Semester

Summer

Date of Graduation

2022

Document Type

Dissertation

Degree Type

PhD

College

School of Pharmacy

Department

Pharmaceutical Systems and Policy

Committee Chair

Usha Sambamoorthi

Committee Co-Chair

Traci LeMasters

Committee Member

Nilanjana Dwibedi

Committee Member

Chan Shen

Committee Member

Amit Ladani

Abstract

Understanding the role of chronic inflammation among older adults is critical because of its implications on chronic inflammatory conditions as well as its interaction with anti-inflammatory medications. Osteoarthritis (OA) is a heterogeneous multi-faceted joint disease with multi-tissue involvement of varying severity, and increasing evidence demonstrates a key role of chronic inflammation in its pathogenesis. Approximately 30 million adults in the United States have OA, and it is reported that a large proportion (43%) of them are older than 65 years. OA is typically treated using non-steroidal anti-inflammatory drugs (NSAIDs) for minimizing pain and reducing inflammation. NSAIDs have consistently shown clinically relevant efficacy in anti-inflammation and pain reduction. However, due to their anti-inflammatory properties, NSAIDs may also have spillover effects on chronic inflammation, resulting in an effect on chronic inflammatory conditions such as cancer and depression. Published studies have shown mixed findings about NSAIDs role in disease prevention as well as exacerbation. In addition, NSAIDs are also well-established for their potential adverse effects on cardiovascular, gastrointestinal, and renal systems, especially among older adults. The literature is limited on the effect of NSAIDs on chronic inflammatory conditions such as cancer and depression, and its overall economic burden taking into account its anti-inflammatory effect and adverse effects. Thus, it is imperative to assess the incidence of chronic inflammatory conditions in association with NSAIDs use and its economic burden among older adults with OA in a real-world care setting. Therefore, this dissertation pursued three related aims: 1) to identify whether prescription NSAIDs is one of the leading predictors of incident cancer and assess its direction of association with incident cancer among older adults with OA; 2) to assess the association of prescription NSAIDs with incident depression among older adults with OA and cancer; and 3) to estimate high-cost use, examine factors associated with high-cost users among older adults with OA and identify the leading predictors of healthcare costs among older NSAID users with OA. This study leveraged data from multiple diverse sources to have a complete understanding of the outcomes. For Aims 1 and 2, a retrospective cohort study was designed using Surveillance, Epidemiology, and End Results (SEER) - Medicare claims data, 5% non-cancer random sample of Medicare beneficiaries from SEER regions, zip-code and census tract-level data for the beneficiaries living in the SEER-region, and Area Healthcare Resource Use Files (AHRF) from the years 2006 through 2016. Aim 3 utilized three panels (2016 - 2019) from the nationally representative Medical Expenditure Panel Survey (MEPS) data for the longitudinal study. The study cohort had a high prevalence of NSAIDs use (52.5%), with nearly one in three individuals (28.8%) using NSAIDs for a long-term period. Using the eXtreme Gradient Boosting (XGBoost) classification model and Shapley additive explanations (SHAP) interpretation techniques, the five leading predictors identified were included zip-level median income, zip-level poverty, cumulative NSAIDs days, education, and geographical region. Cumulative NSAIDs days was among the top predictors and had a non-linear relationship with incident cancer. For aim 2, cumulative NSAIDs days was the sixth leading predictor of incident depression among older adults with OA and cancer, however, their association was complex and varied by the cumulative NSAIDs days. In the third aim study cohort of older adults with OA, the mean annual total healthcare expenditures was $14,788 (SE 435.7). In the adjusted logistic regression model of factors associated with high cost, after taking into account comorbid chronic inflammatory conditions and potential NSAIDs-related adverse effect related conditions among other covariates, cumulative NSAIDs days was associated with high-cost, where older adults using NSAIDs for 60 days had an odds ratio of 0.81 (95% CI 0.80 – 0.81). Baseline log-transformed annual total healthcare expenditures was the top predictor, followed by age, female, polypharmacy, and opioid use in the total annual healthcare expenditures model among older OA adults with NSAIDs. Overall, these findings indicate a key role of NSAIDs in the development of chronic inflammatory conditions, cancer, and depression among OA patients. This is highly relevant because a high number of OA patients use NSAIDs chronically for disease management and our studies reported an association between the duration of NSAIDs use and the incidence of cancer and depression. This study also provides evidence that disease management of patients with chronic conditions is complex and may need the addition of strategies such as collaborative care and medication management therapy plans. Finally, several social determinants of health indicators were top predictors of cancer and depression incidence, demonstrating the importance of targeting these modifiable risk factors.

Embargo Reason

Publication Pending

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