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.

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.

Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study.

Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4 vs .Q1 , 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4 vs .Q1 , 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI ≥ 25 and with sugar intake in those with BMI < 25. Moreover, inverse associations with starch and GI were observed in subjects with BMI < 25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI ≥ 25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people.

Anthropometry and the Risk of Lung Cancer in EPIC.

The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings.

Comparison of abdominal adiposity and overall obesity in relation to risk of small intestinal cancer in a European Prospective Cohort.

BACKGROUND: The etiology of small intestinal cancer (SIC) is largely unknown, and there are very few epidemiological studies published to date. No studies have investigated abdominal adiposity in relation to SIC. METHODS: We investigated overall obesity and abdominal adiposity in relation to SIC in the European Prospective Investigation into Cancer and Nutrition (EPIC), a large prospective cohort of approximately half a million men and women from ten European countries. Overall obesity and abdominal obesity were assessed by body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Multivariate Cox proportional hazards regression modeling was performed to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Stratified analyses were conducted by sex, BMI, and smoking status. RESULTS: During an average of 13.9 years of follow-up, 131 incident cases of SIC (including 41 adenocarcinomas, 44 malignant carcinoid tumors, 15 sarcomas and 10 lymphomas, and 21 unknown histology) were identified. WC was positively associated with SIC in a crude model that also included BMI (HR per 5-cm increase = 1.20, 95 % CI 1.04, 1.39), but this association attenuated in the multivariable model (HR 1.18, 95 % CI 0.98, 1.42). However, the association between WC and SIC was strengthened when the analysis was restricted to adenocarcinoma of the small intestine (multivariable HR adjusted for BMI = 1.56, 95 % CI 1.11, 2.17). There were no other significant associations. CONCLUSION: WC, rather than BMI, may be positively associated with adenocarcinomas but not carcinoid tumors of the small intestine. IMPACT: Abdominal obesity is a potential risk factor for adenocarcinoma in the small intestine.

Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort.

PURPOSE: The aim of the study was to assess associations between intake of combined soft drinks (sugar sweetened and artificially sweetened) and fruit and vegetable juices and the risk of hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBC) and biliary tract cancers (GBTC) using data from the European Prospective Investigation into Cancer and Nutrition cohort of 477,206 participants from 10 European countries. METHODS: After 11.4 years of follow-up, 191 HCC, 66 IHBC and 236 GBTC cases were identified. Hazard ratios and 95% confidence intervals (HR; 95% CI) were estimated with Cox regression models with multivariable adjustment (baseline total energy intake, alcohol consumption and intake pattern, body mass index, physical activity, level of educational attainment and self-reported diabetes status). RESULTS: No risk associations were observed for IHBC or GBTC. Combined soft drinks consumption of >6 servings/week was positively associated with HCC risk: HR 1.83; 95% CI 1.11-3.02, p trend = 0.01 versus non-consumers. In sub-group analyses available for 91% of the cohort artificially sweetened soft drinks increased HCC risk by 6% per 1 serving increment (HR 1.06, 95% CI 1.03-1.09, n cases = 101); for sugar-sweetened soft drinks, this association was null (HR 1.00, 95% CI 0.95-1.06; n cases = 127, p heterogeneity = 0.07). Juice consumption was not associated with HCC risk, except at very low intakes (<1 serving/week: HR 0.60; 95% CI 0.38-0.95; p trend = 0.02 vs. non-consumers). CONCLUSIONS: Daily intake of combined soft drinks is positively associated with HCC, but a differential association between sugar and artificially sweetened cannot be discounted. This study provides some insight into possible associations of HCC with sugary drinks intake. Further exploration in other settings is required.

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.

Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study.

UNLABELLED: The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR = 0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend = 0.04; per 10 nmol/L increase: IRR = 0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. CONCLUSION: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required.

Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations.

General and abdominal adiposity are associated with a high risk of developing colorectal cancer (CRC), but the role of these exposures on cancer survival has been less studied. The association between pre-diagnostic anthropometric characteristics and CRC-specific and all-cause death was examined among 3,924 men and women diagnosed with CRC between 1992 and 2009 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Over a mean follow-up period of 49 months, 1,309 deaths occurred of which 1,043 (79.7%) were due to CRC. In multivariable analysis, pre-diagnostic BMI ≥ 30 kg/m(2) was associated with a high risk for CRC-specific (HR = 1.26, 95% CI = 1.04-1.52) and all-cause (HR = 1.32, 95% CI = 1.12-1.56) death relative to BMI <25 kg/m(2). Every 5 kg/m(2) increase in BMI was associated with a high risk for CRC-specific (HR = 1.10, 95% CI = 1.02-1.19) and all-cause death (HR = 1.12, 95% CI = 1.05-1.20); and every 10 cm increase in waist circumference was associated with a high risk for CRC-specific (HR = 1.09, 95% CI = 1.02-1.16) and all-cause death (HR = 1.11, 95% CI = 1.05-1.18). Similar associations were observed for waist-to-hip and waist-to-height ratios. Height was not associated with CRC-specific or all-cause death. Associations tended to be stronger among men than in women. Possible interactions by age at diagnosis, cancer stage, tumour location, and hormone replacement therapy use among postmenopausal women were noted. Pre-diagnostic general and abdominal adiposity are associated with lower survival after CRC diagnosis.

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: evidence from the EPIC cohort.

To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2-2.0) and 1.8 (1.1-2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4-2.4) and 7.4 (2.8-19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9-1.9) and 2.3 (1.3-4.1) for CT seropositivity, and 1.4 (1.0-2.0) and 1.5 (0.9-2.6) for HHV-2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR = 10.2 (3.3-31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non-STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV-2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development.

Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort.

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation.

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (α- and ß-carotene, canthaxanthin, ß-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (α-, ß- and γ- and δ-tocopherol) and dietary consumption of ß-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary ß-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.

Today's Mediterranean Diet in Greece: Findings from the National Health and Nutrition Survey-HYDRIA (2013-2014).

BACKGROUND: This study aimed to investigate the food and macronutrient intake of the population in Greece and evaluate its adherence to the Greek traditional Mediterranean diet. METHODS: Adults over 18 years old (n = 4011) were included from the 2013-2014 National Health and Nutrition survey-HYDRIA. Dietary intake was collected using two 24-h recall interviews and a nonquantitative food frequency questionnaire. Macronutrient intakes were calculated using an updated version of the Greek FCT. RESULTS: Only 28.3% of the adult population had high adherence to the Greek traditional Mediterranean diet, with a higher percentage (39.7%) observed for participants over 65 years compared to those under 65 years (25.5%). Differences in adherence to the MD were observed among the four geographical regions in Greece. Younger adults had a higher intake of meat, cereals, alcoholic and nonalcoholic beverages, and sugar products than older individuals who consumed more vegetables, fruits, legumes, dairy, fish, and lipids (mainly from olive oil). Adults do not meet the international dietary recommendations for the intake of several foods and macronutrients. CONCLUSIONS: The adult Greek population, especially younger people, has headed away from the Greek traditional Mediterranean diet. These observations indicate potential detrimental consequences in terms of morbidity and mortality.

Diagnosis and Management of a Young Girl With Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) Linked to a Novel Mutation.

A nine-year-old girl with a two-month history of fever and generalized malaise, along with intermittent abdominal pain, immigrant myalgia, throat pain, anorexia, and long-standing failure to thrive, was admitted to our department for further investigation and treatment. Detailed medical history revealed recurrent inflammation attacks from a very young age and a heavily burdened family history. Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) was highly suspected. Genetic screening was performed and several members of the family were found to be carriers of C73Y mutation in exon 3, which is a novel tumor necrosis factor superfamily receptor 1A (TNFRSF1A) mutation. The girl was treated with an interleukin-1ß inhibitor, canakinumab, which induced immediate and complete remission of disease that interestingly lasted for a long period even after medication discontinuation.

Vigabatrin-Induced Encephalopathy in a 5.5-Month-Old Girl with Infantile Spasms due to Tuberous Sclerosis.

A 5.5-month-old female infant with tuberous sclerosis complex presented with infantile spasms and was treated with vigabatrin. As her condition did not improve, she was given adrenocorticotropic hormone (ACTH) intramuscularly which stopped the spasms and improved the electroencephalogram (EEG) abnormalities. However, she developed encephalopathy with apathy, drowsiness, and generalized slowing in the EEG. Discontinuation of vigabatrin quickly improved her symptoms and reversed the EEG slowing. A high index of suspicion is required in order to diagnose vigabatrin-induced encephalopathy, especially as the underlying disorders of these patients can be erroneously considered the cause of the observed encephalopathy.

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): 1-54] 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.

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.

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, 2-18years, 688 of whom underwent lipid screening in a regular check-up (group A); and 317 were dyslipidemic (LDL-C ≥130mg/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.

Self-rated health and all-cause and cause-specific mortality of older adults: Individual data meta-analysis of prospective cohort studies in the CHANCES Consortium.

OBJECTIVES: To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as "at-least-good". STUDY DESIGN: Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982-2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses. MAIN OUTCOME MEASURES: All-cause, cardiovascular and cancer mortality. RESULTS: Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH "fair" or "poor" vs. "at-least-good" was associated with increased mortality: HRs 1.46 (95% CI 1·23-1.74) and 2.31 (1.79-2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence). CONCLUSION: SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to "feel healthy" and "be healthy".