Effect Of Nonsteroidal Anti-inflammatory Drug Use Research Articles

No Effect of NSAID Use on Efficacy of Zoledronate: A Post-Hoc Analysis of a Randomized Trial in Osteopenic Older Women.

Bisphosphonates are widely used for the prevention and treatment of osteoporosis. Non-steroidal anti-inflammatory drugs (NSAIDs) are also widely used among the older population group at high risk of fractures. NSAIDs have been shown to impact on bone turnover, and a recent re-analysis of a clinical trial of clodronate found that NSAID use at baseline abrogated any effect of clodronate on either bone density (BMD) or fracture risk. To determine whether NSAIDs influence the efficacy of other bisphosphonates, we have re-analyzed our 6-year randomized controlled trial of zoledronate in 2000 osteopenic postmenopausal women. NSAID use was reported at baseline in 38% of the cohort and anytime use was reported by 65%. The evolution of the zoledronate effects on BMD were almost identical whether or not women were using NSAIDs at baseline, and were significant in both sub-groups at all BMD sites (P < 0.0001). The significant reduction in the risk of fracture in those allocated to zoledronate (P < 0.0001) showed no interaction with baseline use of NSAIDs (P = 0.33) nor with NSAID use at any time during the study (P = 0.28). The odds of fracture were significantly reduced in both NSAID users and non-users. We conclude that the present analysis provides no support for the suggestion that NSAIDs interfere with the efficacy of potent bisphosphonates in terms of their effects on bone density or fracture.

Perioperative systemic nonsteroidal anti-inflammatory drugs (NSAIDs) in women undergoing breast surgery.

Perioperative systemic nonsteroidal anti-inflammatory drugs (NSAIDs) in women undergoing breast surgery.

Non-steroidal anti-inflammatory drugs, polygenic risk score and colorectal cancer risk.

The regular use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced colorectal cancer (CRC) risk. To explore whether this association varies according to background polygenic risk for CRC. Data were collected from a large population-based case-control study on CRC in Germany. A polygenic risk score (PRS) based on 140 CRC-related risk loci was used to quantify the genetic risk. The associations of regular use of NSAIDs (≥2times per week for at least 1year) with CRC risk were estimated in the whole population and in subgroups according to PRS levels using multivariable logistic regression. The impact of NSAIDs on CRC risk was compared to PRS using the 'genetic risk equivalent' (GRE), a recently developed metric for effective risk communication. In total 5129 CRC cases and 4093 controls were included in this analysis. The regular use of NSAIDs (including aspirin) was associated with reduced CRC risk [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.59, 0.74], as was regular use of aspirin only (OR 0.73, 95% CI 0.65, 0.83), without indication of interaction with the PRS (P=0.10 and 0.22 respectively). The effect of NSAID use was equivalent to the effect of having a 32 percentiles lower PRS (GRE -32, 95% CI -41, -22). The regular use of NSAIDs is associated with greatly reduced CRC risk regardless of individual genetic profile. With an equivalent reduction of relative risk across all polygenic risk groups, absolute risk reduction would be expected to be strongest among those with the highest polygenic risk score.

Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk.

Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk. Genetically predicted gene expressions were tested for interaction with NSAID use on colorectal cancer risk among 19,258 colorectal cancer cases and 18,597 controls from 21 observational studies. A Mixed Score Test for Interactions (MiSTi) approach was used to jointly assess G × E effects which are modeled via fixed interaction effects of the weighted burden within each gene set (burden) and residual G × E effects (variance). A false discovery rate (FDR) at 0.2 was applied to correct for multiple testing. Among the 4,840 genes tested, genetically predicted expression levels of four genes modified the effect of any NSAID use on colorectal cancer risk, including DPP10 (PG×E = 1.96 × 10-4), KRT16 (PG×E = 2.3 × 10-4), CD14 (PG×E = 9.38 × 10-4), and CYP27A1 (PG×E = 1.44 × 10-3). There was a significant interaction between expression level of RP11-89N17 and regular use of aspirin only on colorectal cancer risk (PG×E = 3.23 × 10-5). No interactions were observed between predicted gene expression and nonaspirin NSAID use at FDR < 0.2. By incorporating functional information, we discovered several novel genes that interacted with NSAID use. These findings provide preliminary support that could help understand the chemopreventive mechanisms of NSAIDs on colorectal cancer.

Non-steroidal Anti-inflammatory Drugs and the Risk of Pneumonia Complications: A Systematic Review.

There have been concerns regarding the safety of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with respiratory infections. However, to date, the quality of the evidence has not been systematically assessed. The purpose of this systematic review was to evaluate the role of NSAIDs on pneumonia complications. OVID MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Google Scholar were searched. Studies that examined pneumonia complications in patients who had taken NSAIDs before onset of symptoms were identified. Quality assessment was conducted using the Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) assessment tool, which was adapted to include biases that were pertinent to this question. The search strategy identified 1721 potential studies through the 5 primary databases and searching reference lists. Of these, 10 studies met the inclusion criteria, including 5 nested case-control studies, 2 population-based case-control studies, and 3 cohort studies. In total, 59,724 adults were included from 4 of the studies (range = 57-59,250) and 1217 children from 5 studies (range = 148-540). All studies demonstrated a positive association; in adults (odds ratio/risk ratio range = 1.8-8.1) and children (odds ratio/risk ratio range = 1.9-6.8). Studies were limited by moderate or serious risk of confounding bias, exposure misclassification, and protopathic biases and sparse data bias. The results of this review demonstrate that published studies on the effect of NSAIDs use and risk of pneumonia complications are subject to a number of biases. These results should not be extrapolated as evidence of harm for NSAIDs, including ibuprofen, in respiratory ailments but highlight the need for more methodologically robust studies to evaluate this potential relationship.

Oral non-steroidal anti-inflammatory drug use in recreational runners participating in Parkrun UK: Prevalence of use and awareness of risk.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in endurance running and by elite athletes. We examined the pattern of use of NSAIDs, the purpose of use and knowledge of the adverse effects of NSAID use in a population of recreational runners at Parkrun UK. An online observational non-interventional cross-sectional survey of Parkrun UK participants being over the age of 18, on Parkrun UK's mailing list, and residing in the UK. Runners (n=806) had a high use of NSAIDs in the past 12months (87.8%). The average age of respondents was 48.39years. There was a significant association between those taking an oral NSAID in the last twelve months and those with a sporting injury (χ2 =10.89, df=1, n=797, P=0.001). Ibuprofen was the most commonly used NSAID (81.1%). A third of runners had experienced an adverse drug reaction associated with NSAIDs, usually gastrointestinal. Half of runners used NSAIDs with no advice, and patient information leaflets were the most common source for those that had advice. Ninety-four per cent of runners would like more information on the harms and benefits of NSAIDs. Some recreational runners have a high use of NSAIDs, which is chronic in nature and a potential health risk. Recreational runners want more information on the harms and benefits of NSAIDs. Race event organizers should provide evidence-based advice on the use of NSAIDs.

Effect of NSAID Use on Bone Healing in Pediatric Fractures: A Preliminary, Prospective, Randomized, Blinded Study.

This study aimed to investigate if nonsteroidal anti-inflammatory drugs (NSAIDs) used in the acute phase of bone healing in children with fractures result in delayed union or nonunion as compared with patients who do not take NSAIDs for pain control during this same time period. In this prospective, randomized, parallel, single-blinded study, skeletally immature patients with long bone fractures were randomized to 1 of 2 groups for their postfracture pain management. The NSAID group was prescribed weight-based ibuprofen, whereas the control group was not allowed any NSAID medication and instead prescribed weight-based acetaminophen. Both groups were allowed to use oxycodone for breakthrough pain. The primary outcome was fracture healing assessed at 2, 6, and 10 weeks. One-hundred-two patients were enrolled between February 6, 2014 and September 23, 2016. Ninety-five patients (with 97 fractures) completed a 6-month follow-up (46 patients with 47 fractures in the control group and 49 patients 50 fractures in the NSAID group). None achieved healing at 1 to 2 weeks. By 6 weeks, 37 of 45 patients (82%) of control group and 46 out of 50 patients (92%) of ibuprofen group had healed fractures (P=0.22). At 10 to 12 week follow-up, 46 (98%) of the control group fractures were healed and 50 (100%) of the ibuprofen group fractures were healed. All were healed by 6 months. Healing was documented at a mean of 40 days in the control group and 31 days in the ibuprofen group (P=0.76). The mean number of days breakthrough oxycodone was used was 2.4 days in the control group and 1.9 days in the NSAID group (P=0.48). Ibuprofen is an effective medication for fracture pain in children and its use does not impair clinical or radiographic long bone fracture healing in skeletally immature patients. Level I-therapeutic.

Impact of Concomitant Medication Administered at the Time of Initiation of Nivolumab Therapy on Outcome in Non-small Cell Lung Cancer.

To investigate potential association between administration of corticosteroids, antibiotics, probiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAID), statins and metformin and outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. A total of 224 patients with advanced NSCLC treated at nine comprehensive cancer centers were analyzed in this national retrospective study. Survival statistics were evaluated using Kaplan-Meier method and Cox analysis. Only corticosteroid use had a significant negative effect on the objective response rate. In the univariate analysis, there was no significant effect of the studied concomitant medications on the efficacy of nivolumab. In a subsequent multifactorial analysis, a possible positive effect of the concomitant use of NSAID at the initiation of nivolumab treatment was revealed. The results of the present retrospective exploratory analysis underscore the importance of knowing the exact type of concomitant medication, the route of administration, the dose of medication, and the region of the ongoing study. The present data indicated a significantly higher rate of progression in patients treated with corticosteroids and the possible positive effect of NSAID use at the initiation of nivolumab treatment.

Effects of NSAID use on bone healing: A meta-analysis of retrospective case–control and cohort studies within clinical settings

IntroductionThis meta-analysis aims to determine whether non-steroidal anti-inflammatory drug (NSAID) use is significantly associated with adverse bone healing outcomes within clinical settings, including trauma and elective spine settings. It will also explore bone healing outcomes with the type, route, dosage and duration of NSAID exposure and aims to demonstrate the effects of various other confounding factors on bone healing outcomes.MethodsElectronic databases including MedLine, Embase and Cochrane were searched from January 1975 to December 2017. A distinct analysis of observational long bone and spine studies in adult populations was performed, assessing the effects of NSAID exposure on bone healing. Studies from paediatric population and randomised trials also underwent separate assessment in the synthesis. Meta-analysis was conducted in compliance with QUORUM and PRISMA guidelines.ResultsQuantitative assessment of observational studies suggested a significant risk of bone healing complications with NSAID exposure across each clinical group: long bone (p = 0.0004) and spine (p = 0.02). Analysis of paediatric studies revealed a non-significant association of poor outcomes with NSAID use (p = 0.36), while assessment of randomised trials demonstrated a statistically significant risk of complications following NSAID administration (p = 0.04). Meta-regression further suggested smoking to be a substantial confounder associated with adverse bone healing outcomes (p &lt; 0.00001).ConclusionInclusion of only fair and moderate-quality retrospective cohort and case–control studies in the current synthesis limits the clinical application of its findings and therefore warrants the need for further research. Thus, attempts to conduct high-quality prospective cohort and randomised trials to study the effects of NSAID use on bone healing would be very helpful and will provide a basis for more extensive research in future.

Effects Of Nsaid Use On Biomarkers Of Kidney Stress Following A Marathon

The use of nonsteroidal anti-inflammatory drugs (NSAID) is common practice by participants in marathons and other endurance events. Previous research suggests that renal stress is apparent immediately following marathon completion. However, the potential exacerbating effect of NSAID use during a marathon is not well-understood. PURPOSE: Investigate the effect of NSAID use on biomarkers of renal stress following a marathon. METHODS: Twenty-two volunteer participants (14 males, 8 females; 38 ± 10.2y, 70.7 ± 10.1kg, 171.0 ± 7.7cm) at the Kansas City Marathon were recruited and assigned to either a control (n = 15) or NSAID (n = 7) group based on planned or habitual use. Pre-race NSAID ingestion was self-reported as 9.15 ± 4.62 mg/kg of ibuprofen (n=4) or 3.75 ± 1.73mg/kg naproxen sodium (n=3). Urine samples were collected pre-marathon, post-marathon, and 24-h post-marathon. Samples were stored at -80°C and later analyzed for urinary neutrophil gelatinase lipocalin (uNGAL) and urinary cystatin C (uCyC). A robust two-way mixed ANOVA with trimmed means was utilized to account for potential outliers. When significant interaction or main effects were observed, pairwise comparisons were calculated using robust bootstrapped effect sizes with 95% confidence intervals. RESULTS: Immediately post-marathon, there was a significant increase in uNGAL (Cohen’s dR = 0.47 95%C.I. [0.23,0.85]) but there was no longer a significant elevation by 24-h post-marathon (Cohen's dR = 0.16 95%C.I. [-0.61,3.36]). There were no significant effects detected for Cystatin C. Further, NSAID ingestion did not affect uCyC or uNGAL values. CONCLUSION: Renal stress biomarkers suggest potential kidney tubular injury immediately post-marathon, but potential renal stress was negated by 24-h of recovery. Moderate NSAID ingestion before the marathon did not affect kidney stress biomarkers.

Effects of Perioperative Nonsteroidal Anti-inflammatory Drug Administration on Soft Tissue Healing: A Systematic Review of Clinical Outcomes After Sports Medicine Orthopaedic Surgery Procedures.

Background:The effects of perioperative nonsteroidal anti-inflammatory drugs (NSAIDs) on soft tissue healing in humans have yet to be established.Purpose:To systematically review the literature addressing the effects of perioperative NSAID administration on soft tissue healing and clinical patient outcomes.Study Design:Systematic review; Level of evidence, 3.Methods:This review study was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. A review of the literature regarding the existing evidence for clinical effects of NSAID use on soft tissue healing was performed through use of the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980 to present), and MEDLINE. Inclusion criteria for articles were as follows: outcome studies after soft tissue (ligament, meniscus, tendon, muscle) healing after surgical procedure with perioperative NSAID administration, at least 1 year of follow-up, English language, and human participants.Results:A total of 466 studies were initially retrieved, with 4 studies satisfying all inclusion criteria. Among the surgical procedures reported, 93% of the patients (4144/4451) underwent anterior cruciate ligament (ACL) reconstruction, 3% (120/4451) underwent rotator cuff repair, 3% (155/4451) underwent Bankart shoulder repair, and 1% (32/4451) underwent meniscal repair. The reported surgical failure rate among patients administered NSAIDs was 3.6% (157/4360). The reported surgical failure rate among control participants not given NSAIDs was 3.7% (147/3996). NSAID use showed no statistically significant effect on need for reoperation in meniscal repair (P = .99), ACL reconstruction (P = .8), and Bankart repair (P = .8) compared with no NSAID administration. Celecoxib administration had a significantly higher rate of retear (37%) after rotator cuff repair compared with ibuprofen (7%) (P = .009).Conclusion:Insufficient data are available to definitively state the effects of perioperative NSAIDs on soft tissue healing. Use of NSAIDs should be considered on a case-by-case basis and may not affect healing rates following either meniscal, ACL, rotator cuff, or Bankart repair. However, celecoxib (a selective COX-2 inhibitor) may inhibit tendon-to-bone healing in rotator cuff repair. Further research through clinical trials is required to fully determine whether NSAIDs have an adverse effect on soft tissue healing.

Use of nonsteroidal anti-inflammatory drugs to prevent heterotopic ossification after spinal cord injury: a retrospective chart review.

Retrospective chart review. The objective of this study is to evaluate the efficacy of nonsteroidal anti-inflammatory drug (NSAID) prophylaxis for heterotopic ossification (HO) in the acute phase after spinal cord injury (SCI). Acute rehabilitation hospital in California, USA. This retrospective chart review (October 2013-March 2017) included individuals with motor complete SCI followed by the SCI service within 60 days of injury. Group demographics and HO diagnosis were compared in those who received and those who did not receive NSAID prophylaxis. A backward stepwise multiple regression was employed to assess the predictive association between injury characteristics and HO prophylaxis on HO diagnosis. A total of 108 AIS A and B cases were included, and 27 received ≥ 15 days of therapy (overall range 6-44 days). Logistic regression analysis revealed those who received ≥ 15 days of NSAID prophylaxis had an odds ratio of 0.1 of being diagnosed with HO compared with those who did not (95% CI, 0.02 to 0.52). Significant predictors of HO diagnosis were tracheostomy (OR 2.8, 95% CI, 1.05 to 7.5), urinary tract infection (OR 4.3, 95% CI, 1.5 to 12.2), and pressure injury (OR 3.3, 95% CI, 1.1 to 9.5). Adverse effects of NSAID use were minimal. NSAID prophylaxis appears to help prevent HO development during the acute phase after SCI. Prospective study with prolonged follow up is necessary to confirm the long-term efficacy of HO prevention and to further evaluate safety following spinal fusion. None.

Tibia fractures and NSAIDs. Does it make a difference? A multicenter retrospective study

PurposeThe purpose of this study was to compare healing time for diaphyseal tibia fractures (OTA/AO 42 A, B, C) treated with intramedullary nailing (IMN) in one geographic cohort using nonsteroidal anti-inflammatory drugs (NSAIDs) for post-operative pain control to that of another geographic cohort using opioid medications. The groups represent differing cultural approaches to post-operative pain control. We hypothesized there would be no difference in healing time. MethodsTibia fractures presenting at two level I trauma centers located in different countries between January 1, 2010 and December 31, 2017 were retrospectively screened for enrollment. Fractures classified as OTA/AO 42 A, B, or C that were treated with IMN and had radiographic follow up to union were included. At hospital discharge, one cohort (n = 190) was prescribed NSAIDs and the other (n = 182) was prescribed opioids for pain control. Each analgesic method represented the standard of care for that location. Fracture union was defined as cortical bridging in at least 3 out of 4 cortices on AP and lateral radiographs. The primary outcome was healing time on radiographic evaluation. ResultsThere was no statistically significant difference in healing time between the opioid and NSAID groups: 185 vs 180.5 days respectively (p = 0.64). Both groups had similar mean age. Student t-tests were run to compare rates of tobacco use, diabetes mellitus (DM), open fractures, and polytrauma between the two groups. The opioid cohort had statistically significant higher rates of tobacco use, DM, and polytrauma. The NSAID cohort, however, had a larger number of open fractures. ConclusionThe difference in healing time between the NSAID and opioid groups was not statistically significant. The deleterious effect of NSAID use on fracture healing has been debated for decades. Numerous animal studies have supported this theory; however, high quality clinical studies in humans have not provided convincing evidence to substantiate this negative effect. Our study suggests that NSAIDs may be used safely and effectively in the acute phase of fracture healing without significantly increasing the risk of delayed union or nonunion. Prospective randomized studies are necessary to rule out the negative effect of NSAIDS on bone healing.

Survival as a Function of Nonsteroidal Anti-inflammatory Drug Use in Patients with Glioblastoma

BackgroundFindings of both case control and in vitro investigations suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may play a beneficial role in the occurrence, growth, and subsistence of glioblastoma multiforme (GBM) brain tumor in humans.ObjectiveIn the present retrospective cohort study, we assessed the impact of NSAID use on survival in patients diagnosed with and treated for GBM brain tumors.MethodsThe impact of NSAID use and six other potential prognostic indicators of survival were assessed in 71 patients treated for GBM brain tumors from February 2011 to June 2016. Survival analysis and cross-tabulation analyses were performed to examine the potential relationship between NSAID use and occurrence of intracranial hemorrhage over the course of treatment for GBM.ResultsKaplan-Meier analysis revealed no significant difference in survival between patients with and without NSAID use (p = 0.75; 95% CI: 10.12, 18.13). Multiple Cox regression analysis identified only treatment with chemotherapy as imposing any statistically significant effect on survival (Hazard Ratio (HR) = 3.31; p < 0.001; 95% CI: 1.80, 6.07). Cross-tabulation revealed no significant effect of NSAID use on occurrence of hemorrhage during treatment, X2 (2, N = 71) = 0.65, p2-Sided = 0.42, (Fisher’s Exact Test: p2-sided = 0.56, p1-sided = 0.31).ConclusionThese results suggest that history of NSAID use is not a determinant of survival in GBM patients. More rigorous, prospective investigations of the effect of NSAID use on tumor progression are necessary before the utility of this family of drugs in the treatment of GBM can be adequately appraised.

Nonsteroidal Anti-inflammatory Drugs and Clinical Outcomes among Men with Prostate Cancer: A Systematic Review and Meta-analysis

AbstractBackground: Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown properties of inhibiting the progression of prostate cancer (PCa) in preclinical studies. However, epidemiological studies yield mixed results on the effectiveness of NSAIDs in PCa. Objective: The objective of this study was to determine the effect of NSAID use on clinical outcomes in PCa using systematic review and meta-analysis. Methods: Original articles published until the 1st week of October, 2016, were searched in electronic databases (Medline-Ovid, PubMed, Scopus, The Cochrane Library, and Web of Science) for studies on NSAID use in PCa. The main clinical outcomes for the review were: PCa-specific (PCM) and all-cause mortality (ACM), biochemical recurrence (BCR), and metastases. Meta-analysis was performed to calculate the pooled hazard ratio (pHR) and their 95% confidence interval (95% CI). Heterogeneity between the studies was examined using I2 statistics. Appropriate subgroup analyses were conducted to explore the reasons for heterogeneity. Results: Out of 4216 retrieved citations, 24 observational studies and two randomized controlled studies with a total of 89,436 men with PCa met the inclusion criteria. Overall, any NSAID use was not associated with PCM, ACM, and BCR, with significant heterogeneity. Neither precancer treatment aspirin use (pHR: 1.00, 95% CI: 0.83, 1.19, P = 0.97, 5 studies, I2: 51%) nor postcancer treatment aspirin use (pHR: 0.94, 95% CI: 0.72, 1.23, P = 0.67, 8 studies, I2: 86%) was associated with PCM. Similar findings, that is, no significant association was observed for NSAID use and ACM or BCR overall, and in subgroup by types of NSAID use, and NSAID use following radiation or surgery. Conclusion: Although NSAID use was not associated with ACM, PCM, or BCR among men with PCa, significant heterogeneity remained in the included studies even after subgroup analyses.

Association Between Non-Steroidal Anti-Inflammatory Drug Use and Cognitive Decline: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used medications in the elderly. They have been widely studied as possible preventive agents against cognitive decline because of the properties of anti-inflammatories, which sustain cerebral blood flow and mitigate the neurotoxicity of microglial cells. However, the results remain controversial. Our objective was to assess the effects of NSAID use on the risk of cognitive decline. We reviewed and quantitatively synthesized the evidence from prospective cohort studies via a meta-analysis. We identified pertinent studies by searching the PubMed, EMBASE, and China National Knowledge Infrastructure databases through to December 2015 and by reviewing the reference lists of retrieved articles. We used fixed- or random-effects models to pool relative risks (RRs) with 95% confidence intervals (CIs) and performed sensitivity analyses to evaluate the robustness of the results. Small-study effect was evaluated using Egger's test and funnel plots. Of the 2171 articles identified through searching the databases, ten articles including 11 prospective cohort studies were eligible. Overall, NSAID use was associated with a 13% decreased risk of cognitive decline (pooled RR 0.87; 95% CI 0.81-0.94). In subgroup analysis, the pooled RRs were 0.89 (95% CI 0.81-0.98) for follow-up time ≥5years, 0.85 (95% CI 0.75-0.96) for follow-up time <5years, and 0.85 (95% CI 0.78-0.93) for studies conducted in North America, respectively. Sensitivity analyses found results to be robust. No evidence of significant small-study effect was identified. This meta-analysis of prospective cohort studies indicates that NSAID use may be associated with a decreased risk of cognitive decline. Larger, high-quality randomized controlled trials are needed to verify the effects of NSAID use on the risk of cognitive decline.

The Effect of Over-the-Counter Medication on Symptom Severity Following Sport-Related Concussion

PURPOSE: Although over-the-counter (OTC) medications are commonly administered following sport-related concussion, their effect on reducing symptoms remains unknown. We sought to examine the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and melatonin on post-concussion symptom severity. METHODS: We conducted a prospective cohort study of patients who presented to a sport concussion clinic within 21 days of injury. We examined the effect of NSAID use on the sum of “Headache” and “Pressure in the Head” scores (HA score) on the post-concussion symptom scale (PCSS) endorsed by the international consensus on concussion in sport. In addition, we examined the effect of melatonin on “Trouble Falling Asleep” scores (Sleep score). Patients who reported taking NSAIDs (n=30) and melatonin (n=16) were matched by age, gender, HA or Sleep score respectively, and overall PCSS scores with controls (n=70 and 35 respectively) who did not report the use of these medications. Mean differences in PCSS scores from the initial clinic visit and first follow-up visit were compared by repeated measures ANOVA. RESULTS: There was significant improvement in mean HA score for both NSAID users (6.4 vs. 3.7; p<0.001) and non-users (6.6 vs.2.8; p<0.001). The mean difference in HA score between initial visit and follow-up visit of NSAID users was not significantly different than that of non-users (2.7 vs. 3.8; p=0.102). Similarly, there was significant improvement in Sleep score between visits in both melatonin users (3.8 vs. 2.0; p<0.001) and non-users (3.7 vs. 1.6; p<0.001) showed. The mean difference in Sleep score between initial visit and follow-up visit, however, did not differ between those who used melatonin and those who didn’t (1.8 vs. 2.1; p=0.691). CONCLUSION: Headache symptom severity and difficulty falling asleep are commonly treated following concussion using OTC medications such as NSAIDs and melatonin. Our results suggest that symptom severity improves over time, but this effect may not be enhanced by the use of OTC medications.

Use of Nonsteroidal Anti-Inflammatory Drugs and Risk of Chronic Kidney Disease in Subjects With Hypertension: Nationwide Longitudinal Cohort Study.

Limited studies have examined the effects of nonsteroidal anti-inflammatory drug (NSAID) use on the risk of chronic kidney disease (CKD), especially in subjects with hypertension. Using National Health Insurance claims data in Taiwan, we conducted a propensity score-matched cohort study to investigate the relationship between NSAID use and CKD in subjects with hypertension. A total of 31976 subjects were included in this study: subjects not taking any NSAIDs in 2007 (n=10782); subjects taking NSAIDs for 1 to 89 days in 2007 (n=10605); and subjects taking NSAIDs for ≥90 days in 2007 (n=10589). We performed multivariable proportional hazard models to determine the relationship between NSAID use and CKD. The results showed that NSAID use was associated with a 1.18-fold increased risk of CKD in subjects taking NSAIDs for 1 to 89 days; and a 1.32-fold increased risk of CKD in hypertension subjects taking NSAIDs for ≥90 days, compared with subjects not taking any NSAIDs, after controlling for the confounding factors. In subgroup analyses, subjects taking NSAIDs for ≥90 days, >1 defined daily dose per day or taking NSAIDs >15 cumulative defined daily doses had a greater risk of CKD than subjects not taking any NSAID, but not for congestive heart failure, stroke, cancer, osteoarthritis, or rheumatoid arthritis. These results provide supportive evidence that NSAID use is associated with increased risk of CKD in subjects with hypertension. It is important to closely monitor the effects of NSAID use, particularly in patients with hypertension, a susceptible population for CKD.

Abstract 4590: Polymorphisms in cell-cycle related genes modify the effect of NSAIDs on the risk of colorectal cancer

Abstract 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 &amp;gt;1/month for &amp;gt;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&amp;lt;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

Use of nonsteroidal anti-inflammatory drugs and reduced breast cancer risk among overweight women.

Chronic inflammation is associated with increased risk of multiple cancers, including breast cancer. Adipose tissues produce proinflammatory cytokines, and obesity is a risk factor for postmenopausal breast cancer. We evaluated the association of regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) with breast cancer risk, overall and by body mass index (BMI) and tumor subtypes defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We conducted a population-based, case-control study involving 5,078 women aged 25-75 years who were recruited primarily from the Nashville metropolitan area of Tennessee. Multivariate unconditional logistic regression models were used to estimate odds ratios and 95 % confidence intervals for breast cancer risk after adjusting for multiple potential confounding factors. Regular use of any NSAID was associated with significantly reduced breast cancer risk (OR 0.78; 95 % CI 0.69-0.89). This association was observed for regular use of baby aspirin only (OR 0.82, 95 % CI 0.69-0.99), other NSAIDs only (OR 0.81, 95 % CI 0.69-0.95), and both baby aspirin and other NSAIDs (OR 0.52, 95 % CI 0.40-0.69). These significant inverse associations were found among overweight women (BMI ≥25 kg/m(2)) overall and by subtypes of breast cancer, but not among women with BMI <25 kg/m(2) (P for interaction = 0.023). Regular use of NSAIDs was inversely associated with breast cancer risk, particularly among overweight women. Overweight women may benefit more from the protective effects of NSAID use than normal-weight women.