Aspirin Nonsteroidal Anti-inflammatory Drugs Research Articles

A Nationwide Population-Based Cohort Study of Dementia Risk Among Acid Suppressant Users

Data regarding the potential link between acid suppressant use and dementia are inconsistent. This study assessed the association between cumulative exposure to proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) and dementia risk among Korean adults. A population-based longitudinal study was conducted using the Korean National Health Insurance Corporation claims database merged with national health examination data for 2002-2013. The study cohort included 70,529 subjects who were dementia-free in 2007. Incident dementia was assessed throughout follow-up until 2013. Exposure to acid suppressants prior to 2007 was assessed using a standardized defined daily dose system. Potential associations between acid suppressant use and dementia risk were analyzed using time-dependent Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs). There were 1,297 cases of dementia during the study period. Multivariate analyses identified several factors associated with dementia risk: old age, female, current smoker, Type 2 diabetes, comorbidities, and use of nonaspirin nonsteroidal anti-inflammatory drugs. H2RA users had a significantly increased risk of dementia compared with non-H2RA users (HR 1.31, 95% CI 1.13-1.51), whereas PPI use was not associated with increased risk. Our results indicate that exposure to H2RAs (but not PPIs) is associated with increased dementia risk. Further randomized controlled trials and basic research examining the underlying mechanism are needed to confirm this association.

Chemoprevention of Barrett's Esophagus and Esophageal Adenocarcinoma.

Barrett's esophagus is common in Western countries, but progression to esophageal adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether benefits outweigh risks given an otherwise healthy population. This will depend on the particular population at risk and the relative safety of a potential preventive agent. Most evidence regarding the potential benefit of chemoprevention of Barrett's esophagus and prevention of progression to esophageal adenocarcinoma is based on observational studies such as case-control and cohort studies. Given the potential benefits and relatively low risks, patients with BE should receive once-daily PPI therapy, but routine use of twice-daily PPI is not recommended unless necessitated by poor control of reflux symptoms or esophagitis. Recent data suggest that the inverse associations between aspirin/NSAID use and esophageal adenocarcinoma may be the result of reducing neoplastic progression (from metaplasia to dysplasia and carcinoma) rather than initiation of Barrett's esophagus. While substantial associative data suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk of progression of Barrett's esophagus, the low risk of progression and the potential risks (gastrointestinal bleeding, complicated ulcer disease, hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular risk. Chemoprevention after mucosal ablation in those at highest risk of post-ablation recurrence (dysplastic Barrett's) is currently under investigation.

Nonsteroidal anti-inflammatory drugs and cancer pain.

This review aims to appraise the most recent evidence for the use of NSAIDS in cancer pain. The Cochrane review reveals the paucity of high-quality evidence for the use of NSAIDS for cancer pain, highlighting methodological considerations for future research. There is limited evidence for the role of combined NSAIDs (celecoxib and diclofenac) alongside opioids for cancer pain. Recent retrospective data suggests NSAIDS may contribute to better pain control in hospitalized patients. In elderly patients in the last weeks of life, retrospective data shows a reduction in NSAID prescribing, without significant implications for pain relief. A recent systematic review looking at the increased risk of anastomotic leaks versus the survival benefits in cancer patients prescribed NSAIDs post oncological surgery was inconclusive. Considering the prescription of PPIs for gastroprotection, studies in the general population suggest potential risks of long-term use, including renal dysfunction and greater risk of fractures. Although current evidence for the anticancer properties of NSAIDS is based on retrospective cohort studies, there may be a role for aspirin and nonaspirin NSAIDs in reducing the risk of cancer. Given the lack of quality evidence, NSAIDS should be prescribed on a case by case basis in discussion with the patient, with regular review of efficacy, whilst balancing the ongoing benefits and risks of continued use, taking into account the patient's likely prognosis.

Analgesic Use and Ovarian Cancer Risk: An Analysis in the Ovarian Cancer Cohort Consortium.

Aspirin use is associated with reduced risk of several cancers. A pooled analysis of 12 case-control studies showed a 10% decrease in ovarian cancer risk with regular aspirin use, which was stronger for daily and low-dose users. To prospectively investigate associations of analgesic use with ovarian cancer, we analyzed data from 13 studies in the Ovarian Cancer Cohort Consortium (OC3). The current study included 758 829 women who at study enrollment self-reported analgesic use, among whom 3514 developed ovarian cancer. Using Cox regression, we assessed associations between frequent medication use and risk of ovarian cancer. Dose and duration were also evaluated. All statistical tests were two-sided. Women who used aspirin almost daily (≥6 days/wk) vs infrequent/nonuse experienced a 10% reduction in ovarian cancer risk (rate ratio [RR] = 0.90, 95% confidence interval [CI] = 0.82 to 1.00, P = .05). Frequent use (≥4 days/wk) of aspirin (RR = 0.95, 95% CI = 0.88 to 1.03), nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs; RR = 1.00, 95% CI = 0.90 to 1.11), or acetaminophen (RR = 1.05, 95% CI = 0.88 to 1.24) was not associated with risk. Daily acetaminophen use (RR = 1.28, 95% CI = 1.00 to 1.65, P = .05) was associated with elevated ovarian cancer risk. Risk estimates for frequent, long-term (10+ years) use of aspirin (RR = 1.15, 95% CI = 0.98 to 1.34) or nonaspirin NSAIDs (RR = 1.19, 95% CI = 0.84 to 1.68) were modestly elevated, although not statistically significantly so. This large, prospective analysis suggests that women who use aspirin daily have a slightly lower risk of developing ovarian cancer (∼10% lower than infrequent/nonuse)-similar to the risk reduction observed in case-control analyses. The observed potential elevated risks for 10+ years of frequent aspirin and NSAID use require further study but could be due to confounding by medical indications for use or variation in drug dosing.

Clinical Outcomes of Aspirin Interaction with Other Non-Steroidal Anti-Inflammatory Drugs: A Systematic Review.

Concomitant use of some non-Aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) reduces the extent of platelet aggregation of Aspirin (acetylsalicylic acid). This is while many observational studies and clinical trials suggest that Aspirin reduces cardiovascular (CV) risk attributed to the use of NANSAIDs. Thus, the therapeutic outcome of the interaction needs to be assessed. We searched various databases up to October 2017 for molecular interaction studies between the drugs and long-term clinical outcomes based on randomized clinical trials and epidemiological observations that reported the effect estimates of CV risks (OR, RR or HR; 95% CI) of the interacting drugs alone or in combinations. Comparisons were made between outcomes after Aspirin alone, NANSAIDs alone and Aspirin with naproxen, ibuprofen, celecoxib, meloxicam, diclofenac or rofecoxib. In total, 32 eligible studies (20 molecular interactions studies and 12 observational trials) were found. Conflicting in vitro/in vivo/ex vivo platelet aggregation data were found for ibuprofen, naproxen and celecoxib. Nevertheless, for naproxen, the interaction at the aggregation level did not amount to a loss of cardioprotective effects of Aspirin. Similarly, for ibuprofen, the results overwhelmingly suggest no negative clinical CV outcomes following the combination therapy. Meloxicam and rofecoxib neither interacted with Aspirin at the level of platelet aggregation nor altered clinical outcomes. The clinical outcomes data for celecoxib and diclofenac are in conflict. Aspirin appears to maintain its cardioprotective effect in the presence of naproxen, ibuprofen, meloxicam and rofecoxib. The limited available data suggest that the effect of interaction at the platelet aggregation level may dissipate shortly, or the reduced platelet aggregation yielded by the interaction may be sufficient for cardioprotection; i.e., no need for near complete aggregation. In addition, cardioprotective effect of Aspirin, despite reduced platelet aggregation caused by NANSAIDs, may be through its involvement in other mechanisms such as the renin-angiotensin system and/or metabolism of arachidonic acid to biologically active compounds mediated by cytochrome P450.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Impact of Aspirin and Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs on Outcomes in Patients with Metastatic Renal Cell Carcinoma

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated an anti-tumorigenic effect in several cancers. However, their use is associated with an increased risk in renal cell carcinoma (RCC) and their effect has not been assessed in patients with metastatic disease. Objective: We investigated the impact of NSAIDs on survival outcomes in patients with metastatic RCC (mRCC). Methods: We conducted a pooled retrospective analysis of 4,736 mRCC patients treated on phase II and III clinical trials. Patients were categorized as: aspirin (ASA) only users, non-ASA NSAIDs only users, ASA and non-ASA NSAIDs users, and NSAIDs non-users. The primary endpoint was overall survival (OS). Progression free survival (PFS), overall response rate (ORR) and adverse events (AEs) were secondary endpoints. OS and PFS were estimated using the Kaplan–Meier method and were assessed using multivariate Cox regression analysis. Results: We identified 457 (10%) ASA only users, 639 (13%) non-ASA NSAIDs only users, 61 (1%) ASA and non-ASA NSAIDS users, and 3579 (76%) NSAIDs non-users. OS and PFS were significantly worse in non-ASA NSAIDs users compared to the NSAIDs non-users (OS hazard ratio (HR): 1.47, p < 0.0001, median 11.6 versus 21.1 months; PFS HR: 1.29, p < 0.0001, median 4.6 versus 7.4 months). There was no difference in survival in ASA users or ASA and non-ASA NSAIDs users compared to NSAIDs non-users. Conclusions: Our analysis demonstrates that NSAIDs do not confer a survival advantage in mRCC patients. Further studies are warranted to elucidate the interaction of NSAIDS with targeted therapy in mRCC.

Electrochemical synthesis of nitrogen-doped carbon quantum dots decorated copper oxide for the sensitive and selective detection of non-steroidal anti-inflammatory drug in berries

We report a sensitive non-steroidal anti-inflammatory drug aspirin (ASA) sensor studies using the nitrogen-doped carbon quantum dots (N-CQD) decorated copper oxide (Cu2O). A simplistic approach of electrochemical deposition method has been used to prepare the N-CQD incorporated with copper oxide (N-CQD/Cu2O) and the resulting composite has characterized by analytical techniques. Modified glassy carbon electrode of N-CQD/Cu2O/GCE is developed and is used for the sensor studies of aspirin. The modified N-CQD/Cu2O/GCE has exhibited a higher current (Ipa) response to the oxidation process when compared to N-CQD/GCE, Cu2O/GCE and bare GCE. Furthermore, it has shown a good linear range of 1–907 µM with a limit of detection (LOD) ∼0.002 µM and sensitivity ∼21.87 µA µM−1 cm-2. The developed sensor has displayed outstanding repeatability, stability and accumulation time along with better electro-catalytic response in berries for real-life application.

NSAID Exposure and Risk of Alzheimer's Disease: An Updated Meta-Analysis From Cohort Studies.

Background: Initial observational studies and a systematic review published recently have suggested that non-steroidal anti-inflammatory drug (NSAID) use has the trend to be associated with reduced risk of Alzheimer's disease (AD), while results remain conflicting. Thus, we performed an updated meta-analysis to reevaluate the evidence on this association.Methods: Data sources from PUBMED, Embase and Cochrane Library from inception through April 2017 were searched by two independent reviewers. Eligible cohort studies were selected according to predefined keywords. We did a meta-analysis of available study data using a random-effects model to calculate overall relative risks (RRs) for associations between NSAID exposure and AD risk.Results: From 121 potentially relevant studies, 16 cohort studies including 236,022 participants, published between 1995 and 2016, were included in this systematic review. Meta-analysis demonstrated that current or former NSAID use was significantly associated with reduced risk of AD (RR, 0.81, 95% CI0.70 to 0.94) compared with those who did not use NSAIDs. This association existed in studies including all NSAID types, but not in aspirin (RR, 0.89, 95% CI 0.70 to 1.13), acetaminophen (RR, 0.87, 95% CI 0.40 to 1.91) or non-aspirin NSAID (RR, 0.84, 95% CI 0.58 to 1.23).Conclusions: Current evidence suggests that NSAID exposure might be significantly associated with reduced risk of AD. However, further large-scale prospective studies are needed to reevaluate this association, especially the associations in individual NSAID type.

Aspirin Use and Risk of Hepatocellular Carcinoma in a National Cohort Study of Korean Adults

The effect of aspirin on the risk of hepatocellular carcinoma (HCC) remains unclear. We investigated the association between aspirin use and HCC development in a region where viral hepatitis prevails. We conducted a population-based cohort study including a total of 460,755 participants who were tracked to identify incidents of HCC since 2007. The use of drug before the index date was assessed and standardized by the Defined Daily Dose system. We calculated the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between aspirin use and HCC occurrence, using Cox proportional hazard regression models. There were 2,336 cases of HCC during the period of 2,965,500 person-years. Overall, aspirin users had a lower HCC risk (HR, 0.87; 95% CI, 0.77–0.98) than non-users in a dose-response manner (Ptrend = 0.002). The protective effect of aspirin was amplified when combined with those of non-aspirin non-steroidal anti-inflammatory drugs (HR, 0.65; 95% CI, 0.50–0.85). Subgroup analyses revealed a significant chemopreventive effect of aspirin in individuals who were young, were male, or had viral hepatitis, whereas no protective effect was observed in patients with liver cirrhosis. Our results, suggesting different carcinogenic pathways between viral and non-viral etiologies, may validate the design of future intervention trials of aspirin for HCC prevention in eligible populations.

Selective association of nonaspirin NSAIDs with risk of diverticulitis.

The purpose of this study is to investigate the association of intake of nonsteroidal anti-inflammatory drugs (NSAIDs) and in particular nonaspirin NSAIDs and compare it with other risk factors for the progression of diverticulosis to diverticulitis in patients who underwent colonoscopy. A total of 194 patients who underwent complete colonoscopy in our center between 2012 and 2016 were recruited: 144 with diverticulosis without prior diverticulitis (median age 71years, 59.7% men) and 50 with diverticulitis (median age 64years, 54.0% men). Data concerning current and previous medication as well as concomitant diseases were collected using a structured questionnaire and by revision of patients medical charts. Patients with diverticulitis were significantly (p < 0.001) younger as compared to individuals with plain diverticulosis (median age 64 versus 71years, respectively). The intake of NSAIDs significantly (p = 0.002) increased the risk of prior diverticulitis (OR 3.2, 95% CI 1.5-6.9). In the multivariate model, both age (p < 0.001) and NSAIDs (p = 0.03) proved to be independent determinants of diverticulitis. When analyzing aspirin intake, it was not associated with diverticulitis. Our study demonstrates, in line with previous reports, that intake of NSAIDs is associated with diverticulitis. We show in particular that nonaspirin NSAIDs might be selectively associated with diverticulitis. These results point to divergent role of aspirin and nonaspirin NSAIDs in the development of diverticulitis.

The Relationship Between Nonsteroidal Anti-inflammatory Drug Use and Age-related Macular Degeneration

To describe the relationship between the incidence of age-related macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use. Prospective cohort study. This study consisted of participants in the California Men's Health Study. Those who completed surveys in 2002-2003 and 2006 were included. Men who self-reported use of aspirin, ibuprofen, naproxen, valdecoxib, celecoxib, and/or rofecoxib at least 3days per week were considered NSAID users. Patients were categorized as non-users, former users, new users, or longer-term users based on survey responses. NSAID use was also categorized by type: any NSAIDs, aspirin, and/or non-aspirin NSAIDs. Age, race/ethnicity, smoking status, education, income, alcohol use, and Charlson comorbidity index score were included in the multivariate analysis as risk factors for AMD. A total of 51 371 men were included. Average follow-up time was 7.4 years. There were 292 (0.6%) and 1536 (3%) cases of exudative and nonexudative AMD, respectively. Longer-term use of any NSAID was associated with lower risk of exudative AMD (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.96, P= .029). New users of any NSAIDs (HR= 0.79, 95% CI 0.68-0.93, P= .0039) and aspirin (HR= 0.82, 95% CI 0.70-0.97, P= .018) had a lower risk of nonexudative AMD, although this trend did not persist in longer-term users. The relationship between exudative or nonexudative AMD and the remaining categories of NSAID use were not significant. The overall impact of NSAIDs on AMD incidence is small; however, the lower risk of exudative AMD in longer-term NSAID users may point to a protective effect and deserves further study as a possible mechanism to modulate disease risk.

Pharmacological potential of sulfated polygalactopyranosyl-fucopyranan from the brown seaweed Sargassum wightii

A sulfated polygalactopyranosyl-fucopyranan characterized as ∙∙∙∙ → 1)-α-Fucp-(2SO3−)-(3 → 1)-α-Fucp-(2SO3−)-(4 → 1)-β-Galp-(4 → 1)-β-Galp-(4 → ∙∙∙∙ was isolated from the brown seaweed Sargassum wightii and evaluated for pharmacological properties with reference to antioxidant, anti-inflammatory, antidiabetic, and antihypertensive activities using different in vitro models. The sulfated polygalactopyranosyl-fucopyranan displayed potential di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+) radical scavenging, and Fe2+ ion chelating activities (IC90 ~ 1 mg mL−1). The studied polysaccharide displayed higher anti-inflammatory selectivity towards inducive pro-inflammatory enzyme cyclooxygenase-2 (COX-2, IC90 1.13 mg mL−1) than constitutive cyclooxygenase-1 (COX-1, IC90 > 1.20 mg mL−1) resulting in greater selectivity index (IC90 COX-2/COX-1, 0.93) than synthetic non-steroidal anti-inflammatory drug aspirin (0.88) and also showed potent lipoxygenase-5 inhibition (LOX-5, IC90 1.02 mg mL−1). The studied polysaccharide displayed significantly higher (P < 0.05) antidiabetic properties compared to the antidiabetic agents acarbose and diprotein-A in terms of α-amylase (IC90 0.93 mg mL−1), α-glucosidase (IC90 1.48 mg mL−1), and dipeptidyl peptidase-4 (IC90 0.11 mg mL−1) enzyme inhibition potentials. The sulfated polygalactopyranosyl-fucopyranan also displayed potential antihypertensive activity with reference to angiotensin-converting enzyme-I inhibitory activity (IC90 0.2 mg mL−1). Extensive spectroscopic experiments in conjugation with monosaccharide compositional analysis attributed (1 → 3)-linked α-fucopyranose units in the polygalactofucan chain with C-2 sulfation and C-4 substituents as O-acetyl/O-methyl/(1 → 4)-linked β-galactopyranose. The previously undescribed sulfated polygalactopyranosyl-fucopyranan could function as a potential pharmacophore lead against inflammation, type 2 diabetics, hypertension and utilization as natural antioxidant.

Advances in the Therapy of Bleeding Peptic Ulcer

Peptic ulcer bleeding remains an important medical emergency. Important recent advances are reviewed. These include further support for a more restrictive transfusion strategy aiming for a target haemoglobin of 70-90 g/L. The Glasgow-Blatchford score remains the most useful assessment score for identifying the lowest risk patients suitable for outpatient management and predicting the need for intervention. Newer scores such as the AIMS65 and Progetto Nazionale Emorragia Digestive score (PNED) may be more accurate in predicting mortality. Pre-endoscopy erythromycin improves outcomes and is underused. A new disposable Doppler probe appears to provide more accurate determination of both rebleeding risk and the success of endoscopic therapy than purely visual guidance. Over-the-scope clips and haemostatic powders appear to have some role as endoscopic salvage therapies. Non- H. pylori, non-aspirin/non-steroidal anti-inflammatory drug (NSAID) ulcers contribute to an increasing percentage of bleeding peptic ulcers and are associated with a high rebleeding rate. The optimal management of these ulcers remains to be determined.

Mutation of TGFβ-RII eliminates NSAID cancer chemoprevention.

Non-steroidal anti-inflammatory drugs (NSAIDs) exhibit anti-neoplastic (chemoprevention) activity for sporadic cancers and the hereditary cancer predisposition Lynch syndrome (LS/HNPCC). However, the mechanism of NSAID tumor suppression has remained enigmatic. Defects in the core mismatch repair (MMR) genes MSH2 and MLH1 are the principal drivers of LS/HNPCC. Previous work has demonstrated that the villin-Cre+/−Msh2flox/flox (VpC-Msh2) mouse is a reliable model for LS/HNPCC intestinal tumorigenesis, which is significantly suppressed by treatment with the NSAID aspirin (ASA) similar to human chemoprevention. Here we show that including a TGFβ receptor type-II (Tgfβ-RII) mutation in the VpC-Msh2 mouse (villin-Cre+/−Msh2flox/floxTgfβ−RIIflox/flox) completely eliminates NSAID tumor suppression. These results provide strong genetic evidence that TGFβ signaling and/or effectors participate in NSAID-dependent anti-neoplastic processes and provide fresh avenues for understanding NSAID chemoprevention and resistance.

Associations between Use of Specific Analgesics and Concentrations of Amyloid-β 42 or Phospho-Tau in Regions of Human Cerebral Cortex.

Analgesics are commonly used by older adults, raising the question of whether their use might contribute to dementia risk and neuropathologic changes of Alzheimer's disease (AD). The Adult Changes in Thought (ACT) study is a population-based study of brain aging and incident dementia among people 65 years or older who are community dwelling and not demented at entry. Amyloid-β (Aβ)42 and phospho-tau were quantified using Histelide in regions of cerebral cortex from 420 brain autopsies. Total standard daily doses of prescription opioid and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) exposure during a defined 10-year exposure window were identified using automated pharmacy dispensing data and used to classify people as having no/low, intermediate, or high exposure. People with high NSAID exposure had significantly greater Aβ42 concentration in middle frontal gyrus and superior and middle temporal gyri, but not inferior parietal lobule; no Aβ42 regional concentration was associated with prescription opioid usage. People with high opioid usage had significantly greater concentration of phospho-tau in middle frontal gyrus than people with little-to-no opioid usage. Consistent with our previous studies, findings suggest that high levels of NSAID use in older individuals may promote Aβ42 accumulation in cerebral cortex.

Maintenance use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk.

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may have a preventive effect against prostate cancer. However, evidence is limited and still controversial, especially considering non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). Swedish nationwide population-based cohort study including all long-term (≥180 days) adult male users of aspirin (n = 419,931) or NSAIDs (n = 223,437) followed from the first dispense date until the first cancer diagnosis, death or 31 December 2012, whichever occurred first. The risk of prostate cancer was measured as standardized incidence ratios (SIR) and 95% confidence intervals (CI), assessing duration of use, age and concomitant statins intake, comparing to the general male background population of the same age in Sweden. The overall SIR suggests that maintenance use of aspirin decreases the risk of prostate cancer (SIR = 0.87, 95% CI 0.85-0.88), in particular if used ≥5 years (SIR = 0.31, 95% CI 0.30-0.32). The overall risk was decreased (SIR = 0.87, 95% CI 0.85-0.90) among other NSAIDs users, and again in particular among longer-term users (≥3 years) with SIR = 0.58 (95% CI 0.53-0.63). When statins users were excluded from all aspirin users, there was no remaining association with prostate cancer (SIR = 0.99, 95% CI 0.96-1.02), only if taken ≥5 years (SIR = 0.31, 95% CI 0.29-0.34). For non-aspirin NSAIDs users, the protective effect remained after exclusion of statins users (SIR = 0.92, 95% CI 0.88-0.95). This population-based cohort study provides evidence for a protective effect of aspirin and other NSAIDs against prostate cancer, in particular for longer durations of use, yet concomitant use of statins strongly influences the risk among aspirin users.

Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies

Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from theHealth Professionals Follow-up Study and Nurses' HealthStudy using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin,in396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were notassociated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; Ptrend 0.81; comparing participants in thehighest quintile with those in the lowest quintile of plasma salicylurate). Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies.

Anti-inflammatory drug use and progressive supranuclear palsy

BackgroundAnti-inflammatory drug use, particularly ibuprofen, has been associated with a lower risk of Parkinson's disease. Microglial activation and inflammatory cytokine expression have been shown to be pathological features of progressive supranuclear palsy. We examined the association between NSAID use and risk of PSP, disease severity and age at onset. MethodsThe ENGENE-PSP multicenter case-control study recruited incident PSP cases who met the NINDS-PSP Society diagnostic criteria and age-, sex- and race-matched controls primarily from the same geographical areas. All subjects underwent standardized interviews to obtain data on demographics, residential history, medication history and lifetime occupational history. NSAID use was specifically queried by telephone interview using a standardized questionnaire. ResultsInformation was obtained on anti-inflammatory drug exposure in 276 cases and 278 controls. No association was found between NSAID exposure and risk of PSP, age at onset or rate of change of UPDRS motor subscale, PSP Rating Scale or Mattis Dementia Rating Scale scores. This lack of association persisted when NSAID exposure was measured considering any NSAIDs, ibuprofen only, ASA only or non-ibuprofen, non-aspirin NSAIDs. ConclusionsThese results do not suggest an important association between NSAID use and PSP occurrence or expression. Despite the large size of our study, confidence intervals were wide. To rule out small associations, very large sample sizes will be required.

Effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials

BackgroundBeneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established.MethodsOur objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA).ResultsIn patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80–160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70–0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44–0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300–325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68–1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59–0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33–0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal.ConclusionOur findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.

Association between nonsteroidal anti-inflammatory drugs use and risk of central nervous system tumors: a dose-response meta analysis.

Although studies have examined the association between nonsteroidal anti-inflammatory drugs (NSAIDs) use and central nervous system (CNS) tumors risk, the results are inconclusive. Here, we conducted a dose-response meta-analysis in order to investigate the correlation between NSAIDs use and CNS tumors risk. Up to July 2017, 12 studies were included in current meta-analysis. NSAIDs use was significantly associated with a lower risk of CNS tumors. Furthermore, non-aspirin NSAIDs or aspirin use are significantly associated with a lower risk of CNS tumors. Additionally, NSAIDs use was associated with significantly a lower risk of glioma, glioblastoma but not meningioma. Subgroup analysis showed consistent findings. Furthermore, a significant dose-response relationship was observed between NSAIDs use and CNS tumors risk. Increasing cumulative 100 defined daily dose of NSAIDs use was associated with a 5% decrement of CNS tumors risk, increasing NSAIDs or non-aspirin NSAIDs or aspirin use (per 3 prescriptions increment) was associated with a 7%, 7%, 10% decrement of CNS tumors risk, increasing per 2 year of duration of NSAIDs or non-aspirin NSAIDs or aspirin use was associated with a 6%, 8%, 6% decrement of CNS tumors risk. Considering these promising results, NSAIDs use might provide helpful for reducing CNS tumors risk. Large sample size and different ethnic population are warranted to validate this association.