Objective The effect of short and long term non-steroidal anti-inflammatory agents (NSAIDs) use on structural change is equivocal. We estimate the extent to which recent and long-term use of prescription NSAIDs relieve symptoms and delay structural progression among patients with radiographically confirmed osteoarthritis (OA) of the knee. Methods We applied a new-user design among participants with confirmed OA not reporting NSAID use at enrollment in the Osteoarthritis Initiative. Participants were evaluated for changes in the Western Ontario and McMaster Universities Arthritis Index, WOMAC (n=1,846) and joint space width measured using serial x-rays and a customized software tool (n=1,116) over 4 years. We used marginal structural modeling to estimate the effect of NSAIDs. Results Compared to participants who never reported prescription NSAID use, those reporting use at 1 or 2 assessments had no clinically important changes, but those reporting prescription NSAID use on all 3 assessments had on average 0.88 point improvement over the follow-up period (95% Confidence Interval (CI): -0.46 to 2.22) in Pain, 0.72 point improvement (95% CI: -0.12 to 1.56) in Stiffness, 4.27 points improvement (95% CI: -0.31 to 8.84) in Function, and decreased by 0.28mm in joint space width (95% CI: -0.06 to 0.62) less than no use. Recent NSAID use findings were not clinically or statistically significant. Conclusions Long term but not recent NSAID use was associated with a priori defined minimally important clinical change in stiffness, function and structural change but not in pain. While showing modest clinical importance, estimates did not reach statistical significance.
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.
Objective To estimate the extent that smoking history is associated with symptoms and disease progression among individuals with radiographically confirmed knee OA. Method Both cross-sectional (baseline) and longitudinal studies employed data from the Osteoarthritis Initiative (n= 2,250 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.
Purpose: To provide contemporary estimates of pain by level of cognitive impairment among US nursing home residents without cancer. Methods: Newly admitted US nursing home residents without cancer assessed with the Minimum Data Set 3.0 at admission (2010-2016) were eligible (n=8,613,080). The Cognitive Function Scale was used to categorize level of cognitive impairment. Self-report or staff-assessed pain was used based on a 5-day look-back period. Estimates of adjusted prevalence ratios (aPR) were derived from modified Poisson models. Results: Documented prevalence of pain decreased with increased levels of cognitive impairment in those who self-reported pain (68.9% no/mild, 32.9% severe) and those with staff-assessed pain (50.6% no/mild, 37.2% severe staff-assessed pain). Relative to residents with no/mild cognitive impairment, pharmacologic pain management was less prevalent in those with severe cognitive impairment (self-reported: 51.3% severe vs 76.9% in those with no/mild; staff assessed: 52.0% severe vs 67.7% no/mild). Conclusion: Pain was less frequently documented in those with severe cognitive impairment relative to those with no/mild impairments. Failure to identify pain may result in untreated or undertreated pain. Interventions to improve evaluation of pain in nursing home residents with cognitive impairment are needed.
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