Seeber B.,Innsbruck Medical University |
Ziehr S.C.,Innsbruck Medical University |
Gschlieer A.,Innsbruck Medical University |
Gschlieer A.,Medical University of Vienna |
And 7 more authors.
Contraception | Year: 2012
Background: The levonorgestrel-releasing intrauterine system (LNG-IUS) is well accepted as an easy-to-use contraceptive with an excellent side-effect profile. It contains a reservoir of 52 mg of levonorgestrel (LNG) with continuous release of the steroid. Its contraceptive use is approved for 5 years. The aim of this study was to determine the plasma concentration of LNG and its variation with time in patients with in-dwelling LNG-IUS Mirena®. Study Design: In this study, we determined LNG plasma concentrations in 110 women with LNG-IUS at different time points of use. Time from insertion of the system in the study population ranged from 20 days to 11.1 years. Quantitative LNG levels were determined using a validated liquid chromatography-tandem mass spectrometry assay. Results: The mean±SD LNG plasma level in all women was 147±59 pg/mL. A highly significant negative correlation between LNG plasma level and LNG-IUS time of use could be demonstrated. In the first year of use, LNG plasma level was as high as 191±71 pg/mL, decreasing to 157±68 pg/mL in the second year and 134±41 pg/mL in the third year. Even after exceeding the recommended period of LNG-IUS use, systemic LNG concentrations were detectable: 133±38 pg/mL in the sixth year, 133±48 pg/mL in the seventh year and 117±45 pg/mL in the eighth year. Furthermore, a significant negative correlation between LNG plasma level and body mass index could be shown. Conclusion: Systemic LNG concentrations can be found in all patients with LNG-IUS IUS. However, concentrations are much lower than in other forms of LNG application. Moreover, this study demonstrates that a systemic effect of LNG-IUS can also be found after the recommended contraceptive lifespan of 5 years. © 2012 Elsevier Inc. All rights reserved.
PubMed | Institute Salud del Nino, Hopital Necker Enfants Malades, Instituto Ortopedico Gaetano Pini, Landeskrankenhaus Bregenz and 19 more.
Type: Clinical Trial, Phase III | Journal: Arthritis & rheumatology (Hoboken, N.J.) | Year: 2015
The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease-modifying antirheumatic drugs were previously established in a phase III study that included a 4-month open-label lead-in period, a 6-month double-blind withdrawal period, and a long-term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient-reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup.Patients enrolled in the phase III trial could enter the open-label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double-blind period.One hundred fifty-three (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patient-years) of adverse events decreased during the LTE phase (433.61 events during the short-term phase [combined lead-in and double-blind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time.Long-term abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and quality-of-life benefits in patients with JIA.
Hasija R.,University of Genoa |
Pistorio A.,University of Genoa |
Ravelli A.,University of Genoa |
Demirkaya E.,University of Genoa |
And 17 more authors.
Arthritis and Rheumatism | Year: 2011
Objective To evaluate response to therapy over a 24-month period in a large prospective international cohort of patients with juvenile dermatomyositis (DM). Methods The study included 145 patients with recent-onset juvenile DM and 130 juvenile DM patients experiencing disease flare, all of whom were <18 years old. Disease activity parameters and therapeutic approaches in 4 geographic areas were analyzed at baseline and at 6, 12, and 24 months. Response was assessed according to the Pediatric Rheumatology International Trials Organization (PRINTO) juvenile DM response criteria, and data were reported "as observed" and in the intent-to-treat (ITT) population. Results Patients with recent-onset juvenile DM at baseline had higher baseline disease activity and greater improvement over 24 months when compared to juvenile DM patients experiencing disease flare at baseline. Methotrexate (MTX) or high-dose corticosteroids were administered more frequently to patients with recent-onset juvenile DM, compared to juvenile DM patients experiencing disease flare, who were more likely to receive cyclosporine. Compared to patients from Western and Eastern Europe, a higher proportion of patients from South and Central America and North America received pulse steroids, and the average steroid dosage was higher in the North American and South and Central American patients. The use of MTX was similar in all 4 regions, while cyclosporin A was more frequently used in Western Europe. In the "as observed" analysis, 57.9% of the patients with recent-onset juvenile DM and 36.4% of the patients experiencing disease flare (P < 0.001) reached at least a 70% response by PRINTO criteria at 6 months; these proportions had increased at month 24 to 78.4% and 51.2%, respectively (P < 0.001). Corresponding results of the ITT analysis were much lower, with only one-third of the patients able to maintain the initial assigned therapy over 24 months. Conclusion Patients with recent-onset juvenile DM are more likely to achieve significant clinical improvement over 24 months, when compared to patients experiencing flares of juvenile DM. Internationally, various therapeutic approaches are used to treat this disease. Copyright © 2011 by the American College of Rheumatology.
PubMed | Landeskrankenhaus Bregenz, University Childrens Hospital, Metabolic, Paracelsus Medical University and 2 more.
Type: | Journal: JIMD reports | Year: 2016
Barth syndrome is known as a highly recognizable X-linked disorder typically presenting with the three hallmarks: (left ventricular non-compaction) cardiomyopathy, neutropenia, and 3-methylglutaconic aciduria. Furthermore, growth retardation, mild skeletal myopathy, and specific facial features as well as mitochondrial dysfunction in muscle are frequently seen. Underlying mutations are found in TAZ and lead to defective cardiolipin remodeling.Here, we report atypical clinical manifestations of TAZ mutations in two male patients initially presenting with growth retardation and very mild skeletal myopathy. As other phenotypic hallmarks were missing, Barth syndrome had not been suspected in these patients. One of them has been incidentally diagnosed in the frame of an in-depth cardiolipin research analysis, while the underlying genetic defect was unexpectedly identified in the second one by exome sequencing.These cases underline that TAZ mutations might well be an underdiagnosed cause of skeletal myopathy and growth retardation and do not necessarily manifest with the full clinical picture of Barth syndrome.
PubMed | Landeskrankenhaus Bregenz, Hacettepe University, Innsbruck Medical University, University of Zürich and 3 more.
Type: Journal Article | Journal: Journal of inherited metabolic disease | Year: 2016
Arginase 1 (ARG1) deficiency is a rare urea cycle disorder (UCD). This hypothesis-generating study explored clinical phenotypes, metabolic profiles, molecular genetics, and treatment approaches in a cohort of children and adults with ARG1 deficiency to add to our understanding of the underlying pathophysiology.Clinical data were retrieved retrospectively from physicians using a questionnaire survey. Plasma aminoacids, guanidinoacetate (GAA), parameters indicating oxidative stress and nitric oxide (NO) synthesis as well as asymmetric dimethylarginine (ADMA) were measured at a single study site.Nineteen individuals with ARG1 deficiency and 19 matched controls were included in the study. In patients, paraparesis, cognitive impairment, and seizures were significantly associated suggesting a shared underlying pathophysiology. In patientsplasma GAA exceeded normal ranges and plasma ADMA was significantly elevated. Compared to controls, nitrate was significantly higher, and the nitrite:nitrate ratio significantly lower in subjects with ARG1 deficiency suggesting an advantage for NO synthesis by inducible NO synthase (iNOS) over endothelial NOS (eNOS). Logistic regression revealed no significant impact of any of the biochemical parameters (including arginine, nitrates, ADMA, GAA, oxidative stress) or protein restriction on long-term outcome.Three main hypotheses which must be evaluated in a hypothesis driven confirmatory study are delineated from this study: 1) clinical manifestations in ARG1 deficiency are not correlated with arginine, protein intake, ADMA, nitrates or oxidative stress. 2) GAA is elevated and may be a marker or an active part of the pathophysiology of ARG1 deficiency. 3) Perturbations of NO metabolism merit future attention in ARG1 deficiency.
Huemer M.,Landeskrankenhaus Bregenz |
Simma B.,Landeskrankenhaus Feldkirch |
Mayr D.,Landeskrankenhaus Bregenz |
Moslinger D.,Vienna University Hospital |
And 5 more authors.
Journal of Inherited Metabolic Disease | Year: 2012
Introduction Free asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide synthases (NOS). Suppression of nitric oxide (NO) synthesis increases the risk of atherosclerosis. Nevertheless, in the condition of oxidative stress, NOS blockade by ADMA may exert protective effects. Protein metabolism is altered in patients with phenylketonuria (PKU) on dietary treatment and as shown recently, oxidative stress is high in PKU. Since free ADMA concentrations are determined by both protein metabolism and oxidative stress we hypothesized, that free ADMA levels may be elevated in PKU patients. Design Sixteen patients with PKU on dietary treatment (mean age 10.1±5.2 yrs), and 91 healthy children (mean age 11.6± 3.7 yrs) participated in a cross sectional study. Results ADMA, total homocysteine (tHcy) and blood glucose were lower and the L-arginine/ADMA ratio was higher in PKU patients compared to controls. No significant correlation was present between phenylalanine (Phe) concentrations, protein intake, and lipid profile, history of cardiovascular disease or ADMA. Discussion In contrast to our hypothesis, ADMA was lower and the L-arginine/ADMA ratio was higher in PKU patients. Therefore, in PKU patients, the regulating function of ADMA on NO synthesis is altered and may thus contribute to oxidative stress. © SSIEM and Springer 2012.
Moschel M.,Landeskrankenhaus Feldkirch |
Wohlgenannt D.,Landeskrankenhaus Bregenz
European Surgery - Acta Chirurgica Austriaca | Year: 2015
Background: Epidural anaesthesia is considered as a basic element of enhanced recovery after surgery (ERAS). In regard of the expenditure and the possible complications, the authors established a modified protocol without epidural analgesia. Methods: In this prospective single-centre study, 64 consecutive patients undergoing elective colorectal surgery were treated according to the concept of ERAS, replacing epidural analgesia with infiltration of the incision lines. Results: Adequate pain control was possible in 52 (81 %) patients; 55 (86 %) did not need any antiemetic drugs, 41 (64 %) tolerated solid food on the first postoperative day and 51 (80 %) had first bowel movement until day 2. Discharge was possible on day 4.3, overall complication rate was 19 % and 30-day mortality was 3 %. Conclusions: ERAS in elective colon surgery is feasible using local infiltration of the incision line resulting in comparable outcome in regard of pain control, intestinal paralysis and complications. © 2015, Springer-Verlag Wien.
PubMed | Landeskrankenhaus Bregenz, Robert Bosch GmbH, Innsbruck Medical University, Landeskrankenhaus Bludenz and 5 more.
Type: Journal Article | Journal: International journal of public health | Year: 2016
Elevated hip fracture incidence is a major public health problem looming to aggravate in industrialized countries due to demographic developments. We report hip fracture incidence and expected future cases from Vorarlberg, the westernmost province of Austria, results potentially representative of Central European populations.Crude and standardized hip fracture incidence rates in Vorarlberg 2003-2013 are reported. Based on the age-specific incidence in 2013 or trends 2003-2013, we predict hip fractures till 2050.Female age-standardized hip fracture incidence decreased 2005-2013, whereas for men, the trend was rather unclear. Uncorrected forecasts indicate that by 2050, female and male cases will each have more than doubled from 2015 in all demographic core scenarios. Corrected by incidence trends before 2013, cases are expected to drop among women but rise among men.We anticipate rising hip fracture numbers in Vorarlberg within the next decades, unless prevention programs that presumably account for decreasing incidence rates, particularly among women since 2005, take further effect to counteract the predicted steady increase due to demographic changes. Concomitantly, augmented endeavors to target the male population by these programs are needed.
Huemer M.,Landeskrankenhaus Bregenz |
Huemer M.,University of Zürich |
Simma B.,Landeskrankenhaus Feldkirch |
Mayr D.,Landeskrankenhaus Bregenz |
And 6 more authors.
Journal of Pediatrics | Year: 2011
Objective: Although high levels of asymmetric dimethylarginine (ADMA) are associated with an increased risk for vasculopathy in adults, elevated ADMA concentrations also have been found in healthy young children. Patients with diabetes mellitus type 1 (DM1) are at risk for vasculopathy, and because the function of ADMA in the development of vascular symptoms is incompletely understood, we investigated ADMA concentrations in pediatric patients with DM1 compared with healthy age- and sex-matched individuals. Study design: This cross-sectional study included 85 pediatric patients with DM1 and 89 age- and sex-matched healthy controls. Results: ADMA concentrations were significantly lower in the patients with DM1 and were inversely correlated with hemoglobin A1c concentrations. Conclusions: Besides its vasoprotective function, nitric oxide itself may exert oxidative stress by generating free radicals. In these circumstances, ADMA would protect the system from nitric oxide overproduction and perpetuation of oxidative stress. This theory is supported by the physiologically higher ADMA concentrations in healthy children. Thus, low ADMA concentrations in children with DM1 may be an indicator of impaired protection against oxidative stress. Copyright © 2011 Mosby Inc. All rights reserved.