Effects on blood pressure and cardiovascular risk of variations in patients' adherence to prescribed antihypertensive drugs: role of duration of drug action.

P>Aim: To determine the effects of imperfect adherence (i.e. occasionally missing prescribed doses), and the influence of rate of loss of antihypertensive effect during treatment interruption, on the predicted clinical effectiveness of antihypertensive drugs in reducing mean systolic blood pressure (SBP) and cardiovascular disease (CVD) risk.Method:The effects of imperfect adherence to antihypertensive treatment regimens were estimated using published patterns of missed doses, and taking into account the rate of loss of antihypertensive effect when doses are missed (loss of BP reduction in mmHg/day; the off-rate), which varies between drugs. Outcome measures were the predicted mean SBP reduction and CVD risk, determined from the Framingham Risk Equation for CVD.Results:In patients taking 75% of prescribed doses (typical of clinical practice), only long-acting drugs with an off-rate of similar to 1 mmHg/day were predicted to maintain almost the full mean SBP-lowering effect throughout the modelled period. In such patients, using shorter-acting drugs (e.g. an off-rate of similar to 5-6 mmHg/day) was predicted to lead to a clinically relevant loss of mean SBP reduction of > 2 mmHg. This change also influenced the predicted CVD risk reduction; in patients with a baseline 10-year CVD risk of 27.0% and who were taking 75% of prescribed doses, a difference in off-rate from 1 to 5 mmHg/day led to a predicted 0.5% absolute increase in 10-year CVD risk.Conclusions:In patients who occasionally miss doses of antihypertensives, modest differences in the rate of loss of antihypertensive effect following treatment interruption may have a clinically relevant impact on SBP reduction and CVD risk. While clinicians must make every effort to counsel and encourage each of their patients to adhere to their prescribed medication, it may also be prudent to prescribe drugs with a low off-rate to mitigate the potential consequences of missing doses.

Assessment of skinfold thickness equations in estimating body composition in children with inflammatory bowel

Introduction: Growth is a central process in paediatrics. Weight and height evaluation are therefore routine exams for every child but in some situation, particularly inflammatory bowel disease (IBD), a wider evaluation of nutritional status needs to be performed. The assessment of body composition is essential in order to maintain acceptable growth using the following techniques: Dual-energy X-ray absorptiometry (DEXA), bio-impedance-analysis (BIA) and anthropometric measurements (skinfold thickness skin), the latter being most easily available and most cost effective. Objectives: To assess the accuracy of skinfold equations in estimating percentage body fat (%BF) in children with inflammatory bowel disease (IBD), compared with assessment of body fat dual energy X-ray absorptiometry (DEXA). Methods: Twenty-one patients (11 females, 10 males; mean age: 14.3 years, range 12 - 16 years) with IBD (Crohn's disease n = 15, ulcerative colitis n = 6)). Estimated%BF was computed using 6 established equations based on the triceps, biceps, subscapular and suprailiac skinfolds (Deurenberg, Weststrate, Slaughter, Durnin & Rahaman, Johnston, Brook) and compared to DEXA. Concordance analysis was performed using Lin's concordance correlation and the Bland-Altman limits of agreement method. Results: Durnin & Rahaman's equation shows a higher Lin's concordance coefficient with a small difference amongst raw values for skinfolds and DEXA compared to the other equations. Correlation coefficient between mean and difference is close to zero with a non-significant Bradley-Blackwood test. Conclusion: Body composition in paediatric IBD patients using the Durnin & Rahaman skinfold-equation adequately reflects values obtained by DEXA.

Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours.

AIM: Total imatinib concentrations are currently measured for the therapeutic drug monitoring of imatinib, whereas only free drug equilibrates with cells for pharmacological action. Due to technical and cost limitations, routine measurement of free concentrations is generally not performed. In this study, free and total imatinib concentrations were measured to establish a model allowing the confident prediction of imatinib free concentrations based on total concentrations and plasma proteins measurements. METHODS: One hundred and fifty total and free plasma concentrations of imatinib were measured in 49 patients with gastrointestinal stromal tumours. A population pharmacokinetic model was built up to characterize mean total and free concentrations with inter-patient and intrapatient variability, while taking into account α1 -acid glycoprotein (AGP) and human serum albumin (HSA) concentrations, in addition to other demographic and environmental covariates. RESULTS: A one compartment model with first order absorption was used to characterize total and free imatinib concentrations. Only AGP influenced imatinib total clearance. Imatinib free concentrations were best predicted using a non-linear binding model to AGP, with a dissociation constant Kd of 319 ng ml(-1) , assuming a 1:1 molar binding ratio. The addition of HSA in the equation did not improve the prediction of imatinib unbound concentrations. CONCLUSION: Although free concentration monitoring is probably more appropriate than total concentrations, it requires an additional ultrafiltration step and sensitive analytical technology, not always available in clinical laboratories. The model proposed might represent a convenient approach to estimate imatinib free concentrations. However, therapeutic ranges for free imatinib concentrations remain to be established before it enters into routine practice.

Evaluation of a multicomponent worksite health promotion program for cardiovascular risk factors-correcting for the regression towards the mean effect.

BACKGROUND: We assessed the impact of a multicomponent worksite health promotion program for0 reducing cardiovascular risk factors (CVRF) with short intervention, adjusting for regression towards the mean (RTM) affecting such nonexperimental study without control group. METHODS: A cohort of 4,198 workers (aged 42 +/- 10 years, range 16-76 years, 27% women) were analyzed at 3.7-year interval and stratified by each CVRF risk category (low/medium/high blood pressure [BP], total cholesterol [TC], body mass index [BMI], and smoking) with RTM and secular trend adjustments. Intervention consisted of 15 min CVRF screening and individualized counseling by health professionals to medium- and high-risk individuals, with eventual physician referral. RESULTS: High-risk groups participants improved diastolic BP (-3.4 mm Hg [95%CI: -5.1, -1.7]) in 190 hypertensive patients, TC (-0.58 mmol/l [-0.71, -0.44]) in 693 hypercholesterolemic patients, and smoking (-3.1 cig/day [-3.9, -2.3]) in 808 smokers, while systolic BP changes reflected RTM. Low-risk individuals without counseling deteriorated TC and BMI. Body weight increased uniformly in all risk groups (+0.35 kg/year). CONCLUSIONS: In real-world conditions, short intervention program participants in high-risk groups for diastolic BP, TC, and smoking improved their CVRF, whereas low-risk TC and BMI groups deteriorated. Future programs may include specific advises to low-risk groups to maintain a favorable CVRF profile.

Electrical colonic stimultation reduces mean transit time in a porcine model

Rapport de synthèse : Introduction : La stimulation électrique représente une nouvelle modalité thérapeutique de divers troubles digestifs. Dans la constipation par exemple, le péristaltisme colique peut être activé par un système électrique alimenté par une batterie. La présente étude a pour but de démontrer l'impact d'une stimulation électrique directe du côlon sur le temps de transit moyen, en utilisant un modèle expérimental chronique porcin. L'effet de la stimulation et du matériel implanté dans la paroi colique est également évalué. Matériel et méthode : Trois paires d'électrodes ont été implantées dans la paroi cæcale de douze porcs anesthésiés. Avant implantation, un temps de transit colique de référence a été déterminé chez chaque animal par utilisation de marqueurs radio-opaques. Cette évaluation a été répétée quatre semaines après implantation, sous stimulation factice, et cinq semaines après implantation, sous stimulation électrique. Des trains séquentiels et aboraux de stimulation (10 V ; 120 Hz ; 1 ms) ont été appliqués quotidiennement durant six jours, en utilisant un stimulateur externe fonctionnant sur batteries. Pour chaque série de marqueurs, une valeur moyenne a été calculée à partir du temps de transit individuel des porcs. Un examen microscopique du cæcum a été systématiquement entrepris après sacrifice des animaux. Résultats : Une réduction du temps de transit moyen a été observée après stimulation électrique (19h ± 13 ; moyenne ± DS), comparativement au temps de référence (34h ± 7 ; p=0.045) et au temps de transit après stimulation factice (36h ± 9 ; p=0.035). L'examen histologique a montré la présence d'une inflammation chronique minime, autour des électrodes. Conclusion : Le temps de transit colique porcin peut être réduit, en conditions expérimentales chroniques, par une stimulation électrique directe et séquentielle de l'intestin. Des lésions tissulaires limitées ont été occasionnées par la stimulation ou le matériel implanté. La stimulation électrique colique représente certainement une approche prometteuse du traitement de certains troubles spécifiques du côlon, avant tout fonctionnels.

Electrical colonic stimultation reduces mean transit time in a porcine model

Rapport de synthèse : Introduction : La stimulation électrique représente une nouvelle modalité thérapeutique de divers troubles digestifs. Dans la constipation par exemple, le péristaltisme colique peut être activé par un système électrique alimenté par une batterie. La présente étude a pour but de démontrer l'impact d'une stimulation électrique directe du côlon sur le temps de transit moyen, en utilisant un modèle expérimental chronique porcin. L'effet de la stimulation et du matériel implanté dans la paroi colique est également évalué. Matériel et méthode : Trois paires d'électrodes ont été implantées dans la paroi cæcale de douze porcs anesthésiés. Avant implantation, un temps de transit colique de référence a été déterminé chez chaque animal par utilisation de marqueurs radio-opaques. Cette évaluation a été répétée quatre semaines après implantation, sous stimulation factice, et cinq semaines après implantation, sous stimulation électrique. Des trains séquentiels et aboraux de stimulation (10 V ; 120 Hz ; 1 ms) ont été appliqués quotidiennement durant six jours, en utilisant un stimulateur externe fonctionnant sur batteries. Pour chaque série de marqueurs, une valeur moyenne a été calculée à partir du temps de transit individuel des porcs. Un examen microscopique du cæcum a été systématiquement entrepris après sacrifice des animaux. Résultats : Une réduction du temps de transit moyen a été observée après stimulation électrique (19h ± 13 ; moyenne ± DS), comparativement au temps de référence (34h ± 7 ; p=0.045) et au temps de transit après stimulation factice (36h ± 9 ; p=0.035). L'examen histologique a montré la présence d'une inflammation chronique minime, autour des électrodes. Conclusion : Le temps de transit colique porcin peut être réduit, en conditions expérimentales chroniques, par une stimulation électrique directe et séquentielle de l'intestin. Des lésions tissulaires limitées ont été occasionnées par la stimulation ou le matériel implanté. La stimulation électrique colique représente certainement une approche prometteuse du traitement de certains troubles spécifiques du côlon, avant tout fonctionnels.

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Pulse oximetry and transcutaneous oxygen tension for detection of hypoxemia in critically ill infants and children.

We tested the performance of transcutaneous oxygen monitoring (TcPO2) and pulse oximetry (tcSaO2) in detecting hypoxia in critically ill neonatal and pediatric patients. In 54 patients (178 data sets) with a mean age of 2.4 years (range 1 to 19 years), arterial saturation (SaO2) ranged from 9.5 to 100%, and arterial oxygen tension (PaO2) from 16.4 to 128 mmHg. Linear correlation analysis of pulse oximetry vs measured SaO2 revealed an r value of 0.95 (p less than 0.001) with an equation of y = 21.1 + 0.749x, while PaO2 vs tcPO2 showed a correlation coefficient of r = 0.95 (p less than 0.001) with an equation of y = -1.04 + 0.876x. The mean difference between measured SaO2 and tcSaO2 was -2.74 +/- 7.69% (range +14 to - 29%) and the mean difference between PaO2 and tcPO2 was +7.43 +/- 8.57 mmHg (range -14 to +49 mmHg). Pulse oximetry was reliable at values above 65%, but was inaccurate and overestimated the arterial SaO2 at lower values. TcPO2 tended to underestimate the arterial value with increasing PaO2. Pulse oximetry had the best sensitivity to specificity ratio for hypoxia between 65 and 90% SaO2; for tcPO2 the best results were obtained between 35 and 55 mmHg PaO2.

Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption

Résumé : Description : Ce travail de thèse évalue l'impact de la consommation importante d'alcool sur les facteurs de risque cardiovasculaire et l'estimation du risque cardiovasculaire à 10 ans (risque de développer une maladie coronarienne}, dans une population avec une consommation moyenne élevée d'alcool. La consommation modérée d'alcool a été liée à un risque plus faible de développer une maladie coronarienne. Cependant, les données concernant la consommation importante d'alcool et le risque de développer une maladie coronarienne sont conflictuelles. Il y a également peu d'études dans lesquelles les consommations importantes d'alcool ont pu être évaluées en raison du petit nombre de sujets présentant une telle consommation. Résultats: Nous avons utilisé les données de l'étude CoLaus, une étude populationnelle qui inclut des adultes, âgés de 35 à 75 ans, de la ville de Lausanne. Nous avons inclus 5'769 participants, sans maladie cardiovasculaire, pour lesquels la consommation d'alcool d'une semaine a été catégorisée en 0, 1 à 6, 7 à 13, 14 à 20, 21 à 27, 28 à 34 et >=35 verres/semaine et en non-consommateur (0 verre/semaine), consommateur modéré (1 à 13 verres/semaine), important (14 à 34 verres/semaine) et très important (>= 35). La tension artérielle et les lipides ont été mesurés et le risque de développer une maladie coronarienne à 10 ans a été calculé en utilisant le score de Framingham. 73% des participants consommaient de l'alcool; 16% étaient des consommateurs importants et 2% des consommateurs très importants. L'analyse rnultivariée a montré une augmentation du cholestérol HDL avec la consommation d'alcool (de 1.570.01 [moyenne +- erreur standard] chez les non consommateurs à 1.880.03 mmol/L chez les consommateurs très importants), des triglycérides (1.17+-1.01 à 1.32+-1.05 mmol/L) et des valeurs de tension artérielle systolique (127.4+-0.4 à 132.2+-.4 mm Hg) et diastolique (78.7+-0.3 à 81.7+-0.9 mm Hg, toutes les valeurs de p pour trend<0.001). Quant au risque de développer une maladie coronarienne à 10 ans, il a augmenté de 4.31%+-0.10 à 4.90%+-0.37 (p=0.03) avec la consommation d'alcool, en décrivant une courbe en J. En examinant le type de consommation, on a vu que la consommation de vin a plus d'effet sur l'augmentation des valeurs de cholestérol HDL, alors que la consommation de bière ou de spiritueux a plus d'effet sur l'augmentation des valeurs de triglycérides. Conclusions et perspectives: Nos résultats montrent qu'en ce qui concerne l'estimation du risque cardiovasculaire à 10 ans, l'effet protecteur de la consommation d'alcool disparaît pour des consommations très importantes, car l'effet bénéfique des valeurs augmentées de cholestérol HDL est contrecarré par l'augmentation des valeurs de tension artérielle. Quant aux différents types d'alcool, d'autres études sont nécessaires pour mieux évaluer leur effet spécifique sur les facteurs de risque cardiovasculaire.

Use of hand-to-hand impedancemetry to predict body composition of African women as measured by air displacement plethysmography.

OBJECTIVES: To test the validity of a simple, rapid, field-adapted, portable hand-held impedancemeter (HHI) for the estimation of lean body mass (LBM) and percentage body fat (%BF) in African women, and to develop specific predictive equations. DESIGN: Cross-sectional observational study. SETTINGS: Dakar, the capital city of Senegal, West Africa. SUBJECTS: A total sample of 146 women volunteered. Their mean age was of 31.0 y (s.d. 9.1), weight 60.9 kg (s.d. 13.1) and BMI 22.6 kg/m(2) (s.d. 4.5). METHODS: Body composition values estimated by HHI were compared to those measured by whole body densitometry performed by air displacement plethysmography (ADP). The specific density of LBM in black subjects was taken into account for the calculation of %BF from body density. RESULTS: : Estimations from HHI showed a large bias (mean difference) of 5.6 kg LBM (P<10(-4)) and -8.8 %BF (P<10(-4)) and errors (s.d. of the bias) of 2.6 kg LBM and 3.7 %BF. In order to correct for the bias, specific predictive equations were developed. With the HHI result as a single predictor, error values were of 1.9 kg LBM and 3.7 %BF in the prediction group (n=100), and of 2.2 kg LBM and 3.6 %BF in the cross-validation group (n=46). Addition of anthropometrical predictors was not necessary. CONCLUSIONS: The HHI analyser significantly overestimated LBM and underestimated %BF in African women. After correction for the bias, the body compartments could easily be estimated in African women by using the HHI result in an appropriate prediction equation with a good precision. It remains to be seen whether a combination of arm and leg impedancemetry in order to take into account lower limbs would further improve the prediction of body composition in Africans.

Transjugular liver biopsy: prospective evaluation of the angle formed between the hepatic veins and the vena cava main axis and modification of a semi-automated biopsy device in cases of an unfavorable angle.

In cases of transjugular liver biopsies, the venous angle formed between the chosen hepatic vein and the vena cava main axis in a frontal plane can be large, leading to technical difficulties. In a prospective study including 139 consecutive patients who underwent transjugular liver biopsy using the Quick-Core biopsy set, the mean venous angle was equal to 49.6 degrees. For 21.1% of the patients, two attempts at hepatic venous catheterization failed because the venous angle was too large, with a mean of 69.7 degrees. In all of these patients, manual reshaping of the distal curvature of the stiffening metallic cannula, by forming a new mean angle equal to 48 degrees , allowed successful completion of the procedure in less than 10 min.

Comparison of central macular thickness (CMT) measurement between time domain and spectral domain (SD) optical coherence tomography (OCT) and reproducibility of SD OCT in active neovascular AMD

Purpose: To evaluate the reproducibility of Cirrus-SD OCT measurements and to compare central macular thickness (CMT) measurements between TD-Stratus and SD-Cirrus OCT in patients with active exudative AMD. Methods: Consecutive case series of patients with active exudative AMD seen in the Medical Retina Department. Patients underwent 1 scan with Stratus (macular thickness map protocol) and 5 scans with Cirrus (Macular Cube protocol) at the same visit by the same experienced examiner. To be included, patients best-corrected visual acuity (BCVA) had to be >20/200 while all scans had to be of sufficient quality, well-centered and at least one Cirrus scan with CMT >300 microns. The repeatability of the SD Cirrus was estimated by using all 5 CMT measurements and the mean of the Cirrus measurements was compared with the CMT obtained by TD Stratus. Results: Cirrus OCT demonstrated high intraobserver repeatability at the central foveal region (ICC 96%). The mean of the CMT measurements was 321microns for Stratus and 387 microns for Cirrus. The average difference was 65m (SD=30). The coefficient of concordance between Stratus and Cirrus CMT measurements was rho=0,749 with a high precision and a moderate accuracy. The equation of the line of regression between Stratus and meanCirrus is given by the following: M_stratus = 0,848 x m_cirrus - 4,496 (1).Conclusions: The Cirrus macular cube protocol allows reproducible CMT measurements in patients with active exudative AMD. In cases of upgrading from TD to SD use and vice versa, there is the possibility to predict the measurements by using the equation (1). These real life data and conclusions can help in improving our clinical management of patients with neovascular AMD.