Corticosteroids and hip fracture risk in elderly respiratory patients: EPIC-Greece cohort

INTRODUCTION: In an ageing population the prevalence of osteoporosis and chronic respiratory diseases is expected to increase in the near future. Interestingly, several forms of corticosteroids, drugs implicated in osteoporosis pathogenesis, are prescribed to respiratory patients without taking into consideration their age and risk for osteoporotic fractures. The aim of this study was to investigate the risk for hip fracture of the elder individuals who are taking corticosteroids for respiratory disease, including inhalers. MATERIAL AND METHODS: Data on incident hip fractures were collected through the active follow-up for all individuals participating in the Greek segment of the European Prospective Investigation into Cancer and Nutrition (EPIC-Greece) study who were 60 years or older at recruitment and reported "a doctor's diagnosis" of respiratory disease. Socio-demographic, life-style, health status data and use of corticosteroids were recorded from the baseline and follow-up questionnaires. Cox regression models were applied to estimate hazard ratios (HRs) adjusting for relevant confounders. RESULTS: We observed an increase in hip fracture risk with corticosteroid intake overall (HR: 1.68, 95% CI: 0.85-3.34). Increased risk persisted when we restricted our analysis to participants taking any form of corticosteroids for obstructive lung disease (HR: 1.40, 95% CI: 0.64-3.06) and to those using only inhalers (HR: 1.58, 95% CI: 0.71-3.50). However, these positive associations did not reach the nominal level of significance probably due to the small number of participants with hip fractures during follow-up. CONCLUSION: Hip fracture risk should be taken into consideration when recommending corticosteroids to the elder respiratory patients, including inhalers

Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer: A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort

Background: Acrylamide was classified as “probably carcinogenic to humans (group 2A)” by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case–control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent. Methods: A nested case–control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk. Results: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96–3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94–3.83, respectively); however, no linear dose–response trends were observed. Conclusion: This EPIC nested case–control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC. Impact: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk

Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested case-control study of 1,072 cases of lymphoid malignancies and 1,072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF-I concentration was not associated with overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third = 0.77 [95% CI = 0.57-1.03], ptrend  = 0.06). There was no statistical evidence of heterogeneity in this association with IGF-I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (pheterogeneity for all  ≥ 0.05). There were no associations between IGF-I concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF-I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF-I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF-I concentrations with lymphoma subtypes.The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A11692, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)

Corticosteroids and hip fracture risk in elderly respiratory patients: EPIC-Greece cohort

Introduction: In an ageing population the prevalence of osteoporosis and chronic respiratory diseases is expected to increase in the near future. Interestingly, several forms of corticosteroids, drugs implicated in osteoporosis pathogenesis, are prescribed to respiratory patients without taking into consideration their age and risk for osteoporotic fractures. The aim of this study was to investigate the risk for hip fracture of the elder individuals who are taking corticosteroids for respiratory disease, including inhalers. Material and methods: Data on incident hip fractures were collected through the active follow-up for all individuals participating in the Greek segment of the European Prospective Investigation into Cancer and Nutrition (EPIC-Greece) study who were 60 years or older at recruitment and reported “a doctor’s diagnosis” of respiratory disease. Socio-demographic, life-style, health status data and use of corticosteroids were recorded from the baseline and follow-up questionnaires. Cox regression models were applied to estimate hazard ratios (HRs) adjusting for relevant confounders. Results: We observed an increase in hip fracture risk with corticosteroid intake overall (HR: 1.68, 95% CI: 0.85–3.34). Increased risk persisted when we restricted our analysis to participants taking any form of corticosteroids for obstructive lung disease (HR: 1.40, 95% CI: 0.64–3.06) and to those using only inhalers (HR: 1.58, 95% CI: 0.71–3.50). However, these positive associations did not reach the nominal level of significance probably due to the small number of participants with hip fractures during follow-up. Conclusion: Hip fracture risk should be taken into consideration when recommending corticosteroids to the elder respiratory patients, including inhalers. © 2017 PTChP

Rheumatoid arthritis and cancer riskresults from the Greek European prospective investigation into cancer and nutrition cohort

To investigate the relative risk of cancer development in rheumatoid arthritis (RA) patients in Greece after taking into consideration treatment modalities. The present analysis used data on the medical history of 26 331 participants in the Greek arm of the European Prospective Investigation into Cancer and Nutrition that were collected at enrollment and thereafter during active follow-up. A history of RA and of drug treatment for the disease, as reported at baseline examination, was linked to cases of cancer reported during follow-up. A total of 91 (9.9%) patients with RA developed a cancer compared with 1542 (6.1%) patients without RA. The overall hazard ratios of all cancers increased 25% [95% confidence interval (CI): 1-54] among participants with prevalent RA, and almost all the site-specific incident cancer sites considered had rate ratios above unity. In terms of the contribution of RA medication, the hazard ratios of patients treated with salicylates was close to unity (1.07, 95% CI: 0.69-1.65), whereas those who were not treated with salicylates had a 31% (95% CI: 3-67) increased risk for cancer incidence compared with those without RA at baseline. RA patients have excess cancer risk because of either underlying complex disease pathways or treatment agents targeting immune function. Administration of salicylates appears to reduce the risk of developing malignancies. © 2018 Wolters Kluwer Health, Inc. All rights reserved

Rheumatoid arthritis and cancer risk[BULLET OPERATOR]results from the Greek European prospective investigation into cancer and nutrition cohort

To investigate the relative risk of cancer development in rheumatoid arthritis (RA) patients in Greece after taking into consideration treatment modalities. The present analysis used data on the medical history of 26 331 participants in the Greek arm of the European Prospective Investigation into Cancer and Nutrition that were collected at enrollment and thereafter during active follow-up. A history of RA and of drug treatment for the disease, as reported at baseline examination, was linked to cases of cancer reported during follow-up. A total of 91 (9.9%) patients with RA developed a cancer compared with 1542 (6.1%) patients without RA. The overall hazard ratios of all cancers increased 25% [95% confidence interval (CI): 1\u201354] among participants with prevalent RA, and almost all the site-specific incident cancer sites considered had rate ratios above unity. In terms of the contribution of RA medication, the hazard ratios of patients treated with salicylates was close to unity (1.07, 95% CI: 0.69\u20131.65), whereas those who were not treated with salicylates had a 31% (95% CI: 3\u201367) increased risk for cancer incidence compared with those without RA at baseline. RA patients have excess cancer risk because of either underlying complex disease pathways or treatment agents targeting immune function. Administration of salicylates appears to reduce the risk of developing malignancies

Comparing calculated LDL-C with directly measured LDL-C in healthy and in dyslipidemic children

Background LDL-C is one of the strongest markers for atherosclerosis and therapeutic decisions in children are based on its levels. Friedewald formula (FF) which is usually used for the calculation of LDL-C (cLDL-C); and Anandaraja's formula (AF) may under- or overestimate actual levels. Objective To compare cLDL-C with directly measured LDL-C (dLDL-C) as a screening tool and to evaluate dyslipidemic children. Methods The study population consisted of 1005 children, 2–18 years, 688 of whom underwent lipid screening in a regular check-up (group A); and 317 were dyslipidemic (LDL-C ≥ 130 mg/dl) (group B). A fasting serum lipid profile was assessed. LDL-C was measured using a homogenous assay and was calculated using FF and AF. Results Each method of calculating LDL-C was highly correlated to dLDL-C. Using FF, cLDL-C was lower than dLDL-C in 75.6% (group A) and in 77.3% (group B) of children; the mean difference was significant in dyslipidemic group. Moreover, in group B, 25% of children with boundary high and 12% with high dLDL-C would be misclassified. Using AF, LDL-C was higher than dLDL-C; the mean difference was significant in group A. Based on cLDL-C, 52% of group A with borderline dLDL-C and 27.5% of group B children with boundary high dLDL-C would be considered as dyslipidemic and eligible for medication respectively. Conclusions Comparing two methods of calculated LDL-C with directly measured LDL-C. FF was more accurate as a screening tool while AF was more accurate in the evaluation and follow-up of the dyslipidemic group. © 2016 The Canadian Society of Clinical Chemist

Molecular and clinical spectrum of four pedigrees of TRAPS in Greece: Results from a national referral center

Objective: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominantly inherited autoinflammatory disease caused by mutations of the TNFRSF1A gene. To address the association between TNFRSF1A mutations and clinical phenotype, we analyzed four pedigrees of TRAPS patients. Methods: Four Greek patients with TRAPS-like clinical features were screened for TNFRSF1A mutations by sequencing exons 2, 3 and 4. Following positive testing, twenty-two members of their families were also genetically and clinically screened. Results: Twenty-six members of four unrelated Greek families were investigated. The C73Y (c.305G>A) mutation of the TNFRSF1A gene was identified in five patients, with two of the five carrying a concomitant R92Q variation. We also identified seven C73W (c.306C>G), two T50M (c.236C>T) and seven R92Q (c.362G>A) carriers. Symptoms varied and the C73Y, C73W and T50M mutations were associated with the most severe clinical manifestations. The R92Q phenotype ranged from asymptomatic to mild disease. Molecular modelling linked pathogenicity with aberrant TNFRSF1A disulphide bond formation. Conclusion: In this first pedigree analysis of TRAPS in Greece, we identified the rare C73Y TNFRSF1A mutation. A wide clinical spectrum was observed with the C73Y, C73W and T50M mutations that affect TNFRSF1A disulphide bonds and are associated with worse symptoms. © 2019 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved