Evaluation of vardenafil for the treatment of subjective tinnitus: a controlled pilot study

<p>Abstract</p> <p>Background</p> <p>Vardenafil (Levitra^®) represents a potent and highly selective phosphodiesterase type 5 (PDE5) inhibitor, which is established for treatment of various diseases. There are several unpublished reports from patients stating that vardenafil has a considerable therapeutic effect on their concomitant tinnitus. This pilot study was conducted to specifically assess the effect of vardenafil in patients with chronic tinnitus.</p> <p>Methods</p> <p>This trial was based on a prospective, randomized, double-blind, placebo-controlled, parallel group design. Fourty-two consecutive subjects with mon- or binaural chronic tinnitus received 10 mg vardenafil (N = 21) or matching placebo tablets (N = 21) administered orally twice a day over a period of 12 weeks. Clinical examination and data acquisition took place at each visit: at baseline, after 4 weeks, after 12 weeks (end of treatment with study medication), and at non-medicated follow-up after 16 weeks. Assessment of clinical effectiveness was based on a standardized tinnitus questionnaire (TQ), the Short Form 36 health survey (SF-36), audiometric measurements (mode, pitch and loudness of tinnitus; auditory thresholds) and biomarkers of oxidative stress in patients' blood (malondialdehyde, protein carbonyl, homocysteine and total antioxidative status). Therapeutic efficacy was evaluated by comparison of subjective and objective parameters with baseline data between both treatment groups (ANCOVA).</p> <p>Results</p> <p>Vardenafil had no superior efficacy over placebo in the treatment of chronic tinnitus during this study. The primary efficacy criterion 'TQ total score' failed to demonstrate significant improvement compared to placebo. Subjective reports of TQ subscales and general quality of life areas (SF-36), objective audiometric examinations as well as investigated biomarkers for oxidative stress did not reveal any significant treatment effects. The safety profile was favorable and consistent with that in other vardenafil studies.</p> <p>Conclusion</p> <p>Although hypoxia and ischemia play a special role in the pathogenesis of tinnitus, the PDE5-inhibitor-induced increase of nitric oxide-mediated vasodilatation exerted no specific influence on tinnitus symptomatology. Considering the unclear risk of rarely associated hearing impairment, systemic application of vardenafil or other PDE5 inhibitors prove to be not appropriate for therapy of chronic tinnitus.</p

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Goethes Faust : Erster Teil / Edited With Introduction And Commentary By Julius Goebel Havard University

GOETHES FAUST : ERSTER TEIL / EDITED WITH INTRODUCTION AND COMMENTARY BY JULIUS GOEBEL HAVARD UNIVERSITY Goethes Faust : Erster Teil / Edited With Introduction And Commentary By Julius Goebel Havard University (1) Einband (1) Titelseite (3) Titelseite (6) Widmung (8) Preface (10) Introduction (18) Zueignung (70) Vorspiel auf dem Theater (72) Prolog im Himmel (80) Nacht (88) Vor dem Thor (106) Studierzimmer (122) Auerbachs Keller in Leipzig (161) Hexenküche (179) Straße (194) Abend (199) Spaziergang (205) Der Nachbarin Haus (209) Straße (219) Garten (222) Ein Gartenhäuschen (231) Wald und Höhle (233) Gretchens Stube (240) Marthens Garten (242) Am Brunnen (250) Zwinger (253) Nacht (255) Dom (264) Walpurgisnacht (267) Walpurgisnachtstraum oder Oberon und Titanias ... (286) Trüber Tag (295) Nacht, offen Feld (299) Kerker (300) Notes (312

Memorator Votivus : Reverend. Dominorum, Dei Gratia, Abbatum, Imperialis Monasterii S. Johannis Baptistae, Ordinis D. Benedicti, Anno Christi 936. ab Imperatore Ottone Magno, Magdeburgi, 23. Annis ante Archi-Episcopalem Sedem, fundati, & hinc, Anno 968. in Montem Pathenopolitanum, (unde Bergense dictum,) translati ; A prima fundatione, usq[ue] ad Annum 1660, quo Reverend. Dn. Sebastianus Goebelius, Dresdensis, rite & canonice Abbas eligebatur, honorifice introductus, ab infra dicto

Auctore M. Johanne FrentzelnDrei Abbildungen: Insignia Monasterii Bergensis. Effigies Beatiss. Fundatoris. Insignia moderni Abbatis. - Darunter in zwei Spalten eine chronologische Namensliste der Äbte von 936 bis ins Jahr 1660. - In der dritten Spalte: Gratulatio Votiva ... - Am Ende: Nomina Membrorum Coenobii supra dicti, hoc Anno 1660, praesentiumVorlageform des Erscheinungsvermerks: Lipsiae, Typis Johannis-Erici Hahnii, Anno MDCLX

Programma De Casv Fvnesto Praestantissimi Civis Caroli Henrici Goebelii Ivrivm Candidati P. P. In Academia Ienensi.

PROGRAMMA DE CASV FVNESTO PRAESTANTISSIMI CIVIS CAROLI HENRICI GOEBELII IVRIVM CANDIDATI P. P. IN ACADEMIA IENENSI. Programma De Casv Fvnesto Praestantissimi Civis Caroli Henrici Goebelii Ivrivm Candidati P. P. In Academia Ienensi. ([1]) Titelseite ([1]) Text ([2]