Inappropriate Nonsteroidal Anti-Inflammatory Drug Use

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This Month in Gastroenterology

THU0624 UNDERSTANDING ETHNIC DIFFERENCES IN THE UTILIZATION OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS FOR OSTEOARTHRITIS

NSAIDs, Risks, and Gastroprotective Strategies: Current Status and Future

Evidence from some studies suggest that osteoarthritis (OA) patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) that are not in accordance with their cardiovascular (CV) or gastrointestinal (GI) risk profiles. However, no such study has been carried out in the United States. Therefore, we sought to examine the prevalence and predictors of potentially inappropriate NSAIDs use in older adults (age > 65) with OA using machine learning with real-world data from Optum De-identified Clinformatics® Data Mart. We identified a retrospective cohort of eligible individuals using data from 2015 (baseline) and 2016 (follow-up). Potentially inappropriate NSAIDs use was identified using the type (COX-2 selective vs. non-selective) and length of NSAIDs use and an individual’s CV and GI risk. Predictors of potentially inappropriate NSAIDs use were identified using eXtreme Gradient Boosting. Our study cohort comprised of 44,990 individuals (mean age 75.9 years). We found that 12.8% individuals had potentially inappropriate NSAIDs use, but the rate was disproportionately higher (44.5%) in individuals at low CV/high GI risk. Longer duration of NSAIDs use during baseline (AOR 1.02; 95% CI:1.02–1.02 for both non-selective and selective NSAIDs) was associated with a higher risk of potentially inappropriate NSAIDs use. Additionally, individuals with low CV/high GI (AOR 1.34; 95% CI:1.20–1.50) and high CV/low GI risk (AOR 1.61; 95% CI:1.34–1.93) were also more likely to have potentially inappropriate NSAIDs use. Heightened surveillance of older adults with OA requiring NSAIDs is warranted.

A Narrative Review:The use of the topical nonsteroidal anti-inflammatory drugs (NSAID) ibuprofen for the treatment of knee osteoarthritis. Supporting clinician decision-making in the first-line treatment of osteoarthritis.Objective:To open discussion at a clinical level on the guidelines for the pharmacological management of osteoarthritis of the knee, this narrative review looks into the use of topical NSAID being a clinically effective, safe, and cost-efficient treatment compared to an oral alternative.Background:With the over prescription of NSAIDs in the age of above 65 years, there has been a call for increased restrictions of the sale of oral preparations of NSAIDs. It is our view that there is still a lack of awareness in the benefit of topical NSAIDs to the patient (no evidence of adverse reactions recorded by the Joint Formulary Committee [JFC] to date) as well as provider (topical application is cheaper as a National Health Service [NHS] prescription).Methods:Key online resources included PubMed, Athens, Cochrane Library, Google Scholar, MEDLINE, and relevant clinical and commissioning guidelines with the final date of data collection in March 2017. We also contacted the manufacturer and license holder directly for further clarification. Randomized, double-blind control studies, commissioned reports, International Guidelines, MEHA Guidelines, and license holder data were included. Where possible studies included had to have fair randomization and adhere to key treatment pathways as highlighted by National Institute for Health and Clinical Excellence (NICE) and other guidelines.Discussion:Current guidelines advise that patients who seek initial treatment of osteoarthritis of the knee should consider a combination of treatment modalities, including pharmacological therapies, particularly the use of NSAIDs. At a clinical level, a reoccurring issue identified with this advice is the inappropriate use of oral NSAIDs, and the concern that the risks associated with ease of access (“over the counter”), and overuse, may result in systemic adverse events in this cohort of patients. Multiple studies have examined the negative effect of oral NSAIDs and the associated risks of use. We were unable to source studies that showed any adverse systemic events from the use of topical NSAIDs; however, there are good quality trials comparing oral to topical NSAIDs, showing similar levels of efficacy at 6 and 12 weeks.Conclusion:Topical NSAIDs provide good levels of pain relief in subjects with mild to moderate knee osteoarthritis. There is also evidence for the use of the topical application being a clinically effective, safe, and cost-efficient treatment.

Osteoarthritis (OA) is a degenerative arthritis affecting over 30 million Americans most of whom are over 65 years or older. Its clinical management is complicated by several disease- and treatment-specific factors. These include the co-occurrence of cardiovascular and gastrointestinal disorders (CV-GID), the inappropriate use of non-steroidal anti-inflammatory drugs (NSAID) to manage pain, and the risk of certain age-related chronic conditions like Alzheimer’s disease and related dementia (ADRD). Moreover, older adults with OA are at a higher risk of CV-GID, inappropriate NSAID use, and ADRD. Additionally, these factors can also affect one another in both a positive and a negative way. For example, the long-term use of NSAID has been shown to increase the risk for cardiovascular and gastrointestinal disorders. On the other hand, their use has been shown to decrease the risk of ADRD in some studies. NSAID use is disproportionately higher among older adults, so the benefits or risks associated with such use should be taken into account while making treatment decisions. However, there is a gap in our understanding of the clinical and demographic factors that increase the risk of co-occurring CV-GID, inappropriate NSAID use, and ADRD in older adults with OA. This dissertation pursued three related aims to fill this knowledge gap: 1) identify the leading predictors of CV-GID; 2) identify the leading predictors of inappropriate NSAID use; and 3) examine whether duration of NSAID use is a leading predictor of ADRD and how other factors affect this relationship using a combination of machine learning techniques. All three aims used a retrospective, longitudinal, cohort study design using de-identified commercial health insurance insurance claims data from Optum De-identified Clinformatics Data Mart for years 2015 through 2017. OA was identified from these data using a combination of International Classification of Disease – 9th Revision and 10th Revision (ICD-9 and ICD-10) codes. Using a random forest classifier, we identified age, cardiac arrhythmia, and the duration of opioid use to be the top three leading predictors of CV-GID in our study cohort. In the second aim, we found that around 13% of older adults with OA were prescribe NSAIDs not in accordance with their CV and GI risk profile (i.e. inappropriate NSAID use). Using an eXtreme Gradient Boosting classifier and Shapley Additive eXplanations, we found durations of non-selective and selective NSAID use to be the top two predictors of inappropriate NSAID use. Older adults with low CV and high GI or

Non-steroidal anti-inflammatory drugs use may protect against development of oesophageal adenocarcinoma. To define the consequences of non-steroidal anti-inflammatory drugs use in patients with Barrett's oesophagus. Records of all Barrett's oesophagus/oesophageal adenocarcinoma patients examined in Blackpool-Wyre-Fylde area were reviewed. All surviving patients completed validated questionnaires. Use of non-steroidal anti-inflammatory drugs of any type and at any frequency was more prevalent in Barrett's oesophagus patients [147 (38%) Barrett's oesophagus vs. 30 (26%) oesophageal adenocarcinoma, P = 0.02]. Daily use of non-steroidal anti-inflammatory drugs was more prevalent in Barrett's oesophagus patients [88 (23%) Barrett's oesophagus vs. 14 (12%) oesophageal adenocarcinoma, P = 0.02], due to more prevalent consumption of non-aspirin non-steroidal anti-inflammatory drugs [48 (13%) Barrett's oesophagus vs. four (4%) oesophageal adenocarcinoma, P = 0.009]. There was no difference between the two groups in usage of either daily low-dose aspirin or of occasional non-steroidal anti-inflammatory drugs. In logistic regression analysis any use of non-steroidal anti-inflammatory drugs [odds ratio (OR) = 0571 (95% CI: 0.359-0.909), P = 0.018] and daily use of non-aspirin non-steroidal anti-inflammatory drugs [OR = 0.297 (95% CI: 0.097-0.911), P = 0.034] were significant protective factors. Non-steroidal anti-inflammatory drugs use did not affect the survival of oesophageal adenocarcinoma patients. Oesophageal adenocarcinoma and Barrett's oesophagus consuming non-steroidal anti-inflammatory drugs did not differ in upper gastrointestinal bleeding [26 (15%) non-steroidal anti-inflammatory drugs consumers vs. 29 (9%) non-consumers, P = 0.08], oesophageal ulcers [31 (18%) non-steroidal anti-inflammatory drug consumers vs. 49 (15%) non-consumers, P = 0.43] or stricturing [19 (11%) non-steroidal anti-inflammatory drug consumers vs. 41 (13%) non-consumers, P = 0.58]. (i) Daily use of non-steroidal anti-inflammatory drugs is more prevalent in Barrett's oesophagus than oesophageal adenocarcinoma patients, because of a more prevalent use of non-aspirin non-steroidal anti-inflammatory drugs. (ii) Use of non-steroidal anti-inflammatory drugs in Barrett's oesophagus patients is safe if acid suppression is adequate.

Introduction: Observational and experimental evidence demonstrate that non-steroidal anti-inflammatory drug (NSAID) use reduces the incidence and recurrence of colorectal neoplasia. Consistent with such observations, recent studies have also suggested an inverse association between NSAID use, particularly long-term use, and colorectal cancer (CRC) mortality. We examined the association between aspirin and non-aspirin NSAID use and colorectal mortality among post-menopausal women enrolled in the clinical trial and observational study arms of the Women's Health Initiative (WHI). Methods: We investigated the effect of NSAID use on colorectal cancer mortality among 160,143 women enrolled in the WHI with available follow up data who did not report a prior history of colorectal cancer at the time of study entry. Women provided details on aspirin and non-aspirin NSAID use at both study baseline and three years after enrollment. Reported cases of colorectal cancers were locally confirmed based on medical records and also centrally adjudicated. Cause of death was determined according to centralized medical record and death certificate review; routine linkages were made to National Death Index files to ensure the completeness of vital status information. There were 2,119 confirmed cases of colorectal cancer and 492 deaths among WHI participants where the listed cause of death was colorectal cancer. Cox proportional hazards regression was used to examine the relationship between NSAID use (at study baseline and at year 3 of study follow-up) and colorectal cancer mortality and to estimate hazard ratios and 95% confidence intervals. We conducted a sensitivity analysis that excluded women who developed colorectal cancer within the first three years following study enrollment (n=180) in order to restrict the study question to examining the role of NSAID use prior to diagnosis on colorectal cancer mortality. Results: Reported use of NSAIDs at study baseline, including aspirin, ibuprofen, and prescription NSAIDs, was not associated with colorectal cancer mortality (HR: 0.93; 95% CI 0.76–1.14). However, among women who lived to year 3 after study enrollment (n=156,440; 98% of participants), those who reported use of NSAIDs at both baseline and year 3 experienced reductions in colorectal cancer mortality of approximately 30% (HR: 0.72; 95% CI 0.54–0.95) compared to women who did not report use at both time points. Results from the sensitivity analysis demonstrated that prolonged pre-diagnostic NSAID use (use at both baseline and year 3) was significantly associated with reduced colorectal cancer mortality (HR: 0.70; 95% CI 0.52–0.93). Conclusion: Our results suggest that use of NSAIDs is associated with lower colorectal cancer mortality among post-menopausal women, particularly in women who use these medications for longer periods of time prior to diagnosis. This association may reflect an effect of NSAID use in decreasing the incidence of new tumors and/or an effect in lowering rates of disease progression. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A69.

Background and Objectives: Self-medication and inappropriate use of non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics are major public health concerns, particularly in settings with variable access to healthcare. Understanding patterns of medication use and renal risk perception can inform targeted interventions. This study examined NSAID and antibiotic use, self-medication behaviors, and renal risk awareness among Romanian primary care patients, with attention to urban-rural differences. Materials and Methods: A cross-sectional survey was conducted among 201 primary care patients (101 rural, 100 urban). Data on NSAID and antibiotic use, self-medication practices, sources of recommendation, and renal risk perception were collected using a study-specific questionnaire. Multivariable logistic regression was applied to identify predictors of frequent NSAID use, inappropriate antibiotic use, self-medication frequency, and high perceived renal risk. Results: NSAID use was nearly universal (95%), with frequent use strongly associated with non-professional recommendations. Antibiotic misuse was more common in rural participants and largely driven by informal acquisition. Self-medication patterns differed by residence: rural participants reported system- or access-related reasons and reliance on non-professional sources, while urban participants engaged in frequent, convenience-driven self-medication. Although most participants were aware of potential renal harm, this did not consistently lead to safer behaviors. Higher educational level and trust in healthcare professionals predicted increased perceived renal risk, whereas rural residence was associated with lower risk perception. Conclusions: Medication misuse is influenced more by recommendation sources, access barriers, and trusted information pathways than by knowledge alone. Interventions should focus on improving professional guidance, addressing informal recommendation networks, and tailoring strategies to urban-rural contexts.

The risk of colorectal cancer (CRC) is determined by the interplay of genetic and environmental factors. The aim of this study was to identify the association between polymorphisms in cell-cycle related genes and risk of colorectal cancer, and to evaluate the interaction with non-steroidal anti-inflammatory drug (NSAID) use. Patients with incident CRC were recruited in the framework of DACHS, a German population based case-control study. Altogether, 1756 cases and 1781 controls were genotyped for 223 candidate or tagging SNPs in 30 cell-cycle related genes using the Illumina GoldenGate Assay. The associations between polymorphisms and the risk of colorectal cancer were assessed with multivariate logistic regression. Effect modification by NSAIDs (use >1/month for >1 year) was tested by using a multiplicative interaction term. Haplotype analysis was performed using the haplo.stats R package. None of the studied SNPs were significantly associated with CRC after multiple test correction. NSAID use lowered the risk of colorectal cancer with an odds ratio (OR) of 0.59 (Confidence interval, CI: 0.51-0.69, p = 9.58*10-11). Several polymorphisms in and near cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) showed interaction with NSAID use. However, only one signal remained significant after FDR correction; the homozygous wild genotype (GG) of rs2069408 neutralizes the protective effect of NSAID use (interaction p<0.001, FDR q = 0.018). The effect of NSAID use on CRC risk according the rs2069408 genotypes were the following (OR, 95%CI): 0.82 (0.65-1.02) for GG, 0.51 (0.42-0.61) for GA and 0.31 (0.22-0.45) for AA genotypes. Although non-significant after multiple test correction, interactions with NSAID use was observed at the rs4134950 polymorphism of the E2F3 gene (interaction p = 0.003, FDR q = 0.152) and at rs17187428 (interaction p = 0.004, FDR q = 0.164) and rs773108 (interaction p = 0.005, FDR q = 0.166) in MYC. The haplotype analysis revealed six haplotype blocks in and near the genes E2F3, CDK2, CDK1, CDK6 and MYC that showed significant interaction with NSAID use regarding the risk of colorectal cancer. A possible mechanism of the interaction between NSAIDs and cell-cycle genes could be mediated via the cell-cycle related effects of MYC, the expression of which is regulated by the Wnt/ß-catenin pathway. This pathway plays a central role in colorectal cancer and was previously found to be inhibited by NSAIDs. The analyses of additional SNPs are ongoing to better understand the mechanism of the interaction between NSAID use and cell-cycle related genes. Citation Format: Reka Toth, Yesilda Balavarca, Dominique Scherer, Nina Habermann, Katharina Buck, Akke Botma, Elisabeth J. Kap, Axel Benner, Alexis Ulrich, Michael Hoffmeister, Hermann Brenner, Barbara Burwinkel, Jenny Chang-Claude, Cornelia M. Ulrich. Polymorphisms in cell-cycle related genes modify the effect of NSAIDs on the risk of colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4590. doi:10.1158/1538-7445.AM2015-4590

Introduction: Over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used despite conferring risk for adverse cardiovascular events (ACEs). ACEs disproportionately affect Black individuals, yet patterns of OTC NSAID and high-potency powder NSAID (HPP-NSAID) use among different racial groups remains understudied. Hypothesis: We hypothesized that use of OTC NSAIDs and HPP-NSAIDs is higher among Black individuals. Methods: We analyzed data from the North Carolina Colon Cancer study, a population-based case-control study in 1996-2000. Participants at risk of ACEs, defined as self-reported hypertension, diabetes, heart disease, or smoking history ≥ 20 years, were included in our analysis. Primary outcomes were any OTC NSAID use and HPP-NSAID use. Secondary outcomes included regular use of the primary outcome variables. Using multivariable logistic regression, we quantified the independent association of the outcomes with race after adjusting for age, sex, education, poverty, and pain interfering with daily activities. We investigated the effect modifications of poverty status and educational attainment separately on the noted associations. Results: Of the 1286 participants at risk for ACEs, 583 (45%) reported Black, 695 (54%) White, and 8 (<1%) Other race. Overall, 665 (52%) reported any NSAID use and 204 (16%) reported HPP-NSAID use. Any NSAID use was reported by 329 (57%) Black participants compared to 332 (48%) White participants. HPP-NSAID use was reported by 126 (22%) Black participants compared to 76 (11%) White participants. Of users, 174 (26%) reported regular NSAID use and 37 (18%) reported regular HPP-NSAID use; this pattern was similar across race. In multivariable analysis, Black (versus White) race was independently associated with higher odds of NSAID use (odds ratio [OR] 1.4 95% confidence interval [1.1, 1.8]). Pain interfering with daily activities (OR 1.4 [1.1, 1.8]) was also associated with NSAID use and older age was negatively associated with NSAID use (OR 0.96 [0.95, 0.97]). After adjustment, Black race was associated with HPP-NSAID use (OR 1.8 [1.3, 2.6]). Male sex (OR 1.6 [1.2, 2.3]) and being in or near poverty (OR 1.6 [1.0, 2.3]) were also independently associated with HPP-NSAID use and older age (OR 0.96 [0.94, 0.97]) and educational attainment of some college or greater (OR 0.5 [0.3, 0.7]) were negatively associated with HPP-NSAID use. The associations between race and either outcome were not significantly moderated by educational attainment nor poverty status. Conclusions: In this population-based study, Black individuals at risk of ACEs had higher odds of any NSAID and HPP-NSAID use than White participants, even after controlling for pain and socio-economic status. Further research is necessary to determine the impact of this differential use on established inequities in cardiovascular outcomes.

Simple SummaryNon-steroidal anti-inflammatory drugs (NSAIDs) are a group of commonly used drugs which target inflammation. Because inflammation is a critical component in cancer development, NSAID was proposed to reduce the risk of breast cancer by some studies. However, the results are inconsistent between studies. Moreover, there are insufficient data regarding risk of breast cancer with different characteristics, for example cancer subtype and stage, and few studies have investigated whether the risk will differ by breast density or previous breast disorders. Therefore, we investigated the association between use of NSAIDs and risk of breast cancer using data on NSAID use and breast cancer diagnosis from women in Sweden in general and women from a breast cancer screening program. Overall, we did not have strong evidence to support an association between the use of NSAIDs and the risk of breast cancer. More studies in diverse demographic and geographical settings are needed to confirm our findings.A link has been proposed between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of breast cancer. There is, however, insufficient data regarding the subtype and stage of breast cancer, and few studies have assessed the interaction between the use of NSAIDs and breast density or previous breast disorders. There is also a lack of data from population-based studies. We first conducted a nested case-control study within the general female population of Sweden, including 56,480 women with newly diagnosed breast cancer during 2006–2015 and five breast cancer-free women per case as controls, to assess the association of NSAID use with the risk of incident breast cancer, focusing on subtype and stage of breast cancer as well as the interaction between NSAID use and previous breast disorders. We then used the Karolinska Mammography Project for Risk Prediction of Breast Cancer (Karma) cohort to assess the interaction between NSAID use and breast density in relation to the risk of breast cancer. Conditional logistic regression was used to estimate the hazard ratio (HR) and a 95% confidence interval (CI) was used for breast cancer in relation to the use of aspirin and non-aspirin NSAIDs. In the nested case-control study of the general population, exclusive use of aspirin was not associated with the risk of breast cancer, whereas exclusive use of non-aspirin NSAIDs was associated with a modestly higher risk of stage 0–2 breast cancer (HR: 1.05; 95% CI: 1.02–1.08) but a lower risk of stage 3–4 breast cancer (HR 0.80; 95% CI: 0.73–0.88). There was also a statistically significant interaction between the exclusive use of NSAIDs and previous breast disorders (p for interaction: <0.001). In the analysis of Karma participants, the exclusive use of non-aspirin NSAIDs was associated with a lower risk of breast cancer among women with a breast dense area of >40 cm2 (HR: 0.72; 95% CI: 0.59–0.89). However, the possibility of finding this by chance cannot be ruled out. Overall, we did not find strong evidence to support an association between the use of NSAIDs and the risk of breast cancer.

Lower GI bleeding risk of nonsteroidal anti-inflammatory drugs and antiplatelet drug use alone and the effect of combined therapy

Research to date on sprains, strains, and contusions has focused mainly on the analysis of sports-related injuries, occupational injuries, injuries resulting from automobile accidents, and severe injuries that result in inpatient hospital stays. Little is known about real-world acute sprains, strains, and contusions in an aging population. Patients may be treated with over-the-counter, oral, non-steroidal anti-inflammatory drugs (NSAIDs) for acute sprains, strains, and contusions or may require the use of prescription NSAIDs. For sprains, strains, and contusions treated with prescription NSAIDs, the choice of topical administration or oral administration likely depends on a number of factors such as age and comorbid conditions. The objective of the study was to identify factors associated with the use of a prescription topical NSAID or a prescription oral NSAID for the treatment of sprains, strains, and contusions among patients aged 65-89years enrolled in the Medicare Advantage with Prescription Drug plan. The study sample was selected from the Humana Research Database (Louisville, KY, USA). Study subjects were identified as patients enrolled in Medicare Advantage with Prescription Drug plans, aged 65-89years, having a medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification indicative of an acute sprain, strain, and contusion between 1 January, 2010 and 31 March, 2014 (identification period). The date of the first claim was considered the index date, and subjects were required to have 12 months of continuous enrollment before the index date and a minimum of 3 months continuous enrollment after the index date. Prescription NSAID use during the 3 months after the index sprain, strain, and contusion diagnosis was required for study inclusion and was identified based on a pharmacy claim for a topical or an oral NSAID. Patients with prescription NSAID use leading up to the sprains, strains, and contusions were excluded. Potential factors related to the use of a topical vs. oral NSAID were identified using stepwise logistic regression with backward elimination. After applying the inclusion and exclusion criteria, 42,283 patients were prescribed an oral or topical NSAID (39,294 oral; 2989 topical) within 3 months of the index sprain, strain, and contusion diagnosis. After applying stepwise logistic regression, and retaining variables with statistically significant parameter estimates (p < 0.05), use of topical NSAIDs was higher among female individuals [odds ratio and 95% confidence interval = 1.34 (1.24-1.45)], and appeared to increase with age [odds ratio = 1.04 (1.04-1.05)]. Topical NSAID use was lower in the Midwest region [odds ratio = 0.85 (0.77-0.94)] in comparison to the Southern region. Clinical factors associated with topical NSAID use included Elixhauser Comorbidity Index score [odds ratio = 1.06 (1.04-1.09)], medication burden [odds ratio = 1.06 (1.04-1.08), pill burden [odds ratio = 1.02 (1.01-1.03), specific comorbid conditions, including site-specific osteoarthritis of the upper arm [odds ratio = 2.34 (1.19-4.60)], ankle/foot [odds ratio = 1.46 (1.14-1.87)], or lower leg [odds ratio = 1.21 (1.07-1.36)], myofascial pain [odds ratio = 1.31 (1.21-1.42)], gastrointestinal/hepatic disorders [odds ratio = 1.15 (1.05-1.25)], systemic/central pain [odds ratio = 1.12 (1.01-1.23)], and cataracts [odds ratio = 1.10 (1.02-1.20)]. Conversely, a diagnosis of diabetes mellitus was related to use of an oral NSAID rather than a topical NSAID [odds ratio = 0.86 (0.78-0.94)]. Diagnosis of the index sprain, strain, and contusion in an emergency department instead of a physician's office was also associated with oral NSAID use [odds ratio = 0.42 (0.37-0.47)]. Topical NSAIDs were used less often than oral NSAIDs following a sprain, strain, or contusion. Age, medication burden, pill burden, evidence of gastrointestinal disorder, and evidence of certain pain-related conditions were significant factors associated with topical NSAID as opposed to oral NSAID use. In comparison to oral NSAIDs, topical NSAIDs were more likely to be prescribed in a physician's office than an emergency department, possibly because a patient's physician has a better understanding of the patient's concomitant medications and comorbidities. Although topical NSAIDs were more likely to be used than oral NSAIDs in patients with gastrointestinal disorders, the use of oral NSAIDs among patients with gastrointestinal bleeding was substantial.