@article{EliasHeuschmannSchmittetal.2013, author = {Elias, Johannes and Heuschmann, Peter U. and Schmitt, Corinna and Eckhardt, Frithjof and Boehm, Hartmut and Maier, Sebastian and Kolb-M{\"a}urer, Annette and Riedmiller, Hubertus and M{\"u}llges, Wolfgang and Weisser, Christoph and Wunder, Christian and Frosch, Matthias and Vogel, Ulrich}, title = {Prevalence dependent calibration of a predictive model for nasal carriage of methicillin-resistant Staphylococcus aureus}, series = {BMC Infectious Diseases}, journal = {BMC Infectious Diseases}, doi = {10.1186/1471-2334-13-111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96091}, year = {2013}, abstract = {Background Published models predicting nasal colonization with Methicillin-resistant Staphylococcus aureus among hospital admissions predominantly focus on separation of carriers from non-carriers and are frequently evaluated using measures of discrimination. In contrast, accurate estimation of carriage probability, which may inform decisions regarding treatment and infection control, is rarely assessed. Furthermore, no published models adjust for MRSA prevalence. Methods Using logistic regression, a scoring system (values from 0 to 200) predicting nasal carriage of MRSA was created using a derivation cohort of 3091 individuals admitted to a European tertiary referral center between July 2007 and March 2008. The expected positive predictive value of a rapid diagnostic test (GeneOhm, Becton \& Dickinson Co.) was modeled using non-linear regression according to score. Models were validated on a second cohort from the same hospital consisting of 2043 patients admitted between August 2008 and January 2012. Our suggested correction score for prevalence was proportional to the log-transformed odds ratio between cohorts. Calibration before and after correction, i.e. accurate classification into arbitrary strata, was assessed with the Hosmer-Lemeshow-Test. Results Treating culture as reference, the rapid diagnostic test had positive predictive values of 64.8\% and 54.0\% in derivation and internal validation corhorts with prevalences of 2.3\% and 1.7\%, respectively. In addition to low prevalence, low positive predictive values were due to high proportion (> 66\%) of mecA-negative Staphylococcus aureus among false positive results. Age, nursing home residence, admission through the medical emergency department, and ICD-10-GM admission diagnoses starting with "A" or "J" were associated with MRSA carriage and were thus included in the scoring system, which showed good calibration in predicting probability of carriage and the rapid diagnostic test's expected positive predictive value. Calibration for both probability of carriage and expected positive predictive value in the internal validation cohort was improved by applying the correction score. Conclusions Given a set of patient parameters, the presented models accurately predict a) probability of nasal carriage of MRSA and b) a rapid diagnostic test's expected positive predictive value. While the former can inform decisions regarding empiric antibiotic treatment and infection control, the latter can influence choice of screening method.}, language = {en} } @article{HaringPettingerBeaetal.2013, author = {Haring, Bernhard and Pettinger, Mary and Bea, Jennifer W. and Wactawski-Wende, Jean and Carnahan, Ryan M. and Ockene, Judith K. and Wyler von Ballmoos, Moritz and Wallace, Robert B. and Wassertheil-Smoller, Sylvia}, title = {Laxative use and incident falls, fractures and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative}, series = {BMC Geriatrics}, journal = {BMC Geriatrics}, doi = {10.1186/1471-2318-13-38}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-95960}, year = {2013}, abstract = {Background Laxatives are among the most widely used over-the-counter medications in the United States but studies examining their potential hazardous side effects are sparse. Associations between laxative use and risk for fractures and change in bone mineral density [BMD] have not previously been investigated. Methods This prospective analysis included 161,808 postmenopausal women (8907 users and 151,497 nonusers of laxatives) enrolled in the WHI Observational Study and Clinical Trials. Women were recruited from October 1, 1993, to December 31, 1998, at 40 clinical centers in the United States and were eligible if they were 50 to 79 years old and were postmenopausal at the time of enrollment. Medication inventories were obtained during in-person interviews at baseline and at the 3-year follow-up visit on everyone. Data on self-reported falls (≥2), fractures (hip and total fractures) were used. BMD was determined at baseline and year 3 at 3 of the 40 clinical centers of the WHI. Results Age-adjusted rates of hip fractures and total fractures, but not for falls were similar between laxative users and non-users regardless of duration of laxative use. The multivariate-adjusted hazard ratios for any laxative use were 1.06 (95\% confidence interval [CI], 1.03-1.10) for falls, 1.02 (95\% CI, 0.85-1.22) for hip fractures and 1.01 (95\% CI, 0.96-1.07) for total fractures. The BMD levels did not statistically differ between laxative users and nonusers at any skeletal site after 3-years intake. Conclusion These findings support a modest association between laxative use and increase in the risk of falls but not for fractures. Its use did not decrease bone mineral density levels in postmenopausal women. Maintaining physical functioning, and providing adequate treatment of comorbidities that predispose individuals for falls should be considered as first measures to avoid potential negative consequences associated with laxative use.}, language = {en} } @phdthesis{Kruempel2013, author = {Kr{\"u}mpel, Christian}, title = {Die Rolle des Multidrug Resistance Associated Protein-1 bei der Tumornekrosefaktor-α vermittelten Apoptose in Endothelzellen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-93681}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Die endotheliale Dysfunktion stellt eine der Hauptursachen f{\"u}r die Entstehung von Atherosklerose an humanen Gef{\"a}ßw{\"a}nden dar und ist somit auch wesentlich an der Entstehung von kardiovaskul{\"a}ren Erkrankungen beteiligt. Das proinflammatorische Zytokin Tumornekrosefaktor-α (TNF-α) gilt als einer der Hauptinduktoren der endothelialen Dysfunktion. Da bei der Endothelzellapoptose unter TNF-α diverse rezeptorvermittelte oxidative Prozesse innerhalb der Zelle ablaufen, sollte im Rahmen dieser Arbeit untersucht werden, inwiefern das Multidrug Resistance Associated Protein-1 (MRP-1) bei diesen oxidativen Prozessen und bei der Modulation der TNF-α-Signalkaskade involviert ist.}, subject = {Tumor-Nekrose-Faktor}, language = {de} } @phdthesis{Thomas2013, author = {Thomas, Nicolai}, title = {Einfluss der EKG-Telemetrie auf die strukturellen Abl{\"a}ufe im Herzinfarktnetz Mainfranken bei der Versorgung von Patienten mit ST-Streckenhebungsmyokardinfarkt (STEMI)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83769}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Beim akuten Herzinfarkt betr{\"a}gt die 30-Tages-Mortalit{\"a}t immer noch rund 50\%. Die H{\"a}lfte dieser Todesf{\"a}lle geschieht in den ersten 2 Stunden nach Symptombeginn. Zielf{\"u}hrend in der Therapie ist die schnelle Wiederer{\"o}ffnung der verschlossenen Coronararterie. Die Leitlinien der ESC (European Society of Cardiology) empfehlen die prim{\"a}re perkutane Coronarintervention (PPCI) in einem Zeitfenster von weniger als 120 bzw. 90 Minuten nach first medical contact (FMC) durchzuf{\"u}hren. Eine Optimierung der akuten Infarktversorgung erscheint vor diesem Hintergrund dringend erforderlich. Prim{\"a}re Zielgr{\"o}ße des Projekts ist die Verk{\"u}rzung der Contact-to-ballon-Zeit (C2B), also die Zeit zwischen FMC bis zur Ballondilatation. Voraussetzung f{\"u}r schnelle Reaktionszeiten und damit auch f{\"u}r schnelle C2B-Zeiten ist eine sichere und schnelle EKG-Diagnose bereits am pr{\"a}klinischen Einsatzort. Aber, Unsicherheiten bei der STEMI-Diagnostik sind gegenw{\"a}rtig. Um eine Verbesserung der STEMI-Versorgung zu gew{\"a}hrleisten, wurde im Herzinfarktnetz Mainfranken die telemetrische 12-Kanal-EKG-{\"U}bertragung im Pilotversuch eingef{\"u}hrt. In der vorliegenden Arbeit wurde mit Hilfe eines prospektiv erhobenen Patientenregisters untersucht, welchen Einfluss die Etablierung telemetrischer Verfahren in der Akutversorgung von STEMI-Patienten hat. Sowohl die strukturellen Abl{\"a}ufe im Rahmen des Herzinfarktnetzwerkes als auch der klinische Outcome der Patienten wurden untersucht und dokumentiert. Insgesamt erf{\"u}llten {\"u}ber sechs Studienquartale (vom 01.01.2009 bis 30.09.2010) hinweg 310 Patienten die Einschlusskriterien. Die Ergebnisse zeigen, dass durch eine sichere, pr{\"a}klinische EKG-Diagnose mit Hilfe telemetrischer Verfahren, die C2B-Intervalle im Studienzeitraum signifikant reduziert wurden. Auch die innerklinische Behandlung wurde merklich beschleunigt. Zusammenfassend k{\"o}nnen mit Hilfe der telemetrischen EKG-{\"U}bertragung vier wesentliche Punkte verbessert werden. 1. die sichere Diagnosestellung des STEMI; 2. der gezielte Prim{\"a}rtransport in das n{\"a}chstgelegene, geeignete Interventionszentrum; 3. das organsierte Bypassing der n{\"a}chstgelegenen Nicht-Interventionsklinik und somit die Vermeidung von Sekund{\"a}rtransporten; 4. das Bypassing der Notaufnahme und der Intensivstation der Interventionsklinik und somit die Direkt{\"u}bergabe im HKL.}, subject = {Herzinfarkt}, language = {de} } @phdthesis{Devine2013, author = {Devine, Eric}, title = {Increased removal of protein bound uremic toxins through reversible modification of the ionic strength during hemodiafiltration}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83583}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {A large number of metabolic waste products accumulate in the blood of patients with renal failure. Since these solutes have deleterious effects on the biological functions, they are called uremic toxins and have been classified in three groups: 1) small water soluble solutes (MW < 500 Da), 2) small solutes with known protein binding (MW < 500 Da), and 3) middle molecules (500 Da < MW < 60 kDa). Protein bound uremic toxins are poorly removed by conventional hemodialysis treatments because of their high protein binding and high distribution volume. The prototypical protein bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are associated with the progression of chronic kidney disease, cardiovascular outcomes, and mortality of patients on maintenance hemodialysis. Furthermore, these two compounds are bound to albumin, the main plasma protein, via electrostatic and/or Van-der-Waals forces. The aim of the present thesis was to develop a dialysis strategy, based on the reversible modification of the ionic strength in the blood stream by increasing the sodium chloride (NaCl) concentration, in order to enhance the removal of protein bound substances, such as IS and pCS, with the ultimate goal to improve clinical patient outcomes. Enhancing the NaCl concentration ([NaCl]) in both human normal and uremic plasma was efficient to reduce the protein bound fraction of both IS and pCS by reducing their binding affinity to albumin. Increasing the ionic strength was feasible during modified pre-dilution hemodiafiltration (HDF) by increasing the [NaCl] in the substitution fluid. The NaCl excess was adequately removed within the hemodialyzer. This method was effective to increase the removal rate of both protein bound uremic toxins. Its ex vivo hemocompatibility, however, was limited by the osmotic shock induced by the high [NaCl] in the substituate. Therefore, modified pre-dilution HDF was further iterated by introducing a second serial cartridge, named the serial dialyzers (SDial) setup. This setting was validated for feasibility, hemocompatibility, and toxin removal efficiency. A better hemocompatibility at similar efficacy was obtained with the SDial setup compared with the modified pre-dilution HDF. Both methods were finally tested in an animal sheep model of dialysis to verify biocompatibility. Low hemolysis and no activation of both the complement and the coagulation systems were observed when increasing the [NaCl] in blood up to 0.45 and 0.60 M with the modified pre-dilution HDF and the SDial setup, respectively. In conclusion, the two dialysis methods developed to transitory enhance the ionic strength in blood demonstrated adequate biocompatibility and improved the removal of protein bound uremic toxins by decreasing their protein bound fraction. The concepts require follow-on clinical trials to assess their in vivo efficacy and their impact on long-term clinical outcomes.}, subject = {H{\"a}modiafiltration}, language = {en} } @phdthesis{Kaempf2013, author = {K{\"a}mpf, Tanja}, title = {Definition eines klinisch relevanten Morbus Fabry mit Hilfe des Biomarkers Lyso Gb3 bei Patienten mit einer alpha- Galaktosidase Mutation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77819}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Der Morbus Fabry ist eine sehr heterogenetische und heteroph{\"a}notypische Krankheit. Ursache der Erkrankung liegt in der Mutation des alpha- Galaktosidase Gens. Es kommt zur Akkumulation von Glykosphingolipiden. Man kann den klassischen Typ von mehreren Varianten unterscheiden. Es konnte bisher noch keine Genotyp- Ph{\"a}notyp Relation hergestellt werden. In unsere Studie wurden 124 Fabry Patienten eingeschlossen. Vier klinische Dom{\"a}nen wurden beurteilt (Herz, Nieren, Nervensystem, Fabry-Symptome). Daneben wurden genetische Analysen und Labortests (inklusive Lyso Gb3) durchgef{\"u}hrt. Die Studie besitzt einen zweiteiligen Aufbau: in die Evaluationsstudie wurden alle bisher bekannten Mutationen eingeschlossen, w{\"a}hrend die bisher unbekannten Mutationen der Validierungsstudie zugeteilt wurden. Es konnte gezeigt werden, dass mithilfe des Biomarkers Lyso Gb3 die Schwere der Erkrankung vorausgesagt werden kann (insbesondere bei Frauen) und die Diagnostik erleichtert werden kann. Eine bisher unbekannte Mutation kann jetzt viel besser eingeordnet werden, da man mithilfe des Biomarkers Lyso Gb3 zwischen atypischer und klassischer Variante unterscheiden kann und man durch den Biomarker die Krankheitskapazit{\"a}t einer Mutation beurteilen kann.}, subject = {Fabry-Krankheit}, language = {de} }