Shao-Hsien Liu

Effects of Prescription Nonsteroidal Antiinflammatory Drugs on Symptoms and Disease Progression Among Patients With Knee Osteoarthritis

The effect of short‐term and long‐term use of nonsteroidal antiinflammatory drugs (NSAIDs) on structural change is equivocal. The aim of this study was to estimate the extent to which short‐ and long‐term use of prescription NSAIDs relieve symptoms and delay structural progression among patients with radiographically confirmed osteoarthritis (OA) of the knee.

Association of objectively measured physical activity and metabolic syndrome among U.S. adults with osteoarthritis

To investigate the association between objectively measured physical activity and metabolic syndrome among adults with osteoarthritis (OA).

The relationship between smoking and knee osteoarthritis in the Osteoarthritis Initiative.

OBJECTIVE To estimate the extent that smoking history is associated with symptoms and disease progression among individuals with radiographically confirmed knee Osteoarthritis (OA). METHOD Both cross-sectional (baseline) and longitudinal studies employed data from the Osteoarthritis Initiative (OAI) (n = 2250 participants). Smoking history was assessed at baseline with 44% current or former smokers. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to measure knee pain, stiffness, and physical function. Disease progression was measured using joint space width (JSW). We used adjusted multivariable linear models to examine the relationship between smoking status and exposure in pack years (PY) with symptoms and JSW at baseline. Changes in symptoms and JSW over time were further assessed. RESULTS In cross-sectional analyses, compared to never-smokers high PY (≥15 PY) was associated with slightly greater pain (beta 0.36, 95% CI: 0.01-0.71) and stiffness (beta 0.20, 95% CI: 0.03-0.37); and low PY (<15 PY) was associated with better JSW (beta 0.15, 95% CI: 0.02-0.28). Current smoking was associated with greater pain (beta 0.59, 95% CI: 0.04-1.15) compared to never-smokers. These associations were not confirmed in the longitudinal study. Longitudinally, no associations were found between high or low PY or baseline smoking status with changes in symptoms (at 72 months) or JSW (at 48 months). CONCLUSION Cross-sectional findings are likely due residual confounding. The more robust longitudinal analysis found no associations between smoking status and symptoms or JSW. Long-term smoking provides no benefits to knee OA patients while exposing them to other well-documented serious health risks.

Implementation and reporting of causal mediation analysis in 2015: a systematic review in epidemiological studies.

BackgroundCausal mediation analysis is often used to understand the impact of variables along the causal pathway of an occurrence relation. How well studies apply and report the elements of causal mediation analysis remains unknown.MethodsWe systematically reviewed epidemiological studies published in 2015 that employed causal mediation analysis to estimate direct and indirect effects of observed associations between an exposure on an outcome. We identified potential epidemiological studies through conducting a citation search within Web of Science and a keyword search within PubMed. Two reviewers independently screened studies for eligibility. For eligible studies, one reviewer performed data extraction, and a senior epidemiologist confirmed the extracted information. Empirical application and methodological details of the technique were extracted and summarized.ResultsThirteen studies were eligible for data extraction. While the majority of studies reported and identified the effects of measures, most studies lacked sufficient details on the extent to which identifiability assumptions were satisfied. Although most studies addressed issues of unmeasured confounders either from empirical approaches or sensitivity analyses, the majority did not examine the potential bias arising from the measurement error of the mediator. Some studies allowed for exposure-mediator interaction and only a few presented results from models both with and without interactions. Power calculations were scarce.ConclusionsReporting of causal mediation analysis is varied and suboptimal. Given that the application of causal mediation analysis will likely continue to increase, developing standards of reporting of causal mediation analysis in epidemiological research would be prudent.

Factors Associated with the Use of Hyaluronic Acid and Corticosteroid Injections among Patients with Radiographically Confirmed Knee Osteoarthritis: A Retrospective Data Analysis

PURPOSE Despite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving these injections is scarce. We describe the use of injections among adults with radiographically confirmed knee OA and identify factors associated with injection use. METHODS We used publicly available data from the Osteoarthritis Initiative (OAI), an international collaboration sponsored by the National Institutes of Health, and included participants with ≥1 radiographically confirmed knee OA (Kellgren-Lawrence grade ≥2 [definite osteophytes and possible joint space narrowing (JSN) on anteroposterior weight-bearing radiograph]) at baseline. We matched 415 participants who received at least 1 HA and/or CO injection during the 6-month interval before 1 of the first 7 annual follow-up assessments to 1841 injection nonusers by randomly selecting a study visit to match the distribution observed in the injection users. Multinomial logistic regression models were used for identifying factors associated with injection use, including sociodemographic and clinical/functional factors. FINDINGS Eighteen percent of the 2256 patients identified as having knee OA had received at least 1 injection (years 1-7, 16.9%, 13.7%, 16.6%, 13.5%, 15.9%, 13.5%, and 9.9%, respectively), most commonly with CO (68.4%). HA and CO were more commonly injected in those with a higher annual household income (adjusted odds ratio [aOR] [95% CI] with HA, US ≥

Longterm Effectiveness of Intraarticular Injections on Patient-reported Symptoms in Knee Osteoarthritis

50,000 vs <

Adults with incident accelerated knee osteoarthritis are more likely to receive a knee replacement: data from the Osteoarthritis Initiative

25,000, 3.63; [1.20-10.99]) and less commonly in black patients (HA, 0.19 [0.06-0.55]). Greater Kellgren-Lawrence grade (grade 4 vs 2) was associated with an increased likelihood (aOR [95% CI]) of having received HA (4.79 [2.47-9.30]), CO (1.56 [1.04-2.34]), or both (4.94 [1.99-12.27]). IMPLICATIONS The receipt of HA or CO injection may be associated with higher socioeconomic positioning and indicators of greater disease severity in patients with knee OA.

Reply to: Is it appropriate to classify all kinds of nonsteroidalanti-inflammatory drugs together for assessing the treatment of kneeosteoarthritis?

Objective. We examined the longterm effectiveness of corticosteroid or hyaluronic acid injections in relieving symptoms among persons with knee osteoarthritis (OA). Methods. Using Osteoarthritis Initiative data, a new-user design was applied to identify participants initiating corticosteroid or hyaluronic acid injections (n = 412). Knee symptoms (pain, stiffness, function) were measured using The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We used marginal structural models adjusting for time-varying confounders to estimate the effect on symptoms of newly initiated injection use compared to nonusers over 2 years of followup. Results. Among 412 participants initiating injections, 77.2% used corticosteroid injections and 22.8% used hyaluronic acid injections. About 18.9% had additional injection use after initiation, but switching between injection types was common. Compared to nonusers, on average, participants initiating a corticosteroid injection experienced a worsening of pain (yearly worsening: 1.24 points, 95% CI 0.82–1.66), stiffness (yearly worsening: 0.30 points, 95% CI 0.10–0.49), and physical functioning (yearly worsening: 2.62 points, 95% CI 0.94–4.29) after adjusting for potential confounders with marginal structural models. Participants initiating hyaluronic acid injections did not show improvements of WOMAC subscales (pain: 0.50, 95% CI −0.11 to 1.11; stiffness: −0.07, 95% CI −0.38 to 0.24; and functioning: 0.49, 95% CI −1.34 to 2.32). Conclusion. Although intraarticular injections may support the effectiveness of reducing symptoms in short-term clinical trials, the initiation of corticosteroid or hyaluronic acid injections did not appear to provide sustained symptom relief over 2 years of followup for persons with knee OA.

Objectively Measured Physical Activity and Symptoms Change in Knee Osteoarthritis.

We aimed to determine if knees with incident accelerated knee osteoarthritis (AKOA) were more likely to receive a knee replacement (KR) than those with common knee osteoarthritis (KOA) or no KOA. We conducted a nested cohort study using data from baseline and the first 9 years of the Osteoarthritis Initiative (OAI). Eligible knees had no radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2). We classified 3 groups using KL grades from the first 8 years of the OAI: 1) AKOA: knee progressed to advance-stage KOA (KL 3/4) in ≤ 4 years, 2) common KOA: knee increased in KL grade (excluding AKOA), and 3) No KOA: no change in KL grade by 8 years. The outcome was a KR (partial or total) at or before the 9-year OAI visit. We conducted a logistic regression with generalized linear mixed model and adjusted for age, body mass index, and sex. Overall, 14% of knees with AKOA received a KR by the 9th year compared with 1% and < 1% of those with common or no KOA, respectively. Knees that developed AKOA were > 80x and ~ 25x more likely to receive a KR than knees with no KOA or incident common KOA (adjusted odds ratio = 25.08; 95% confidence interval = 9.63-65.34). In conclusion, approximately 1 in 7 knees that develop AKOA received a KR; however, KRs were rare in the OAI among other knees with no radiographic KOA at baseline. Urgent steps are needed to identify adults at high-risk for AKOA and develop prevention strategies regarding the modifiable risk factors.

Comparison of self-report and objective measures of physical activity in US adults with osteoarthritis.

To the Editor: We read with great interest the article by Lapane et al (1) regarding the effect of shortand long-term use of prescription nonsteroidal antiinflammatory drugs (NSAIDs) on symptoms and structural progression among patients with radiographically confirmed osteoarthritis (OA) of the knee. This prospective observational study suggested that long-term, but not short-term, NSAID use was associated with an a priori–defined minimally important clinical change in stiffness, physical function, and joint space width, but not pain. We appreciate the authors’ work; however, some worthwhile issues need to be explored. The authors classified 12 different kinds of NSAIDs together to assess the effect on knee OA of these drugs as a whole. Every NSAID has distinguishing characteristics with respect to therapeutic effect, safety, and price. For example, results of a recent high-quality network meta-analysis clearly indicated that naproxen, ibuprofen, and diclofenac, but not celecoxib, were statistically significantly superior to acetaminophen in terms of pain relief for patients with knee OA (2). There are 2 main types of NSAIDs: traditional NSAIDs (ibuprofen, naproxen, diclofenac, etc.) and celecoxib (the only selective NSAID currently available in America) (3). We are interested in learning about the results of this subgroup analysis (traditional versus selective NSAIDs). In addition, no information about the NSAID doses was available. The population of NSAID recipients in this study was largely heterogeneous. Consequently, we are not sure whether such conclusions have instructional significance for clinical practice. Aside from the implications for clinical practice, we are also worried about the reliability of the positive conclusion. The authors stated that long-term NSAID use was associated with clinical changes in stiffness, physical function, and joint space width. However, the 95% confidence intervals included 0, which could be interpreted as evidence that there is no real difference between long-term NSAID recipients and nonrecipients and that long-term NSAID use has no effect (4). The authors admitted that the estimates did not reach statistical significance, which indicates that a Type II error may exist. In other words, a significance test failed to identify the real clinical difference. Although the evidence showed that the a priori–defined minimally important clinical change had been reached, the possibility that the positive results of the study were due to chance could not be ruled out. We admit that the clinical significance is of importance, but we would like to emphasize the fact that statistical significance does not ensure truth and careful attention should be paid to false-positive errors. Furthermore, other issues need to be noted. First, the authors indicated that evidence regarding long-term effects of oral NSAIDs is still lacking, and their effect on structural changes in the joint has not been well established. However, the clinical efficacy and safety of celecoxib, as well as the effects of celecoxib on progression of knee OA over 2 years, have been reported previously (5,6). Second, according to the Osteoarthritis Research Society International atlas (7), joint space narrowing and formation of osteophytes should be determined for knee OA. We are curious about why the progression of osteophytes was not assessed. Third, patients in observational studies differ from those in clinical trials by, for example, the wider spectrum of coexisting illness included in observational studies, which could result in a good generalizability (8). However, the multivariable model was not adjusted for certain underlying diseases, such as diabetes mellitus and hypertension. Finally, it should be noted that safety is an extremely important index for assessing oral NSAIDs, especially for long-term use. The authors admitted that discontinuation rates of prescription NSAIDs have been reported to exceed 85% within 6 months of initiation. We would like more information regarding the side effects of NSAID use in this study. We value the contributions of Lapane et al, and we are very interested in the authors’ response to these issues.