This Month in Gastroenterology

Objective To evaluate the relation between Parkinson’s disease and prior use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large cohort of men.Design Case-control analysis nested in the Physicians’ Health Study....

Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status ( Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

BACKGROUND: In Thailand, 67.2% of the population widely uses analgesics including nonsteroidal anti-inflammatory drugs (NSAIDs), which may lead to serious side effects. However, the information of regular NSAIDs used in Thailand is still limited.METHODS: A mixed method cross-sectional study was conducted. Quantitative data were collected using questionnaires to determine the prevalence and factors associated with regular NSAID use. The qualitative study was conducted using group and in-depth interviews to determine the knowledge, attitudes and practices of NSAID users.RESULTS: Of 771 participants, the prevalence of NSAID use was 31.1 and regular NSAID use was 7.4. Age, pain at the hips or thighs and pain score were independent factors associated with regular NSAID use. The qualitative study indicated that the use of NSAIDs was influenced by drug effectiveness, sources of NSAIDs and consideration of benefits and risks of the drugs.CONCLUSION: This was the first report on the prevalence and associated factors of regular NSAID use in Thailand. In this community, nonprescribed NSAIDs might cause some serious side effects and undesirable drug interaction. Information on side effects of pain medications should be disseminated to the public including guidelines on how to use pain medications.

The role of aspirin in the prevention of pancreatic cancer: A nested case-control study in the UK Biobank

<div>Abstract<p>A low-meat diet and regular use of nonsteroidal anti-inflammatory drugs (NSAID) have been associated with decreased mortality among colorectal cancer (CRC) patients. Here, we investigated the association between prediagnosis usual meat consumption and CRC-specific mortality, and whether meat consumption modifies the previously noted association between NSAID use and CRC-specific mortality among women in the California Teachers Study cohort. Women joining the California Teachers Study in 1995-1996 without prior CRC diagnosis, diagnosed with incident CRC during follow-up through December 2007, were eligible for inclusion. Meat intake (frequency and serving size) and NSAID use (aspirin or ibuprofen use) were ascertained via self-administered questionnaires before diagnosis. Vital status and cause of death were determined by linkage with mortality files. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios for death and 95% confidence intervals. Prediagnosis meat consumption was not associated with CRC-specific mortality among 704 CRC patients (and 201 CRC-specific deaths), comparing patients in the lowest consumption tertile (0-5.4 medium-sized servings/wk) to those in the higher consumption tertiles. Regular NSAID use (1-3 times/wk, 4-6 times/wk, daily) versus none was associated with decreased CRC-specific mortality among patients in the lowest meat consumption tertile (hazard ratio, 0.22; 95% CI, 0.06-0.82), but not among patients in the higher meat intake tertiles. The previously observed mortality risk reduction among female CRC patients associated with regular NSAID use was restricted to patients who reported low meat intake before diagnosis. These findings have implications for CRC survivorship and tertiary CRC prevention. Cancer Prev Res; 3(7); 865–75. ©2010 AACR.</p></div>

Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of non-Hodgkin lymphoma (NHL), although previous results have been inconsistent. The current study investigated the effects of regular aspirin or acetaminophen use on non-Hodgkin lymphoma risk among 625 individuals with primary, incident NHL and 2512 age and sex matched hospital controls with non-neoplastic conditions who completed a comprehensive epidemiologic questionnaire. Results indicate that regular aspirin use may be associated with decreased NHL risk among men [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI), 0.65--1.04], but not among women (aOR 0.93, 95% CI, 0.71--1.23). In contrast, regular acetaminophen use was associated with elevated NHL risk among women (aOR 1.71, 95% CI, 1.18--2.50) but not among men (aOR 0.75, 95% CI, 0.48--1.17). Other studies have demonstrated that acetaminophen is associated with transient decreases in DNA repair, and lymphocytes may be particularly susceptible to DNA damage, suggesting a mechanism for the elevated NHL risk observed.

African Americans have the highest colon cancer incidence and mortality rates among all US ethnic groups. Epidemiologic studies suggest that use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a reduced risk of colon cancer, but no study to date with adequate sample size has reported on the association among African Americans. The authors examined the association between NSAID use and risk of colon cancer in a population-based, case-control study in North Carolina that enrolled 731 African-American (294 cases, 437 controls) and 960 White (349 cases, 611 controls) participants between 1996 and 2000. Odds ratios were calculated using unconditional logistic regression for categories of NSAIDs and colon cancer risk. Inverse associations between regular NSAID use and colon cancer were similar for African Americans (odds ratio = 0.41, 95% confidence interval: 0.22, 0.77) and Whites (odds ratio = 0.48, 95% confidence interval: 0.28, 0.83) but stronger for women than men. Inverse associations were slightly weaker for occasional versus regular NSAID use, but they were similar for aspirin and nonaspirin NSAID use. These results add new knowledge suggesting that the protective effect of NSAIDs against colon cancer is similar among African Americans and Whites.

Non-melanoma skin cancer and NSAID use in women with a history of skin cancer in the Women's Health Initiative

Long-Term Use of Acetaminophen, Aspirin, and Other Non-Steroidal Anti-Inflammatory Drugs and Risk of Hematologic Malignancies: Results From the Large, Prospective VITamins and Lifestyle (VITAL) Cohort Study

Background: Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) show indisputable promise as cancer chemoprevention agents. While aspirin and NSAID use have been suggested to lower risk of developing pancreatic cancer, the results of several epidemiological studies are not in consensus. Methods: Using a case-control design, we examined the association between aspirin, NSAID and acetaminophen use and the risk of pancreatic cancer. We enrolled 904 histological or clinically documented pancreatic ductal adenocarcinoma cases, and 1,223 age and gender matched healthy clinic-based controls evaluated at Mayo Clinic from April 2004 and September 2010. All subjects were ≥ 55 years old and self-reported by questionnaire their use of aspirin, NSAIDs, and acetaminophen at ages 41-60, along with extensive epidemiologic and demographic information. Multivariate logistic regression analysis was used to estimate risk of pancreatic cancer after adjusting for potential confounders. Results: The use of aspirin was associated with a decreased risk of pancreatic cancer. The unadjusted odds ratio (OR) associated with aspirin use ≥ 1 day/month, compared with never or < 1 day/month, was 0.79 [95% confidence interval (CI) 0.65. 0.96, p = 0.015]. This effect remained significant [OR 0.71, 95% CI 0.58,0.87, p = 0.0008], after adjusting for the potential confounders of body mass index and smoking status (never, former, current). The inverse relationship was stronger among former smokers (OR 0.61, 95% CI 0.46, 0.82, p =0.0008) than never and current smokers, although there was not a statistically significant interaction (Pintereaction = 0.333). NSAID and acetaminophen use was not associated with the risk of pancreatic cancer. Conclusions: Results from this large case-control study suggest that aspirin use, but not non-aspirin NSAID use, was associated with lower risk of developing pancreatic cancer and was more pronounced among former smokers than never and current smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1902. doi:10.1158/1538-7445.AM2011-1902

The association between the use of nonsteroidal antiinflammatory drugs (NSAID) and large bowel cancer was examined in a hospital-based case-control study of 511 patients with colorectal cancer and 500 age-sex matched control subjects. Regular NSAID use was defined as at least 3 times per week for 1 or more years before the date of hospital admission. Odds ratios (OR) were calculated by the duration of NSAID use and according to the medical reasons given for taking NSAIDs. The prevalences of regular NSAID use were 15% for male patients, 8% for female patients, and 20% for control subjects. Overall, NSAID use was associated with a statistically significant risk reduction in men (OR = 0.64; 95% confidence interval [CI], 0.42-0.97) and in women (OR = 0.32; 95% CI, 0.18-0.57). The estimate decreased with duration among men but increased with duration among women. The risk reduction among patients who took NSAIDs to prevent heart disease was 0.67 (95% CI, 0.38-1.13) for men and 0.43 (95% CI, 0.12-1.59) for women. For treating headache pain, the OR was 0.5 (95% CI, 0.23-1.09) for men and 0.64 (95% CI, 0.25-1.62) for women. The use of NSAID was not found to be associated with the stage of cancer at diagnosis. The OR for daily acetaminophen use was 1.07 (95% CI, 0.35-3.23) for men and 0.59 (95% CI, 0.27-1.25) for women. The regular use of NSAIDs was associated with an overall significant risk reduction of colorectal cancer in men and in women. Among female patients, the greater protective effect associated with short term NSAID use compared with long term NSAID use may reflect a sampling bias.

Background: Aspirin may help to prevent dementia through its antiplatelet and anti-inflammatory effects, but findings from previous studies are mixed. Considering the length of the preclinical phase of dementia, early initiation of regular aspirin use may be more protective against dementia than later initiation. In this study, we explored the association of regular aspirin use initiated during and after midlife with the risk of dementia. Methods: Using data from 1996 to 2013 on 10,398 ARIC participants, we assessed the association of self-reported prior duration of regular aspirin use which was collected during 1996-1998 (as the baseline of this study) with incident dementia after the baseline. Dementia cases were identified based on: in-person dementia ascertainment from 2011 to 2013; the Telephone Interview for Cognitive Status (TICS) or informant interviews on dementia; and hospital discharge codes/death certificate code by surveillance through 2013. The relative hazards of dementia across categories of the duration of regular aspirin use prior to baseline (<2 years, 2 to <5 years, and ≥ 5 years) were compared to no regular use by Cox proportional hazard models. We adjusted for potential confounders, including demographic variables and major dementia risk factors at baseline. In sensitivity analyses, propensity score weighting was applied. Subgroup analyses were conducted by age, gender, race, APOE, and diabetes status. Results: Participants had a median age of 62 (IQR: 58, 67) at baseline. 55.8% (5,805 of 10,398) were female and 20.6% (2,147 of 10,398) were African American. Lower but non-significant relative hazards (HR) were observed among participants with regular aspirin use for < 2 years (HR: 0.85; 95% CI: 0.69 to 1.04) and ≥ 5 years (HR: 0.87; 95% CI: 0.68 to 1.11), but not for the 2-5 year interval. With propensity score weighting, regular aspirin use < 2 years achieved marginal significance (HR: 0.79; 95% CI: 0.63 to 0.99), while the effect of regular aspirin use ≥ 5 years changed towards null (HR: 1.04; 95%CI: 0.75 to 1.46). Without a prior hypothesis, an interaction was found for diabetes status (p = 0.016) with a significant protective association of ever regular aspirin use compared to no regular use among non-diabetic participants (HR: 0.82; 95%CI: 0.69 to 0.98). Conclusions: We found a non-significant protective association of regular aspirin use at late-middle life with onward incident dementia in a community-dwelling population. Data suggest persons with fewer comorbidities, specifically without diabetes, might be more susceptible to the preventive effect of aspirin use on dementia. Our results are subject to confounding by indication, suggesting the need for additional studies in populations which have different covariate structures than ARIC.

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

Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the development of lung tumors in experimental animals. To the authors' knowledge there are little data regarding whether regular use of NSAIDs reduces the risk of developing lung carcinoma in humans. The association between lung carcinoma risk and regular use of NSAIDs, including aspirin, was evaluated in a hospital-based case-control study of 1038 patients and 1002 controls. The relative risk estimate of lung carcinoma associated with using NSAIDs 3 times a week or more for 1 or more years demonstrated an odds ratio (OR) of 0.68 (95% confidence interval [95% CI], 0.53-0.89). Results were similar when separated by lung histologic type. The association varied by smoking status. The OR was 1.28 (95% CI, 0.73-2.25) in never-smokers and 0.60 (95% CI 0.45-0.80) in ever-smokers. The smoking-specific risk estimates for aspirin were similar to those for all NSAIDs. The results of the current study suggest a possible chemoprotective benefit with the use of NSAIDs among individuals who are former or current smokers.

Gastrointestinal Bleeding in Children Following Ingestion of Low‐dose Ibuprofen