The effect of tobacco smoking and treatment strategy on the one-year mortality of patients with acute non-ST-segment elevation myocardial infarction

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to investigate whether a previously shown survival benefit resulting from routine early invasive management of unselected patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) may differ according to smoking status and age.</p> <p>Methods</p> <p>Post-hoc analysis of a prospective observational cohort study of consecutive patients admitted for NSTEMI in 2003 (conservative strategy cohort [CS]; n = 185) and 2006 (invasive strategy cohort [IS]; n = 200). A strategy for transfer to a high-volume invasive center and routine early invasive management was implemented in 2005. Patients were subdivided into current smokers and non-smokers (including ex-smokers) on admission.</p> <p>Results</p> <p>The one-year mortality rate of smokers was reduced from 37% in the CS to 6% in the IS (p < 0.001), and from 30% to 23% for non-smokers (p = 0.18). Non-smokers were considerably older than smokers (median age 80 vs. 63 years, p < 0.001). The percentage of smokers who underwent revascularization (angioplasty or coronary artery bypass grafting) within 7 days increased from 9% in the CS to 53% in the IS (p < 0.001). The corresponding numbers for non-smokers were 5% and 27% (p < 0.001). There was no interaction between strategy and age (p = 0.25), as opposed to a significant interaction between strategy and smoking status (p = 0.024). Current smoking was an independent predictor of one-year mortality (hazard ratio 2.61, 95% confidence interval 1.43-4.79, p = 0.002).</p> <p>Conclusions</p> <p>The treatment effect of an early invasive strategy in unselected patients with NSTEMI was more pronounced among smokers than non-smokers. The benefit for smokers was not entirely explained by differences in baseline confounders, such as their younger age.</p

Compuestos no- estructurales de cementos comerciales y aserrín de maderas Argentinas

En el procesamiento mecánico de la madera se generan importantes volúmenes de residuos los cuales en su mayor parte aún no se emplean en la fabricación de componentes para la construcción. En este trabajo investigativo, se evaluó el comportamiento de un compuesto no-estructural de aserrín de dos especies de maderas argentinas combinadas con tres tipos de cementos comerciales. Partículas de maderas (Eucalyptus grandis y Poplar sp) fueron sometidas a diversos tratamientos y combinadas con tres tipos de cementos comerciales (CPC40, ARI50 y CPP40). Inicialmente, la eficiencia de la reacción fue investigada por medio del ensayo calorimétrico (curva de hidratación). A seguir, probetas cilíndricas fueron sometidas al ensayo de compresión simple, después de 14 días de fabricación. Al mismo tiempo, la velocidad del pulso ultrasónico (VPU) fue evaluada durante la etapa de endurecimiento de las mezclas. Los resultados obtenidos se mostraron muy coherentes entre sí, permitiendo destacar los efectos de los factores naturaleza de la madera, tipo de cemento y tipo de tratamiento, además de las interacciones entre estos factores. La combinación más efectiva fue el empleo de partículas de E. grandis, combinadas indistintamente con los cementos CPC40 o ARI50, adicionados con 3% de cloruro de calcio

Monitoring children and adolescents with severe obesity: body mass index (BMI), BMI z-score or percentage above the International Obesity Task Force overweight cut-off?

AIM: Body mass index (BMI) metrics are widely used as a proxy for adiposity in children with severe obesity. The BMI expressed as the percentage of a cut-off percentile for overweight or obesity has been proposed as a better alternative than BMI z-scores when monitoring children and adolescents with severe obesity. METHODS: Annual changes in BMI, BMI z-score and the percentage above the International Obesity Task Force overweight cut-off (%IOTF-25) were compared with dual-energy X-ray absorptiometry (DXA) derived body fat (%BF-DXA) in 59 children and adolescents with severe obesity. RESULTS: The change in %BF-DXA was correlated with the change in %IOTF-25 (r = 0.68) and BMI (r = 0.70), and somewhat less with the BMI z-score (r = 0.57). Cohen's Kappa statistic to detect an increase or decrease in %BF-DXA was fair for %IOTF-25 (κ = 0.25; p = 0.04) and BMI (κ = 0.33; p = 0.01), but not for the BMI z-score (κ = 0.08; p = 0.5). The change in BMI was positively biased due to a natural increase with age. CONCLUSION: Changes in the BMI metrics included in the study are associated differently with changes in %BF-DXA. The BMI z-score is widely used to monitor changes in adiposity in children and adolescents with severe obesity, but the %IOTF-25 might be a better alternative.status: publishe

Lifestyle Treatment of children and adolescents with severe obesity - results after one year

BACKGROUND: Lifestyle interventions for children and adolescents with severe obesity show moderate short-term effects on weight reduction internationally. We evaluated treatment results at two Norwegian specialist outpatient clinics. MATERIAL AND METHOD: We performed a retrospective analysis of data from children and adolescents between 3 and 18 years of age collected in 2012-2016. Children and adolescents with severe obesity who attended their one-year follow-up were included. We included in the analyses the following body weight measures: percentage overweight as defined by the International Obesity Task Force cut-off (% IOTF-25); BMI standard deviation score; waist circumference standard deviation score; and body fat percentage at the start of treatment and at one-year follow-up. RESULTS: Of 568 children and adolescents who started treatment, 416 (73 %) attended the one-year check-up. A total of 271 (65 %) patients achieved a reduction in %IOTF-25, while 228 patients (55 %) reduced their BMI standard deviation score. There was a statistically significant mean reduction of all four registered body weight measurements. Altogether 54 of 325 children (17 %) changed category from severe obesity to obesity, 8 (2 %) went from severe obesity to overweight, and 8 of 91 children (9 %) changed category from obesity to overweight or normal weight. The proportion of participants with a reduction of more than 5 % in %IOTF-25 was 43 % (177/416), and a reduction in BMI standard deviation score of more than 0.25 was observed in 23 % (95/416) of participants. Girls responded on average more poorly to the intervention than boys. There was no clinically significant difference in results between the treatment centres. INTERPRETATION: After one year of treatment of children and adolescents with severe obesity in two specialist healthcare centres, we found a moderate mean reduction in weight, waist circumference and body fat percentage, but with large interindividual variation.status: publishe

Impact of type 2 diabetes on in vivo activities and protein expressions of cytochrome P450 in patients with obesity

Previous studies have not accounted for the close link between type 2 diabetes mellitus (T2DM) and obesity when investigating the impact of T2DM on cytochrome P450 (CYP) activities. The aim was to investigate the effect of T2DM on in vivo activities and protein expressions of CYP2C19, CYP3A, CYP1A2, and CYP2C9 in patients with obesity. A total of 99 patients from the COCKTAIL study (NCT02386917) were included in this cross-sectional analysis; 29 with T2DM and obesity (T2DM-obesity), 53 with obesity without T2DM (obesity), and 17 controls without T2DM and obesity (controls). CYP activities were assessed after the administration of a cocktail of probe drugs including omeprazole (CYP2C19), midazolam (CYP3A), caffeine (CYP1A2), and losartan (CYP2C9). Jejunal and liver biopsies were also obtained to determine protein concentrations of the respective CYPs. CYP2C19 activity and jejunal CYP2C19 concentration were 63% (-0.39 [95% CI: -0.82, -0.09]) and 40% (-0.09 fmol/mu g protein [95% CI: -0.18, -0.003]) lower in T2DM-obesity compared with the obesity group, respectively. By contrast, there were no differences in the in vivo activities and protein concentrations of CYP3A, CYP1A2, and CYP2C9. Multivariable regression analyses also indicated that T2DM was associated with interindividual variability in CYP2C19 activity, but not CYP3A, CYP1A2, and CYP2C9 activities. The findings indicate that T2DM has a significant downregulating impact on CYP2C19 activity, but not on CYP3A, CYP1A2, and CYP2C9 activities and protein concentrations in patients with obesity. Hence, the effect of T2DM seems to be isoform-specific

Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity

Aim Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls. Methods This trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (&lt;1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both &lt;800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations. Results Mean +/- SD weight loss from baseline was similar in the RYGB-group (13 +/- 2.4%) and the diet group (10.5 +/- 3.9%) at week 9, but differed at year 2 (RYGB -30 +/- 6.9%, diet -3.1 +/- 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference -0.30 [-0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities. Conclusion Our findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed

Correlations between 4 beta-hydroxycholesterol and hepatic and intestinal CYP3A4 : protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range

Purpose Variability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4 beta-hydroxycholesterol (4 beta OHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4 beta OHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range. Methods The patients (n = 96; 78 with obesity and 18 normal or overweight individuals) were included from the COCKTAIL-study (NCT02386917). Plasma samples for analysis of 4 beta OHC and midazolam concentrations, and liver (n = 56) and jejunal (n = 38) biopsies were obtained. The biopsies for determination of CYP3A4 protein concentration and microsomal activity were obtained during gastric bypass or cholecystectomy. In vivo CYP3A4 phenotyping was performed using semi-simultaneous oral (1.5 mg) and intravenous (1.0 mg) midazolam. Results 4 beta OHC concentrations were positively correlated with hepatic microsomal CYP3A4 activity (rho = 0.53, p &lt; 0.001), and hepatic CYP3A4 concentrations (rho = 0.30, p = 0.027), but not with intestinal CYP3A4 concentrations (rho = 0.18, p = 0.28) or intestinal microsomal CYP3A4 activity (rho = 0.15, p = 0.53). 4 beta OHC concentrations correlated weakly with midazolam absolute bioavailability (rho = - 0.23, p = 0.027) and apparent oral clearance (rho = 0.28, p = 0.008), but not with systemic clearance (rho = - 0.03, p = 0.81). Conclusion These findings suggest that 4 beta OHC concentrations reflect hepatic, but not intestinal, CYP3A4 activity. Further studies should investigate the potential value of 4 beta OHC as an endogenous biomarker for individual dose requirements of intravenously administered CYP3A4 substrate drugs