Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.

BACKGROUND: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear. OBJECTIVE: To examine whether coffee consumption is associated with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: 10 European countries. PARTICIPANTS: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition). MEASUREMENTS: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800). RESULTS: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels. LIMITATIONS: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once. CONCLUSION: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country. PRIMARY FUNDING SOURCE: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.

Risk of post-colonoscopy colorectal cancer due to incomplete adenoma resection: A nationwide, population-based cohort study.

BACKGROUND: Most post-colonoscopy colorectal cancers (PC-CRCs) are thought to develop from missed or incompletely resected adenomas. AIMS: We aimed to assess the incidence rate of PC-CRC overall and per colorectal segment, as a proxy for PC-CRC due to incomplete adenoma resection, and to identify adenoma characteristics associated with these PC-CRCs. METHODS: We performed a nationwide, population-based cohort study, including all patients with a first colorectal adenoma between 2000-2010 in the Dutch Pathology Registry (PALGA). Outcomes were the incidence rate of PC-CRC overall and of PC-CRC in the same colorectal segment, occurring between six months and five years after adenoma resection. A multivariable Cox proportional hazard analysis was performed to identify factors associated with PC-CRCs in the same segment. RESULTS: We included 107,744 patients (mean age 63.4 years; 53.6% male). PC-CRC was detected in 1031 patients (0.96%) with an incidence rate of 1.88 per 1000 person years. PC-CRC in the same segment was found in 323 of 133,519 adenomas (0.24%) with an incidence rate of 0.56 per 1000 years of follow-up. High-grade dysplasia (hazard ratio (HR) 2.54, 95% confidence interval (CI) 1.99-3.25) and both villous (HR 2.63, 95% CI 1.79-3.87) and tubulovillous histology (HR 1.80, 95% CI 1.43-2.27) were risk factors for PC-CRC in the same segment. CONCLUSIONS: Approximately one-third of PC-CRCs are found in the same colorectal segment after adenoma resection and could therefore be a consequence of incomplete adenoma resection, occurring in one in 400 adenomas. The risk of PC-CRC in the same segment is increased in adenomas with high-grade dysplasia or (tubulo)villous histology.

Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage.

BACKGROUND: We recently identified 700 genes whose expression levels were predictive of chronic lymphocytic leukemia (CLL) in a genome-wide gene expression analysis of prediagnostic blood from future cases and matched controls. We hypothesized that a large fraction of these markers were likely related to early disease manifestations. Here we aim to gain a better understanding of the natural history of the identified markers by comparing results from our prediagnostic analysis, the only prediagnostic analysis to date, to results obtained from a meta-analysis of a series of publically available transcriptomics profiles obtained in incident CLL cases and controls. RESULTS: We observed considerable overlap between the results from our prediagnostic study and the clinical CLL signals (p-value for overlap Bonferroni significant markers 0.01; p-value for overlap nominal significant markers < 2.20e-16). We observed similar patterns with time to diagnosis and similar functional annotations for the markers that were identified in both settings compared to the markers that were only identified in the prediagnostic study. These results suggest that both gene sets operate in similar pathways. CONCLUSION: An overlap exists between expression levels of genes predictive of CLL identified in prediagnostic blood and expression levels of genes associated to CLL at the clinical stage. Our analysis provides insight in a set of genes for which expression levels can be used to follow the time-course of the disease; providing an opportunity to study CLL progression in more detail in future studies.

Variation in palliative care of esophageal cancer in clinical practice: factors associated with treatment decisions.

Various treatments are available for the palliation of esophageal cancer, but the optimal therapeutic approach is unclear. This study aimed to assess the palliative treatment modalities used in patients with inoperable esophageal cancer and to identify factors associated with treatment decisions. A population-based, retrospective cohort study was conducted using data from the nationwide Netherlands Cancer Registry and medical records of seven participating hospitals. Patients diagnosed with stage III-IV inoperable esophageal or gastric cardia cancer in the central part of the Netherlands between 2001 and 2010 were included. Logistic regression analyses were performed to identify determinants of treatment choices. In total, 736 patients were initially treated with best supportive care (21%), stent placement (19%), chemotherapy (18%), external beam radiotherapy (EBRT) (16%), brachytherapy (6%), a combination of EBRT and brachytherapy (6%), a combination of chemotherapy and EBRT (5%) or another treatment (9%). The palliative approach varied for disease stage (P < 0.01) and hospital of diagnosis (P < 0.01). Independent factors affecting treatment decisions were age, degree of dysphagia, tumor histology, tumor localization, disease stage, and hospital of diagnosis. For example, patients diagnosed in one hospital were less likely to be treated with EBRT than with stent placement compared to patients in another hospital (odds ratio 0.20, 95% confidence interval 0.07-0.59). In conclusion, the initial palliative approach of patients with inoperable esophageal cancer varies widely and is not only associated with patient- and disease-related factors, but also with hospital of diagnosis. These findings suggest a lack of therapeutic guidance and highlight the need for more evidence on palliative care strategies for esophageal cancer.

Higher quality of life after metal stent placement compared with plastic stent placement for malignant extrahepatic bile duct obstruction: a randomized controlled trial.

OBJECTIVE: For palliation of extrahepatic bile duct obstruction, self-expandable metal stents (SEMS) are superior to plastic stents in terms of stent patency and occurrence of stent dysfunction. We assessed health-related quality of life (HRQoL) after stent placement to investigate whether this also results in a difference in HRQoL between patients treated with a plastic stent or SEMS. PATIENTS AND METHODS: This randomized multicenter trial included 219 patients who were randomized to receive plastic stent (n=73) or SEMS [uncovered (n=75) and covered (n=71); n=146] placement. HRQoL was assessed with two general questionnaires (EQ-5D-3L and QLQ-C30) and one disease-specific questionnaire (PAN-26). Scores were analyzed using linear mixed model regression and included all patients with baseline and at least one follow-up measurement. RESULTS: HRQoL data were available in 140 of 219 patients (64%); 71 patients (32%) declined participation and in eight patients (4%) only baseline questionnaires were available. On the QLQ-C30, the interaction between follow-up time and type of stent was significantly different on two of five functional scales [physical functioning (P=0.004) and emotional functioning (P=0.01)] in favor of patients with a SEMS. In addition, patients with SEMS reported significantly less frequent symptoms of fatigue (P=0.01), loss of appetite (P=0.02), and nausea and vomiting (0.04) over time. The EQ-VAS score decreased with time in both treatment groups, indicating a statistically significant decrease in HRQoL over time. CONCLUSION: In patients with inoperable malignant extrahepatic bile duct obstruction, SEMS placement results in better scores for general and disease-specific HRQoL over time compared with plastic stent placement.

Growth rate of small pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: results from an endoscopic ultrasound based cohort study.

Background and aims In multiple endocrine neoplasia type 1 (MEN1), endoscopic ultrasound (EUS) is used for identification and follow-up of pancreatic neuroendocrine tumors (PNETs). The role of EUS in surveillance of small ( < 20 mm) PNETs is unclear, mostly because the natural course of these lesions is largely unknown. We aimed to determine annual growth and incidence rate of small PNETs in patients with MEN1 using EUS-based surveillance. Patients and methods Linear array EUS procedures in patients with MEN1 between 2002 and 2015 were identified. Number, size, and location of PNETs were recorded. Annual growth of PNETs < 20 mm identified at the initial EUS ("prevalent" PNETs) and during follow-up ("incident" PNETs) was calculated using mixed model linear regression analysis. Results A total of 54 patients were identified and 38 patients were included. In all, 226 PNETs were identified (median size 5.0 mm, interquartile range 3.7 - 7.5) of which 124 (55 %) were prevalent and 102 (45 %) were incident PNETs. Annual incidence rate was 0.79 PNETs/year (95 % confidence interval [CI] 0.73 to 0.87). Overall growth rate was 0.10 mm/year (95 %CI 0.02 to 0.19; P = 0.01); PNETs < 10 mm (n = 198) did not grow (P = 0.23), whereas PNETs ≥ 10 mm (n = 28) grew 0.44 mm/year (95 %CI 0.10 to 0.78; P = 0.01). Prevalent PNETs grew 0.21 mm/year (95 %CI 0.10 - 0.32; P < 0.001), whereas incident PNETs did not grow (P = 0.26). Conclusions The annual growth rate of small, solid PNETs in patients with MEN1 is lower than previously thought. Surveillance intervals could probably be prolonged without compromising safety.

Exposure to Ambient Air Pollution and the Risk of Inflammatory Bowel Disease: A European Nested Case-Control Study.

BACKGROUND: Industrialization has been linked to the etiology of inflammatory bowel disease (IBD). AIM: We investigated the association between air pollution exposure and IBD. METHODS: The European Prospective Investigation into Cancer and Nutrition cohort was used to identify cases with Crohn's disease (CD) (n = 38) and ulcerative colitis (UC) (n = 104) and controls (n = 568) from Denmark, France, the Netherlands, and the UK, matched for center, gender, age, and date of recruitment. Air pollution data were obtained from the European Study of Cohorts for Air Pollution Effects. Residential exposure was assessed with land-use regression models for particulate matter with diameters of <10 µm (PM10), <2.5 µm (PM2.5), and between 2.5 and 10 µm (PMcoarse), soot (PM2.5 absorbance), nitrogen oxides, and two traffic indicators. Conditional logistic regression analyses were performed to calculate odds ratios (ORs) with 95 % confidence intervals (CIs). RESULTS: Although air pollution was not significantly associated with CD or UC separately, the associations were mostly similar. Individuals with IBD were less likely to have higher exposure levels of PM2.5 and PM10, with ORs of 0.24 (95 % CI 0.07-0.81) per 5 µg/m(3) and 0.25 (95 % CI 0.08-0.78) per 10 µg/m(3), respectively. There was an inverse but nonsignificant association for PMcoarse. A higher nearby traffic load was positively associated with IBD [OR 1.60 (95 % CI 1.04-2.46) per 4,000,000 motor vehicles × m per day]. Other air pollutants were positively but not significantly associated with IBD. CONCLUSION: Exposure to air pollution was not found to be consistently associated with IBD.

Dairy Products, Dietary Calcium, and Risk of Inflammatory Bowel Disease: Results From a European Prospective Cohort Investigation.

BACKGROUND: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are limited. We investigated the association between prediagnostic intake of these foods and dietary calcium, and the subsequent development of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, and cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n = 110) or UC (n = 244) during follow-up were matched with 4 controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking. RESULTS: Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI, 0.32-1.19, p trend = 0.19) and 0.63 (95% CI, 0.28-1.42, p trend = 0.23) for CD, and 0.80 (95% CI, 0.50-1.30, p trend = 0.40) and 0.81 (95% CI, 0.49-1.34, p trend = 0.60) for UC, respectively. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI, 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI, 0.49-1.47). CONCLUSIONS: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect.

Evolution of Costs of Inflammatory Bowel Disease over Two Years of Follow-Up.

BACKGROUND: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. METHODS AND FINDINGS: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). CONCLUSIONS: BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.

Comparison of Costs and Quality of Life in Ulcerative Colitis Patients with an Ileal Pouch-Anal Anastomosis, Ileostomy and Anti-TNFα Therapy.

BACKGROUND AND AIMS: More data are warranted on the economic impact of different treatment strategies in ulcerative colitis (UC) patients. We compared the costs and quality of life of UC patients with a pouch reconstruction, an ileostomy or anti-tumour necrosis factor α (TNFα) therapy. METHODS: UC patients filled out 3-monthly questionnaires for 2 years. Differences in 3-monthly healthcare costs, productivity costs and patient costs were tested using mixed model analysis. Quality of life was assessed employing the ) and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Out of 915 UC patients, 81 (9%) had a pouch and 48 (5%) an ileostomy, and 34 (4%) were on anti-TNFα therapy. Anti-TNFα-treated patients reported high UC related-healthcare costs per 3 months (€5350). Medication use accounted for 92% of healthcare costs. UC-attributable healthcare costs were 3-fold higher in ileostomy patients compared with pouch patients (€1581 versus €407; p < 0.01). Main cost drivers in ileostomy patients were healthcare costs and ileostomy supplies (2 and 23% of healthcare costs, respectively). In pouch patients, the main cost driver was hospitalization, accounting for 50% of healthcare costs. Productivity loss did not differ between pouch and ileostomy patients (€483 versus €377; p < 0.23), but was significantly higher in anti-TNFα-treated patients (€1085). No difference was found in IBDQ scores, but pouch patients were found to have higher quality-adjusted life years than ileostomy patients and anti-TNFα-treated patients (0.90 [interquartile range 0.78-1.00] versus 0.84 [0.78-1.00] and 0.84 [0.69-1.00], respectively; p < 0.01). CONCLUSION: Patients receiving anti-TNFα therapy reported the highest healthcare cost, in which medication use was the major cost driver. Ileostomy patients were three times more expensive than pouch patients due to frequent hospitalization and ileostomy supplies.

Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely.

Cost Efficacy of Metal Stents for Palliation of Extrahepatic Bile Duct Obstruction in a Randomized Controlled Trial.

BACKGROUND & AIMS: Endoscopic stents are placed for palliation of extrahepatic bile duct obstruction. Although self-expandable metal stents (SEMS) remain patent longer than plastic stents, they are more expensive. We aimed to evaluate which type of stent (plastic, uncovered SEMS [uSEMS], or partially covered SEMS [pcSEMS]) is the most effective and we assessed costs. METHODS: We performed a multicenter randomized trial in 219 patients at 18 hospitals in The Netherlands from February 2008 through February 2013. Patients were assigned randomly for placement of a plastic stent (n = 73), uSEMS (n = 75), or pcSEMS (n = 71) during endoscopic retrograde cholangiopancreatography. Patients were followed up for up to 1 year. Researchers were not blinded to groups. The main study end points included functional stent time and costs. RESULTS: The mean functional stent times were 172 days for plastic stents, 288 days for uSEMS, and 299 days for pcSEMS (P < .005 for uSEMS and pcSEMS vs plastic). The initial placement of plastic stents (€1042 or $1106) cost significantly less than placement of SEMS (€1973 or $2094) (P = .001). However, the total cost per patient at the end of the follow-up period did not differ significantly between plastic stents (€7320 or $7770) and SEMS (€6932 or $7356) (P = .61). Furthermore, in patients with short survival times (≤3 mo) or metastatic disease, the total cost per patient did not differ between plastic stents and SEMS. No differences in costs were found between pcSEMS and uSEMS. CONCLUSIONS: Although placement of SEMS (uncovered or partially covered) for palliation of extrahepatic bile duct obstruction initially is more expensive than placement of plastic stents, SEMS have longer functional time. The total costs after 1 year do not differ significantly with stent type. Dutch Clinical Trial Registration no: NTR1361.

Self-reported disability in patients with inflammatory bowel disease largely determined by disease activity and illness perceptions.

BACKGROUND: The inflammatory bowel disease (IBD) disability index has recently been introduced to measure patients' physical, psychological, familial, and social limitations associated with IBD. We assessed factors related to self-reported disability and the relationship between disability and direct health care costs. METHODS: A large cohort of patients with Crohn's disease (CD) and ulcerative colitis (UC) was prospectively followed for 2 years by 3 monthly web-based questionnaires. At 2 years, patients completed the IBD disability index, with lower score indicating more disability. Linear regression analysis was used to examine the impact of demographics, clinical characteristics, and illness perceptions on self-reported disability. Trends in direct health care costs across the disability severity groups minimal, mild, moderate, and severe, were tested. RESULTS: A total of 554 patients with CD and 424 patients with UC completed the IBD disability index (response rate, 45%). Both clinical characteristics and illness perceptions significantly contributed to self-reported disability (45%-47%, P = 0.000 and 8%-12%, P = 0.000, respectively). Patients with CD scored lower on the self-reported IBD disability index than patients with UC (0.255 versus 3.890, P < 0.000), indicating more disability in patients with CD. Factors independently associated with higher self-reported disability rates were increased disease activity, illness identity (higher number of symptoms attributed to IBD), and stronger emotional response. Disease duration and disease phenotype were not associated with self-reported disability. Direct health care costs increased with the worsening of self-reported disability (P = 0.000). CONCLUSIONS: More disability was reported by patients with CD than by UC. Self-reported disability in IBD was mainly determined by clinical disease activity and illness perceptions but not by disease duration or disease phenotype.

Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk.

Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and ß-carotene, lycopene, ß-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma ß-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and ß-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of ß-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted.

Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).

Risk of neoplastic progression in Barrett's esophagus diagnosed as indefinite for dysplasia: a nationwide cohort study.

BACKGROUND AND STUDY AIMS: A histological diagnosis of "indefinite for dysplasia" (IND) in Barrett's esophagus is used when a diagnosis of genuine dysplasia is equivocal. The aim of the present study was to assess the risk of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) after a diagnosis of IND in a nationwide cohort of patients with Barrett's esophagus. PATIENTS AND METHODS: Patients with a first diagnosis of IND in Barrett's esophagus between 2002 and 2011 were selected from a nationwide registry of histopathology diagnoses in The Netherlands. Patients were followed up until treatment for HGD, detection of EAC, or date of last endoscopy contact with biopsy sampling. RESULTS: In total, 1258 patients met the inclusion criteria, of whom 842 (66.9 %) underwent endoscopic follow-up. Patients were followed for a total of 2585 person-years (mean ± SD 3.01 ±â€Š2.6). Median duration until first follow-up endoscopy was 1.2 years (interquartile range 0.3 - 1.8 years). The progression rate from IND to the combined end point of HGD or EAC was 2.0 (95 % confidence interval [CI] 1.5 - 2.6) per 100 person-years and progression to EAC was 1.2 (95 %CI 0.8 - 1.6). After excluding cases with HGD or EAC within 1 year after IND diagnosis (n = 16), the progression rates were 1.4 (95 %CI 1.0 - 1.9) and 0.8 (95 %CI 0.5 - 1.2) per 100 person-years for HGD or EAC and EAC, respectively. CONCLUSION: In this large, population-based, cohort of patients with Barrett's esophagus, the incidence rate of HGD or EAC following a diagnosis of IND was 1.4 per 100 person-years. The results demonstrate the need for additional studies to select the subgroup of IND patients with an increased risk of neoplastic progression.

Back/joint pain, illness perceptions and coping are important predictors of quality of life and work productivity in patients with inflammatory bowel disease: a 12-month longitudinal study.

BACKGROUND AND AIMS: Back and joint pain are the most common extraintestinal symptoms reported by patients with inflammatory bowel disease (IBD). We assessed the impact of back/joint pain, illness perceptions, and coping on quality of life (QOL) and work productivity in patients with IBD. METHODS: Our cohort included 155 IBD patients with and 100 without arthropathy. Arthropathy was defined as daily back pain for ≥3 months and/or peripheral joint pain and/or joint swelling over the last year. At baseline and at 12 months, patients completed questionnaires on the extent of back/joint pain, IBD disease activity, illness perceptions, coping, QOL, and work productivity. The impact of back/joint pain, illness perceptions and coping on QOL and work productivity was determined, using linear mixed models. RESULTS: In total, 204 IBD patients (72% Crohn's disease, 40% male, mean age 44 ± 14 years) completed questionnaires at both time points. At both time points, IBD patients with back/joint pain reported a significantly lower QOL and work productivity compared with IBD patients without back/joint pain. Predictors of low QOL were back/joint pain (ß = -1.04, 95% confidence interval [CI] -1.40, -0.68), stronger beliefs about the illness consequences (ß = -0.39, 95% CI -0.59, -0.18) and emotional impact of IBD (ß = -0.47, 95% CI -0.66, -0.28), and the coping strategy 'decreasing activity' (ß = -0.26, 95% CI -0.48, -0.03). Predictors of work productivity were back/joint pain (ß = 0.22, 95% CI 0.07, 0.37) and illness consequences (ß = 0.14, 95% CI 0.06, 0.22). CONCLUSION: Back/joint pain, illness perceptions, and coping are significant predictors of QOL and work productivity, after controlling for disease activity.

No decrease in the rate of early or missed colorectal cancers after colonoscopy with polypectomy over a 10-year period: a population-based analysis.

BACKGROUND & AIMS: It is not clear whether the incidence of missed or early colorectal cancers (CRCs) has decreased over time. We compared the rates of missed or early CRC after polypectomy between 1996 and 2006, and aimed to identify risk factors for these. METHODS: We performed a population-based, case-control study linking data from the Dutch Pathology Registry with data from The Netherlands Cancer Registry. Of all patients with an incident CRC in 1996 and 2006, we identified whether colonic histology specimens were available in the preceding 3 years. Patients with early or missed CRC were defined as those with previous colonic histology in the 6 to 36 months preceding CRC diagnosis. We performed multivariate logistic regression analysis to identify factors associated with missed or early CRCs. RESULTS: CRC was diagnosed in 6941 patients in 1996 and in 10,963 patients in 2006. The proportion of patients with early or missed CRC was 1.7% of all CRC patients in 1996 and 2.3% in 2006 (P = .012). Early or missed CRCs had a lower tumor, nodal, and metastasis stage than regularly diagnosed CRCs (P < .001), but rate of survival, adjusted for TNM stage, did not differ. CRCs of the right colon and transverse colon and splenic flexure were associated with a missed or early CRC (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.80-3.05; and OR, 2.14; 95% CI, 1.49-3.08, respectively), as was male sex (OR, 1.31; 95% CI, 1.06-1.62). CONCLUSIONS: Based on an analysis of the Dutch population, there has been no decrease in the occurrence of missed or early CRCs over a 10-year period. Location in the right side of the colon was an independent risk factor for missed or early CRCs.

Use of two-part regression calibration model to correct for measurement error in episodically consumed foods in a single-replicate study design: EPIC case study.

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.

Fruit and vegetable intake and cause-specific mortality in the EPIC study.

Consumption of fruits and vegetables is associated with a lower overall mortality. The aim of this study was to identify causes of death through which this association is established. More than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition study were included, of which 25,682 were reported deceased after 13 years of follow-up. Information on lifestyle, diet and vital status was collected through questionnaires and population registries. Hazard ratios (HR) with 95% confidence intervals (95% CI) for death from specific causes were calculated from Cox regression models, adjusted for potential confounders. Participants reporting consumption of more than 569 g/day of fruits and vegetables had lower risks of death from diseases of the circulatory (HR for upper fourth 0.85, 95% CI 0.77-0.93), respiratory (HR for upper fourth 0.73, 95% CI 0.59-0.91) and digestive system (HR for upper fourth 0.60, 95% CI 0.46-0.79) when compared with participants consuming less than 249 g/day. In contrast, a positive association with death from diseases of the nervous system was observed. Inverse associations were generally observed for vegetable, but not for fruit consumption. Associations were more pronounced for raw vegetable consumption, when compared with cooked vegetable consumption. Raw vegetable consumption was additionally inversely associated with death from neoplasms and mental and behavioral disorders. The lower risk of death associated with a higher consumption of fruits and vegetables may be derived from inverse associations with diseases of the circulatory, respiratory and digestive system, and may depend on the preparation of vegetables and lifestyle factors.