated associations between allopurinol use pattern and indicators of gout severity. RESULTS: 22,056 individuals were followed for a maximum of 3.0 years (17,410 with 3 years of follow-up). 9092 (41.2%) were non-persistent with allopurinol. Higher risks of non-persistence were associated with female sex (HR, 95% CI: 1.28, 1.23-1.33), dementia (1.23, 1.11-1.35), and an outpatient visit for gout in the prior year (1.19, 1.09-1.29). There were 12,964 (58.8%) allopurinol adherers, 4618 interrupters (20.9%), and 4474 (20.3%) discontinuers. Allopurinol interrupters and discontinuers had indicators of more severe gout over time compared to adherers, including greater odds of being prescribed prednisone. CONCLUSION: Allopurinol non-persistence and interruptions were frequent in individuals with diabetes and gout and were associated with prescriptions for prednisone. Suboptimal allopurinol adherence may not only increase the risk of gout complications in this population but also potentially diabetes complications through greater prednisone use and its negative effects on glycemic control.