Felodipine-metoprolol combination tablet: A valuable option to initiate antihypertensive therapy?

The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/β-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic ≤90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment. Am J Hypertens 1999;12:915-920 © 1999 American Journal of Hypertension, Lt

Liver grafts procured and discarded by all Belgian centers and transplanted within Eurotransplant network: analysis of cause to decline, a Be-LIAC study

The annual balance between imports and exports of grafts is a matter of debate. We examined the Eurotransplant database of all liver grafts procured within Belgium and Luxemburg which were exported and transplanted abroad. The aim of our study was to analyse the reasons for graft refusal by all Belgian transplant centres and early postoperative evolution. Database between 2015 and 2019 included donor characteristics, reason of offer decline, graft and recipient survival. During the 4 year period 329 grafts were procured in Belgium and transplanted abroad. 163 were exported for HU recipients, 17 no national match recipients (8 AB group, 2 pediatric and 7 other reasons), 19 pay back, 15 splits, 11 not mentioned. Hundred and four grafts were declined by all Belgian centres. Forty seven were declined primary offers and fifty seven livers were distributed by extended allocation. Between them we find out four DCD donors, 83 for medical reasons (age, cytolysis, size mismatch and steatosis). Thirteen livers were accepted and declined at arrival for size mismatch (kept as rescue offer in the same centre). One donor was unstable and two were rejected for positive HCV virology. Only one liver who was primary accepted for a split was transplanted as a whole liver. Two patients presented primary graft nonfunction and three primary graft dysfunction. All of them were retransplanted. Thirteen patients died in the early 3 month postoperative period. Even though higher mortality is expected from marginal grafts, better acceptance rate could be achieved at a national level

Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe

Archaeological evidence indicates that pig domestication had begun by ~10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ~8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local Euro-pean wild boars, although it is also possible that European wild boars were domesticated independently without any genetic con-tribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Simultaneous 24-hour monitoring of intraocular pressure and arterial blood pressure in patients with progressive and non-progressive primary open-angle glaucoma.

We measured and compared diurnal and nocturnal blood pressure (BP) with the Space Labs Holter in progressive and non-progressive glaucomatous patients with a satisfactory diurnal control of IOP in order to identify any link between a progressive worsening of their visual field (VF) defects and the characteristics of their nocturnal BP "dip". Ambulatory 24-hour BP monitoring and inpatient IOP curves were done on two consecutive days on 36 patients (17 women, 19 men, mean age 67.44 +/- 8.06 years) with moderate to severe POAG and good diurnal therapeutic control of IOP (daytime IOP < or = 21 mm Hg). Depending on the stability or progression of their VF defects during the last two years, the patients were classified in two groups: the progressive group comprised 24 patients (14 women, 10 men) and the stable group 12 patients (9 men, 3 women). We compared local and systemic risk factors for POAG, mean and maximum daytime and nighttime IOP in each group. The mean systolic and diastolic daytime BP, mean systolic and diastolic nighttime BP and the nocturnal systolic and diastolic BP dip were calculated for each patient. The distribution of these parameters was then statistically compared with normal reference values and for the two groups. The groups were closely comparable as regards their IOP 24-hour profile. The overall mean daytime, nighttime, and nocturnal dips fell within the normal range of the reference population. We found a significanty smaller systolic and diastolic BP dip in the progressive group and a broader distribution of the lower values both for systolic and diastolyc BP in the progressive group. A broader distribution of the lower values for systolic and diastolic BP dip was also noticed when progressive patients were compared with the reference population. The relative absence of a nocturnal BP dip may be interpreted as another disturbing factor in the self-regulatory mechanisms of the optic nerve head in glaucoma

Cleanability assessment of model solid surfaces with a radial-flow cell

The cleanability of several model solid substrates (glass, stainless steel, polystyrene and polytetrafluoroethylene-PTFE) was studied with a radial-flow cell. Two soiling methods were used to mimic splashing with oil; a thin layer chromatography sprayer giving a narrower and more reproducible oil droplet size distribution was preferred. Glass was the most cleanable substrate, a result which may be consistent with the presence of a swelling gel-like layer at the surface. For the other substrates, the mechanical action exerted by the fluid played a major role in oil removal; however the detergent seemed to intervene after about 5-10 min, facilitating cleaning of PTFE. Oil droplet removal took place only at high wall shear stress, in zones where flow conditions where not well controlled making it impossible to evaluate the wall shear stresses needed for oil droplet removal. Evaluation of cleanability by using the radial-flow cell is restricted to variations of wall shear stresses in a range below 3 N m(-2). (C) 2007 Elsevier B.V. All rights reserved

Possible Influence of Surfactants and Proteins on the Efficiency of Contact Agar Microbiological Surface Sampling

Agar contact microbiological sampling techniques, based on a transfer of the microorganisms present on a surface to a culture medium, are widely used to assess and control surface cleanliness and to evaluate microbial contamination levels. The effectiveness of these techniques depends on many environmental parameters that influence the strength of attachment of the bacteria to the surface. In the present study, stainless steel and high density polyethylene surfaces were inoculated with known concentrations of Staphylococcus epidermidis. Following an experimental design, the surfaces were sampled with different types of replicate organism direct agar contact plates and Petrifilm; results indicated that recovery rates were influenced by the presence of egg white albumin or Tween 80 in the inoculum solutions or by the introduction of surfactants into the contact agar of the microbiological sampling techniques. The techniques yielded significantly different results, depending on sampling conditions, underlining the need for a standardization of laboratory experiments to allow relevant comparisons of such techniques

Use of a radial-flow cell for the cleanability assessment of solid surfaces.

peer reviewe

Pathophysiologic mechanisms underlying dobutamine- and exercise-induced wall motion abnormalities.

BACKGROUND: Dobutamine and exercise echocardiography are accepted as tests of comparable efficacy for the diagnosis of coronary artery disease. Although dobutamine has been classified as "exercise simulating," the mechanisms of ischemia with dobutamine and exercise have not been well studied. This study sought to compare the determinants of myocardial oxygen consumption. METHODS AND RESULTS: We studied 54 patients with coronary artery disease undergoing dobutamine and exercise stress. A subgroup of 13 patients with comparable degrees of wall motion abnormalities and ST-segment changes during both stresses were selected to compare the determinants of ischemia in comparable circumstances. Dobutamine was infused to a mean maximal dose of 32+/-8 microg/kg/min, and exercise was stopped at an average of 135+/-25 W. The mean regional wall motion score was not statistically different between the two protocols (p = 0.27). At the onset of wall motion abnormalities and peak stress, the heart rate increased significantly less during dobutamine than during exercise (106+/-23 vs 126+/-19 beats/min, p < 0.001). The same was true of systolic blood pressure (155+/-21 vs 205+/-24 mm Hg, p < 0.001) and the rate-pressure product (16.5+/-4.6 vs 25.9+/-5, p < 0.001). Cardiac volumes were similar during both tests. CONCLUSIONS: Ischemia occurs at a lower level of external cardiac work during dobutamine than during exercise stress. We suspect that additional mechanisms, such as the oxygen wasting effect of dobutamine, may be responsible for this observation