Adherence to Healthy Lifestyle Prior to Infection and Risk of Post-COVID-19 Condition.

Importance: Few modifiable risk factors for post-COVID-19 condition (PCC) have been identified. Objective: To investigate the association between healthy lifestyle factors prior to SARS-CoV-2 infection and risk of PCC. Design, Setting, and Participants: In this prospective cohort study, 32 249 women in the Nurses' Health Study II cohort reported preinfection lifestyle habits in 2015 and 2017. Healthy lifestyle factors included healthy body mass index (BMI, 18.5-24.9; calculated as weight in kilograms divided by height in meters squared), never smoking, at least 150 minutes per week of moderate to vigorous physical activity, moderate alcohol intake (5 to 15 g/d), high diet quality (upper 40% of Alternate Healthy Eating Index-2010 score), and adequate sleep (7 to 9 h/d). Main Outcomes and Measures: SARS-CoV-2 infection (confirmed by test) and PCC (at least 4 weeks of symptoms) were self-reported on 7 periodic surveys administered from April 2020 to November 2021. Among participants with SARS-CoV-2 infection, the relative risk (RR) of PCC in association with the number of healthy lifestyle factors (0 to 6) was estimated using Poisson regression and adjusting for demographic factors and comorbidities. Results: A total of 1981 women with a positive SARS-CoV-2 test over 19 months of follow-up were documented. Among those participants, mean age was 64.7 years (SD, 4.6; range, 55-75); 97.4% (n = 1929) were White; and 42.8% (n = 848) were active health care workers. Among these, 871 (44.0%) developed PCC. Healthy lifestyle was associated with lower risk of PCC in a dose-dependent manner. Compared with women without any healthy lifestyle factors, those with 5 to 6 had 49% lower risk (RR, 0.51; 95% CI, 0.33-0.78) of PCC. In a model mutually adjusted for all lifestyle factors, BMI and sleep were independently associated with risk of PCC (BMI, 18.5-24.9 vs others, RR, 0.85; 95% CI, 0.73-1.00, P = .046; sleep, 7-9 h/d vs others, RR, 0.83; 95% CI, 0.72-0.95, P = .008). If these associations were causal, 36.0% of PCC cases would have been prevented if all participants had 5 to 6 healthy lifestyle factors (population attributable risk percentage, 36.0%; 95% CI, 14.1%-52.7%). Results were comparable when PCC was defined as symptoms of at least 2-month duration or having ongoing symptoms at the time of PCC assessment. Conclusions and Relevance: In this prospective cohort study, pre-infection healthy lifestyle was associated with a substantially lower risk of PCC. Future research should investigate whether lifestyle interventions may reduce risk of developing PCC or mitigate symptoms among individuals with PCC or possibly other postinfection syndromes.

The COronavirus Pandemic Epidemiology (COPE) Consortium: A Call to Action.

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

A Role for Clusterin in Exfoliation Syndrome and Exfoliation Glaucoma?

The multifunctional protein clusterin (CLU) is a secreted glycoprotein ubiquitously expressed throughout the body, including in the eye. Its primary function is to act as an extracellular molecular chaperone, preventing the precipitation and aggregation of misfolded extracellular proteins. Clusterin is commonly identified at fluid-tissue interfaces, and has been identified in most body fluids. It is a component of exfoliation material, and CLU mRNA is reduced in eyes with exfoliation syndrome compared with controls. SNPs located in the CLU genomic region have been associated with Alzheimer disease (AD) at the genome-wide level and several CLU SNPs located in an apparent regulatory region have been nominally associated with XFS/XFG in Caucasians with European ancestry and in south Indians. Interestingly, clusterin associates with altered elastic fibers in human photoaged skin and prevents UV-induced elastin aggregation in vitro. In light of the known geographic risk factors for XFS/XFG, which could include UV light, investigations of CLU-geographic interactions could be of interest. Future studies investigating rare CLU variation and other complex interactions including gene-gene interactions in XFS/XFG cases and controls may also be fruitful. Although CLU has been considered as a therapeutic target in AD, cancer and dry eye, a role for clusterin in XFS/XFG needs to be better defined before therapeutic approaches involving CLU can be entertained.

Sex hormone levels and risk of primary open-angle glaucoma in postmenopausal women.

OBJECTIVE: We evaluated the relation of prediagnostic sex hormone levels in postmenopausal women with primary open-angle glaucoma (POAG) and intraocular pressure (IOP). METHODS: Among postmenopausal participants of the Nurses' Health Study, POAG cases (n = 189; diagnosed 1990-2008) and controls (n = 189) were matched on age, fasting status, and postmenopausal hormone use at blood draw (1989-1990). Plasma concentrations of estrone sulfate, estradiol, testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate were assessed. The primary outcome was POAG; in secondary analyses, among cases only, we evaluated maximum untreated IOP at diagnosis. Multivariable-adjusted logistic/multiple linear regression models were used to evaluate tertiles (Ts) of biomarker levels and the two outcomes, adjusting for various potential confounders. RESULTS: We observed no significant associations of estrone, estradiol, sex hormone binding globulin, or dehydroepiandrosterone sulfate with POAG risk or with maximum IOP at glaucoma diagnosis among cases. Suggestive significant associations were observed with highest testosterone and POAG risk (T3 vs T1 multivariable-adjusted odds ratio 1.84; 95% confidence interval 1.02, 3.33; P trend 0.10). Similarly, for maximum IOP at diagnosis among cases only (mean 8 years after blood draw), higher testosterone was significantly associated with higher IOP (multivariable-adjusted difference in IOP T3 vs T1 2.17 mm Hg; 95% confidence interval 0.34, 3.99; P trend 0.02). CONCLUSIONS: Overall, plasma sex hormone levels in postmenopausal women were not associated with POAG risk; however, a trend of higher testosterone levels being associated with higher POAG risk and higher IOP at diagnosis was observed and needs confirmation.

A survey of preoperative blood tests in primary open-angle glaucoma patients versus cataract surgery patients.

PURPOSE: To investigate biomarker differences in routine preoperative blood tests performed on primary open-angle glaucoma (POAG) case and control patients presenting for anterior segment eye surgery. METHODS: POAG cases and age-related cataract surgery patients (controls) who underwent anterior segment surgery at Massachusetts Eye and Ear from January 2009 through March 2012 were identified by retrospective record review. Patients with diabetes mellitus, secondary glaucoma, and cataract due to trauma or steroid exposure were excluded. Data on demographic features, preoperative ophthalmological and medical diagnosis, blood pressure, anthropometric measures, basic metabolic panel, and complete blood count were extracted from the medical records. Univariate differences in lab values between POAG cases and controls were assessed using unpaired t tests. Multivariate logistic regression analysis was completed to determine the independent associations of biomarkers with POAG. RESULTS: A total of 150 cases and 150 age-related controls were included. In multivariate analysis, higher AG was inversely associated with POAG (odds ratio [OR] = 0.90; 95% confidence interval [CI], 0.80-1.00), and higher Cl- level was positively associated with POAG (OR = 1.15; 95% CI, 1.02-1.29). The lower AG in POAG patients could be explained by higher IgG levels as the available data in post hoc analysis showed a nonsignificant trend toward higher IgG in cases compared to controls (17 vs 23; 1142 ± 284 mg/dl vs 1028 ± 291 mg/dl; P = 0.22). Furthermore, in multivariable analysis, a higher red blood cell count was also associated with POAG (OR = 1.91; 95% CI, 1.11-3.28). CONCLUSIONS: Patients with POAG presenting for anterior segment surgery had a lower AG compared to age-related cataract surgery patients. The etiology of this reduced gap is unclear but the possible contribution of IgG warrants further exploration. The etiology of higher red blood cell counts in POAG cases is unknown and deserves further exploration.

Clinical characteristics of acute appendiceal diverticulitis.

PURPOSE: Diverticulitis of vermiform appendix is known as a rare cause of acute appendicitis, most of which are diagnosed after surgery. We compared appendiceal diverticulitis with acute appendicitis to study the clinical characteristics of appendiceal diverticulitis. METHODS: Among 1,029 patients who received appendectomy from January 2009 to May 2011, 38 patients with appendiceal diverticulitis (diverticulitis group) were compared with 98 randomly collected patients with acute appendicitis (appendicitis group) during the same period. Patients' characteristics, clinical features, laboratory findings, operative findings, and postoperative course were compared between the two groups. RESULTS: Thirty-eight patients (3.7%) were pathologically diagnosed with acute appendiceal diverticulitis among 1,029 cases of appendectomy. The mean age of patients in the diverticulitis group was significantly older than that of the appendicitis group (49.0 ± 15.2 years vs. 25.4 ± 14.2 years, P < 0.05). Mean duration of preoperative symptoms was longer in the diverticulitis group (3.6 ± 3.8 days vs. 1.8 ± 3.2 days, P < 0.05). The site of abdominal pain, fever, signs of localized peritonitis, accompanying gastrointestinal symptoms, and white blood cell count showed no differences between the two groups. Twenty-five patients (65.8%) of the diverticulitis group and 10 patients (10.2%) of the appendicitis group showed perforation of appendix (P < 0.05). Mean operating time and postoperative hospital stay were longer in the diverticulitis group (55.3 ± 28.8 minutes vs. 41.4 ± 17.8 minutes, 6.8 ± 3.4 days vs. 4.9 ± 1.5 days, P < 0.05). CONCLUSION: Acute diverticulitis of the appendix can be classified into quite different disease entities compared with acute appendicitis. Regarding high rates of perforation, immediate surgical treatment is needed for patients with a high index of suspicion of acute diverticulitis of the appendix.

Small-cell neuroendocrine carcinoma of the breast.

A small-cell carcinoma is one of the histologic subtypes of primary neuroendocrine carcinomas of the breast. A small-cell carcinoma is a rare entity of the breast and exhibits similar morphologic features as neuroendocrine tumors of the gastrointestinal tract and lung. We present the imaging and pathologic findings of a primary small-cell neuroendocrine carcinoma of the breast. This is the first report of a primary small-cell carcinoma arising from the breast in Korea.

Endothelial nitric oxide synthase gene variants and primary open-angle glaucoma: interactions with hypertension, alcohol intake, and cigarette smoking.

OBJECTIVE: To evaluate whether an association between risk of any of the factors of hypertension, alcohol intake, and cigarette smoking and the risk of primary open-angle glaucoma (POAG) depended on nitric oxide synthase 3 (NOS3) gene variants. METHODS: Two functional single-nucleotide polymorphisms (SNPs) (T-786C [rs2070744] and Glu298Asp [rs1799983]) and 2 tagging SNPs (rs7830 and rs3918188) were evaluated in nested case-control studies from the Nurses' Health Study (1980-2002) and the Health Professionals' Follow-up Study (1986-2002). Participants were 40 years of age or older and white, and were followed up biennially. We included 527 incident case patients with POAG and 1539 control participants, matched by cohort, age, and eye examination at the matched case patients' diagnosis dates. Cohort-specific relative risks were estimated using multivariable conditional logistic regression and were pooled using meta-analytic methods. RESULTS: The association between hypertension and POAG depended on T-786C SNP variants. Compared with TT homozygotes without hypertension, the TT homozygotes with hypertension were at significantly higher risk of POAG (relative risk,1.45 [95% confidence interval, 1.01-2.08]); however, among carriers of the variant (C) allele, hypertension was not associated with POAG (P interaction = .007). Similarly, compared with CC homozygotes with the rs7830 tagging SNP who never smoked, CC homozygotes who were past or current smokers were at significantly higher risk of POAG (relative risk, 1.63 [95% confidence interval, 1.15-2.31]); however, among carriers of the variant allele (A), smoking was not associated with POAG (P interaction = .004). Interactions were not observed with alcohol intake. CONCLUSIONS: The associations between hypertension and cigarette smoking in relation to POAG depended on NOS3 SNPs.

Total antioxidant capacity of diet in relation to cognitive function and decline.

BACKGROUND: Epidemiologic evidence on the association of individual antioxidant vitamins and cognition is inconsistent. OBJECTIVE: We evaluated the total antioxidant capacity of diets on the basis of the ferric-reducing antioxidant power (FRAP) assay in relation to cognition in older women. DESIGN: Starting in 1995, we used a telephone-based cognitive assessment to evaluate cognitive function on 3 occasions at 2-y intervals in 16,010 participants aged ≥70 y in the Nurses' Health Study. In 1980, and every 4 y thereafter, we collected dietary information by using a semiquantitative food-frequency questionnaire (FFQ). For each participant, we combined FFQ data with food- and supplement-specific FRAP values to obtain FRAP scores; these data were averaged from 1980 until the initial cognitive interview to reflect long-term diets. We used multivariable-adjusted linear regression to estimate mean differences in initial cognitive function and slopes of decline across quintiles of FRAP scores. RESULTS: In multivariable-adjusted models, there was an association between higher total FRAP scores and better cognitive function at the first interview (P for trend = 0.003 for global scores with all cognitive tests combined; mean difference = 0.04 standard units; 95% CI: 0.01, 0.08 standard units, comparing the highest and lowest quintiles). A weaker association was observed for dietary FRAP scores (excluding supplements) and initial global scores (P for trend = 0.05). However, prospective analyses of cognitive decline indicated no associations with total or dietary FRAP scores in models adjusted for multiple potential confounders (P for trend = 0.3 and 0.5 for global scores, respectively). CONCLUSION: We observed no clear evidence of a consistent association between the total antioxidant capacity of diets and cognition in this cohort of older women.

Antioxidant intake and risks of rheumatoid arthritis and systemic lupus erythematosus in women.

Antioxidants may protect against development of rheumatoid arthritis or systemic lupus erythematosus by combating oxidative stress. The authors identified and confirmed incident cases of rheumatoid arthritis and systemic lupus erythematosus among 184,643 US women followed in the Nurses' Health Study and Nurses' Health Study II cohorts in 1980-2004. Semiquantitative food frequency questionnaires assessed intakes of vitamins A, C, and E and alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin from foods and supplements. The authors examined total antioxidant intake by calculating a "ferric-reducing ability of plasma" score, a new method for quantifying the total antioxidant effect of a food based on the reduction of ferric to ferrous iron by antioxidants. Cumulative updated total energy-adjusted dietary intakes were used. Associations between intake of each nutrient and incident rheumatoid arthritis and systemic lupus erythematosus were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results from the cohorts were pooled meta-analytically by using random-effects models. The authors identified 787 incident rheumatoid arthritis cases and 192 systemic lupus erythematosus cases for whom prospective dietary information was available. In these large, prospective cohorts of women, antioxidant intake was not associated with the risk of developing either rheumatoid arthritis or systemic lupus erythematosus.

Lifestyle, nutrition, and glaucoma.

The only proven strategy to prevent primary open-angle glaucoma (POAG) is the use of ocular hypotensive therapy among people diagnosed with ocular hypertension. In this review, various modifiable lifestyle factors, such as exercise, diet, and cigarette smoking, that may influence intraocular pressure and that have been studied in relation to the risk of developing POAG are discussed. Epidemiologic studies on lifestyle factors are few, and the current evidence suggests that there are no environmental factors that are clearly associated with POAG; however, a few factors merit further study. This review also outlines future directions for research into the primary prevention of POAG.

Dietary fat intake and cognitive decline in women with type 2 diabetes.

OBJECTIVE: Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications-both associated with cognitive decline-may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes. RESEARCH DESIGN AND METHODS: Beginning in 1995-1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged >or=70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake. RESULTS: Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI -0.24 to -0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis. CONCLUSIONS: These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes.

Low dose aspirin and cognitive function in the women's health study cognitive cohort.

OBJECTIVE: To determine whether low dose aspirin protects women aged 65 or more against cognitive decline. DESIGN: Cohort study within both arms of the women's health study, a randomised, double blind, placebo controlled trial of low dose aspirin for the primary prevention of cardiovascular disease and cancer, 1992-5. SETTING: Women's health study, 1998-2004. PARTICIPANTS: 6377 women aged 65 or more. INTERVENTIONS: Low dose aspirin (100 mg on alternate days) or placebo for a mean of 9.6 years. MAIN OUTCOME MEASURES: Women had three cognitive assessments at two year intervals by telephone. The battery to assess cognition included five tests measuring general cognition, verbal memory, and category fluency. The primary prespecified outcome was a global score, averaging performance across all tests. The key secondary outcome was a verbal memory score, averaging performance on four measures of verbal memory. RESULTS: At the initial assessment (mean 5.6 years after randomisation) cognitive performance in the aspirin group was similar to that of the placebo group (mean difference in global score -0.01, 95% confidence interval -0.04 to 0.02). Mean decline in the global score from the first to the final cognitive assessment was also similar in the aspirin compared with placebo groups (mean difference 0.01, -0.02 to 0.04). The risk of substantial decline (in the worst 10th centile of decline) was also comparable between the groups (relative risk 0.92, 0.77 to 1.10). Findings were similar for verbal memory; however, a 20% lower risk was observed for decline in category fluency with aspirin (relative risk 0.80, 0.67 to 0.97). CONCLUSION: Long term use of low dose aspirin does not provide overall benefits for cognition among generally healthy women aged 65 or more.

Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women.

PURPOSE: To study the relation between type 2 diabetes mellitus (T2DM) and incident primary open-angle glaucoma (POAG) in women. DESIGN: Prospective cohort analysis. PARTICIPANTS: Seventy-six thousand three hundred eighteen women enrolled in the Nurses' Health Study (NHS). METHODS: Women enrolled in the NHS from 1980 to 2000 were observed. Eligible participants were at least 40 years old, did not have POAG at baseline, and reported receiving eye examinations during follow-up. Potential confounders were assessed on biennial questionnaires, and a diagnosis of T2DM was confirmed on a validated supplemental questionnaire. During follow-up, 429 self-reported POAG cases confirmed by medical chart review were identified. MAIN OUTCOME MEASURES: Multivariable rate ratios (RRs) of POAG and associated 95% confidence intervals (CIs) obtained from proportional hazards models. RESULTS: After controlling for age, race, hypertension, body mass index, physical activity, alcohol intake, smoking, and family history of glaucoma, T2DM was positively associated with POAG (RR = 1.82 [95% CI = 1.23-2.70]). Nonetheless, the association did not strengthen with longer duration of diabetes: RR = 2.24 (95% CI = 1.31-3.84) for duration < 5 years versus RR = 1.54 (95% CI = 0.90-2.62) for duration > or = 5 years). In secondary analyses, to evaluate the potential for detection bias we controlled for additional factors such as the number of eye examinations, but T2DM remained positively associated with POAG. CONCLUSION: Type 2 diabetes mellitus is associated with an increased risk of POAG in women.

Decreased identification rate of sentinel lymph node after neoadjuvant chemotherapy.

We prospectively studied the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy by comparing the identification rate and the false-negative rate (FNR) with the results obtained from the patients without chemotherapy. From October 2001 to March 2003, a total of 284 consecutive patients who underwent SLNB and axillary lymph node dissection (ALND) at the Center for Breast Cancer, National Cancer Center were enrolled. Of the 284 patients, 54 underwent neoadjuvant chemotherapy prior to operation. The sentinel lymph node (SLN) was mapped by radioactive colloid alone or in combination with blue dye. All SLNs were evaluated by 2 mm serial sections after hematoxylin-eosin staining. The overall SLN identification rate was 91.9% (261/284): 72.2% (39/54) of the patients after chemotherapy and 96.5% (222/230) of the patients without chemotherapy. These results suggest that preoperative chemotherapy significantly affects lymphatic mapping ( p< 0.001). Among the patients with chemotherapy, there were 3 false negatives in 39 successfully mapped tumors, yielding an FNR of 11.1% (3/27), a negative prediction value (NPV) of 80.0% (12/15), and an accuracy of 92.3% (36/39). There were 10 false negatives among 222 successfully detected patients without chemotherapy, yielding an FNR of 9.9% (10/101), an NPV of 92.4% (121/131), and an accuracy of 95.5% (212/222). These results were not statistically different when compared ( p > 0.05). Although the SLN identification rate significantly decreased after neoadjuvant chemotherapy, SLNB could accurately predict axillary status. Thus SLNB can be an alternative to ALND even after neoadjuvant chemotherapy in cases of successful identification of the SLN.

Sentinel lymph node biopsy after neoadjuvant chemotherapy.

BACKGROUND: We surveyed single-center and multi-center studies pertaining to sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy to compare the results with those of our current study to evaluate the feasibility and accuracy of SLNB after neoadjuvant chemotherapy. METHODS: From October 2001 to July 2003, 80 patients who had neoadjuvant chemotherapy underwent curative surgery and axillary lymph node dissection (ALND) after SLNB at the Center for Breast Cancer, National Cancer Center. A MEDLINE search was performed using the keywords breast cancer, sentinel lymph node biopsy, and neoadjuvant chemotherapy. RESULTS: Our results showed that 42 (52.6%) of 80 patients had downstaging of the primary tumor; 9 patients (11.3%) had pathologic complete response (pCR) and 33 (41.3%) had pathologic partial response (pPR). 26 patients (32.5%) showed complete axillary clearance after neoadjuvant chemotherapy. Among them, 5 patients (6.3%) revealed pCR of both the primary tumor and axillary metastasis. SLNB was successful in 61 of 80 patients (76.3%) and there were 3 false negatives, yielding a false negative rate (FNR) of 7.3% (3/41), a negation prediction value (NPV) of 87.0%(20/23), and an accuracy of 95.1% (58/61). Thirteen out of 16 studies retrieved by to MEDLINE pertaining SLNB after neoadjuvant chemotherapy concluded its feasibility and accuracy with a identification rate of 82%-100% and a FNR of 17-100%. CONCLUSION: Most studies, including ours, concluded that SLNB after neoadjuvant chemotherapy is accurate and could be an alternative to ALND.

A prospective study of aspirin use and the risk of pancreatic cancer in women.

BACKGROUND: In vitro experiments and limited animal studies suggest that aspirin and nonsteroidal anti-inflammatory drugs may inhibit pancreatic carcinogenesis. Because few studies have examined the association between aspirin use and pancreatic cancer in humans and the results have been inconsistent, we examined the relationship between aspirin use and the development of pancreatic cancer in the Nurses' Health Study. METHODS: Among 88 378 women without cancer at baseline, we documented 161 cases of pancreatic cancer during 18 years of follow-up. Aspirin use was first assessed at baseline in 1980 and updated biennially thereafter. All statistical tests were two-sided. RESULTS: Participants were classified according to history of aspirin use. In a multivariable analysis, the risk of pancreatic cancer was not associated with current regular aspirin use (defined as two or more standard tablets per week; relative risk [RR] = 1.20, 95% confidence interval [CI] = 0.87 to 1.65), compared with use of fewer than two tablets per week. Increasing duration of regular aspirin use, compared with non-use, was associated with a statistically significant increase in risk: Women who reported more than 20 years of regular aspirin use had an increased risk of pancreatic cancer (RR = 1.58, 95% CI = 1.03 to 2.43; P(trend) =.01). Among women who reported aspirin use on at least two of three consecutive biennial questionnaires compared with consistent non-users of aspirin, the risk increased with dose (one to three tablets per week: RR = 1.11, 95% CI = 0.70 to 1.76; four to six tablets per week: RR = 1.29, 95% CI = 0.70 to 2.40; seven to 13 tablets per week: RR = 1.41, 95% CI = 0.76 to 2.61; and > or = 14 tablets per week: RR = 1.86, 95% CI = 1.03 to 3.35) (P(trend) =.02). CONCLUSION: Extended periods of regular aspirin use appear to be associated with a statistically significantly increased risk of pancreatic cancer among women.