| 61. |
- Duell, Eric J, et al.
(författare)
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Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition
- 2010
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:12, s. 1384-1393
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Tidskriftsartikel (refereegranskat)abstract
- The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.
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| 62. |
- Ekelund, Ulf, et al.
(författare)
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Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288,498 men and women.
- 2011
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Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 93, s. 826-835
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The protective effect of physical activity (PA) on abdominal adiposity is unclear. OBJECTIVE: We examined whether PA independently predicted gains in body weight and abdominal adiposity. DESIGN: In a prospective cohort study [the EPIC (European Prospective Investigation into Cancer and Nutrition)], we followed 84,511 men and 203,987 women for 5.1 y. PA was assessed by a validated questionnaire, and individuals were categorized into 4 groups (inactive, moderately inactive, moderately active, and active). Body weight and waist circumference were measured at baseline and self-reported at follow-up. We used multilevel mixed-effects linear regression models and stratified our analyses by sex with adjustments for age, smoking status, alcohol consumption, educational level, total energy intake, duration of follow-up, baseline body weight, change in body weight, and waist circumference (when applicable). RESULTS: PA significantly predicted a lower waist circumference (in cm) in men (β = -0.045; 95% CI: -0.057, -0.034) and in women (β = -0.035; 95% CI: -0.056, -0.015) independent of baseline body weight, baseline waist circumference, and other confounding factors. The magnitude of associations was materially unchanged after adjustment for change in body weight. PA was not significantly associated with annual weight gain (in kg) in men (β = -0.008; 95% CI: -0.02, 0.003) and women (β = -0.01; 95% CI: -0.02, 0.0006). The odds of becoming obese were reduced by 7% (P < 0.001) and 10% (P < 0.001) for a one-category difference in baseline PA in men and women, respectively. CONCLUSION: Our results suggest that a higher level of PA reduces abdominal adiposity independent of baseline and changes in body weight and is thus a useful strategy for preventing chronic diseases and premature deaths.
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| 63. |
- Emaus, Marleen J., et al.
(författare)
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Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:12, s. 2887-2899
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Tidskriftsartikel (refereegranskat)abstract
- Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3: 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3: 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.
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| 64. |
- Ferrando, Carlos, et al.
(författare)
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Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV) : a multicentre, randomised, controlled clinical trial
- 2024
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Ingår i: The Lancet Respiratory Medicine. - : Elsevier. - 2213-2600 .- 2213-2619. ; 12:3, s. 195-206
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Tidskriftsartikel (refereegranskat)abstract
- Background It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. Methods This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age >= 18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lungprotective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. Findings Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0 center dot 39 [95% CI 0 center dot 28 to 0 center dot 56]), with an absolute risk difference of -9 center dot 23 (95% CI -12 center dot 55 to -5 center dot 92). Recruitment manoeuvre-related adverse events were reported in five patients. Interpretation Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. Funding Instituto de Salud Carlos III and the European Regional Development Funds. Copyright (c) 2023 Elsevier Ltd. All rights reserved.
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| 65. |
- Ferrando, Carlos, et al.
(författare)
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Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE) : study protocol for a randomized controlled trial
- 2015
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. Methods: This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra-and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra-and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. Discussion: The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications.
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| 66. |
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| 67. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 68. |
- Fortner, Renée T., et al.
(författare)
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Anti-Mullerian hormone and endometrial cancer : a multi-cohort study
- 2017
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 117:9, s. 1412-1418
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. Methods: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. AntiMullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. Results: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog(2): 1.07 (0.99-1.17)), or with any of the examined subgroups. Conclusions: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.
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| 69. |
- Fortner, Renée T., et al.
(författare)
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Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels : Results from the EPIC cohort
- 2018
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:7, s. 1355-1360
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Tidskriftsartikel (refereegranskat)abstract
- CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; p(het)=0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection. What's new? Although CA125, a mucin produced in epithelial cells, is a known marker for ovarian cancer, complementary biomarkers are necessary for reliable early cancer detection. Here, the authors examined autoantibodies against CA125 as potential pre-diagnosis markers. Although anti-CA125 levels did not discriminate between ovarian cases and controls, discrimination of CA125 differed by levels of its antibody, with the highest discrimination among women with the highest antibody levels. The authors propose that CA125 and anti-CA125 may act synergistically for ovarian cancer early detection.
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| 70. |
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