Blood pressure monitoring through pharmacies and team-based care of hypertension.

In the last issue of Blood Pressure Monitoring, (James K, Dolan E, O'Brien E. Making ambulatory blood pressure monitoring accessible in pharmacies. Blood Press Monit 2014;19:134-139) elegantly reported for the first time the characteristics of patients attending pharmacies for ambulatory blood pressure measurement (ABPM) and showed that they were similar to those undergoing ABPM through primary care practices. The authors concluded that pharmacies could be a valuable resource to perform ABPM. In the continuity of this study, we would like to emphasize the results of recent studies as well as recommenda-tions of pharmacist involvement in the management of hypertension, more specifically in a team approach.

Abaisser la pression arterielle: urgent ou pas urgent? [How urgent is it to decrease high blood pressure?]

Severe hypertension represents a frequent problem for the general practitioner. One has to decide if the blood pressure needs to be decreased immediately (hypertensive emergency), or if the blood pressure maybe progressively decreased in a few hours and normalized in a few days (hypertensive crisis). Thus it is crucial to identify on the basis of the clinical history and a careful physical examination, the patients for whom the arterial blood pressure elevation represents an acute danger for organ damage or a vital threat in the absence of immediate blood pressure control. In the case of hypertensive crisis, oral medication is usually sufficient (slow release or GITS nifedipine, nitroglycerin, labetalol, captopril). The hypertensive emergency sometimes requires an oral medication before the admission to the emergency room, then followed by intravenous drug administration (sodium nitroprussiate, nitroglycerin, labetalol).

Discrepancies between office and ambulatory blood pressure: clinical implications.

BACKGROUND: Recent trials have documented no benefit from small reductions in blood pressure measured in the clinical office. However, ambulatory blood pressure is a better predictor of cardiovascular events than office-based blood pressure. We assessed control of ambulatory blood pressure in treated hypertensive patients at high cardiovascular risk. METHODS: We selected 4729 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. Patients were aged >/=55 years and presented with at least one of the following co-morbidities: coronary heart disease, stroke, and diabetes with end-organ damage. An average of 2 measures of blood pressure in the office was used for analyses. Also, 24-hour ambulatory blood pressure was recorded at 20-minute intervals with a SpaceLabs 90207 device. RESULTS: Patients had a mean age of 69.6 (+/-8.2) years, and 60.8% of them were male. Average time from the diagnosis of hypertension to recruitment into the Registry was 10.9 (+/-8.4) years. Mean blood pressure in the office was 152.3/82.3 mm Hg, and mean 24-hour ambulatory blood pressure was 133.3/72.4 mm Hg. About 60% of patients with an office-pressure of 130-139/85-89 mm Hg, 42.4% with office-pressure of 140-159/90-99 mm Hg, and 23.3% with office-pressure > or =160/100 mm Hg were actually normotensive, according to 24-hour ambulatory blood pressure criteria (<130/80 mm Hg). CONCLUSION: We suggest that the lack of benefit of antihypertensive therapy in some trials may partly be due to some patients having normal pressure at trial baseline. Ambulatory monitoring of blood pressure may allow for a better assessment of trial eligibility.

T-Cell Receptors Binding Orientation over Peptide/MHC Class I Is Driven by Long-Range Interactions.

Crystallographic data about T-Cell Receptor - peptide - major histocompatibility complex class I (TCRpMHC) interaction have revealed extremely diverse TCR binding modes triggering antigen recognition. Understanding the molecular basis that governs TCR orientation over pMHC is still a considerable challenge. We present a simplified rigid approach applied on all non-redundant TCRpMHC crystal structures available. The CHARMM force field in combination with the FACTS implicit solvation model is used to study the role of long-distance interactions between the TCR and pMHC. We demonstrate that the sum of the coulomb interactions and the electrostatic solvation energies is sufficient to identify two orientations corresponding to energetic minima at 0° and 180° from the native orientation. Interestingly, these results are shown to be robust upon small structural variations of the TCR such as changes induced by Molecular Dynamics simulations, suggesting that shape complementarity is not required to obtain a reliable signal. Accurate energy minima are also identified by confronting unbound TCR crystal structures to pMHC. Furthermore, we decompose the electrostatic energy into residue contributions to estimate their role in the overall orientation. Results show that most of the driving force leading to the formation of the complex is defined by CDR1,2/MHC interactions. This long-distance contribution appears to be independent from the binding process itself, since it is reliably identified without considering neither short-range energy terms nor CDR induced fit upon binding. Ultimately, we present an attempt to predict the TCR/pMHC binding mode for a TCR structure obtained by homology modeling. The simplicity of the approach and the absence of any fitted parameters make it also easily applicable to other types of macromolecular protein complexes.

Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations.

Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations. We studied systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) averaged over multiple years in 46,629 individuals of European ancestry. We identified 39 trait-variant associations across 19 independent loci (p < 5 × 10(-8)); five associations (in four loci) uniquely identified by our LTA analyses included those of SBP and MAP at 2p23 (rs1275988, near KCNK3), DBP at 2q11.2 (rs7599598, in FER1L5), and PP at 6p21 (rs10948071, near CRIP3) and 7p13 (rs2949837, near IGFBP3). Replication analyses conducted in cohorts with single-visit BP data showed positive replication of associations and a nominal association (p < 0.05). We estimated a 20% gain in statistical power with long-term average (LTA) as compared to single-visit BP association studies. Using LTA analysis, we identified genetic loci influencing BP. LTA might be one way of increasing the power of genetic associations for continuous traits in extant samples for other phenotypes that are measured serially over time.

THE ADULA NAPPE: STRATIGRAPHY, STRUCTURE AND KINEMATICS OF AN EXHUMED HIGH-PRESSURE NAPPE

This study analyses the stratigraphy, structure and kinematics of the northern part of the Adula nappe of the Central Alps. The Adula nappe is one of the highest basement nappes in the Lower Penninic nappe stack of the Lepontine Dome. This structural position makes possible the investigation of the transition between the Helvetic and North Penninic paleogeographic domains. The Adula nappe is principally composed of crystalline basement rocks. The investigation of the pre-Triassic basement shows that it contains several Palaeozoic detrital metasedimentary formations dated from the Cambrian to the Ordovician. These formations contain also some volcanic or intrusive magmatic rocks. Ordovician metagranites dated at ~450 Ma are also a common rock-type of the Adula basement. These formations underwent Alpine and Variscan deformation and metamorphism. Permian granites (Zervreila orthogneiss, dated at ~290 Ma) have intruded this pre-structured basement in a post-orogenic geodynamic context. Due to their age, the Zervreila orthogneiss are good markers for alpine deformation. The stratigraphy of the Mesozoic and Paleogene sedimentary cover of the Adula nappe is essential to unraveling its pre- orogenic history. The autochthonous cover is assigned to a North Penninic Triassic series that testifies for a transition between the Helvetic and Briançonnais Triassic domains. The Adula domain goes through an emersion during the Middle Jurassic, and is part of a topographic high during the first phase of the Alpine rift. The sediments of the late Middle Jurassic show a drowning phase associated with a tectonic activity and a breccia formation. In the neighbouring domains, coeval with the drowning phase in the Adula domain, a strong extensional crustal delamination and a scattered magmatic activity is associated with the main opening of the North Penninic domain. The Upper Jurassic of the Adula nappe is characterized by a carbonate formation comparable with those in the Helvetic or Subbriaçonnais domains. Flysch s.l. deposition starts probably at the end of the Cretaceous. These sediments are deposited on a large unconformity testifying for a Cretaceous sedimentary gap. The Adula nappe exhibits a very complex structure. This structure is formed by several deformation phases. Two ductile deformations are responsible for the nappe emplacement. The first deformation phase is associated with a folding compatible with a top-to-south movement at the top of the nappe. The second phase is dominant and pervasive throughout the whole nappe. It goes with a strong north vergent folding and the main nappe emplacement. These two phases cause the exhumation and emplacement of a coherent, although pre-structured, piece of continental crust. Two further deformation phases postdate the nappe emplacement. - Ce travail concerne l'étude géologique de la partie nord de la nappe de l'Adula dans les Alpes centrales. La nappe de l'Adula est l'une des nappes cristallines la plus élevée dans la pile des nappes du Pennique inférieur des Alpes lepontines. Cette position particulière permet d'étudier la transition entre les nappes des domaines helvétique et pennique inférieur. La nappe de l'Adula est principalement composée de socle cristallin : l'étude de l'histoire géologique du socle est donc l'un des thèmes de cette recherche. Ce socle contient plusieurs formations métasédimentaires paléozoïques du Cambrien à I'Ordovicien. Ces métasédiments sont issus de formations clastiques comprenant souvent des roches magmatiques volcaniques et intrusives. Ces métasédiments ont subi les cycles orogéniques varisque et alpin. La nappe de l'Adula contient plusieurs corps magmatiques granitiques métamorphisés. Les premiers métagranites sont Ordovicien et témoignent d'un environnement de marge active. Ces granites sont aussi polymétamorphiques. Les deuxièmes métagranites sont représentés par les orthogneiss de type Zervreila. Ce métagranite est d'âge permien (-290 Ma). Il est mis en place dans un contexte tectonique post-orogénique. Ce granite est un maqueur de la déformation alpine car il n'est pas affecté par les orogenèses précédentes, flippy Le contenu stratigraphique des roches mésozoïques et cénozoiques de la couverture sédimentaire de la nappe de l'Adula est'important pour en étudier son histoire pré-alpine. La couverture autochtone est composée d'une série d'âge triasique d'affinité nord-pennique, un faciès qui marque la transition entre les domaines helvétiques et briançonnais au Trias. Le domaine paléogéographique représenté dans la nappe de l'Adula connaît une émersion pendant le Jurassique moyen. Cette émersion marque le commencement du rift dans le domaine alpin. La sédimentation de la fin du Jurassique moyen est marquée par une transgression marine accompagnée par des mouvements tectoniques et la formation d'une brèche. Cette transgression est contemporaine des importants mouvements tectoniques et des manifestations magmatiques dans les unités voisines qui marquent la phase principale d'ouverture du bassin nord-pennique. Le Jurassique supérieur est caractérisé par l'instauration d'une sédimentation carbonatée comparable à celle du domaine helvétique ou subbriançonnais. Une sédimentation flyschoïde, probablement du Crétacé à Tertiaire, est déposée sur une importante discordance qui témoigne d'une lacune au Crétacé. La structure complexe de la nappe de l'Adula témoigne de nombreuses phases de déformation. Ces phases de déformation sont en partie issues de la mise en place de la nappe et de déformations plus tardives. La mise en place de la nappe produit deux phases de déformation ductile : la première produit un plissement compatible avec un cisaillement top-vers-le sud dans la partie supérieure de la nappe; la deuxième produit un intense plissement qui accompagne la mise en place de la nappe vers le nord. Ces deux phases de déformation témoignent d'un mécanisme d'exhumation par déformation ductile d'un bloc cohérent.

Long-term outcome of preterm infants treated with nasal continuous positive airway pressure

RESUME La ventilation en pression positive continue (Continuous Positive Airway Pressure, CPAP), utilisée pour la première fois chez. les prématurés en 1971, est une technique actuellement très largement utilisée dans les unités néonatales. L'utilisation de la CPAP présente de nombreux avantages à court terme: diminution de la fraction maximale inspirée d'oxygène, de la durée de l'oxygénothérapie, du taux d'intubation et donc du recours à une ventilation mécanique, réduction de l'utilisation des amines, des curares et de la morphine, possible prévention de l'apparition d'une bronchodysplasie pulmonaire, et possibles réductions du nombre d'infections postnatales et des entérocolites nécrosantes. Mais peu d'études existent concernant les effets à long terme de la CPAP sur le neurodéveloppement et la croissance, qui constituent l'objectif de la présente étude. L'utilisation systématique de la CPAP comme alternative à la ventilation mécanique a été introduite à Lausanne en 1998. La population cible de cette étude est constituée des prématurés nés à moins de 32 semaines de gestation ou pesant moins de 1500 g à la naissance; ils ont été systématiquement suivis jusqu'en âge préscolaire dans le cadre de l'étude de cohorte «Unité de Développement, CHUV». L'originalité de ce travail réside dans le fait d'évaluer le neurodéveloppement et la croissance à long terme d'enfants prématurés traités préférentiellement avec la CPAP, en comparaison avec un groupe historique contrôle traité par d'autres modes ventilatoires, en tenant compte de nombreux autres paramètres néonataux. Du point de vue du neurodéveloppement, l'usage, de la CPAP montre une tendance à diminuer l'incidence d'hémorragie intraventriculaire et le risque d'avoir un mauvais neurodéveloppement à 6 mois. Ces résultats positifs sur le neurodéveloppement s'estompent à l'âge de 18 mois, où persiste néanmoins une valeur plus élevée du quotient de développement, et disparaissent complètement en âge préscolaire. Du point de vue de la croissance, l'utilisation de la CPAP ne montre aucun effet sur le poids, mais par contre un effet positif sur la taille à 6 et 18 mois et sur le périmètre crânien à 6 mois, 18 mois et en âge préscolaire. Malgré le caractère non randomisé de cette étude, les résultats positifs obtenus ici permettent sans conteste de s'assurer d'une utilisation de la CPAP sans effet négatif sur le neurodéveloppement et la croissance, et fournissent donc un argument supplémentaire pour l'utilisation systématique de la CPAP chez les prématurés.

Blood pressure target attainment in the background of guidelines: the very elderly in Swiss primary care.

Background There are only a few trials for the very elderly population (>79 years). No consensus, which blood pressure (BP) goals and substances should be applied, has been found yet. This survey was undertaken to investigate how octogenarians are treated and attain BP targets in the Swiss primary care. Methods Data from 4594 hypertensive patients were collected within 7 days. Eight hundred and seventy-seven patients met the requirement to be >79 years. We assessed substances/combinations and investigated pulse pressure and target blood pressure attainment (TBPA) using three different recommendations [Canadian Hypertension Education Program (CHEP), Swiss Society of Hypertension (SSH), European Society of Hypertension-European Society of Cardiology (ESH-ESC)]. Secondarily, we compared TBPA attained by angiotensin-converting enzyme inhibitor (ACEI)/diuretic (D), angiotensin receptor blocker (ARB)/D and calcium channel blocker (CCB)/D with any other dual therapy and investigated whether Ds/beta-blockers (BBs) or Ds/renin angiotensin-converting enzyme inhibitors (RAAS-Is) lead to higher TBPA. Finally, we assessed the impact of drug administration, practical work experience, location and specialization of GPs on TBPA. Results Octogenarians attained target blood pressure (TBP) between 44% (ESH-ESC) and 74% (SSH). Optimal/normal BP was reached in 22.8% of patients. Pulse pressure <65 mmHg was shown in 66.4% of patients. Monotherapy was most commonly applied followed by dual single-pill combination with ARB/D (46.5%) or ACEI/D (36.0%). No benefit in TBPA was found comparing a RAASI/D and CCB/D treatment with any other dual combination. There was also no difference between BB/D and RAAS-I/D combination therapy and between single-pill combination and dual free combinations. Conclusions GPs adhere to the use of substances proven in outcome trials and attain high TBP. No difference in meeting BP goals could be found using different drug classes. There is an unmet need to harmonize recommendations and to add additional information for the treatment of octogenarians.

Renal and neurohormonal responses to increasing levels of lower body negative pressure in men.

BACKGROUND: The stimulation of efferent renal sympathetic nerve activity induces sequential changes in renin secretion, sodium excretion, and renal hemodynamics that are proportional to the magnitude of the stimulation of sympathetic nerves. This study in men investigated the sequence of the changes in proximal and distal renal sodium handling, renal and systemic hemodynamics, as well as the hormonal profile occurring during a sustained activation of the sympathetic nervous system induced by various levels of lower body negative pressure (LBNP). METHODS: Ten healthy subjects were submitted to three levels of LBNP ranging between 0 and -22.5 mm Hg for one hour according to a triple crossover design, with a minimum of five days between each level of LBNP. Systemic and renal hemodynamics, renal water and sodium handling (using the endogenous lithium clearance technique), and the neurohormonal profile were measured before, during, and after LBNP. RESULTS: LBNP (0 to -22.5 mm Hg) induced an important hormonal response characterized by a significant stimulation of the sympathetic nervous system and gradual activations of the vasopressin and the renin-angiotensin systems. LBNP also gradually reduced water excretion and increased urinary osmolality. A significant decrease in sodium excretion was apparent only at -22.5 mm Hg. It was independent of any change in the glomerular filtration rate and was mediated essentially by an increased sodium reabsorption in the proximal tubule (a significant decrease in lithium clearance, P < 0.05). No significant change in renal hemodynamics was found at the tested levels of LBNP. As observed experimentally, there appeared to be a clear sequence of responses to LBNP, the neurohormonal response occurring before the changes in water and sodium excretion, these latter preceding any change in renal hemodynamics. CONCLUSIONS: These data show that the renal sodium retention developing during LBNP, and thus sympathetic nervous stimulation, is due mainly to an increase in sodium reabsorption by the proximal segments of the nephron. Our results in humans also confirm that, depending on its magnitude, LBNP leads to a step-by-step activation of neurohormonal, renal tubular, and renal hemodynamic responses.

Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods.

Voriconazole (VRC) is a broad-spectrum antifungal triazole with nonlinear pharmacokinetics. The utility of measurement of voriconazole blood levels for optimizing therapy is a matter of debate. Available high-performance liquid chromatography (HPLC) and bioassay methods are technically complex, time-consuming, or have a narrow analytical range. Objectives of the present study were to develop new, simple analytical methods and to assess variability of voriconazole blood levels in patients with invasive mycoses. Acetonitrile precipitation, reverse-phase separation, and UV detection were used for HPLC. A voriconazole-hypersusceptible Candida albicans mutant lacking multidrug efflux transporters (cdr1Delta/cdr1Delta, cdr2Delta/cdr2Delta, flu1Delta/flu1Delta, and mdr1Delta/mdr1Delta) and calcineurin subunit A (cnaDelta/cnaDelta) was used for bioassay. Mean intra-/interrun accuracies over the VRC concentration range from 0.25 to 16 mg/liter were 93.7% +/- 5.0%/96.5% +/- 2.4% (HPLC) and 94.9% +/- 6.1%/94.7% +/- 3.3% (bioassay). Mean intra-/interrun coefficients of variation were 5.2% +/- 1.5%/5.4% +/- 0.9% and 6.5% +/- 2.5%/4.0% +/- 1.6% for HPLC and bioassay, respectively. The coefficient of concordance between HPLC and bioassay was 0.96. Sequential measurements in 10 patients with invasive mycoses showed important inter- and intraindividual variations of estimated voriconazole area under the concentration-time curve (AUC): median, 43.9 mg x h/liter (range, 12.9 to 71.1) on the first and 27.4 mg x h/liter (range, 2.9 to 93.1) on the last day of therapy. During therapy, AUC decreased in five patients, increased in three, and remained unchanged in two. A toxic encephalopathy probably related to the increase of the VRC AUC (from 71.1 to 93.1 mg x h/liter) was observed. The VRC AUC decreased (from 12.9 to 2.9 mg x h/liter) in a patient with persistent signs of invasive aspergillosis. These preliminary observations suggest that voriconazole over- or underexposure resulting from variability of blood levels might have clinical implications. Simple HPLC and bioassay methods offer new tools for monitoring voriconazole therapy.

Systematic difference between blood pressure readings caused by cuff type.

In this study we determine whether blood pressure readings using a cuff of fixed size systematically differed from readings made with a triple-bladder cuff (Tricuff) that automatically adjusts bladder width to arm circumference and assessed subsequent clinical and epidemiological effects. Blood pressure was measured with a standard cuff or a Tricuff in 454 patients visiting an outpatient clinic in the Seychelles (Indian Ocean). Overall means of within-individual standard cuff-Tricuff differences in systolic and diastolic blood pressures were examined in relation to arm circumference and sex. The standard cuff-Tricuff difference in systolic and diastolic blood pressures increased monotonically with circumference (from 4.7 +/- 0.8/3.2 +/- 0.7 mm Hg for arm circumference of 30 to 31 cm to 10.0 +/- 1.1/8.0 +/- 0.9 mm Hg for arm circumference &gt; or = 36 cm) and was larger in women than men. Multivariate linear regression indicated independent effects of arm circumference and sex. Forty percent of subjects with a diastolic blood pressure of &gt; or = 95 mm Hg measured with a standard cuff had values less than 95 mm Hg measured with a Tricuff. Extrapolation to the entire population of the Seychelles decreased the prevalence of blood pressure greater than or equal to 160/95 mm Hg by 11.5% and 24.0% in men and women, respectively, aged 35 to 64 years. The age-adjusted effect of body mass index on systolic and diastolic blood pressures decreased twofold using blood pressure readings made with a Tricuff instead of a standard cuff.(ABSTRACT TRUNCATED AT 250 WORDS)