TY - JOUR A1 - Kasang, Christa A1 - Kalluvya, Samuel A1 - Majinge, Charles A1 - Kongola, Gilbert A1 - Mlewa, Mathias A1 - Massawe, Irene A1 - Kabyemera, Rogatus A1 - Magambo, Kinanga A1 - Ulmer, Albrecht A1 - Klinker, Hartwig A1 - Gschmack, Eva A1 - Horn, Anne A1 - Koutsilieri, Eleni A1 - Preiser, Wolfgang A1 - Hofmann, Daniela A1 - Hain, Johannes A1 - Müller, Andreas A1 - Dölken, Lars A1 - Weissbrich, Benedikt A1 - Rethwilm, Axel A1 - Stich, August A1 - Scheller, Carsten T1 - Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial JF - PLoS One N2 - Background HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. Methods Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/μl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/μl. Results No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/μl compared to -37.42 ± 10.77 cells/μl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. Conclusions This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection. KW - HIV KW - immune activation KW - viral load KW - drug adherence KW - viral replication KW - AIDS KW - HIV infections KW - highly-active antiretroviral therapy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146479 VL - 11 IS - 1 ER - TY - JOUR A1 - Hamouda, Khaled A1 - Oezkur, Mehmet A1 - Sinha, Bhanu A1 - Hain, Johannes A1 - Menkel, Hannah A1 - Leistner, Marcus A1 - Leyh, Rainer A1 - Schimmer, Christoph T1 - Different duration strategies of perioperative antibiotic prophylaxis in adult patients undergoing cardiac surgery: an observational study JF - Journal of Cardiothoracic Surgery N2 - Background All international guidelines recommend perioperative antibiotic prophylaxis (PAB) should be routinely administered to patients undergoing cardiac surgery. However, the duration of PAB is heterogeneous and controversial. Methods Between 01.01.2011 and 31.12.2011, 1096 consecutive cardiac surgery patients were assigned to one of two groups receiving PAB with a second-generation cephalosporin for either 56 h (group I) or 32 h (group II). Patients’ characteristics, intraoperative data, and the in-hospital follow-up were analysed. Primary endpoint was the incidence of surgical site infection (deep and superficial sternal wound-, and vein harvesting site infection; DSWI/SSWI/VHSI). Secondary endpoints were the incidence of respiratory-, and urinary tract infection, as well as the mortality rate. Results 615/1096 patients (56,1%) were enrolled (group I: n = 283 versus group II: n = 332). There were no significant differences with regard to patient characteristics, comorbidities, and procedure-related variables. No statistically significant differences were demonstrated concerning primary and secondary endpoints. The incidence of DSWI/SSWI/VHSI were 4/283 (1,4%), 5/283 (1,7%), and 1/283 (0,3%) in group I versus 6/332 (1,8%), 9/332 (2,7%), and 3/332 (0,9%) in group II (p = 0,76/0,59/0,63). In univariate analyses female gender, age, peripheral arterial obstructive disease, operating-time, ICU-duration, transfusion, and respiratory insufficiency were determinants for nosocomial infections (all ≤ 0,05). Subgroup analyses of these high-risk patients did not show any differences between the two regimes (all ≥ 0,05). Conclusions Reducing the duration of PAB from 56 h to 32 h in adult cardiac surgery patients was not associated with an increase of nosocomial infection rate, but contributes to reduce antibiotic resistance and health care costs. KW - nosocomial infection KW - cardiac surgery KW - antibiotic prophylaxis Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124977 VL - 10 IS - 25 ER - TY - THES A1 - Hain, Johannes T1 - Valuation Algorithms for Structural Models of Financial Networks T1 - Algorithmen zur Bestimmung von Gleichgewichtslösungen in Finanzsystemen mit Kapitalverflechtung N2 - The thesis focuses on the valuation of firms in a system context where cross-holdings of the firms in liabilities and equities are allowed and, therefore, systemic risk can be modeled on a structural level. A main property of such models is that for the determination of the firm values a pricing equilibrium has to be found. While there exists a small but growing amount of research on the existence and the uniqueness of such price equilibria, the literature is still somewhat inconsistent. An example for this fact is that different authors define the underlying financial system on differing ways. Moreover, only few articles pay intense attention on procedures to find the pricing equilibria. In the existing publications, the provided algorithms mainly reflect the individual authors' particular approach to the problem. Additionally, all existing methods do have the drawback of potentially infinite runtime. For these reasons, the objects of this thesis are as follows. First, a definition of a financial system is introduced in its most general form in Chapter 2. It is shown that under a fairly mild regularity condition the financial system has a unique existing payment equilibrium. In Chapter 3, some extensions and differing definitions of financial systems that exist in literature are presented and it is shown how these models can be embedded into the general model from the proceeding chapter. Second, an overview of existing valuation algorithms to find the equilibrium is given in Chapter 4, where the existing methods are generalized and their corresponding mathematical properties are highlighted. Third, a complete new class of valuation algorithms is developed in Chapter 4 that includes the additional information whether a firm is in default or solvent under a current payment vector. This results in procedures that are able find the solution of the system in a finite number of iteration steps. In Chapter 5, the developed concepts of Chapter 4 are applied to more general financial systems where more than one seniority level of debt is present. Chapter 6 develops optimal starting vectors for non-finite algorithms and Chapter 7 compares the existing and the new developed algorithms concerning their efficiency in an extensive simulation study covering a wide range of possible settings for financial systems. N2 - Die vorliegende Dissertation hat die Unternehmensbewertung in Finanzsystemen mit Fremd- und Eigenkapitalverflechtung zum Thema. Die zentrale Eigenschaft dieser Modelle ist, dass zur Bestimmung der Firmenwerte eine Gleichgewichtslösung ermittelt werden muss. Die Zahl der Veröffentlichungen mit dem Schwerpunkt des Nachweises von Existenz- und Eindeutigkeitsaussagen der Gleichgewichte steigt zwar stetig an, allerdings ist die Fachliteratur in diesem Bereich teilweise noch sehr inkonsistent. Beispielsweise existieren je nach Autor unterschiedliche Vorgehensweisen, das zugrunde liegende Finanzsystem zu definieren. Darüber hinaus schenken nur wenige Fachartikel der Frage Beachtung, wie die Lösungsgleichgewichte genau bestimmt werden können. Zuletzt weisen die bereits entwickelten Verfahren den Nachteil auf, dass Sie womöglich unendlich viele Iterationsschritte benötigen bis die gesuchte Lösung exakt erreicht wird. Aus diesen Gründen beinhaltet die vorliegende Dissertation folgende Themen. Im ersten Schritt wird in Kapitel 2 eine möglichst allgemeine Definition eines Finanzsystems eingeführt. Es wird gezeigt dass unter nicht allzu strengen Voraussetzungen die Gleichgewichtslösung dieses Systems eindeutig bestimmt ist. In Kapitel 3 werden in der Fachliteratur zu diesem Thema zu findende Erweiterungen und abweichende Definitionen des Systems vorgestellt und wie diese in das allgemeine Modell aus dem vorherigen Kapitel eingebettet werden können. Danach wird in Kapitel 4 ein Überblick über bereits entwickelte Lösungsverfahren gegeben, wobei die existierenden Prozeduren in ihrem Vorgehen verallgemeinert und deren zugehörige mathematische Eigenschaften aufgezeigt werden. Des weiteren wird im gleichen Kapitel eine komplett neue Klasse von Lösungsverfahren entwickelt, die noch die zusätzliche Information verarbeiten, ob eine Firma für einen gegebenen Zahlungsvektor solvent oder insolvent ist. Als Folge dieses Ansatzes sind diese Algorithmen in der Lage, die exakte Gleichgewichtslösung des Systems in endlich vielen Schritten zu finden. In Kapitel 5 werden die entworfenen Konzepte dann für Finanzsysteme angewendet, in denen mehr als nur eine Schulden-Seniorität berücksichtigt wird. Kapitel 6 leitet optimale Startvektoren der nicht-endlichen Verfahren her und Kapitel 7 vergleicht die bereits existierenden und alle neu entwickelten Lösungsverfahren bezüglich ihrer Laufzeiteffizienz im Rahmen einer ausführlichen Simulationsstudie. KW - Risikomanagement KW - Finanzmathematik KW - Financial Networks KW - Counterparty Risk KW - Numerical Asset Valuation KW - Systemic Risk KW - Structrual Model KW - Unternehmensbewertung KW - Kapitalverflechtung KW - Finanzielle Netzwerke KW - Systemisches Risiko Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128108 ER - TY - JOUR A1 - Horn, Anne A1 - Scheller, Carsten A1 - du Plessis, Stefan A1 - Arendt, Gabriele A1 - Nolting, Thorsten A1 - Joska, John A1 - Sopper, Sieghart A1 - Maschke, Matthias A1 - Obermann, Mark A1 - Husstedt, Ingo W. A1 - Hain, Johannes A1 - Maponga, Tongai A1 - Riederer, Peter A1 - Koutsilieri, Eleni T1 - Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals JF - Journal of Neural Transmission N2 - Dysfunction of dopaminergic neurotransmission has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-naïve HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, suggesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interestingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95 % CI 1.72–8.96; p = 0.001, Fishers exact test). 42.6 % HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5 % uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9 %, respectively, in Germany (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease. KW - HIV KW - HAND KW - dopamine KW - DAT KW - polymorphism KW - CSF Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132385 VL - 120 ER - TY - JOUR A1 - Rudel, Thomas A1 - Prusty, Bhupesh K. A1 - Siegl, Christine A1 - Hauck, Petra A1 - Hain, Johannes A1 - Korhonen, Suvi J. A1 - Hiltunen-Back, Eija A1 - Poulakkainen, Mirja T1 - Chlamydia trachomatis Infection Induces Replication of Latent HHV-6 JF - PLoS ONE N2 - Human herpesvirus-6 (HHV-6) exists in latent form either as a nuclear episome or integrated into human chromosomes in more than 90% of healthy individuals without causing clinical symptoms. Immunosuppression and stress conditions can reactivate HHV-6 replication, associated with clinical complications and even death. We have previously shown that co-infection of Chlamydia trachomatis and HHV-6 promotes chlamydial persistence and increases viral uptake in an in vitro cell culture model. Here we investigated C. trachomatis-induced HHV-6 activation in cell lines and fresh blood samples from patients having Chromosomally integrated HHV-6 (CiHHV-6). We observed activation of latent HHV-6 DNA replication in CiHHV-6 cell lines and fresh blood cells without formation of viral particles. Interestingly, we detected HHV-6 DNA in blood as well as cervical swabs from C. trachomatis-infected women. Low virus titers correlated with high C. trachomatis load and vice versa, demonstrating a potentially significant interaction of these pathogens in blood cells and in the cervix of infected patients. Our data suggest a thus far underestimated interference of HHV-6 and C. trachomatis with a likely impact on the disease outcome as consequence of co-infection. KW - blood KW - chlamydia KW - chlamydia infection KW - chlamydia trachomatis KW - DNA replication KW - macrophages KW - polymerase chain reaction KW - viral load Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96731 ER - TY - JOUR A1 - Stoevesandt, Johanna A1 - Hofmann, Bernd A1 - Hain, Johannes A1 - Kerstan, Andreas A1 - Trautmann, Axel T1 - Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom JF - Allergy, Asthma & Clinical Immunology N2 - Background Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms “double sensitization” or “double positivity” cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients. Objective We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients. Methods Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests. Results Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15). Conclusions Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the culprit stinging insect. KW - Anaphylaxis KW - Double sensitization KW - Field sting KW - Honey bee KW - Hymenoptera venom KW - Immunotherapy KW - Relapse KW - Risk factor KW - Treatment failure KW - Vespula Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96808 UR - http://www.aacijournal.com/content/9/1/33 ER - TY - JOUR A1 - Trautmann, Axel A1 - Seitz, Cornelia S. A1 - Brockow, Knut A1 - Hain, Johannes T1 - Non-steroidal anti-inflammatory drug hypersensitivity: association with elevated basal serum tryptase? N2 - Background It is hypothesized that because of higher mast cell numbers and mediator release, mastocytosis predisposes patients for systemic immediate-type hypersensitivity reactions to certain drugs including non-steroidal anti-inflammatory drugs (NSAID). Objective To clarify whether patients with NSAID hypersensitivity show increased basal serum tryptase levels as sign for underlying mast cell disease. Methods As part of our allergy work-up, basal serum tryptase levels were determined in all patients with a diagnosis of NSAID hypersensitivity and the severity of the reaction was graded. Patients with confirmed IgE-mediated hymenoptera venom allergy served as a comparison group. Results Out of 284 patients with NSAID hypersensitivity, 26 were identified with basal serum tryptase > 10.0 ng/mL (9.2%). In contrast, significantly (P = .004) more hymenoptera venom allergic patients had elevated tryptase > 10.0 ng/mL (83 out of 484; 17.1%). Basal tryptase > 20.0 ng/mL was indicative for severe anaphylaxis only in venom allergic subjects (29 patients; 4x grade 2 and 25x grade 3 anaphylaxis), but not in NSAID hypersensitive patients (6 patients; 4x grade 1, 2x grade 2). Conclusions In contrast to hymenoptera venom allergy, NSAID hypersensitivity do not seem to be associated with elevated basal serum tryptase levels and levels > 20 ng/mL were not related to increased severity of the clinical reaction. This suggests that mastocytosis patients may be treated with NSAID without special precautions. KW - Anaphylaxis KW - Non-steroidal anti-inflammatory drug KW - Mastocytosis KW - Drug allergy KW - Drug reaction KW - Pseudo-allergy Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110399 ER - TY - JOUR A1 - Matlach, Juliane A1 - Dhillon, Christine A1 - Hain, Johannes A1 - Schlunck, Günther A1 - Grehn, Franz A1 - Klink, Thomas T1 - Trabeculectomy versus canaloplasty (TVC study) in the treatment of patients with open-angle glaucoma: a prospective randomized clinical trial JF - Acta Ophthalmologica N2 - Purpose: To compare the outcomes of canaloplasty and trabeculectomy in open-angle glaucoma. Methods: This prospective, randomized clinical trial included 62 patients who randomly received trabeculectomy (n = 32) or canaloplasty (n = 30) and were followed up prospectively for 2 years. Primary endpoint was complete (without medication) and qualified success (with or without medication) defined as an intraocular pressure (IOP) of ≤18 mmHg (definition 1) or IOP ≤21 mmHg and ≥20% IOP reduction (definition 2), IOP ≥5 mmHg, no vision loss and no further glaucoma surgery. Secondary endpoints were the absolute IOP reduction, visual acuity, medication, complications and second surgeries. Results: Surgical treatment significantly reduced IOP in both groups (p < 0.001). Complete success was achieved in 74.2% and 39.1% (definition 1, p = 0.01), and 67.7% and 39.1% (definition 2, p = 0.04) after 2 years in the trabeculectomy and canaloplasty group, respectively. Mean absolute IOP reduction was 10.8 ± 6.9 mmHg in the trabeculectomy and 9.3 ± 5.7 mmHg in the canaloplasty group after 2 years (p = 0.47). Mean IOP was 11.5 ± 3.4 mmHg in the trabeculectomy and 14.4 ± 4.2 mmHg in the canaloplasty group after 2 years. Following trabeculectomy, complications were more frequent including hypotony (37.5%), choroidal detachment (12.5%) and elevated IOP (25.0%). Conclusions: Trabeculectomy is associated with a stronger IOP reduction and less need for medication at the cost of a higher rate of complications. If target pressure is attainable by moderate IOP reduction, canaloplasty may be considered for its relative ease of postoperative care and lack of complications. KW - months follow-up KW - surgical outcomes KW - mitomycin C KW - canaloplasty KW - open-angle glaucoma KW - trabeculectomy KW - glaucoma surgery KW - series KW - phacocanaloplasty KW - phacotrabeculectomy KW - canal surgery KW - cataract surgery KW - flexible microcatheter KW - circumferential viscodilation Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149263 VL - 93 ER -