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"text": "\n7115\nMultislice spiral CT angiography in peripheral arterial occlusive disease: a valuable tool in detecting significant arterial lumen narrowing?\n\nPortugaller, HR\n\nSchoellnast, H\n\nHausegger, KA\n\nTiesenhausen, K\n\nAmann, W\n\nBerghold, A\n\nBeiträge in Fachzeitschriften\nISI:000224277600021\n15114490.0\n10.1007/s00330-004-2289-1\nNone\nThe aim of this study was to evaluate the potential of multislice CT angiography (CTA) in detecting hemodynamically significant (> or =70%) lesions of lower extremity inflow and runoff arteries. Fifty patients (42 men, 8 women; mean age 68 years) with peripheral arterial occlusive disease underwent multislice spiral CTA and digital subtraction angiography (DSA) from the infrarenal aorta to the supramalleolar region. CT parameters were 4x2.5-mm collimation, 15-mm table increment/rotation (pitch 6), and 1.25-mm reconstruction increment. Semitransparent volume rendering technique (STVR) images with semitransparent display of the arterial lumen (opacity: 50%) and vascular calcifications (opacity: 20%), as well as maximum intensity projection (MIP), and MIP together with axial CT studies were independently reviewed for hemodynamically significant lesions (> or =70% cross-sectional area reduction). DSA was the standard of reference. In 46 patients, 260 lesions were found (95 stenoses, 165 occlusions). For detecting > or =70% lesions in all vessel regions, sensitivity and specificity were 84% and 78% (STVR), 89% and 74% (MIP), and 92% and 83% (MIP+axial CT), respectively, with a significantly lower sensitivity of STVR ( p<0.05) and a significantly lower specificity of MIP studies ( p<0.01). Sensitivity and specificity were, respectively, 81% and 93% (STVR), 88% and 75% (MIP). and 92% and 95% (MIP+axial CT) at aortoiliac arteries, 92% and 73% (STVR), 95% and 70% (MIP) and 98% and 70% (MIP+axial CT) at femoropopliteal arteries, as well as 82% and 64% (STVR), 86% and 74% (MIP), and 90% and 74% (MIP+axial CT) at infrapopliteal arteries. Specificity of MIP-CTA was significantly lower in the aortoiliac region ( p<0.01), whereas STVR revealed significantly lower specificity at infrapopliteal arteries ( p<0.05). In the infrapopliteal region, the particular CTA imaging modalities led to misinterpretation regarding stenoses and occlusions in 39-45 cases, whereas only 0-6 significant aortoiliac and femoropopliteal lesions were misinterpreted. Multislice CTA is helpful in detecting hemodynamically significant lesions in peripheral arterial occlusive disease. Since axial CT studies yielded the most correct results, they should always be reviewed additionally. In the infrapopliteal region, exact lesion assessment remains problematic due to small vessel diameters.\n\nBerghold, Andrea\n\nHausegger, Klaus\n\nPortugaller, Rupert\n\nSchoellnast, Helmut\n\nTiesenhausen, Kurt\n\n\n"
},
{
"text": "\n73586\nEnzyme-histochemical studies of griseofulvin-intoxicated mouse livers.\n\nWOLTSCHE, M\n\nZATLOUKAL, K\n\nDENK, H\n\nBeiträge in Fachzeitschriften\nISI:A1991FX84300007\n1658525.0\nNone\nNone\nEnzyme-histochemical studies were conducted on livers of mice chronically fed griseofulvin (GF) in order to produce Mallory bodies (MBs) in hepatocytes. The development of MBs is associated with derangement of the immunohistochemically detectable intermediate filament (IF) cytoskeleton of the cytokeratin (CK) type, although no strict correlation between appearance or involution of MBs and the cytoskeletal alterations exists. Since the function of the IF cytoskeleton and the relationship of its disturbance to cell injury is unknown, the aim of the present study was to correlate the activities of several key enzymes of cellular metabolic pathways with the disturbance of the cytoskeleton architecture. For that purpose enzyme-histochemistry in combination with immunohistochemical CK-IF stainings were performed on identical sections. In GF-intoxicated mouse livers the normal topography of enzyme activities was disturbed, but no strict colocalization of enzymatic and cytoskeletal changes was found. Glucose-6-phosphatase, a microsomal enzyme involved in glucose output and gluconeogenesis, showed elevated activity in MB-free hepatocytes with diminished immunostainable CK-IF cytoskeleton refuting the concept of a disability of those cells to export glucose. It could indeed indicate that those cells without MBs are in the state of recovery. However, these cells could also resemble "hyperactive foci". Glycogen was decreased in MB-containing hepatocytes with disturbed cytoskeleton, and this feature favours the assumption of cell degeneration. On the other hand, the mitochondrial marker enzymes, i.e. succinate dehydrogenase, cytochrome-c-oxidase and 3-hydroxybutyrate dehydrogenase, remained unchanged in altered hepatocytes. Alkaline phosphatase activity at the canalicular pole of GF-intoxicated hepatocytes was elevated, indicating cholestatic features associated with this disorder. However, since altered hepatocytes did not show impairment of oxido-reductase activities, a severe impairment of bile secretion as a consequence of cell damage is unlikely. Unchanged or even increased ATPase activity of altered hepatocytes also indicated their sustained metabolic abilities. The results presented provide indirect evidence that hepatocytes with disturbed IF cytoskeleton do not significantly differ from normal cells with respect to oxidative metabolism, fatty acid synthesis and gluconeogenesis. This suggests that alterations of the IF cytoskeleton associated with GF intoxication and MB formation have no significant adverse influence on the metabolic functions of liver cells, as far as can be assessed by evaluation by enzyme-histochemical staining of several key enzymes.\n\nZatloukal, Kurt\n\n\n"
},
{
"text": "\n121107\nBurden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage.\n\nFalcone, GJ\n\nBiffi, A\n\nDevan, WJ\n\nJagiella, JM\n\nSchmidt, H\n\nKissela, B\n\nHansen, BM\n\nJimenez-Conde, J\n\nGiralt-Steinhauer, E\n\nElosua, R\n\nCuadrado-Godia, E\n\nSoriano, C\n\nAyres, AM\n\nSchwab, K\n\nPera, J\n\nUrbanik, A\n\nRost, NS\n\nGoldstein, JN\n\nViswanathan, A\n\nPichler, A\n\nEnzinger, C\n\nNorrving, B\n\nTirschwell, DL\n\nSelim, M\n\nBrown, DL\n\nSilliman, SL\n\nWorrall, BB\n\nMeschia, JF\n\nKidwell, CS\n\nMontaner, J\n\nFernandez-Cadenas, I\n\nDelgado, P\n\nBroderick, JP\n\nGreenberg, SM\n\nRoquer, J\n\nLindgren, A\n\nSlowik, A\n\nSchmidt, R\n\nFlaherty, ML\n\nKleindorfer, DO\n\nLangefeld, CD\n\nWoo, D\n\nRosand, J\n\non behalf of the International Stroke Genetics Consortium\n\nBeiträge in Fachzeitschriften\nISI:000310432800270\n22933587.0\n10.1161/STROKEAHA.112.659755\nPMC3479325\nBackground and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN.\nMethods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables.\nResults-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score.\nConclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN. (Stroke. 2012; 43: 2877-2883.)\n\nEnzinger, Christian\n\nPichler, Alexander\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n139590\nThe Austrian breast implant register: recent trends in implant-based breast surgery.\n\nWurzer, P\n\nRappl, T\n\nFriedl, H\n\nKamolz, LP\n\nSpendel, S\n\nHoflehner, H\n\nParvizi, D\n\nBeiträge in Fachzeitschriften\nISI:000345134000006\n25320030.0\n10.1007/s00266-014-0407-2\nNone\nDue to the fact that the number of breast implant surgeries for cosmetic and medical purposes is rising yearly, a discussion about the quality of service for both patients and physicians is more important than ever. To this end, we reviewed the Austrian Breast Implant Register with one specific question in mind: What are the trends?\n In the statistical analysis of the Austrian Breast Implant Register, we were able to identify 13, 12 registered breast implants between 2004 and 2012. The whole dataset was then divided into medical and cosmetic groups. We focused on device size, surface characteristics, filling material, device placement and incision site. All factors were considered for all examined years.\n In summary, the most used device had a textured surface (97 %) and silicone gel as the filling material (93 %). The mean size of implants for the cosmetic group was 240 cc, placement was submuscular (58 %) and the incision site was inframammary (67 %). In the medical group, the mean size was 250 cc. Yearly registrations had their peak in 2008 (1, 98 registered devices); from this year on, registrations decreased annually. A slight trend away from subglandular placement in the cosmetic group was noted. Also, the usage of implants with polyurethane surface characteristics has increased since 2008. The smooth surface implants had a peak usage in 2006 and their usage decreased steadily from then on whereas the textured surface was steady over the years.\n Keeping the problems related to the quality of breast implants in mind, we could recommend an obligatory national register. Organisations of surgeons and governments should develop and establish these registers. Furthermore, an all-encompassing international register should be established by the European Union and the American FDA (Food and Drug Administration); this might be useful in comparing the individual country registers and also would help in delivering "evidence based" medicine in cosmetic and medical procedures.\n This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.\n\nKamolz, Lars-Peter\n\nRappl, Thomas\n\nSpendel, Stephan\n\nWurzer, Paul\n\n\n"
},
{
"text": "\n169185\nCultural Competence and Global Health: Perspectives for Medical Education - Position paper of the GMA Committee on Cultural Competence and Global Health.\n\nMews, C\n\nSchuster, S\n\nVajda, C\n\nLindtner-Rudolph, H\n\nSchmidt, LE\n\nBösner, S\n\nGüzelsoy, L\n\nKressing, F\n\nHallal, H\n\nPeters, T\n\nGestmann, M\n\nHempel, L\n\nGrützmann, T\n\nSievers, E\n\nKnipper, M\n\nBeiträge in Fachzeitschriften\nISI:000441607500001\n30186938.0\n10.3205/zma001174\nPMC6120152\nIntroduction: Routine medical care in Germany, Austria and Switzerland is being increasingly impacted by the cultural and linguistic diversity of an ever more complex world. Both at home and as part of international student exchanges, medical students are confronted with different ways of thinking and acting in relation to health and disease. Despite an increasing number of courses on cultural competence and global health at German-speaking medical schools, systematic approaches are lacking on how to integrate this topic into medical curricula. Methodological approach: This paper is based on a structured consensus-building process by a multidisciplinary committee composed of faculty and students. In a first step, a qualitative online survey was carried out in order to establish an inventory of definitions and concepts. After the second step, in which a literature search was conducted and definitions of global health and transcultural and intercultural competence were clarified, recommendations were formulated regarding content, teaching and institutional infrastructure. Based on small-group work and large-group discussions, different perspectives and critical issues were compiled using multiple feedback loops that served to ensure quality. Results: An inventory on the national and international level showed that great heterogeneity exists in regard to definitions, teaching strategies, teaching formats and faculty qualification. Definitions and central aspects considered essential to medical education were thus established for the use of the terms "cultural competence" and "global health". Recommendations are given for implementation, ranging from practical realization to qualification of teaching staff and education research. Outlook: High-quality healthcare as a goal calls for the systematic internationalization of undergraduate medical education. In addition to offering specific courses on cultural competence and global health, synergies would be created through the integration of cultural competence and global health content into the curricula of already existing subject areas. The NKLM (the national competence-based catalogue of learning objectives for undergraduate medical education) would serve as a basis for this.\n\nVajda, Christian\n\n\n"
},
{
"text": "\n170333\nDeveloping definitions for invasive fungal diseases in critically ill adult patients in intensive care units. Protocol of the FUNgal infections Definitions in ICU patients (FUNDICU) project.\n\nBassetti, M\n\nScudeller, L\n\nGiacobbe, DR\n\nLamoth, F\n\nRighi, E\n\nZuccaro, V\n\nGrecchi, C\n\nRebuffi, C\n\nAkova, M\n\nAlastruey-Izquierdo, A\n\nArikan-Akdagli, S\n\nAzoulay, E\n\nBlot, SI\n\nCornely, OA\n\nLass-Flörl, C\n\nKoehler, P\n\nCuenca-Estrella, M\n\nde Lange, DW\n\nDe Rosa, FG\n\nDe Waele, JJ\n\nDimopoulos, G\n\nGarnacho-Montero, J\n\nHoenigl, M\n\nKanj, SS\n\nMaertens, J\n\nMartin-Loeches, I\n\nMuñoz, P\n\nKullberg, BJ\n\nAgvald-Ohman, C\n\nPoulakou, G\n\nRello, J\n\nSanguinetti, M\n\nTaccone, FS\n\nTimsit, JF\n\nTorres, A\n\nVazquez, JA\n\nCalandra, T\n\nfrom the Study Group for Infections in Critically Ill Patients (ESGCIP) and the Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID)\n\nEuropean Society of Intensive Care Medicine (ESICM)\n\nEuropean Confederation of Medical Mycology (ECMM)\n\nMycoses Study Group Education and Research Consortium (MSGERC)\n\nBeiträge in Fachzeitschriften\nISI:000462609900001\n30426598.0\n10.1111/myc.12869\nNone\nThe reliability of diagnostic criteria for invasive fungal diseases (IFD) developed for severely immunocompromised patients is questionable in critically ill adult patients in intensive care units (ICU).\n To develop a standard set of definitions for IFD in critically ill adult patients in ICU.\n Based on a systematic literature review, a list of potential definitions to be applied to ICU patients will be developed by the ESCMID Study Group for Infections in Critically Ill Patients (ESGCIP) and the ESCMID Fungal Infection Study Group (EFISG) chairpersons. The proposed definitions will be evaluated by a panel of 30 experts using the RAND/UCLA appropriateness methods. The panel will rank each of the proposed definitions on a 1-9 scale trough a dedicated questionnaire, in two rounds: one remote and one face-to-face. Based on their median rank and the level of agreement across panel members, selected definitions will be organised in a main consensus document and in an executive summary. The executive summary will be made available online for public comments.\n The present consensus project will seek to provide standard definitions for IFD in critically ill adult patients in ICU, with the ultimate aims of improving their clinical outcome and facilitating the comparison and generalizability of research findings.\n © 2018 Blackwell Verlag GmbH.\n\nHönigl, Martin\n\n\n"
},
{
"text": "\n182403\nEfficacy of teriparatide compared with risedronate on FRAX<sup>®</sup>-defined major osteoporotic fractures: results of the VERO clinical trial.\n\nBody, JJ\n\nMarin, F\n\nKendler, DL\n\nZerbini, CAF\n\nLópez-Romero, P\n\nMöricke, R\n\nCasado, E\n\nFahrleitner-Pammer, A\n\nStepan, JJ\n\nLespessailles, E\n\nMinisola, S\n\nGeusens, P\n\nBeiträge in Fachzeitschriften\nISI:000536417900001\n32474650.0\n10.1007/s00198-020-05463-4\nPMC7497508\nFRAX® calculates the 10-year probability of major osteoporotic fractures (MOF), which are considered to have a greater clinical impact than other fractures. Our results suggest that, in postmenopausal women with severe osteoporosis, those treated with teriparatide had a 60% lower risk of FRAX®-defined MOF compared with those treated with risedronate.\n The VERO trial was an active-controlled fracture endpoint clinical trial that enrolled postmenopausal women with severe osteoporosis. After 24 months, a 52% reduction in the hazard ratio (HR) of clinical fractures was reported in patients randomized to teriparatide compared with risedronate. We examined fracture results restricted to FRAX®-defined major osteoporotic fractures (MOF), which include clinical vertebral, hip, humerus, and forearm fractures.\n In total, 1360 postmenopausal women (mean age 72.1 years) were randomized to receive subcutaneous daily teriparatide (20 μg) or oral weekly risedronate (35 mg). Patient cumulative incidence of ≥ 1 FRAX®-defined MOF and of all clinical fractures were estimated by Kaplan-Meier analyses, and the comparison between treatments was based on the stratified log-rank test. Additionally, an extended Cox model was used to estimate HRs at different time points. Incidence fracture rates were estimated at each 6-month interval.\n After 24 months, 16 (2.6%) patients in the teriparatide group had ≥ 1 low trauma FRAX®-defined MOF compared with 40 patients (6.4%) in the risedronate group (HR 0.40; 95% CI 0.23-0.68; p = 0.001). Clinical vertebral and radius fractures were the most frequent FRAX®-defined MOF sites. The largest difference in incidence rates of both FRAX®-defined MOF and all clinical fractures between treatments occurred during the 6- to 12-month period. There was a statistically significant reduction in fractures between groups as early as 7 months for both categories of clinical fractures analyzed.\n In postmenopausal women with severe osteoporosis, treatment with teriparatide was more efficacious than risedronate, with a 60% lower risk of FRAX®-defined MOF during the 24-month treatment period. Fracture risk was statistically significantly reduced at 7 months of treatment.\n ClinicalTrials.gov Identifier: NCT01709110 EudraCT Number: 2012-000123-41.\n\nFahrleitner-Pammer, Astrid\n\n\n"
},
{
"text": "\n182414\nRisk Stratification Tools and Prognostic Models in Non-muscle-invasive Bladder Cancer: A Critical Assessment from the European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel.\n\nSoukup, V\n\nČapoun, O\n\nCohen, D\n\nHernández, V\n\nBurger, M\n\nCompérat, E\n\nGontero, P\n\nLam, T\n\nMostafid, AH\n\nPalou, J\n\nvan Rhijn, BWG\n\nRouprêt, M\n\nShariat, SF\n\nSylvester, R\n\nYuan, Y\n\nZigeuner, R\n\nBabjuk, M\n\nBeiträge in Fachzeitschriften\nISI:000531657200013\n30470647.0\n10.1016/j.euf.2018.11.005\nNone\nThis review focuses on the most widely used risk stratification and prediction tools for non-muscle-invasive bladder cancer (NMIBC).\n To assess the clinical use and relevance of risk stratification and prediction tools to enhance clinical decision making and counselling of patients with NMIBC.\n The most frequent, currently used risk stratification tools and prognostic models for NMIBC patients were identified by the members of the European Association of Urology (EAU) Guidelines Panel on NMIBC.\n The 2006 European Organization for Research and Treatment of Cancer (EORTC) risk tables are the most widely used and validated tools for risk stratification and prognosis prediction in NMIBC patients. The EAU risk categories constitute a simple alternative to the EORTC risk tables and can be used for comparable risk stratification. In the subgroup of NMIBC patients treated with a short maintenance schedule of bacillus Calmette-Guerin (BCG), the Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model is more accurate than the EORTC risk tables. Both the EORTC risk tables and the CUETO scoring model overestimate the recurrence and progression risks in patients treated according to current guidelines. The new concept of conditional recurrence and progression estimates is very promising during follow-up but should be validated.\n Risk stratification and prognostic models enable outcome comparisons and standardisation of treatment and follow-up. At present, none of the available risk stratification and prognostic models reflects current standards of treatment. The EORTC risk tables and CUETO scoring model should be updated with previously unavailable data and recalculated.\n Non-muscle-invasive bladder cancer is a heterogeneous disease. A risk-based therapeutic approach is recommended. We present available risk stratification and prediction tools and the degree of their validation with the aim to increase their use in everyday clinical practice.\n Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n183012\nCaMKIIδC Drives Early Adaptive Ca<sup>2+</sup> Change and Late Eccentric Cardiac Hypertrophy.\n\nLjubojevic-Holzer, S\n\nHerren, AW\n\nDjalinac, N\n\nVoglhuber, J\n\nMorotti, S\n\nHolzer, M\n\nWood, BM\n\nAbdellatif, M\n\nMatzer, I\n\nSacherer, M\n\nRadulovic, S\n\nWallner, M\n\nIvanov, M\n\nWagner, S\n\nSossalla, S\n\nvon Lewinski, D\n\nPieske, B\n\nBrown, JH\n\nSedej, S\n\nBossuyt, J\n\nBers, DM\n\nBeiträge in Fachzeitschriften\nISI:000579070600008\n32821022.0\n10.1161/CIRCRESAHA.120.316947\nPMC7547876\nCaMKII (Ca2+-Calmodulin dependent protein kinase) δC activation is implicated in pathological progression of heart failure (HF) and CaMKIIδC transgenic mice rapidly develop HF and arrhythmias. However, little is known about early spatio-temporal Ca2+ handling and CaMKII activation in hypertrophy and HF.\n To measure time- and location-dependent activation of CaMKIIδC signaling in adult ventricular cardiomyocytes, during transaortic constriction (TAC) and in CaMKIIδC transgenic mice.\n We used human tissue from nonfailing and HF hearts, 4 mouse lines: wild-type, KO (CaMKIIδ-knockout), CaMKIIδC transgenic in wild-type (TG), or KO background, and wild-type mice exposed to TAC. Confocal imaging and biochemistry revealed disproportional CaMKIIδC activation and accumulation in nuclear and perinuclear versus cytosolic regions at 5 days post-TAC. This CaMKIIδ activation caused a compensatory increase in sarcoplasmic reticulum Ca2+ content, Ca2+ transient amplitude, and [Ca2+] decline rates, with reduced phospholamban expression, all of which were most prominent near and in the nucleus. These early adaptive effects in TAC were entirely mimicked in young CaMKIIδ TG mice (6-8 weeks) where no overt cardiac dysfunction was present. The (peri)nuclear CaMKII accumulation also correlated with enhanced HDAC4 (histone deacetylase) nuclear export, creating a microdomain for transcriptional regulation. At longer times both TAC and TG mice progressed to overt HF (at 45 days and 11-13 weeks, respectively), during which time the compensatory Ca2+ transient effects reversed, but further increases in nuclear and time-averaged [Ca2+] and CaMKII activation occurred. CaMKIIδ TG mice lacking δB exhibited more severe HF, eccentric myocyte growth, and nuclear changes. Patient HF samples also showed greatly increased CaMKIIδ expression, especially for CaMKIIδC in nuclear fractions.\n We conclude that in early TAC perinuclear CaMKIIδC activation promotes adaptive increases in myocyte Ca2+ transients and nuclear transcriptional responses but that chronic progression of this nuclear Ca2+-CaMKIIδC axis contributes to eccentric hypertrophy and HF.\n\nAbdellatif, Mahmoud\n\nDalinac, Natasa\n\nHolzer, Michael\n\nHolzer, Senka\n\nRadulovic, Snjezana\n\nSacherer, Michael\n\nSedej, Simon\n\nVoglhuber, Julia\n\nvon Lewinski, Dirk\n\nWallner, Markus\n\n\n"
},
{
"text": "\n2532\nThe effect of treatment with levothyroxine or iodine on thyroid size and thyroid growth stimulating immunoglobulins in endemic goitre patients.\n\nWilders-Truschnig, MM\n\nWarnkross, H\n\nLeb, G\n\nLangsteger, W\n\nEber, O\n\nTiran, A\n\nDobnig, H\n\nPassath, A\n\nLanzer, G\n\nDrexhage, HA\n\nBeiträge in Fachzeitschriften\nISI:A1993LV81800005\n7900936.0\n10.1111/j.1365-2265.1993.tb02367.x\nNone\nOBJECTIVE We assessed the effect of levothyroxine or iodine on thyroid size and on thyroid growth stimulating immunoglobulins in endemic goitre patients. DESIGN Levothyroxine or iodine was given orally in an open randomized prospective study (100 and 200 mug respectively). PATIENTS Thirty-seven euthyroid patients with diffuse iodine deficiency goitres and thyroid growth stimulating immunoglobulins were studied. MEASUREMENTS Thyroid size, thyroid growth stimulating immunoglobulins (mitosis arrest assay), basal TSH, free T3, free T4, thyroid anti-microsomal antibodies, antithyroglobulin antibodies, anti-TSH receptor antibodies and urinary iodine excretion were measured. RESULTS Thyroid size decreased significantly in both groups, in the levothyroxine group more than in the iodine treated group. Thyroid growth stimulating immunoglobulins levels also decreased significantly in both groups. Between groups there was no statistically significant difference. A statistically significant correlation between thyroid growth stimulating immunoglobulins reduction profiles and goitre size reduction could not be established. TSH levels became suppressed in the levothyroxine group while the T4 values rose; in the iodine treated group TSH levels stayed constant as did T4. None of the patients developed thyroid microsomal or thyroglobulin autoantibodies and/or hyperthyroidism during the treatment. CONCLUSIONS Levothyroxine as well as iodine was effective in reducing thyroid size as well asthyroid growth stimulating immunoglobulins levels in endemic goitre patients. Since in both groups TSH levels were not related to thyroid size reduction, other factors than TSH suppression must be responsible for the observed thyroid size reduction. Iodine itself by virtue of its antiproliferative action on thyrocytes may have had a direct action on the goitre reduction during iodine treatment; however, the levothyroxine dose, containing less iodine, had a similar effect. A complicated picture hence emerges with regard to factors involved in the shrinkage of iodine deficiency goitre during thyroxine or iodine therapy. These findings indicate that TSH and thyroid growth promoting immunoglobulins are not the only influences on the size of endemic goitres, although it cannot be excluded that these two factors contribute to influence the pathogenetic process.\n\nLanzer, Gerhard\n\n\n"
},
{
"text": "\n4922\nTreatment of hydrocephalus determined by the European Orbis Sigma Valve II survey: a multicenter prospective 5-year shunt survival study in children and adults in whom a flow-regulating shunt was used.\n\nHanlo, PW\n\nCinalli, G\n\nVandertop, WP\n\nFaber, JA\n\nBøgeskov, L\n\nBørgesen, SE\n\nBoschert, J\n\nChumas, P\n\nEder, H\n\nPople, IK\n\nSerlo, W\n\nVitzthum, E\n\nBeiträge in Fachzeitschriften\nISI:000183865500010\n12854744.0\n10.3171/jns.2003.99.1.0052\nNone\nOBJECT: The goal of this study was to evaluate the long-term results of a flow-regulating shunt (Orbis Sigma Valve [OSV] II Smart Valve System; Integra NeuroSciences, Sophia Antipolis, France) in the treatment of hydrocephalus, whether it was a first insertion procedure or surgical revision of another type of shunt, in everyday clinical practice in a multicenter prospective study. METHODS: Patients of any age who had hydrocephalus underwent implantation of an OSV II system. The primary end point of the study was defined as any shunt-related surgery. The secondary end point was a mechanical complication (shunt obstruction, overdrainage, catheter misplacement, migration, or disconnection) or infection. The overall 5-year shunt survival rates and survival as it applied to different patient subgroups were assessed. Five hundred fifty-seven patients (48% of whom were adults and 52% of whom were children) were selected for OSV II shunt implantation; 196 patients reached the primary end point. Shunt obstruction occurred in 75 patients (13.5%), overdrainage in 10 patients (1.8%), and infection in 46 patients (8.2%). The probability of having experienced a shunt failure-free interval at 1 year was 71% and at 2 years it was 67%; thereafter the probability remained quite stable in following years (62% at the 5-year follow-up examination). No difference in shunt survival was observed between the overall pediatric (< or = 16 years of age) and adult populations. In the pediatric age group, however, there was a significantly lower rate of shunt survival in children younger than 6 months of age (55% at the 5-year follow-up examination). CONCLUSIONS: In this prospective study the authors demonstrate the effectiveness of flow regulation in the treatment of hydrocephalus both in children and in adults. Flow-regulating shunts limit the incidence of overdrainage and shunt-related complications. The overall 5-year shunt survival rate (62%) compares favorably with rates cited in other recently published series.\n\nEder, Hans\n\n\n"
},
{
"text": "\n73949\nPropofol and methohexital as anesthetic agents for electroconvulsive therapy: a randomized, double-blind comparison of electroconvulsive therapy seizure quality, therapeutic efficacy, and cognitive performance.\n\nGeretsegger, C\n\nNickel, M\n\nJudendorfer, B\n\nRochowanski, E\n\nNovak, E\n\nAichhorn, W\n\nBeiträge in Fachzeitschriften\nISI:000251488800009\n18090696.0\n10.1097/0b013e31814da971\nNone\nBACKGROUND: Propofol is often used as an anesthetic agent for electroconvulsive therapy (ECT). Whether the relatively short seizure duration, resulting from the medication, deteriorates the seizure quality and therapeutic outcomes, or whether propofol might be associated with small but significant post-ECT cognitive impairments, is still a subject of controversy. The purpose of our study was to test these hypotheses in comparison with methohexital. MATERIALS AND METHODS: In a double-blind, controlled study, 50 patients with severe major depression who were to be treated with ECT were randomly assigned to anesthesia with propofol (120.9 +/- 50.0 mg) or methohexital (83 +/- 26.3 mg) and were observed for 2 months. The 2 drugs were compared on the basis of electroencephalography-registered seizure duration, mean blood pressure, as well as pulse frequency, seizure efficacy index, and postictal suppression. Systolic and diastolic blood pressure, and seizure duration and quality were recorded consecutively during ECT treatments. Changes in depressive symptoms and cognitive functions were measured at 5 time points, pre-ECT, after the third to fifth ECT, post-ECT treatment, and at a follow-up examination 2 and 8 weeks after the last ECT treatment. RESULTS: Patients on propofol showed a significantly lower increase in blood pressure post-ECT (P < 0.001), their seizure duration was comparable to patients on methohexital (P = 0.072), and seizure quality was significantly superior, as was measured by the Postictal Suppression Index (P = 0.020), and comparable to the methohexital group as measured by the Seizure Efficacy Index (P = 0.160). The improvement of depressive symptoms and the improvement in cognitive functions were similar in both groups (with the exception of the results from 2 cognition tests). CONCLUSIONS: Propofol, as compared with methohexital, results in a more moderate increase in blood pressure and shorter seizure duration. The seizure quality did not differ significantly between the 2 groups. We detected a tendency toward improved cognitive performance after anesthesia with propofol as compared with methohexital, but with statistical significance in only 2 cognition trials. Therefore, propofol is a safe and efficacious anesthetic for ECT treatment.\n\nNickel, Marius\n\n\n"
},
{
"text": "\n121605\nANTIHYPERTENSIVE EFFICACY AND SAFETY OF OLMESARTAN AND RAMIPRILIN ELDERLY PATIENTS WITH MILD TO MODERATE SYSTOLIC AND DIASTOLICESSENTIAL HYPERTENSION.\n\nMallion, JM\n\nOmboni, S\n\nBarton, J\n\nvan Mieghem, W\n\nNarkiewicz, K\n\nPanzer, PK\n\nPuig, JG\n\nStefanadis, C\n\nZweiker, R\n\n\n\nBeiträge in Fachzeitschriften\nISI:000307482300015\nNone\nNone\nNone\nObjective. To compare the efficacy and safety of olmesartan medoxomil (O) and ramipril (R) in elderly patients with essential arterial hypertension. Methods. After a 2-week placebo washout, 351 elderly hypertensive patients aged 65-89 years (office sitting diastolic blood pressure, DBP, 90-109 mmHg and office sitting systolic blood pressure, SBP, 140-179 mmHg) were randomized double-blind to 12-week treatment with O 10 mg or R 2.5 mg once daily. After the first 2 and 6 weeks, doses could be doubled in non-normalized (blood pressure >= 140/90 mmHg for non-diabetic and >= 130/80 mmHg for diabetic) subjects, up to 40 mg for O and 10 mg for R. Office blood pressures were assessed at randomization, after 2, and 12 weeks of treatment; 24-h ambulatory blood pressure (ABP) was recorded at randomization and after 12 weeks. Results. At week 12, in the intention-to-treat population (170 patients O and 175 R) the rate of normalized subjects was significantly larger in the O group (38.8% vs 26.3% R; p = 0.013). Baseline-adjusted mean sitting office blood pressure reduction at final visit was not significantly greater under O [SBP: 16.6 (95% confidence interval 14.0/19.2) mmHg vs 13.0 (10.4/15.6) mmHg R, p = 0.206; DBP: 11.8 (10.3/13.3) mmHg vs 10.5 (9.0/12.0) mmHg, p = 0.351]. In the subgroup of patients with valid ABP recordings (38 O and 47 R), the reduction in 24-h average blood pressure was significantly (p = 0.01) larger with O [SBP: 8.9 (9.8/8.1) and DBP: 5.7 (6.3/5.1) mmHg] than with R [6.7 (7.9/5.6) and 4, (5.1/3.7) mmHg]. The superiority of O was particularly evident in the last 4 h from the dosing interval. The proportion of patients with drug-related adverse events was comparable in the two groups (4.0% O vs 4.5% R), as well as the number of patients discontinuing study drug because of a side-effect (8 O vs 7 R). Conclusions. In elderly patients with essential arterial hypertension, O provides an effective, prolonged and well tolerated blood pressure control, with significantly better blood pressure normalization than R and represents a useful option among first-line drug treatments of hypertension in this age group.\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n131581\nLong-term outcomes of patients with Wilson disease in a large Austrian cohort.\n\nBeinhardt, S\n\nLeiss, W\n\nStättermayer, AF\n\nGraziadei, I\n\nZoller, H\n\nStauber, R\n\nMaieron, A\n\nDatz, C\n\nSteindl-Munda, P\n\nHofer, H\n\nVogel, W\n\nTrauner, M\n\nFerenci, P\n\nBeiträge in Fachzeitschriften\nISI:000333057500027\n24076416.0\n10.1016/j.cgh.2013.09.025\nNone\nWilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in a well-characterized Austrian cohort of patients with Wilson disease.\n We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes. For 53 patients lost during the follow-up period, those that died and reasons for their death were identified from the Austrian death registry.\n The mean observation period was 14.8 ± 11.4 years (range, 0.5-52.0 years), resulting in 3116 patient-years. Of the patients, 61% presented with hepatic disease, 27% with neurologic symptoms, and 10% were diagnosed by family screening at presymptomatic stages. Patients with a hepatic presentation were diagnosed younger (21.2 ± 12.0 years) than patients with neurologic disease (28.8 ± 12.0; P < .001). In 2% of patients, neither symptoms nor onset of symptoms could be determined with certainty. Most patients stabilized (35%) or improved on chelation therapy (26% fully recovered, 24% improved), but 15% deteriorated; 8% required a liver transplant, and 7.4% died within the observation period (71% of deaths were related to Wilson disease). A lower proportion of patients with Wilson disease survived for 20 years (92%) than healthy Austrians (97%), adjusted for age and sex (P = .03). Cirrhosis at diagnosis was the best predictor of death (odds ratio, 6.8; 95% confidence interval, 1.5-31.03; P = .013) and need for a liver transplant (odds ratio, 07; 95% confidence interval, 0.016-0.307; P < .001). Only 84% of patients with cirrhosis survived 20 years after diagnosis (compared with healthy Austrians, P =.008).\n Overall, patients who receive adequate care for Wilson disease have a good long-term prognosis. However, cirrhosis increases the risk of death and liver disease. Early diagnosis, at a precirrhotic stage, might increase survival times and reduce the need for a liver transplant.\n Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n132117\nNanoparticulate flurbiprofen reduces amyloid-β42 generation in an in vitro blood-brain barrier model.\n\nMeister, S\n\nZlatev, I\n\nStab, J\n\nDocter, D\n\nBaches, S\n\nStauber, RH\n\nDeutsch, M\n\nSchmidt, R\n\nRopele, S\n\nWindisch, M\n\nLanger, K\n\nWagner, S\n\nvon Briesen, H\n\nWeggen, S\n\nPietrzik, CU\n\nBeiträge in Fachzeitschriften\nISI:000329909300001\n24280275.0\n10.1186/alzrt225\nPMC3978673\nThe amyloid-β42 (Aβ42) peptide plays a crucial role in the pathogenesis of Alzheimer's disease (AD), the most common neurodegenerative disorder affecting the elderly. Over the past years, several approaches and compounds developed for the treatment of AD have failed in clinical studies, likely in part due to their low penetration of the blood-brain barrier (BBB). Since nanotechnology-based strategies offer new possibilities for the delivery of drugs to the brain, this technique is studied intensively for the treatment of AD and other neurological disorders.\n The Aβ42 lowering drug flurbiprofen was embedded in polylactide (PLA) nanoparticles by emulsification-diffusion technique and their potential as drug carriers in an in vitro BBB model was examined. First, the cytotoxic potential of the PLA-flurbiprofen nanoparticles on endothelial cells and the cellular binding and uptake by endothelial cells was studied. Furthermore, the biological activity of the nanoparticulate flurbiprofen on γ-secretase modulation as well as its in vitro release was examined. Furthermore, the protein corona of the nanoparticles was studied as well as their ability to transport flurbiprofen across an in vitro BBB model.\n PLA-flurbiprofen nanoparticles were endocytosed by endothelial cells and neither affected the vitality nor barrier function of the endothelial cell monolayer. The exposure of the PLA-flurbiprofen nanoparticles to human plasma occurred in a rapid protein corona formation, resulting in their decoration with bioactive proteins, including apolipoprotein E. Furthermore, luminally administered PLA-flurbiprofen nanoparticles in contrast to free flurbiprofen were able to modulate γ-secretase activity by selectively decreasing Aβ42 levels in the abluminal compartment of the BBB model.\n In this study, we were able to show that flurbiprofen can be transported by PLA nanoparticles across an in vitro BBB model and most importantly, the transported flurbiprofen modulated γ-secretase activity by selectively decreasing Aβ42 levels. These results demonstrate that the modification of drugs via embedding in nanoparticles is a promising tool to facilitate drug delivery to the brain, which enables future development for the treatment of neurodegenerative disorders like AD.\n\nRopele, Stefan\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n147067\nSleep Related Breathing Disorders and Inflammation - The Missing Link? A Cohort Study Evaluating the Interaction of Inflammation and Sleep Related Breathing Disorders and Effects of Treatment.\n\nTroester, N\n\nPalfner, M\n\nSchmidberger, E\n\nOlschewski, H\n\nAvian, A\n\nBeiträge in Fachzeitschriften\nISI:000360965800067\n26356577.0\n10.1371/journal.pone.0137594\nPMC4565554\nSleep related breathing disorders (SRBD) are associated with both obesity and systemic inflammation. While the relationship between obesity and SRBD is established, the causality between inflammation and SRBD remains unclear. In this study we investigated the relation between SRBD and C-reactive protein (CRP) as a parameter of inflammation and the influence of SRBD treatment on CRP with additional regard to changes in metabolic and cardiovascular parameters.\n Polysomnography (PSG) and laboratory data of patients diagnosed with SRBD over a period of 5 years were prospectively collected in a database and retrospectively analysed regarding the association of SRBD (according to apnoea-hypopnoea- index (AHI), duration of events and extent of desaturation) to CRP, blood pressure, cholesterol, fasting plasma glucose, HbA1c, quality of life measured via a visual analogue scale (VAS 0-100%), and the effects of SRBD therapy on these parameters.\n 716 patients were included in the study, 171 with mild SRBD (AHI ≥5 to <15/h), 209 with moderate SRBD (AHI 15 to <30/h), 336 with severe SRBD (AHI ≥30/h). Results according to severity of SRBD. Severe SRBD was significantly associated with elevated levels of CRP (3.7 [1.8-7.0] mg/l, vs. moderate (p = 0.001), and mild SRBD (p<0.001), and higher prevalence of hypertension as compared to moderate and mild SRBD (p<0.001, respectively). Results in highly successful treatment. If SRBD treatment was highly successful (AHI <5/h), CRP and quality of life improved significantly (p = 0.001 and p = 0.002), as did blood pressure (p<0.001 for systolic and diastolic values), although BMI increased (p<0.001). Results in partially successful treatment. If success was defined as reduction of AHI of ≥50%, CRP also decreased (p<0.001), as did blood pressure (p<0.001). Again, BMI increased (p<0.001).\n This is the first study to show an association of SRBD and CRP independently of BMI in a large cohort. The SRBD therapy-induced CRP decrease was not associated with BMI changes or metabolic changes but rather with the magnitude of AHI improvement.\n\nAvian, Alexander\n\nOlschewski, Horst\n\nTröster, Natascha\n\n\n"
},
{
"text": "\n155894\nPilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER trial) - study protocol for a randomized controlled trial.\n\nLozanovski, VJ\n\nHouben, P\n\nHinz, U\n\nHackert, T\n\nHerr, I\n\nSchemmer, P\n\nBeiträge in Fachzeitschriften\nISI:000338455900004\n24894410.0\n10.1186/1745-6215-15-204\nPMC4059031\nPancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with marked resistance to chemo- and radiotherapy. PDA-cancer stem cells (CSCs) are not targeted by current therapies and may be a reason for poor prognosis. Studies indicate that diets rich in cabbage, broccoli, and cauliflower offer cancer preventative and therapeutic benefits. Recent experimental studies have confirmed these findings and demonstrated that isothiocyanate, sulforaphane, and the polyphenol, quercetin, effectively reduced tumor growth and enhanced the sensitivity of the cancer cells to current chemotherapeutics. The aim of the present study is to test the feasibility of a randomized controlled trial on the application of freeze-dried broccoli sprouts in patients with advanced PDA.\n The study is designed as a prospective randomized, double-blinded pilot trial with a treatment and a placebo-controlled arm in a single center setting. A total number of forty patients (18 years or older) in two parallel groups with advanced, surgically non-resectable PDA under palliative chemotherapy are planned for recruitment. Patients in the treatment group will receive fifteen capsules of the study substance per day (90 mg of active sulforaphane) during the chemotherapy treatment course. Patients in the placebo group will receive the same capsule size and portion distribution with inactive substances (mainly methylcellulose). The follow-up duration is one year. Feasibility of the study substance, adverse effects, and patient compliance, as well as levels of serum tumor markers (CEA, CA 19-9), quality of life, and patient overall survival rates will be assessed at defined points of time.\n The POUDER trial is expected to transfer promising experimental and epidemiological data into a clinical pilot study to assess the effectiveness of broccoli sprout extracts in the treatment of advanced PDA. The study objectives will provide data on the clinical feasibility and acceptability of a supportive treatment option accompanying palliative chemotherapy. Based on these results, future clinical studies to create further evidence in this field are possible.\n The POUDER trial has been registered at ClinicalTrials.gov with an ID NCT01879878 and WHO with an ID U1111-1144-2013 on June 13th 2013.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n158644\nB-Cell-Based and Soluble Biomarkers in Body Liquids for Predicting Acute/Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.\n\nJuric, MK\n\nShevtsov, M\n\nMozes, P\n\nOgonek, J\n\nCrossland, RE\n\nDickinson, AM\n\nGreinix, HT\n\nHoller, E\n\nWeissinger, EM\n\nMulthoff, G\n\nBeiträge in Fachzeitschriften\nISI:000391827900001\n28138325.0\n10.3389/fimmu.2016.00660\nPMC5238459\nAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main curative therapy for hematological malignancy such as leukemias, lymphomas, or multiple myelomas and some other hematological disorders. In this therapy, cure of hematological diseases relies on graft-versus-malignancy effects by allogenic immune cells. However, severe posttransplant treatment-associated complications such as acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) limit this approach. Most research into GvHD has concentrated on the aGvHD, while the more complex and multifaceted chronic form has been largely poorly investigated. cGvHD is a multi-organ autoimmune disorder and is the major cause of non-relapse morbidity and mortality following allo-HSCT, occurring in about 50% of patients, or 13, 00-15, 00 patients per year worldwide. Therefore, there is a high medical need for an early prediction of these therapy-associated toxicities. Biomarkers have gained importance over the last decade in diagnosis, in prognosis, and in prediction of pending diseases or side effects. Biomarkers can be cells, factors isolated from target tissues, or soluble factors that can be detected in body fluids. In this review, we aim to summarize some of the recent developments of biomarkers in the field of allo-HSCT. We will focus on cell-based biomarkers (B-cell subsets) for cGvHD and soluble factors including microRNA (miRNA), which are excreted into serum/plasma and urine. We also discuss the potential role of cytosolic and extracellular 70 kDa heat shock proteins (HSP70) as potential biomarkers for aGvHD and their role in preclinical models. Proteomic biomarkers in the blood have been used as predictors of treatment responses in patients with aGvHD for many years. More recently, miRNAs have been found to serve as a biomarker to diagnose aGvHD in the plasma. Another development relates to urine-based biomarkers that are usually detected by capillary electrophoresis and mass spectrometry. These biomarkers have the potential to predict the development of severe aGvHD (grades III-IV), overall mortality, and the pending development of cGvHD in patients posttransplant.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n170512\nAre anticoagulants still indicated in pulmonary arterial hypertension?\n\nOlschewski, H\n\nRich, S\n\nBeiträge in Fachzeitschriften\nISI:000448615000001\n30284508.0\n10.1177/2045894018807681\nPMC6202749\nPulmonary arterial hypertension (PAH) is a type of pulmonary hypertension that is a progressive, fatal disease. Multiple underlying mechanisms for PAH have been identified, including vasoconstriction, intimal proliferation, medial hypertrophy, inflammation, mitochondrial dysfunction, and in situ thrombosis. Because it is an uncommon disease, it has been challenging to identify a specific treatment that targets the dominant disease mechanism in a given patient. Early success demonstrating that some patients (approximately 10%) possess pulmonary vasoreactivity at diagnosis has driven the development of pulmonary vasodilators as the mainstay of treatment. However, while they improve exercise tolerance in clinical trials, their effect on survival is limited. Therapies that target underlying disease mechanisms that affect a majority of patients are clearly needed if we are to significantly improve overall survival. In the actual guidelines, chronic anticoagulation is no longer recommended in patients with idiopathic, hereditary, and drug-induced PAH although there is much indirect evidence for this. There are data from over 40 years which include: (1) pathology studies showing the presence of thrombotic lesions in a majority of patients with PAH, both idiopathic and associated with many other conditions; (2) a similar frequency of thrombotic lesions in patients treated with pulmonary vasodilators as was seen in the years before their use; (3) mechanistic studies showing that procoagulant conditions predispose to the development of intraluminal thrombosis that contributes to vascular remodeling and the progressive nature of the pathologic changes; and (4) observational studies that, with one exception, have demonstrated a substantial survival advantage in patients with PAH treated with oral anticoagulation. Acknowledging that no prospective randomized trial with anticoagulants has ever been done, we recommend a pragmatic approach to the use of anticoagulants in PAH. We suggest that the risks and benefits of chronic anticoagulation be considered in individual patients, and that warfarin be prescribed in patients with PAH, unless they have an increased risk of bleeding. The question of whether direct oral anticoagulants (DOACs) would provide the same benefit as vitamin K antagonists is valid, but presently there are no data at all regarding their use in PAH. However, in patients with PAH in whom warfarin anticoagulation management proves problematic, it is reasonable to switch the patient to a DOAC as is current practice for other conditions.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n179276\nDetailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants.\n\nHansen, ML\n\nPellicer, A\n\nGluud, C\n\nDempsey, E\n\nMintzer, J\n\nHyttel-Sorensen, S\n\nHeuchan, AM\n\nHagmann, C\n\nDimitriou, G\n\nPichler, G\n\nNaulaers, G\n\nCheng, G\n\nVilan, A\n\nTkaczyk, J\n\nKreutzer, KB\n\nFumagalli, M\n\nClaris, O\n\nFredly, S\n\nSzczapa, T\n\nLange, T\n\nJakobsen, JC\n\nGreisen, G\n\nBeiträge in Fachzeitschriften\nISI:000506891100001\n31856902.0\n10.1186/s13063-019-3756-y\nPMC6921567\nInfants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses.\n The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis.\n In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis.\n ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.\n\nPichler, Gerhard\n\n\n"
}
]
}