Jianhao Lin

The high prevalence of knee osteoarthritis in a rural Chinese population: the Wuchuan osteoarthritis study.

OBJECTIVE To estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) in a remote rural region of northern China, and compare them with those reported in Beijing and with data from the Framingham (Massachusetts) cohort. METHODS A population-based cross-sectional survey was conducted among 1,030 residents of Wuchuan County, Inner Mongolia, age > or =50 years. Survey participants, mostly farmers reporting heavy physical occupational activity, completed an interviewer-based questionnaire, and bilateral weight-bearing posteroanterior semiflexed knee radiographs were obtained. RESULTS Whereas the overall prevalence of radiographic knee OA was similar to that demonstrated in the Beijing OA study, men in Wuchuan had approximately double the prevalence of severe radiographic knee OA (prevalence ratio [PR] 2.5, 95% confidence interval [95% CI] 1.6-3.8) and symptomatic knee OA (PR 1.9, 95% CI 1.3-2.9). Women in Wuchuan also had a higher prevalence of both severe radiographic (PR 1.4, 95% CI 1.0-2.0) and symptomatic knee OA (PR 1.6, 95% CI 1.2-2.1) compared with their Beijing counterparts. The prevalence of bilateral OA and lateral compartment disease were 2-3 times higher in both Chinese cohorts compared with estimates from the Framingham OA study. CONCLUSION The prevalence of symptomatic knee OA in rural areas of China is much higher than reported from urban regions of China or in the Framingham cohort. The higher representation of bilateral and lateral compartment disease in China suggests a unique phenotype to OA. These findings will be useful for guiding the distribution of future health care resources and preventive strategies.

The Prevalence of Symptomatic Knee Osteoarthritis in China: Results From the China Health and Retirement Longitudinal Study.

To estimate the prevalence of symptomatic knee osteoarthritis (OA) in China.

Osteoarthritis and all-cause mortality in worldwide populations: grading the evidence from a meta-analysis.

The objective of this study is to investigate the association between osteoarthritis (OA) and all-cause mortality in worldwide populations and to develop recommendations according to GRADE evidence levels. Literature search through Nov 2015 was performed using the electronic databases (including MEDLINE, EMBASE, EBSCO and Cochrane library). The prospective cohort trials that investigated the association between the symptomatic OA (SxOA) or radiological OA (ROA) and all-cause mortality were identified. Hazard ratios (HR) of all-cause mortality in patients with RxOA or ROA were pooled respectively. The evidence quality was evaluated using the GRADE system, while the recommendations were taken according to the quality. Nine of the published literature met the eligible criteria. Meta-analysis revealed that there was no significant difference in the association between SxOA and all-cause mortality (HR = 0.91, 95% CI: 0.68–1.23) and between ROA and all-cause mortality (HR = 1.13, 95% CI: 0.95–1.35). The overall GARDE evidence quality was very low, which will lower our confidence in taking recommendations. To summarize, there was no reliable and confident evidence existed currently in respect of the association between OA and all-cause mortality. Due to the very low level of evidence quality currently, high-quality studies are still required.

Clinical algorithms to aid osteoarthritis guideline dissemination

BACKGROUND Numerous scientific organisations have developed evidence-based recommendations aiming to optimise the management of osteoarthritis (OA). Uptake, however, has been suboptimal. The purpose of this exercise was to harmonize the recent recommendations and develop a user-friendly treatment algorithm to facilitate translation of evidence into practice. METHODS We updated a previous systematic review on clinical practice guidelines (CPGs) for OA management. The guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation for quality and the standards for developing trustworthy CPGs as established by the National Academy of Medicine (NAM). Four case scenarios and algorithms were developed by consensus of a multidisciplinary panel. RESULTS Sixteen guidelines were included in the systematic review. Most recommendations were directed toward physicians and allied health professionals, and most had multi-disciplinary input. Analysis for trustworthiness suggests that many guidelines still present a lack of transparency. A treatment algorithm was developed for each case scenario advised by recommendations from guidelines and based on panel consensus. CONCLUSION Strategies to facilitate the implementation of guidelines in clinical practice are necessary. The algorithms proposed are examples of how to apply recommendations in the clinical context, helping the clinician to visualise the patient flow and timing of different treatment modalities.

Risk Factors for Radiographic Tibiofemoral Knee Osteoarthritis: The Wuchuan Osteoarthritis Study

Objective. To investigate the risk factors of radiographic tibiafemoral knee osteoarthritis (OA). Methods. A population-based cross-sectional survey was conducted in Wuchuan County. A questionnaire and bilateral weight-bearing posterior-anterior semi-flexed knee radiographs were completed and read for Kellgren and Lawrence (K/L) grade and joint space narrowing (JSN; 0–3 scale) in each compartment. An logistic regression analysis was performed for radiographic tibiafemoral, lateral compartment, and medial compartment knee OA, respectively. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results. Age, sex, and knee injury were strongly associated with tibiafemoral, lateral and medial compartment knee OA. BMI also had a dose-response relationship with them. Physical activity level, and physical activity exposure at work, not significantly though, were associated with an elevated risk for this three kinds of knee OA. Conclusions. Physical activity exposure increased the risk of knee OA. It was likely to be the heavier physical activity in Wuchuan osteoarthritis study that counteracted the BMI gap compared with the Beijing and the Framingham OA study. We verified that Chinese had a more valgus alignment of the knee compared with Caucasian population, and this provide a possible explanation why Chinese have a higher prevalence of lateral compartment OA.

Intra-articular Hyaluronic Acid in Treating Knee Osteoarthritis: a PRISMA-Compliant Systematic Review of Overlapping Meta-analysis

Numerous meta-analyses have been conducted aiming to compare hyaluronic acid (HA) and placebo in treating knee osteoarthritis (OA). Nevertheless, the conclusions of these meta-analyses are not in consistency. The purpose of the present study was to perform a systematic review of overlapping meta-analyses investigating the efficacy and safety of HA for Knee OA and to provide treatment recommendations through the best evidence. A systematic review was conducted based on the PRISMA guidelines. The meta-analyses and/or systematic reviews that compared HA and placebo for knee OA were identified. AMSTAR instrument was used to evaluate the methodological quality of individual study. The information of heterogeneity within each variable was fetched for the individual studies. Which meta-analyses can provide best evidence was determined according to Jadad algorithm. Twelve meta-analyses met the eligibility requirements. The Jadad decision making tool suggests that the highest quality review should be selected. As a result, a high-quality Cochrane review was included. The present systematic review of overlapping meta-analyses demonstrates that HA is an effective intervention in treating knee OA without increased risk of adverse events. Therefore, the present conclusions may help decision makers interpret and choose among discordant meta-analyses.

Comparison of two hyaluronic acid formulations for safety and efficacy (CHASE) study in knee osteoarthritis: a multicenter, randomized, double-blind, 26-week non-inferiority trial comparing Durolane to Artz

IntroductionIntra-articular injection of hyaluronic acid (HA) is often used as therapy for knee osteoarthritis because it is less expensive and less aggressive than total knee replacement. Therefore, it is important to document whether HA is safe and efficacious. We tested whether single and multiple injection viscosupplementation with HA is associated with clinically meaningful pain relief in a new randomized clinical trial (RCT). Our objective was to compare safety and efficacy of intra-articular HA in two formulations: one 3.0 ml injection of Durolane versus five 2.5 ml injections of Artz for the treatment of knee osteoarthritis pain.MethodsPatients (N = 349) from the People’s Republic of China were randomized to treatment (Durolane = 175, Artz = 174). The Durolane group received a 3.0 ml injection at week 0 (baseline), with sham skin punctures at weeks 1, 2, 3, and 4. The Artz group received one 2.5 ml injection at each of the same time points. The primary assessment tool was the Likert-type Western Ontario and McMaster University (WOMAC) pain scale at weeks 0, 6, 10, 14, 18, and 26. Secondary assessments were WOMAC physical function, knee stiffness, and global self-assessment, at identical time points. Statistically-controlled analyses were non-inferiority of Durolane over 18, then over 26 weeks, with a priori non-inferiority defined as 8% of the relevant scale. Acetaminophen was permitted as rescue analgesia and all adverse events (AEs) were recorded.ResultsOverall study retention was excellent; 332 patients (95.1%) completed 18 weeks and 319 (91.4%) completed 26 weeks, with no significant retention difference between treatment arms. All variables met non-inferiority criteria over 18 and 26 weeks. Efficacy response in both arms was >90%. Treatment-related AEs were 9.8% (17/174) for Artz and 13.1% (23/175) for Durolane.ConclusionsA single injection of Durolane is non-inferior to 5 injections of Artz over 18 and 26 weeks for pain, physical function, global self-assessment, and knee stiffness. Both treatments were efficacious, safe, and well tolerated.Trial registrationClinicalTrials.gov NCT01295580. Registered 11 February 2011.

Mesenchymal stem cells injections for knee osteoarthritis: a systematic overview

Numerous systematic reviews investigating the effects of mesenchymal stem cells (MSCs) in treating knee osteoarthritis (OA) have been published with controversial conclusion. The purpose of the overview was (1) to perform an overview of systematic reviews investigating MSCs for knee OA and (2) to synthesize evidence qualitatively to assess confidence in the review findings. A systematic search of systematic reviews published through Aug 2017 was conducted using the MEDLINE, EMBASE and Cochrane Library. The methodological quality and risk of bias of included systematic reviews was assessed by AMSTAR instrument and ROBIS tool, respectively. Best evidence choice procedure was conducted according to the Jadad decision algorithm. The systematic reviews with high methodological quality and low risk of bias were selected ultimately for further evidence synthesis based on the CERQual tool. Four systematic reviews were eligible for inclusion. According to the ROBIS tool, there was one systematic review with low risk of bias and three with high risk of bias. Thus, only one systematic review conducted by Pas et al. with highest AMSTAR score and low risk of bias was selected. For all outcomes after evidence synthesis via the CERQual tool, confidence for decision making was either low (self-reported measurement and MRI/histological outcome) or moderate (adverse events). The present study demonstrates that moderate confidence could be placed in safety of MSCs therapy for knee OA, but with low confidence in efficacy outcomes due to limitations of the current evidence. Further high-quality studies with high internal and external validity are still required.

Intra-articular injection of mesenchymal stem cells in treating knee osteoarthritis: a systematic review of animal studies

PURPOSE Mesenchymal stem cells (MSCs) injection has emerged as a novel treatment for knee osteoarthritis (KOA) but with inconsistent results in the experimental studies. Thus, the purpose of the present study is to evaluate the preclinical animal studies of MSCs injection for KOA and to determine the evidence for a role for MSCs in further clinical trials. METHODS A systematic search of KOA animal studies published through Aug 2017 was conducted using the PubMed, Embase and Web of science. Criteria for eligibility were animal studies assessing the therapeutic effects of MSCs intra-articular injection to animals with KOA. The methodological quality of included studies was assessed by the SYRCLE tool for assessing risk of bias in animal intervention studies. Descriptive synthesis was performed. Evidence quality was evaluated based on the Confidence in the Evidence from Reviews of Qualitative research (CERQual) tool. RESULTS Twenty-three KOA animal studies were eligible for inclusion. According to the SYRCLEs tool, all included studies had high risk of bias. Between-study heterogeneity was substantial. The included studies varied in terms of species, modeling methods, MSCs origin, treatment timing, injections frequency, transplantation type and dose of MSCs. The following outcomes, gross morphology, histological analysis, immunohistochemical analysis, radiological evaluation or behavior analysis, were reported in the primary studies. For all outcomes, the evidence quality was low or very low. CONCLUSIONS We do not have absolute confidence to recommend use MSCs injection for KOA clinical trials. Based on the internal and external validity of current animal studies, high quality experimental studies and efforts for effective translation from preclinical studies to clinical trials are still required.

Knee Symptomatic Osteoarthritis, Walking Disability, NSAIDs Use and All-cause Mortality: Population-based Wuchuan Osteoarthritis Study

Knee symptomatic osteoarthritis (SxOA) was associated with all-cause mortality. Walking disability and NSAIDs use have been postulated as potential mechanisms linking knee SxOA to all-cause mortality. Data were collected on ability of walking for 1 kilometer and use of NSAIDs at baseline and death information at follow-up. Subjects with knee SxOA were identified if at least one knee had both radiographic OA and pain. We first fitted a Cox proportional hazards model to examine the relation of knee SxOA to the risk of all-cause mortality. We then used marginal structural models to decompose total effect of knee SxOA on all-cause mortality into indirect and direct effects via walking disability and use of NSAIDs, respectively. Among 1025 subjects, 99 died over 8 years of follow-up. A multivariable adjusted hazard ratio of mortality for SxOA was 1.98 (95% CI: 1.09–3.62). The indirect effect of knee SxOA on all-cause mortality through either a walking disability or NSAIDs use was 1.92 (95% CI: 0.86–4.26) and 1.45 (95% CI: 0.72–2.92), respectively. The corresponding direct effect was 1.08 (95% CI: 0.55–1.12) and 1.35 (95% CI: 0.75–2.44). In this population-based cohort study, high all-cause mortality from knee SxOA was mediated mainly through a walking disability.