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Hypergonadotropic hypogonadism is a major feature of Klinefelter syndrome (KS), assumed to be caused by testicular hormone resistance. It was previously shown that intratesticular testosterone levels in vivo and Leydig cell function in vitro seem to be normal indicating other functional constraints. We hypothesized that impaired testicular vascularization/blood flow could be a co-factor to the observed hypergonadotropic hypogonadism. We evaluated the testicular vascular system by measuring blood vessel sizes during postnatal development and testis blood flow in adult 41,XX^Y* mice. Proportional distribution and size of blood vessels were analyzed during testicular development (1, 3, 5, 7, 10, 21 dpp, 15 wpp). While ratios of the vessel/testis area were different at 15 wpp only, a lower number of smaller and mid-sized blood vessels were detected in adult KS mice. For testicular blood flow determination we applied contrast enhanced ultrasound. Floating and reperfusion time for testicular blood flow was increased in 41,XX^Y* mice (floating: XY* 28.8 ± 1.69 s vs XX^Y* 44.6 ± 5.6 s, p = 0.0192; reperfusion XY* 19.7 ± 2.8 s vs XX^Y*: 29.9 ± 6.2 s, p = 0.0134), indicating a diminished blood supply. Our data strengthen the concept that an impaired vascularization either in conjunction or as a result of altered KS testicular architecture contributes to hormone resistance., Finanziert über die DEAL-Vereinbarung mit Wiley 2019-2022.

Background In the absence of detailed information about the population size and behaviour data of men-who-have-sex-with-men (MSM), the estimation of prevalence rates of sexually transmitted infections (STIs) and the design of public health interventions become difficult. The aim of the present study is to estimate the lower boundary of age-specific population sizes and retrieve self-reported information from this population. Methods We used publicly accessible data from a large online dating and social network website for MSM in Germany to retrieve data on the age and regional distribution of profiles. The profiles were also stratified by their information on the preferred position during anal intercourse, safer sex, and sexual identity. Results A total of 464,873 user profiles correspond to an average 15.2 profiles per 1,000 male inhabitants in Germany, varying between 7.6 and 45.6 across federal states. Although the information on the absolute numbers for different age groups is limited by the search engine, age-specific relative frequencies were found to increase from 12.9 in the age group of 18 to 20 year olds to 24.6 profiles per 1,000 male inhabitants in the 28 to 30 year olds. The data shows age-specific trends for safer sex with an increasing easiness of reporting “never” engaging in safer sex or stating that safer sex “needs discussion” with increasing age. Around one third of profile owners stated to be versatile with respect to the preferred position in anal intercourse. All other options (“only bottom”, “more bottom”, “only top”, “more top”) were preferred equally likely by roughly 10% of profile owners, respectively. Conclusions Online social network or dating sites can provide some information about specific populations in the absence of other data sources. The presented results are the first to report age-specific rates of MSM per 1,000 male inhabitants in Germany and may be useful to estimate age-specific prevalence or incidence rates as well as to inform health promotion activities and modelling studies for MSM in Germany. © 2019 Scholz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background Seasonal influenza contributes substantially to the burden of communicable diseases in Europe, especially among paediatric populations and the elderly. The aim of the present study was to estimate the incidence of seasonal influenza in Germany, the probabilities of related complications and the economic burden of influenza per case and on a population level for different age groups. Methods Claims data from 2012 to 2014 from > 8 million insured of a large German sick-ness fund were analysed. A matched case control study was used on a sub-sample of 100,000 influenza cases to calculate complication rates for ear infections/acute otitis media (AOM) and community-acquired pneumonia (CAP) as well as resource use and costs for seven age groups. Results Incidence of seasonal influenza varies between the years and is highest among infants and children 2 to 5 years of age. AOM is more likely in the younger age groups with up to 14% more patients in the influenza group than in the control group. CAP is more frequently observed in the younger age groups and in influenza patients 60 years and older. The manifestation of one influenza complication (AOM or CAP) significantly in-creases the occurrence of a second complication (AOM or CAP). The economic burden per case is highest in infants (€251.91) and persons over 60 years of age (€131.59). Conclusion The burden of influenza is highest among infants and young children, which is also reflected in the economic burden. Influenza related costs per case are nearly double for infants compared to persons over 60 years of age. Electronic supplementary material The online version of this article (10.1186/s12889-019-7458-x) contains supplementary material, which is available to authorized users.

Entscheidungsträger im Gesundheitswesen sind zunehmend an der Einbindung gesundheitsökonomischer Analysen in den Bewertungsprozess neuer Gesundheitsleistungen interessiert, nicht zuletzt aufgrund steigender Ausgaben im Arzneimittelsektor. Gleichzeitig sind auch pharmazeutische Hersteller bemüht, zu belegen, dass ihre Produkte "good value for money" bieten. Insbesondere bei Empfehlungs- und Erstattungsentscheidungen im Impfstoffsektor gehören gesundheitsökonomische Aspekte mittlerweile in vielen Ländern zum festen Bestandteil des Kriterienkatalogs, der bei der Evidenzbewertung zur Anwendung kommt. Die entscheidungsanalytische Modellierung kann dabei helfen, die Kosteneffektivität von Impfungen zu analysieren. Sie stellt sogar eine Schlüsselmethode bei der Evaluation von Impfungen dar, da sie die Abschätzung langfristiger epidemiologischer und gesundheitsökonomischer Auswirkungen von Impfungen auf Bevölkerungsebene ermöglicht. Vor diesem Hintergrund verfolgt die Dissertationsschrift das Ziel, einen Überblick über spezifische methodische Herausforderungen der modellbasierten gesundheitsökonomischen Evaluation von Impfungen zu geben und auf Basis einer Reihe von Modellierungsstudien die langfristigen epidemiologischen und gesundheitsökonomischen Effekte verschiedener Impfungen in Deutschland zu untersuchen. Die Auswahl der evaluierten Schutzimpfungen umfasst Impfstoffe gegen Humane Papillomviren (HPV), das Varicella-Zoster-Virus (VZV) sowie saisonale Influenza. Mit der Zusammenstellung von acht in Fachzeitschriften publizierten Beiträgen unterschiedlichen Charakters leistet die vorliegende Arbeit einen wichtigen Beitrag zur Erforschung der epidemiologischen und gesundheitsökonomischen Konsequenzen von Impfungen in Deutschland. Die Arbeit stellt zugleich eine wertvolle Grundlage für den Entscheidungsfindungsprozess hinsichtlich der Entwicklung oder Überarbeitung von Impfempfehlungen dar. Die Modellanalyse zu den ökonomischen Effekten der Influenza-Impfung zeigt bspw., dass die routinemäßige Impfung von Kindern und Jugendlichen gegen Influenza aus gesellschaftlicher Perspektive eine kostensparende Intervention darstellt. Wie die in die vorliegende Arbeit eingegangenen modellbasierten Studien demonstrieren, ist die Berücksichtigung der Transmissionsdynamik von hoher Relevanz, um neben direkten Impfeffekten auch indirekte Effekte (z. B. Herdenschutzeffekte) in die Ergebnisse einzubeziehen. Die Zusammenstellung der Beiträge macht dabei ebenfalls deutlich, dass sich indirekte Effekte nicht nur positiv, sondern auch negativ auf die Beurteilung einer Impfung auswirken können. Zukünftig gilt es, die Datenbasis für entscheidungsanalytische Modelle in Deutschland zu verbessern und bislang unberücksichtigte Aspekte in die modellbasierte Evaluation von Impfungen zu integrieren. Dazu zählt u. a. der durch präventive Maßnahmen induzierte Antizipationsnutzen. Bevor entsprechende Effekte jedoch in Modellen berücksichtigt werden können, bedarf es zunächst weiterer Forschung zur Messung dieser Nutzenkomponente.

Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany â a mathematical modelling study (technical appendix). (DOCX 1750 kb)

Background The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model. Methods Based on a mathematical model simulating the transmission dynamics and the natural history of HPV infection and associated diseases (cervical intraepithelial neoplasia, cervical cancer, and genital warts), we estimated the epidemiological and economic consequences of HPV vaccination with both the quadrivalent and bivalent vaccines. In our base case analysis, we assessed the cost-effectiveness of vaccinating 12-year-old girls with a 3-dose schedule. In sensitivity analysis, we also evaluated the use of a 2-dose schedule and assessed the impact of vaccinating boys. Results From a health care payer perspective, incremental cost-effectiveness ratios (ICERs) of a 3-dose schedule were €34,249 per quality-adjusted life year (QALY) for the bivalent and €14,711 per QALY for the quadrivalent vaccine. Inclusion of indirect costs decreased ICERs by up to 40%. When adopting a health care payer perspective, ICERs of a 2-dose approach decreased to €19,450 per QALY for the bivalent and to €3645 per QALY for the quadrivalent vaccine. From a societal perspective, a 2-dose approach using the quadrivalent vaccine was a cost-saving strategy while using the bivalent vaccine resulted in an ICER of €13,248 per QALY. Irrespective of the perspective adopted, additional vaccination of boys resulted in ICERs exceeding €50,000 per QALY, except for scenarios with low coverage (20%) in girls. Conclusions Our model results suggest that routine HPV vaccination of 12-year-old girls with three doses is likely to be cost-effective in Germany. Due to the additional impact on genital warts, the quadrivalent vaccine appeared to be more cost-effective than the bivalent vaccine. A 2-dose schedule of the quadrivalent vaccine might even lead to cost savings when adopting a societal perspective. The cost-effectiveness of additional vaccination of boys was highly dependent on the coverage in girls.