[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.
Lipids in Health and Disease 10/2015; 14(1):131. DOI:10.1186/s12944-015-0134-y · 2.22 Impact Factor
[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.
The Journal of nutritional biochemistry 10/2015; DOI:10.1016/j.jnutbio.2015.08.032 · 3.79 Impact Factor
[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.
The European Journal of Contraception and Reproductive Health Care 08/2015; DOI:10.3109/13625187.2015.1074676 · 1.39 Impact Factor
[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.
PLoS ONE 08/2015; 10(8). DOI:10.1371/journal.pone.0133426 · 3.23 Impact Factor
[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.
MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 04/2015; 28(5). DOI:10.1007/s10334-015-0484-5 · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recombinant human follicle stimulating hormone (r-hFSH) is effective and safe for controlled ovarian stimulation. Bemfola® (Finox AG, Burgdorf, Switzerland), a new biosimilar r-hFSH, has proven comparable non-clinical pharmacological profiles to those of the widely used Gonal-f® (Serono Pharma S.p.A., Bari, Italy). The objective of this study was to show that Bemfola® yields comparable clinical pharmacokinetic (PK) and safety profiles to Gonal-f® in healthy female subjects. In this randomized, Phase I trial conducted in healthy female volunteers (N = 32), a 2-period, balanced 2-treatment crossover design was used. A single subcutaneous dose of 225 IU Bemfola® or Gonal-f® was administered in each treatment period per sequence. Blood was collected for pharmacokinetic analysis until 10 days after each r-hFSH treatment. For down-regulation of endogenous FSH subjects were given a depot injection with leuprolide acetate prior to the study drug in either sequence. Pharmacokinetic data was available for 23 subjects. No appreciable differences in key PK parameters were detected between the r-hFSH products as per non-compartmental PK analysis [i.e. for Bemfola® and Gonal-f® respectively AUC0–192 424.90 and 432.75 IU h/L, C
max 0.98 and 0.95 IU/L, T
max 24.0 h (range 6.0–24.0) and 24.0 h (range 9.0–24.0), t
1/2 43.58 h [standard deviation (SD 14.17)] and 42.58 h (SD 16.47), and K
e 0.0075 1/h (SD 0.003) and 0.0077 1/h (SD 0.002)]. Subgroup analysis for estradiol (E2) response was similar for Bemfola® and Gonal f® (AUC(0-–120)
p = 0.21 and C
p = 0.82). No major safety issues were identified and no immunogenic reaction to r-hFSH was observed. The results of this study indicate that a single dose of Bemfola® exhibits pharmacokinetic and safety profiles comparable to Gonal-f® in healthy young women.
European Journal of Drug Metabolism and Pharmacokinetics 01/2015; DOI:10.1007/s13318-015-0257-6 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Shared electronic health records (EHRs) systems can offer a complete medication overview of the prescriptions of different health care providers. We use health claims data of more than 1 million Austrians in 2006 and 2007 with 27 million prescriptions to estimate the effect of shared EHR systems on drug-drug interaction (DDI) and duplication warnings detection and prevention. The Austria Codex and the ATC/DDD information were used as a knowledge base to detect possible DDIs. DDIs are categorized as severe, moderate, and minor interactions. In comparison to the current situation where only DDIs between drugs issued by a single health care provider can be checked, the number of warnings increases significantly if all drugs of a patient are checked: severe DDI warnings would be detected for 20% more persons, and the number of severe DDI warnings and duplication warnings would increase by 17%. We show that not only do shared EHR systems help to detect more patients with warnings but DDIs are also detected more frequently. Patient safety can be increased using shared EHR systems.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects.
Material and methods:
50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study. Subjects received a single dose of liposomal curcumin (10 - 400 mg/m2; n = 2 - 6 per group) or placebo over 2 hours intravenously.
Dose-dependent increases in the plasma concentrations of curcumin and its metabolite tetrahydrocurcumin (THC) were detected. After the end of drug infusion, curcumin and THC plasma concentrations decreased within 6 - 60 minutes below the limit of quantification. Mean urinary excretion was ~ 0.1% of total systemic clearance. Liposomal curcumin was tolerated well, but a transient red blood cell echinocyte formation with concomitant increase in mean cellular volume was observed at dosages ≥ 120 mg/m2.
Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.
International journal of clinical pharmacology and therapeutics 12/2014; 53(01). DOI:10.5414/CP202076 · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The clinical value of T-wave variability (T-var) for ventricular arrhythmia (VA) risk prediction was evaluated.
Methods and results:
Three 20-min Holter-ECG-based T-var measurements (I1 at baseline, I2 after 6.5 ± 1.6 months and I3 after 13.1 ± 2.0 months) were done in 121 patients. T-var was defined as the amplitude variability of the T-wave with the maximum of T-wave oscillation. The endpoint was a fast, potentially fatal VA (>240 beats/min). During follow-up (20 ± 4 months) 20/121 patients (55% ischemic heart disease, 15% preserved left ventricular ejection fraction [LVEF]) had fast VA terminated by ICD or external shock. Although T-var did not differ between patients with vs. without fast VA at baseline (I1: 10.7 ± 7.3 µV vs. 7.8 ± 4.1 µV, P=0.170), patients with fast VA had higher T-var compared to those without fast VA at 2 subsequent measurements (I2: 14.0 ± 6.5 µV vs. 8.2 ± 3.6 µV, P=0.030; I3: 17.0 ± 5.4 µV vs. 8.8 ± 4.6 µV, P=0.004). The increase in T-var between I1 and I2 was higher in patients with fast VA (∆T-var=7.0 ± 9.3 µV), as compared to patients without (∆T-var=0.4 ± 4.3 µV). After adjustment for LVEF in a multiple logistic regression model, the odds ratio for developing fast VA was 1.1 (P=0.056) for each 1-µV increment in T-var at I1.
T-var is elevated in patients with fast VA, and both elevation of T-var and increase in T-var may complement LVEF in VA risk stratification.