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Voutsinas J.,University of Hawaii at Manoa | Wilkens L.R.,University of Hawaii at Manoa | Franke A.,University of Hawaii at Manoa | Vogt T.M.,Kaiser Permanente | And 3 more authors.
Gut | Year: 2013

Objective: Heterocyclic amines (HAA) are animal carcinogens that are present in meat cooked at high temperature and in tobacco smoke. These compounds require activation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase-2 (NAT2) before they can damage DNA. This study tested the hypotheses that well-done meat and cigarette smoking increase the risk of adenoma, the precursor to most colorectal cancers, especially in individuals with rapid CYP1A2 and rapid NAT2 activities. Design: An endoscopy-based case-control study of adenoma was conducted among Caucasians, Japanese and native Hawaiians to test this hypothesis. The overall diet and consumption of well-done meat cooked by various high-temperature methods were assessed by interview in 1016 patients with a first adenoma and 1355 controls with a normal endoscopy. A caffeine test was used to assess CYP1A2 and NAT2 activities in 635 cases and 845 controls. Logistic regression was used to account for matching factors and potential confounders. Results: Smoking was associated with an increased risk of adenoma. Weak non-significant elevated OR were observed for the main effects of HAA intakes or NAT2 activity. However, the combined effects of HAA intakes and NAT2 activity were statistically significant. Subjects in both the upper tertiles of NAT2 activity and HAA intake were at increased risk of adenoma compared with subjects in the lower tertiles of NAT2 activity and exposure (2-amino-3,4,8-dimethylimidazo[4,5-f] quinoxaline intake OR 1.70, 95% CI I 1.06 to 2.75; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake OR 1.91, 95% CI 1.16 to 3.16; and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine intake OR 2.14, 95% CI 1.31 to 3.49). Conclusion: The data suggest that rapid N-acetylators with high HAA intake may be at increased risk of adenoma.

Oken M.M.,University of Minnesota | Hocking W.G.,Marshfield Clinic Research Foundation | Kvale P.A.,Ford Motor Company | Andriole G.L.,Washington University in St. Louis | And 22 more authors.
JAMA - Journal of the American Medical Association | Year: 2011

Context: The effect on mortality of screening for lung cancer with modern chest radiographs is unknown. Objective: To evaluate the effect on mortality of screening for lung cancer using radiographs in the Prostate, Lung, Colorectal, andOvarian (PLCO) Cancer Screening Trial. Design, Setting, and Participants: Randomized controlled trial that involved 154 901 participants aged 55 through 74 years, 77 445 of whom were assigned to annual screenings and 77 456 to usual care at 1 of 10 screening centers across the United States between November 1993 and July 2001. The data from a subset of eligible participants for the National Lung Screening Trial (NLST), which compared chest radiograph with spiral computed tomographic (CT) screening, were analyzed. Intervention: Participants in the intervention group were offered annual posteroanterior view chest radiograph for 4 years. Diagnostic follow-up of positive screening results was determined by participants and their health care practitioners. Participants in the usual care group were offered no interventions and received their usual medical care. All diagnosed cancers, deaths, and causes of death were ascertained through the earlier of 13 years of follow-up or until December 31, 2009. Main Outcome Measures: Mortality from lung cancer. Secondary outcomes included lung cancer incidence, complications associated with diagnostic procedures, and all-cause mortality. Results: Screening adherence was 86.6% at baseline and 79% to 84% at years 1 through 3; the rate of screening use in the usual care group was 11%. Cumulative lung cancer incidence rates through 13 years of follow-up were 20.1 per 10 000 personyears in the intervention group and 19.2 per 10 000 person-years in the usual care group (rate ratio [RR]; 1.05, 95% CI, 0.98-1.12). A total of 1213 lung cancer deaths were observed in the intervention group compared with 1230 in usual care group through 13 years (mortality RR, 0.99; 95% CI, 0.87-1.22). Stage and histology were similar between the 2 groups. The RR of mortality for the subset of participants eligible for the NLST, over the same 6-year follow-up period, was 0.94 (95% CI, 0.81-1.10). Conclusion Annual screening with chest radiograph did not reduce lung cancer mortality compared with usual care. Trial Registration: clinicaltrials.gov Identifier: NCT00002540. ©2011 American Medical Association. All rights reserved.

Schoen R.E.,University of Pittsburgh | Pinsky P.F.,U.S. National Cancer Institute | Weissfeld J.L.,University of Pittsburgh | Yokochi L.A.,Pacific Health Research and Education Institute | And 6 more authors.
Gastrointestinal Endoscopy | Year: 2012

Background and Objective: Diagnosis of colorectal cancer after negative findings on endoscopic evaluation raises concern about the effectiveness of endoscopic screening. We contrast screening-detected cancers with cancers not detected by screening among participants assigned to flexible sigmoidoscopy (FSG) in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to determine the reasons for the lack of detection of prevalent lesions. Design: Cancers detected within 1 year of a screening FSG with abnormal findings were classified as screening detected. All other cancers were categorized, based on cancer stage and years until detection, as either not detectable or prevalent but not detected at the time of screening. Setting/Patients: A total of 77,447 subjects in the multicenter PLCO trial. Main Outcome Measurements: A total of 977 colorectal cancers were diagnosed with a mean follow-up of 11.5 years. Results: A total of 243 (24.9%) cancers were screening detected, 470 (48.1%) were not detectable at screening, and 264 (27.0%) were considered prevalent but not detected. Among prevalent nondetected lesions, 35.6% (n = 94) were attributed to problems in patient compliance (58 never screened, 34 delayed colonoscopy follow-up, and 2 inadequate bowel preparation), 43.9% (n = 116) were attributable to a limitation in the FSG procedure (97 beyond the reach of the sigmoidoscope and 19 inadequate depth of insertion on FSG), and 20.5% (n = 54) were caused by endoscopist limitation (33 missed on FSG, 21 missed at initial colonoscopy) (P <.0001). Had colonoscopy instead of FSG been used for screening, an additional 15.6% and as many as 19.0% of cancers may have been screening-detected. Limitations: These estimates are reasonable approximations, but biological variability precludes precise determinations. Conclusions: Prevalent nondetected cancers were more often attributable to problems with patient compliance or limitations in the FSG procedure than to missed lesions. Colonoscopy instead of FSG could have moderately increased the detection of cancer via screening. © 2012 American Society for Gastrointestinal Endoscopy.

Schoen R.E.,University of Pittsburgh | Pinsky P.F.,U.S. National Cancer Institute | Weissfeld J.L.,University of Pittsburgh | Yokochi L.A.,Pacific Health Research and Education Institute | And 21 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. METHODS:From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. RESULTS:Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P = 0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P = 0.81). CONCLUSIONS:Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and proximal colon) and mortality (distal colon only). (Funded by the National Cancer Institute; PLCO ClinicalTrials.gov number, NCT00002540.) Copyright © 2012 Massachusetts Medical Society. All rights reserved.

Yazdany J.,University of California at San Francisco | Dudley R.A.,University of California at San Francisco | Chen R.,Pacific Health Research and Education Institute | Lin G.A.,University of California at San Francisco | And 2 more authors.
Arthritis and Rheumatology | Year: 2015

Objective More than 1 in 4 Medicare beneficiaries with rheumatoid arthritis use high-cost biologic disease-modifying antirheumatic drugs (DMARDs), and spending for these drugs has risen sharply for Medicare Part D. Our aim was to conduct the first systematic, national investigation of how Part D plans cover biologic DMARDs and to determine patients' financial burden under current cost-sharing structures. Methods We performed a cross-sectional analysis of Part D plan formularies (n=2,737) in 50 states and Washington, DC using the January 2013 Centers for Medicare and Medicaid Services Prescription Drug Plan Formulary and Pharmacy Network Files. We calculated the percentage of plans covering each DMARD as well as the percentage requiring prior authorization and/or coinsurance. We also compared biologic drug coverage in Medicare Advantage prescription drug plans to that in Medicare Part D stand-alone plans. Results All plans covered at least 1 biologic DMARD, but the vast majority required prior authorizations (95%). Nearly all plans (81-100%) required patients to pay a coinsurance percentage (averaging 29.6% of drug costs) rather than a fixed dollar copayment. This translated into mean out-of-pocket costs of $2,712-$2,774 before reaching the catastrophic phase of coverage, during which beneficiaries pay 5% of drug costs. Medicare Advantage prescription drug plans covered more individual biologic DMARDs (55-100%) than did Medicare Part D stand-alone plans (22-100%), but Medicare Advantage prescription drug plans required higher average coinsurance (31.1% versus 29.0%). In contrast, 6 of 9 nonbiologic DMARDs were covered by nearly all plans without prior authorizations at fixed copayments averaging $5-$10/month. Conclusion Nationally, nearly all Part D plans cover at least 1 biologic DMARD, but the vast majority require cost sharing sufficiently high to risk significant financial burden to patients. © 2015, American College of Rheumatology.

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