Nonsteroidal anti-inflammatory drugs (NSAIDs) and mammographic density

Long-Term Preoperative Nonsteroidal Anti-inflammatory Drug Use Does Not Impact Revision Rate After Repair of Rotator Cuff, Achilles, Distal Biceps, or Quadriceps Tendon

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Association between long-term NSAID use and opioid abuse among patients with breast cancer

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have emerged as potential chemopreventive agents for melanoma. However, the clinical studies have provided contradictory results as to whether NSAIDs reduce the risk of melanoma. Our aim was to assess this association through a detailed meta-analysis of the studies on the subject published in the peer-reviewed literature. Relevant studies were identified by searching PubMed, EMBASE and Web of Science electronic databases up to July 2012. Reference lists from retrieved articles were also reviewed. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the fixed-effects or the random-effects models on the basis of heterogeneity analysis. Subgroup analyses were carried out where data were available. Ten studies involving 490 322 participants contributed to the meta-analysis. The summary RR estimate on the basis of all studies did not indicate that overall NSAIDs use significantly decreases the risk of melanoma (RR=0.94; 95% CI, 0.86-1.03). The use of neither aspirin (RR=0.96; 95% CI, 0.89-1.03) nor nonaspirin NSAIDs (RR=1.05; 95% CI, 0.96-1.14) was associated with the risk of melanoma. Similar results were obtained in the subgroup analyses of cohort studies (RR=1.03; 95% CI, 0.95-1.13), high-intensity NSAID use (the highest dose of NSAID use reported by included studies, RR=1.05; 95% CI, 0.79-1.40), and long-term NSAID use (longest duration of NSAID use reported by included studies, RR=0.87; 95% CI, 0.66-1.14). However, a slight reduction in the risk of melanoma by taking NSAIDs was observed in case-control studies (RR=0.86; 95% CI, 0.80-0.93). In conclusion, the results of our meta-analysis did not indicate that the use of NSAIDs or aspirin is associated with the risk of melanoma. More and in-depth research should focus on those problems in the future.

Spondyloarthritis or spondyloarthropathy (SpA) is a group of related rheumatic disorders, which presents with axial and nonaxial features, affecting structures within the musculoskeletal system, as well as other bodily systems. Both pharmacological and nonpharmacological therapeutic options are available for SpA. For decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been used as the first-line drugs to treat the disease. Research has shown that other than pain relief, NSAIDs have disease-modifying effects in SpA. However, to achieve these effects, continuous and/or long-term NSAID use is usually required. This review will give an overview of SpA, discuss NSAIDs and their disease-modifying effects in SpA, and highlight some of the important adverse effects of long-term and continuous NSAID use, particularly those related to the gastrointestinal, renal, and cardiovascular systems.

Background: Studies suggest that non-steroidal anti-inflammatory drug (NSAID) use may increase risk of renal cell cancer (RCC), but the relationship to the lethal form of RCC remains unknown. Methods: We examined the relationship between NSAID use and RCC risk in two large prospective cohorts: the Nurses’ Health Study and the Health Professionals Follow-up Study. Use of aspirin and other NSAIDs was ascertained in 1990 in the Nurses’ Health Study and in 1986 in the Health Professionals Follow-up Study, and every 2 years thereafter. We evaluated baseline use and duration of NSAID use. We defined the lethal form of RCC as RCC that resulted in death due to the disease. Results: During follow-up of 18 years among 77,524 women and 20 years among 49,403 men, we documented 364 cases of RCC, of which 102 were fatal. Regular use of non-aspirin NSAIDs was associated with an increased overall RCC risk; there was a dose-response relationship between duration of non-aspirin NSAID use and RCC risk; compared with non-regular use, the pooled multivariable relative risks (RRs) were 0.78 (95% CI, 0.58-1.06) for use of less than 4 years, 1.29 (95% CI, 0.95-1.74)) for 4 to less than 10 years, and 2.21 (95% CI 1.39-3.49) for use for 10 or more years (P for trend, 0.0006). Furthermore, non-aspirin NSAID users of 4-10 years (pooled multivariable RR 3.13, 95% CI 1.70-5.77) and more than 10 years (pooled multivariable RR 7.23, 95% CI 2.51-20.83) had a significantly increased risk of lethal RCC. Aspirin use was not associated with increased risk of overall (pooled multivariable RR 1.07, 95% CI 0.84-1.34) or lethal RCC (pooled multivariable RR 1.59, 95% CI 0.85-2.96). Conclusion: Our prospective data suggest that non-aspirin NSAID use is associated with an increased incidence of RCC, especially the lethal form of RCC. Citation Format: Mark A. Preston, Jed-sian Cheng, Glen Barrisford, Alex Sanchez, Adam S. Feldman, Dayron Rodriguez, Toni K. Choueiri, Meir Stampfer, Walter C. Willett, Eunyoung Cho. Nonsteroidal anti-inflammatory drug (NSAID) use and risk of lethal renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-279. doi:10.1158/1538-7445.AM2014-LB-279

Objectives:Non-steroidal anti-inflammatory drugs (NSAID) are widely used for pain control in musculoskeletal conditions. The purpose of this study was to determine if long-term use of NSAIDs increases the incidience of rotator cuff tears.Methods:A retrospective comparative study using a national insurance database was performed. All patients who had a diagnosis of long-term NSAID use with active records in the database for at least 1 year or 2 years were identified. These patients were matched 1:1 to controls without NSAID use based on age, gender, and Elixhauser comorbidity index. Rotator cuff tendon tear rates were compared between each group. Sub-group analyses in the following age-ranges for each sex was also done: 35-45, 46-55, 56-65, 66-75.Results:A total of 499,240 patients who had a history of long-term NSAID use were evaluated. 10,180 patients sustained a rotator cuff tear compared to 7,471 control patients (2.04% vs. 1.50%, respectively), with an adjusted OR of 1.18 (95% CI: 1.14-1.21; P<0.001). Male chronic NSAID users in the 46 to 55 age range had higher rates of rotator cuff tears compared to control patients of the same demographics (OR: 1.41; 95% CI 1.30 – 1.52; P<0.001). Female chronic NSAID users in the 46 to 55 age range had higher rates of rotator cuff tears compared to control patients of the same demographics (OR: 1.40; 95% CI 1.31 – 1.49; P<0.001). Comparable results were seen in the 56-65 age range for both males and females. Further, chronic NSAID users (n=1,888; 18.5%) underwent rotator cuff repair at higher rates compared to controls (n=1,223; 16.4%).Conclusions:Long-term NSAID use significantly increases the rates of rotator cuff tendon tears at the 1-year and 2-year follow-up periods, which is particularly notable in the middle-aged population. These findings suggest that middle aged patients with long-term NSAID use may be at a higher risk for rotator cuff tendon tears.

Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used medications in clinical practice due to their antiinflammatory, analgesic and antipyretic effects. They are usually well tolerated, but in patients with certain risk factors this group of drugs can have a negative influence on the digestive tract (DT) and the cardiovascular system. The results of numerous studies present that all NSAIDs, without exception, can also cause complications of kidney function. Side effects from DT are the most dangerous because of their high frequency and severity. In a third of patients who take NSAIDs symptoms of dyspepsia and gastroesophageal reflux are developed. NSAID-associated gastrointestinal damage has been found to extend beyond the duodenum. It has been confirmed that the frequency of bleeding caused by enteropathy is higher than in gastropathy caused by NSAIDs. New diagnostic methods such as capsule endoscopy and balloon endoscopy have made available and demonstrative negative impact of NSAID use and the need for preventive strategies to the general medical public. Intestinal damage, including inflammation, mucosa erosions, and ulcers, as well as more serious clinical outcomes such as perforation and diverticulitis, have been reported in patients taking long-term NSAIDs. The article presents the results of our own clinical observations of a case of multiple perforations of the intestine with uncontrolled long-term use of various NSAIDs by a patient with severe comorbid pathology. When prescribing NSAIDs, doctors should carefully collect the patient’s medical history regarding concomitant diseases and the drugs he is taking. Today, the effective and safe selection of NSAIDs remains a problem in the clinical practice of a doctor of any specialty, which motivates further searches for preventive strategies to prevent the development of enteropathy with long-term use of NSAIDs.

Professional guidelines advise against regular or long-term NSAID use in most patients with chronic kidney disease (CKD), heart failure (HF), and hypertension (HTN) due to risk of adverse events. Nevertheless, over-the-counter (OTC) NSAIDs are broadly accessible and frequently used among this population. Efforts to decrease high-risk OTC NSAID use have the potential to improve safety and reduce chronic disease burden. This randomized controlled trial evaluated the effectiveness of a brief, electronically-administered educational video in reducing high-risk OTC NSAID use. Adult participants with CKD, HF, and/or HTN who self-identified as regular NSAID users (≥3 times/week for 3 months) were invited to participate. Participants (n = 425) were randomized to either view an electronically-administered educational video informed by the COM-B behavioral change model (VIDEO, n = 223) or the FDA Drug Facts label for NSAIDs (CONTROL, n = 202). Intent to decrease OTC NSAIDs was evaluated via 11-point contemplation ladder immediately and 4 weeks post-intervention, with self-reported NSAID Exposure assessed at 4 weeks. We also evaluated current and recent pain levels at baseline and 4 weeks. Intent to decrease OTC NSAID use (4.28 (SD: 3.45) ladder rungs) and NSAID exposure (20.14 (SD: 13.66) dose-days per month) did not differ between groups at baseline. Intent to decrease OTC NSAID use increased more from baseline to immediately post-intervention in VIDEO vs. CONTROL (1.32 (SD: 2.80) vs. 0.55 (SD: 1.99) rungs, p < 0.001), with greater improvements for those with lower baseline intent. VIDEO and CONTROL were associated with a similar rise in intent to decrease OTC NSAID use (1.92 (SD: 4.41) vs. 1.36 (SD: 3.46), p = 0.150) and a similar decrease in NSAIDs exposure (−32.8% in VIDEO and −36.5% in CONTROL, p = 0.520) 4 weeks post-intervention. Pain levels did not differ between groups. Results suggest that a low-burden, electronically-administered intervention reduce high-risk medication use among patients with CKD, HF, and/or HTN.

Professional guidelines advise against regular or long-term NSAID use in most patients with chronic kidney disease (CKD), heart failure (HF), and hypertension (HTN) due to risk of adverse events. Nevertheless, over-the-counter (OTC) NSAIDs are broadly accessible and frequently used among this population. Efforts to decrease high-risk OTC NSAID use have the potential to improve safety and reduce chronic disease burden. This randomized controlled trial evaluated the effectiveness of a brief, electronically-administered educational video in reducing high-risk OTC NSAID use. Adult participants with CKD, HF, and/or HTN who self-identified as regular NSAID users (≥3 times/week for 3 months) were invited to participate. Participants (n = 425) were randomized to either view an electronically-administered educational video informed by the COM-B behavioral change model (VIDEO, n = 223) or the FDA Drug Facts label for NSAIDs (CONTROL, n = 202). Intent to decrease OTC NSAIDs was evaluated via 11-point contemplation ladder immediately and 4 weeks post-intervention, with self-reported NSAID Exposure assessed at 4 weeks. We also evaluated current and recent pain levels at baseline and 4 weeks. Intent to decrease OTC NSAID use (4.28 (SD: 3.45) ladder rungs) and NSAID exposure (20.14 (SD: 13.66) dose-days per month) did not differ between groups at baseline. Intent to decrease OTC NSAID use increased more from baseline to immediately post-intervention in VIDEO vs. CONTROL (1.32 (SD: 2.80) vs. 0.55 (SD: 1.99) rungs, p < 0.001), with greater improvements for those with lower baseline intent. VIDEO and CONTROL were associated with a similar rise in intent to decrease OTC NSAID use (1.92 (SD: 4.41) vs. 1.36 (SD: 3.46), p = 0.150) and a similar decrease in NSAIDs exposure (-32.8% in VIDEO and -36.5% in CONTROL, p = 0.520) 4 weeks post-intervention. Pain levels did not differ between groups. Results suggest that a low-burden, electronically-administered intervention reduce high-risk medication use among patients with CKD, HF, and/or HTN.

Ankylosing spondylitis (AS) predominantly affects the spine and sacroiliac joints, with rare renal involvement. We investigated the incidence rate and risk factors for chronic kidney disease (CKD) in patients with AS and its relationship with long-term nonsteroidal anti-inflammatory drug (NSAID) use. We retrospectively analyzed data of patients diagnosed with AS from the Korean National Health Insurance service. The 3-month, 6-month, and 1-year Assessment of SpondyloArthritis International Society (ASAS) NSAID Intake Scores were categorized into four groups, as follows: =0, >0 and ≤33.3, 33.3-66.6, and >66.6. Of the 12 000 patients with AS, 150 were identified with CKD, and the incidence rate was 4.64 per 10 000 patient-years. Factors significantly associated with CKD included age ≥60 years, Charlson Comorbidity Index, hypertension, and diabetes mellitus. In the nested case-control analysis, among the ASAS NSAIDs Intake Scores for 0-365 days from diagnosis, the ≥66.6 group had a significantly lower odds ratio than those of the =0 group. The present study established the incidence rate of CKD in Korean patients with AS. Though older age and comorbidities were found to be associated with a higher CKD risk, long-term NSAID use was associated with a lower risk. Therefore, the optimal use of NSAIDs in inflammatory diseases requires extensive research.

Long-term NSAID use after CRPS diagnosis associated with increased risk of peripheral neuropathy and paresthesia.

Back ground and purpose: Few studies have investigated the presence of comorbidity and the outcome of idiopathic adhesive capsulitis, and they usually involved a small number of patients. This study aims to investigate the influence of comorbidity on the duration of non-steroidal anti-inflammatory drug (NSAID) therapy in idiopathic adhesive capsulitis patients using a population-based database.Methods: A population-based cross-sectional study was conducted to examine if comorbidity associated with long-term (＞28 days) NSAID therapy in patients with idiopathic adhesive capsulitis. Records of 439 adhesive capsulitis patients with long-term NSAID therapy and 7,569 adhesive capsulitis patients with? 28 days NSATD therapy were collected. Conditional logistic regression analyses were applied to explore the differences between the two groups in terms of age, gender, and selected systemic comorbid diseases including diabetes mellitus (DM), hyperthyroidism, hypothyroidism, ischemic heart disease, and hyperlipidemia.Result: The OR of hyperlipidemia with long-term N SAID use in patients with adhesive capsulitis was 1.3 14 (95 % CL 1.015-1.700; p=0.038. The OR of age with long-term NSAID use in patients with adhesive capsulitis was 1.02 (95 % CI, 1.011-1.029; p＜0.001). There were no significant differences between the two groups regarding DM, hyperthyroidism, hypothyroidism, ischemic heart disease, and patient gender.Conclusion: This study shows an association between hyperlipidemia and long-term NSAID dmg therapy in idiopathic adhesive capsulitis patients. Cardiovascular risk associates with hyperlipidemia and NSAID medication use. Physicians should, therefore, carefully evaluate the need for NSAID medication treatment in adhesive capulitis patients with concomitant hyperlipidemia. Further investigation is needed to confirm the relationship found in the present study.

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.

IntroductionNon-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting.MethodsWe conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls.ResultsOverall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (<10, 10 to 15, 15+ years) or intensity (low/medium/high) of NSAID use were also close to unity. Regardless of intensity, shorter or long-term NSAID use was not significantly associated with breast cancer risk.ConclusionsOverall, we found no compelling evidence of a reduced risk of breast cancer associated with use of sCox-2 inhibitors, aspirin, or non-selective NSAIDs.