Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer (NSCLC). However, in preclinical ...models and early phase noncomparative studies, pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect.
A randomized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy. Erlotinib 150 mg daily (monotherapy) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous (SQ) or pemetrexed for nonsquamous (NSQ) patients was administered (combination therapy). After completion of chemotherapy, erlotinib was continued daily. Primary end point was progression-free survival (PFS).
Two hundred and thirty-one patients were randomized, 115 in the monotherapy arm and 116 in the combination arm. The adjusted hazard ratio for PFS was 0.76 95% confidence interval (CI) 0.58-1.02; P = 0.06, for overall survival (OS) 0.67 (95% CI 0.49-0.91; P = 0.01) favoring the combination arm. This improvement was primarily observed in NSQ subgroup. Common Toxicity Criteria grade 3+ toxic effect occurred in 20% versus 56%, rash in 7% versus 15% and febrile neutropenia in 0% versus 6% in monotherapy and combination therapy, respectively.
PFS was not significantly different between the arms. OS was significantly improved in the combination arm, an effect restricted to NSQ histology.
NCT00835471.
This study aims to examine the associations of food portion size (PS) with markers of insulin resistance (IR) and clustered of metabolic risk score in European adolescents.
A total of 495 adolescents ...(53.5% females) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study were included. The association between PS from food groups and homeostasis model assessment of insulin resistance (HOMA-IR) index, VO2 max, and metabolic risk score was assessed by multilinear regression analysis adjusting for several confounders. Analysis of covariance (ANCOVA) was used to determine the mean differences of food PS from food groups by HOMA-IR cutoff categories by using maternal education as a covariable.
Larger PS from vegetables in both gender and milk, yoghurt, and milk beverages in males were associated with higher VO2 max, while larger PS from margarines and vegetable oils were associated with lower VO2 max (p < 0.05). Males who consumed larger PS from fish and fish products; meat substitutes, nuts, and pulses; cakes, pies, and biscuits; and sugar, honey, jams, and chocolate have a higher metabolic risk score (p < 0.05). Males with lower HOMA-IR cutoff values consumed larger PS from vegetables, milk, yoghurt, and milk beverages (p < 0.05). Females with lower HOMA-IR cutoff values consumed larger PS from breakfast cereals, while those with higher HOMA-IR cutoff values consumed larger PS from butter and animal fats (p = 0.018).
The results show that larger PS from dairy products, cereals, and high energy dense foods are a significant determinant of IR and VO2 max, and larger PS from food with higher content of sugar were associated with higher metabolic risk score.
The ideal cardiovascular health (iCVH) construct consists of 4 health behaviors (smoking status, body mass index, physical activity and diet) and 3 health factors (total cholesterol, blood pressure ...and fasting glucose). A greater number of iCVH components in adolescence are related to better cardiovascular health, but little is known about the correlates of iCVH in adolescents. Thus, the aim of the study was to examine correlates of iCVH in European adolescents.
The study comprised 637 European adolescents with complete iCVH data. Participants were part of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional, multicenter study conducted in 9 different European countries. Correlates investigated were sex and age, family affluence scale, maternal education, geographic location, sleep time, television viewing, duration of pregnancy, birth weight and breastfeeding. Younger adolescents, those whose mothers had medium/high education or those who watched television less than 2 h per day had a greater number of iCVH components compared to those who were older, had a mother with low education or watched television 2 h or more daily (P ≤ 0.01).
Since in our study older adolescents had worse iCVH than younger adolescents, early promotion of cardiovascular health may be important. Future studies may also investigate the usefulness of limiting television viewing to promote iCVH. Finally, since adolescents of mothers with low education had poorer iCVH, it may be of special interest to tailor public health promotion to adolescents from families with low socioeconomic status.
•Little is known about the correlates of adolescent iCVH (ideal cardiovascular health).•This study included 637 European adolescents from the multi-center HELENA study.•Younger age (<15 y) and less TV viewing (<2 h/day) was related to greater iCVH.•Adolescents of mothers with medium/high education, compared to low, had higher iCVH.•These correlates may be useful for promoting cardiovascular health in adolescence.
Abstract Background and aims Inflammation plays a key role in atherosclerosis and this process seems to appear in childhood. The ideal cardiovascular health index (ICHI) has been inversely related to ...atherosclerotic plaque in adults. However, evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to assess the association between ICHI and inflammation in European adolescents. Methods and results As many as 543 adolescents (251 boys and 292 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional multi-center study including 9 European countries, were measured. C-reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell counts were used to compute an inflammatory score. Multilevel linear models and multilevel logistic regression were used to assess the association between ICHI and inflammation controlling by covariates. Higher ICHI was associated with a lower inflammatory score, as well as with several individual components, both in boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal components of the ICHI had significantly lower inflammatory score and lower levels of the study biomarkers, except CRP. Finally, the multilevel logistic regression showed that for every unit increase in the ICHI, the probability of having an inflammatory profile decreased by 28.1% in girls. Conclusion Results from this study suggest that a better ICHI is associated with a lower inflammatory profile already in adolescence. Improving these health behaviors, and health factors included in the ICHI, could play an important role in CVD prevention.
Although there is a growing interest in the epidemiology of sedentary behaviours, it is unknown whether sedentary behaviour questionnaires are broad markers of sedentary time. The aims of this study ...were to determine the: (i) reliability of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) screen time-based sedentary behaviour questionnaire; and (ii) its validity, i.e. the ability of the questionnaire to correctly rank adolescents according to the objectively measured sedentary time.
A total of 183 adolescents (104 females aged 12.5-17.5 years) were involved in the reliability study. Participants completed the HELENA sedentary questionnaire twice (1 week apart). The validity study comprised 2048 (1212 females) adolescents (12.5-17.5 years of age) included in the HELENA cross-sectional study. Questions included television viewing, computer games, console games, Internet for study and non-study reasons and study during week and weekend days. We compared median values of sedentary time, using accelerometers, by tertiles of self-reported sedentary behaviours and their sum (composite sedentary score).
Reliability study: κ-values showed a good agreement (>0.7), except for Internet for study reasons (0.46 weekdays, 0.33 weekend). The questionnaire correctly classified boys' sedentary time when analysed by specific behaviours and by a composite sedentary score. In girls, median values of objectively measured sedentary time were not different across tertiles of self-reported sedentary behaviours or the composite sedentary score.
The HELENA sedentary questionnaire is reliable, yet only correctly classifies objectively measured sedentary time in boys.
Inflammation may influence the cardio-metabolic profile which relates with the risk of chronic diseases. This study aimed to assess the inflammatory status by metabolic health (MH)/body mass index ...(BMI) category and to assess how inflammatory markers can predict the cardio-metabolic profile in European adolescents, considering BMI.
A total of 659 adolescents (295 boys) from a cross-sectional European study were included. Adolescents were classified by metabolic health based on age- and sex-specific cut-off points for glucose, blood pressure, triglycerides, high density cholesterol and BMI. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin (IL-6), complement factors (C3, C4) and cell adhesion molecules were assessed.
Metabolically abnormal (MA) adolescents had higher values of C3 (p < 0.001) and C4 (p = 0.032) compared to those metabolically healthy (MHy). C3 concentrations significantly increased with the deterioration of the metabolic health and BMI (p < 0.001). Adolescents with higher values of CRP had higher probability of being in the overweight/obese-MH group than those allocated in other categories. Finally, high C3 and C4 concentrations increased the probability of having an unfavorable metabolic/BMI status.
Metabolic/BMI status and inflammatory biomarkers are associated, being the CRP, C3 and C4 the most related inflammatory markers with this condition. C3 and C4 were associated with the cardio-metabolic health consistently.
•Some adolescents already present a metabolically abnormal profile.•This profile is associated with some inflammatory markers and the weight status.•Mean C3 concentrations increase with the deterioration of metabolic/BMI status.•C3 and C4 increase the probability of an unfavorable metabolic/BMI status.
BACKGROUND: Previous studies suggest that dietary protein might play a beneficial role in combating obesity and its related chronic diseases. Total, animal and plant protein intakes and their ...associations with anthropometry and serum biomarkers in European adolescents using one standardised methodology across European countries are not well documented. OBJECTIVES: To evaluate total, animal and plant protein intakes in European adolescents stratified by gender and age, and to investigate their associations with cardio-metabolic indicators (anthropometry and biomarkers). METHODS: The current analysis included 1804 randomly selected adolescents participating in the HELENA study (conducted in 2006–2007) aged 12.5-17.5 y (47% males) who completed two non-consecutive computerised 24-h dietary recalls. Associations between animal and plant protein intakes, and anthropometry and serum biomarkers were examined with General linear Model multivariate analysis. RESULTS: Average total protein intake exceeded the recommendations of World Health Organization and European Food Safety Authority. Mean total protein intake was 96 g/d (59% derived from animal protein). Total, animal and plant protein intakes (g/d) were significantly lower in females than in males and total and plant protein intakes were lower in younger participants (12.5-14.9 y). Protein intake was significantly lower in underweight subjects and higher in obese ones; the direction of the relationship was reversed after adjustments for body weight (g/(kg.d)). The inverse association of plant protein intakes was stronger with BMI z-score and body fat percentage (BF%) compared to animal protein intakes. Additionally, BMI and BF% were positively associated with energy percentage of animal protein. CONCLUSIONS: This sample of European adolescents appeared to have adequate total protein intake. Our findings suggest that plant protein intakes may play a role in preventing obesity among European adolescents. Further longitudinal studies are needed to investigate the potential beneficial effects observed in this study in the prevention of obesity and related chronic diseases.
We report a new measurement of the midrapidity inclusive jet longitudinal double-spin asymmetry, ALL, in polarized pp collisions at center-of-mass energy s=200 GeV. The STAR data place stringent ...constraints on polarized parton distribution functions extracted at next-to-leading order from global analyses of inclusive deep-inelastic scattering (DIS), semi-inclusive DIS, and RHIC pp data. The measured asymmetries provide evidence at the 3sigma level for positive gluon polarization in the Bjorken-x region x>0.05.