[Show abstract][Hide abstract] ABSTRACT: Background/aims:
The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD). A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease.
Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy. Main outcome variable was death.
Overall 114 (18.7%) patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM) type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all p<0.05). In a multivariate Cox regression model the use of calcium channel blockers (HR 1.89), age (HR 1.04), DM type 1 (HR 8.43) and DM type 2 (HR 2.17) and chronic obstructive pulmonary disease (HR 1.66) were associated with mortality (all p < 0.05).
The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD.
No preview · Article · Dec 2015 · Kidney and Blood Pressure Research
[Show abstract][Hide abstract] ABSTRACT: Background:
Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor and aspirin is standard in acute coronary syndrome. DAPT causes more bleeding than single antiplatelet therapy (SAPT) with a P2Y12 inhibitor.
To compare effects of SAPT and DAPT on hemostatic system activation.
In a randomized, parallel-group, double-blind, placebo-controlled study 44 healthy volunteers received clopidogrel (600mg, then 150mg daily) and aspirin (100mg daily) or placebo for 7 days. 44 volunteers received single dose ticagrelor (180mg) and aspirin (300mg) or placebo. ß-thromboglobulin (ß-TG, IU/l) and prothrombin fragment 1.2 (f1.2, nmol/l) were measured in blood from bleeding time incision. Data are given as geometric mean ratio (GMR [95% confidence interval]) to describe the differences in the first 2 hours and as mean differences (Δ [95% confidence interval]) in AUC to discriminate differences in effects over the total observation time.
Clopidogrel/aspirin and clopidogrel/placebo reduced ß-TG by a GMR of 0.51 (0.42; 0.63) and 0.54 (0.46; 0.64) at 2 hours. Ticagrelor/aspirin and ticagrelor/placebo decreased ß-TG by a GMR of 0.38 (0.26; 0.57) and 0.47 (0.31; 0.72). Ticagrelor/aspirin and ticagrelor/placebo reduced f1.2 by a GMR of 0.58 (0.45; 0.75) and 0.55 (0.38; 0.80), clopidogrel did not. Over 24 hours a difference in ß-TG occurred neither between clopidogrel/aspirin and clopidogrel/placebo (ΔAUC=-2.9 [-9.9; 4.1]), nor between ticagrelor/aspirin and ticagrelor/placebo (ΔAUC=-3.5 [-11.8; 4.7]). No difference in f1.2 occurred between clopidogrel/aspirin and clopidogrel/placebo (ΔAUC=-4.2 [-10.2; 1.8]) and between ticagrelor/aspirin and ticagrelor/placebo (ΔAUC=-3.6 [-10.9; 3.7]).
P2Y12 inhibitor mono-therapy and DAPT inhibit hemostatic system activation to a comparable extent. This article is protected by copyright. All rights reserved.
No preview · Article · Dec 2015 · Journal of Thrombosis and Haemostasis
[Show abstract][Hide abstract] ABSTRACT: Background:
Clarithromycin, known as a potent inhibitor of the cytochrome P450 isoenzyme CYP3A, may increase the plasma concentration of statins metabolized by this pathway; therefore, increase the risk of interaction with statins in reference to pharmacokinetic studies. This study aimed to characterize whether the concomitant use of a statin with clarithromycin is associated with serious outcomes among adult persons.
Health claims data of adult persons in the Regional Sickness Fund of Burgenland, Austria, who filled a prescription for clarithromycin between July 1, 2009 and June 30, 2012 were reviewed retrospectively. We assumed that the risk of hospitalisation increases acutely with the indication for taking an antibiotic, whereas statin use can be considered a chronic exposure with a low constant effect on hospitalisation. When defining the population as persons taking clarithromycin and the use of statins as the exposure we could achieve a comparable effect in both groups from the acute condition on hospitalisation. Therefore, we defined exposed patients as those who had overlapping treatment with a statin and unexposed controls as those who had filled a prescription for clarithromycin without concomitant statin therapy. Outcome was defined as a composite of hospital admission or death within 30 days after starting clarithromycin. We used generalised linear regression to model an association between outcome and exposure to statins.
Among 28,484 prescriptions of clarithromycin, 2317 persons were co-exposed to statins. Co-administration of CYP3A4 metabolized statins and clarithromycin was associated with a 2.11 fold increased risk of death or hospitalisation (95 % confidence interval [CI]: 1.79-2.48). This effect was explained by age, evidence of cardiovascular disease, diabetes mellitus and utilization of other antibiotics (multivariable adjusted risk ratio: 1.02, 95 % CI: 0.85-1.22). The sensitivity analyses did not change the significance of effect.
The risk for hospitalisation or death in persons receiving clarithromycin increases with age and cardiovascular disease but is not causally associated with statin-clarithromycine co-administration.
Full-text · Article · Oct 2015 · Lipids in Health and Disease
[Show abstract][Hide abstract] ABSTRACT: Dietary trans-resveratrol (RES) is rapidly metabolized into sulfated and glucuronated conjugates in humans. This study focused on the in vitro determination of the antioxidant capacity of RES and its main physiological metabolites and on its relevance in vivo. In vitro, RES, RES-3-O-sulfate (R3S) and 3-O-glucuronide (R3G) showed antioxidant activities at a concentration of 1mM when compared to Trolox using an assay in which the antioxidant inhibits iron-induced linoleic acid oxidation: 0.87±0.08mM Trolox equivalents (TE) for RES, 0.52±0.01mM TE for R3S and 0.36±0.02mM TE for R3G. At a concentration of 1μM, compounds promoted linoleic acid peroxidation (RES -0.30±0.09mM TE, R3S -0.48±0.05mM TE and R3G -0.57±0.07mM TE). To elucidate whether these effects were reflected in vivo, total antioxidant capacity, reactive oxygen species (ROS), conjugated fatty acid dienes (CD), superoxide dismutase (SOD) and catalase (CAT) activities were determined in human plasma and erythrocytes over 24h, after oral intake of either 0.05g RES as piceid or 5g RES. Oral administration of RES did not show an impact on total antioxidant capacity, ROS or CD. However, enzymatic activities of ROS scavenging SOD and CAT were significantly lower after high-dose compared to low-dose administration of RES (P<.03 and P<.01). In conclusion, in healthy subjects, neither 0.05g nor 5g RES changed blood oxidative state, although our in vitro data point to a prooxidative activity of low concentrations of RES and its metabolites, which could be important in vivo for individuals with compromised antioxidant defense capacity.
No preview · Article · Oct 2015 · The Journal of nutritional biochemistry
[Show abstract][Hide abstract] ABSTRACT: Objectives The aim of the trial was to assess the effect of self-evaluation and sexual diary keeping on female sexual function and depressive symptoms in women diagnosed with sexual dysfunction. Methods A single-arm non-randomised trial included 30 women (53 ± 7 years of age) with female sexual dysfunction (Female Sexual Function Index [FSFI] < 27) and a stable partnership duration of 5–40 years. Female sexual function was assessed by sexual, psychological and gynaecological history taking and validated questionnaires including the FSFI, Female Sexual Distress Scale (FSDS) and Hamilton Depression Scale (HDS), before and after 4 weeks of sexual diary keeping. Results A subjective improvement in communication of sexual problems was reported by 60% of participants; no participants reported any worsening of communication. FSFI and FSDS scores were, respectively, 18.0 ± 7.7 and 22.0 ± 10.0 at baseline and 20.2 ± 7.2 and 20.6 ± 11.5 after 4 weeks. HDS score decreased from 6.0 ± 4.0 at baseline to 4.4 ± 2.7 after 4 weeks (p = 0.042). Conclusions Self-evaluation and sexual diary keeping may improve aspects of sexual life, such as couple communication, without a direct effect on variables measured with validated questionnaires on different domains of sexual function.
No preview · Article · Aug 2015 · The European Journal of Contraception and Reproductive Health Care
[Show abstract][Hide abstract] ABSTRACT: Background:
Phosphate imbalances or disorders have a high risk of morbidity and mortality in patients with chronic kidney disease. It is unknown if this finding extends to mortality in patients presenting at an emergency room with or without normal kidney function.
Methods and patients:
This cross sectional analysis included all emergency room patients between 2010 and 2011 at the Inselspital Bern, Switzerland. A multivariable cox regression model was applied to assess the association between phosphate levels and in-hospital mortality up to 28 days.
22,239 subjects were screened for the study. Plasma phosphate concentrations were measured in 2,390 patients on hospital admission and were included in the analysis. 3.5% of the 480 patients with hypophosphatemia and 10.7% of the 215 patients with hyperphosphatemia died. In univariate analysis, phosphate levels were associated with mortality, age, diuretic therapy and kidney function (all p<0.001). In a multivariate Cox regression model, hyperphosphatemia (OR 3.29, p<0.001) was a strong independent risk factor for mortality. Hypophosphatemia was not associated with mortality (p>0.05).
Hyperphosphatemia is associated with 28-day in-hospital mortality in an unselected cohort of patients presenting in an emergency room.
[Show abstract][Hide abstract] ABSTRACT: Purpose: The objective of this study was to identify hospitalisations in Austria caused by adverse drug reactions (ADR) and to analyse preceding medication for the risk of drug-drug interactions (DDI) based on healthcare billing databases.
Methods: A retrospective study was performed using the billing data of the Austrian health system. The research database of the Main Association of Austrian Social Security Organisations was used, which contains hospital discharge diagnoses and all medications reimbursed from prescriptions for 5,046,325 adult Austrian patients in 2006 and 2007.
Results: 0.4% of the population was discharged with at least one diagnosis indicating an ADR during the observation period. 1.5% of hospitalised patients had a diagnosis related to an ADR. Of these, a DDI was identified in 68% (13,511 subjects) and a severe interaction in 12% (2,412 subjects), respectively.
Conclusions: Billing data provide important information to complement reporting systems for drug safety. These database searches may contribute to signal and hypothesis generation.
Citation: M. Wolzt et al., (2015) Relationship of Drug-Drug Interactions
with Hospital Diagnoses Associated to Adverse Drug Reactions: A
Retrospective Study of Billing Data In Austria. Int J Clin Pharmacol Toxicol,
[Show abstract][Hide abstract] ABSTRACT: This study demonstrates the applicability of semi-LASER localized dynamic (31)P MRS to deeper lying areas of the exercising human soleus muscle (SOL). The effect of accurate localization and high temporal resolution on data specificity is investigated.
To achieve high signal-to-noise ratio (SNR) at a temporal resolution of 6 s, a custom-built human calf coil array was used at 7T. The kinetics of phosphocreatine (PCr) and intracellular pH were quantified separately in SOL and gastrocnemius medialis (GM) muscle of nine volunteers, during rest, plantar flexion exercise, and recovery.
The average SNR of PCr at rest was [Formula: see text] in SOL ([Formula: see text] in GM). End exercise PCr depletion in SOL ([Formula: see text] %) was far lower than in GM ([Formula: see text] %). The pH in SOL increased rapidly and, in contrast to GM, remained elevated until the end of exercise.
(31)P MRS in single-shots every 6 s localized in the deeper-lying SOL enabled quantification of PCr recovery times at low depletions and of fast pH changes, like the initial rise. Both high temporal resolution and accurate spatial localization improve specificity of Pi and, thus, pH quantification by avoiding multiple, and potentially indistinguishable sources for changing the Pi peak shape.
Full-text · Article · Apr 2015 · MAGMA Magnetic Resonance Materials in Physics Biology and Medicine