Hintergrund: Die Anlage einer externen Ventrikeldrainage (EVD) ist ein gängiger Notfalleingriff in der Neurochirurgie, und Infektionen während der Liegezeit treten regelmäßig auf. Für die Antibiotikaprophylaxe bei Patienten mit EVD gibt es jedoch keine allgemeingültige Empfehlung oder Leitlinie. Daher hat jede Klinik ihre eigenen Standards. Fragestellung: Ziel der Arbeit war es herauszufinden, welchen Einfluss die Art der Antibiotikaprophylaxe auf die EVD-Infektionen sowie auf eine mögliche spätere Shuntimplantation und Infektion hat. Zudem sollten weitere Einflussfaktoren für Infektionen und Komplikationen mit einbezogen werden. Material und Methoden: Im Rahmen einer retroperspektiven Analyse von 564 Patienten (267 mit Subarachnoidalblutung, 297 mit intrazerebraler Blutung) aus den Jahren 2009-2015 mit externer Ventrikeldrainage am Universitätsklinikum Dresden wurde der Einfluss der Antibiotikaprophylaxe auf die Infektionen der externen Ventrikeldrainagen sowie auf eine spätere Shuntimplantation und deren Infektion untersucht. Ergebnisse: Insgesamt hatten 37% der Patienten mindestens eine Komplikation der EVD, wobei der größte Anteil der Patienten eine Verstopfung der EVD (13,5%) hatte, gefolgt von Fehllagen (9,2%) und Liquorinfektionen (6,2%). Insbesondere Verstopfungen und Infektionen traten in Kombination mit anderen Komplikationen auf. Durch eine Antibiotikaprophylaxe während der Liegezeit zeigte sich keine erniedrigte Infektionsrate, sondern eher eine leichte, nicht signifikante Steigerung der Infektionsrate. Mit zunehmender Anzahl der EVD-Wechsel, sowie Seitenwechsel, stieg die Infektionsrate signifikant. Auch eine initial okzipitale Lage der EVD war mit einer signifikant erhöhten Infektionsrate verbunden. Patienten, die nicht nur auf Intensivstationen behandelt wurden, zeigten ebenfalls eine erhöhte Infektionsrate. 272 Patienten erhielten einen ventrikuloperitonealen Shunt (61,4% mit SAB, 36,4% mit ICB), wovon bei 23,2% mindestens eine Komplikation auftrat. Hierunter waren 10,4% 51 Infektionen des Shunts. Patienten mit einer ICB hatten, im Gegensatz zu Patienten mit einer SAB, durch eine Infektion keine signifikant höhere Shuntpflichtigkeit. Sowohl bei den EVD- als auch bei den Shuntinfektionen bilden Hautkeime einen entscheidenden Anteil. Schlussfolgerung: In Zusammenschau der Ergebnisse und der Literaturrecherche ist eine Antibiotikaprophylaxe lediglich im Rahmen der operativen Eingriffe gegenüber einer Prophylaxe über die gesamte Liegezeit vorzuziehen. Da insbesondere die Komplikationen Verstopfung und Infektion in Kombination auftreten, ist hierbei besondere Aufmerksamkeit wichtig. Steriles Arbeiten und Vorsicht sind nicht nur im Rahmen der Operation, sondern auch in der täglichen Pflege notwendig, da Hautkeime das Hauterregerspektrum bilden. Die EVD-Anlage sollte, sofern möglich, frontal erfolgen.

Introduction: Since the first outbreaks of Ebola virus disease 1976 in the Democratic Republic of the Congo (DRC) and Sudan there has been recurrent epidemics. The biggest outbreak so far hit West Africa between 2013-2016 when at least 28 600 people were estimated to have been infected and approximately 11 300 died in the most severely affected countries Guinea, Sierra Leone and Liberia. Ebola hemorrhagic fever (EHF) or Ebola virus disease (EVD) is caused by a virus that together with the Marburg virus belongs to the Filovirus family. The Ebola virus can cause hemorrhagic bleeding, has a rapid disease progression rate and a high mortality (25-90%). The symptoms are initially headache, fever, sore throat and muscle pain but during the latter part of the disease the characteristic bleedings from all bodily orifices occurs. Many internal organs do damage and survivors often have persistent sequels and long convalescense. EVD is a zoonosis and might infect antelopes, monkeys, porcupines among others. The natural reservoir is believed to be different species of bats. In august 2018, another outbreak of Ebola was reported in DRC. This was the tenth time the disease hit the country. However, for the first time there was candidate vaccine in clinical trial that could be used during an emergency. Experts within the WHO recommended that vaccination was initiated using Merck`s Ebolavaccine rVSV-∆G-ZEBOV-GP that was ready for a phase III clinical trial. This vaccine had already been used during the West African outbreak and had been known to provide a good safety profile as well as immunogenicity. The second vaccine to be used was a two-dose heterologous prime-boost vaccine regimen called Ad26.ZEBOV/MVA-BN-Filo which was marketed by Johnson&Johnson. Ad26.ZEBOV was given as a first dose to prime the immune system and then MVA-BN-Filo was administered as a second dose approximately 8 weeks later as a booster. This vaccine regimen had also been showing promising results in phase I and II clinical trials. Objective: This degree project was made in attempt to answer the issue: How effective and safe are the new Ebola vaccines against EVD? Methods: To answer this question, a literature study was conducted. The outbreak in DRC was ongoing by the time of this degree project and there were no phase III trials conducted for the Ad26.ZEBOV/MVA-BN-Filo vaccine regimen. A lot of information was therefore retrieved from WHO, Doctors without borders, and so on. Merck`s vaccine had been prequalified and received the generic name Ervebo in the fall of 2018. Randomised clinical trials (RCT) and clinical trials regarding Ervebo was downloaded from the internet using the search engine PubMed that`s accessing different databases. Results: Both Ervebo and the 2-dose vaccine regimen Ad26.ZEBOV/MVA-BN-Filo initiated an immune response against ebolavirus that was almost 100%. The most frequent solicited local and systemic adverse events were injection site pain and headache, myalgia and fever. All adverse events were reported to be mild and resolved in a short period of time. No severe adverse events were reported. Discussion: The biggest challenge in the future will concern how to initiate vaccination strategies in countries with a lack of financial resources and infrastructure as well as ongoing armed conflicts (mainly DRC). Conclusion: The new vaccines against Ebola virus infection are all effective with a good safety profile. / Bakgrund: Sedan de första utbrotten av ebolafeber 1976 i Demokratiska republiken Kongo (DRK) och Sudan har epidemier blossat upp med jämna mellanrum. Det hittills största utbrottet drabbade Västafrika 2013-2016 då minst 28 600 beräknades ha smittats och minst 11 300 avled i de hårdast drabbade länderna Guinea, Sierra Leone och Liberia. Ebolafeber, eller ebola hemorragisk feber, orsakas av ett virus som tillsammans med Marburgviruset hör till familjen Filovirus. Ebolaviruset kan orsaka hemorragiska blödningar, har snabbt sjukdomsförlopp och hög dödlighet (25-90%). Symptomen är inledningsvis influensaliknande men under den senare delen av sjukdomsförloppet förekommer de karaktäristiska blödningarna från alla kroppsöppningar. Många inre organ tar skada och överlevare har ofta bestående men och lång konvalescens. Ebolafeber är en zoonos och kan drabba antiloper, olika sorters apor m fl. Den naturliga reservoaren tros vara olika arter av fladdermöss. I augusti 2018 rapporterades om ännu ett utbrott av ebolafeber i DRK, det 10:e i ordningen. En avgörande skillnad vid detta utbrott var att det nu fanns kandidatvaccin i kliniska studier att tillgå. En expertgrupp inom WHO rekommenderade att vaccination inledddes med rVSV-∆G-ZEBOV, ett ebolavaccin tillverkat av Merck redo för kliniska studier fas III. Detta vaccin hade använts redan under utbrottet i Västafrika och visat goda resultat vad gällde immunogenicitet och säkerhet. Det andra vaccinet att sättas in var Ad26.ZEBOV/MVA-BN-Filo, tillhandahållet av Johnson&Johnson. Detta bestod av två olika doser som gavs med ca 8 veckors mellanrum, ofta kallat ”prime/boost”-vaccin. Även för Ad26.ZEBOV/MVA-BN-Filo fanns dokumenterade positiva resultat. Syfte: Detta examensarbetet gjordes med syftet att svara på frågeställningen: Hur effektiva och säkra är de nya vaccinen mot ebolafeber? Metod: För att svara på frågan gjordes en litteraturstudie. När detta examensarbete författades pågick fortfarande utbrottet i DRK och fas III studierna för Ad26.ZEBOV/MVA-BN-Filo var inte avslutade. Mycket information fick hämtas från olika hemsidor, bl a WHO och Läkare utan gränser. Mercks vaccin prekvalificerades hösten 2019 och gavs handelsnamnet Ervebo. För detta vaccin fanns fler RCT-studier tillgängliga, vilka uteslutande valdes m h a sökmotorn PubMed som är länkad till olika databaser. Resultat: Både singeldosvaccinet Ervebo och dubbeldosvaccinen Ad26.ZEBOV/MVA-BN-Filo konstaterades ge ett nästan 100%-igt immunsvar mot ebolavirus. I den mån biverkningar förekom var de milda och övergående. Den mest rapporterade lokala biverkningen var ömhet vid injektionsstället och de vanligaste systemiska biverkningarna var huvudvärk, myalgi och feber. Diskussion: Den största utmaningen i framtiden blir att inleda vaccinationsprogram i länder med bristande finansiella resurser och infrastruktur samt pågående väpnade konflikter (främst DRK). Slutsatsen blev att de nya vaccinen mot ebolafeber är effektiva och säkra vid behandling mot ebolavirusinfektion.

The mental health of healthcare workers during the Ebola outbreak in West Africa was a serious concern for healthcare professionals and the mental health field. One area in West Africa where healthcare workers played a significant role during the Ebola outbreak of 2014 and 2015 was Sierra Leone. This qualitative research study was designed to explore the perceptions of Sierra Leoneans healthcare workers' mental health, how they coped, and treatment they received while providing care for Ebola virus patients. This study, with a phenomenological research approach, used purposeful sampling to recruit 10 healthcare workers to participate in semi structured, open-ended interviews. The stress theory model and a hermeneutic phenomenology conceptual framework were used as a lens of analysis to understand the views of healthcare workers who worked directly with Ebola virus patients in Freetown, Sierra Leone. The results of the analysis of the collected data produced 9 major themes. The major themes suggest that healthcare workers experienced mental health symptoms such as depression and anxiety, personal thoughts and feelings such as insomnia, and suicidal ideation. Strategies for coping included using the Bible; and the detrimental impact included facing discrimination after the Ebola outbreak. Most of the healthcare workers blame the government for not providing adequate coping resources, which led to the personal consequence of hopelessness. This study may benefit mental health professionals working in an epidemic. Additionally, this study may contribute to social change by providing a deeper understanding of the mental health system and healthcare workers in Freetown, Sierra Leone.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Este trabalho se propÃe a investigar e propor diferentes tÃcnicas de estimaÃÃo de canal de mÃltiplas entradas e mÃltiplas saÃdas (MIMO) para sistemas de comunicaÃÃo multiusuÃrio operando em regime de interferÃncia em cenÃrio de mÃltiplas cÃlulas. AtenÃÃo particular à dada ao caso onde as estaÃÃes rÃdio-base sÃo equipadas com arranjos de antenas apresentando grande quantidade de antenas, configurando o que se tem referido na literatura como sistemas de comunicaÃÃo MIMO de grande dimensÃo (VL-MIMO, do inglÃs: very large MIMO). Algumas destas tÃcnicas exploram as propriedades das grandes matrizes aleatÃrias e sÃo menos afetadas pela contaminaÃÃo de pilotos. Nesta dissertaÃÃo, os parÃmetros do canal VL-MIMO sÃo estimados a partir de uma decomposiÃÃo em autovalores (EVD, do inglÃs: eigenvalue-decomposition) da matriz de covariÃncia na saÃda do arranjo de antenas receptoras. Esta tÃcnica se mostra menos sensÃvel à presenÃa de interferÃncia do que outras que nÃo exploram propriedades especÃficas da matriz de canal VL-MIMO, como à o caso da soluÃÃo clÃssica dos mÃnimos quadrados (LS, do inglÃs: least-squares). Nesse contexto, propÃe-se ainda uma soluÃÃo para o fator de ambiguidade multiplicativa do mÃtodo baseado em EVD, utilizando um simples produto de Khatri-Rao. Na segunda parte desta dissertaÃÃo, as propriedades dos sistemas VL-MIMO sÃo empregadas num problema de localizaÃÃo de fontes, a fim de determinar a direÃÃo de chegada (DOA) dos sinais incidentes sobre o arranjo, provenientes da cÃlula em questÃo. Explorando o subespaÃo de representaÃÃo dos sinais interferentes, propÃe-se o uso de um algoritmo de classificaÃÃo de tipo MUSIC para estimar a matriz de canal de forma cega. O mÃtodo proposto converte os altos ganhos de resoluÃÃo dos arranjos VL-MIMO em capacidade de reduÃÃo de interferÃncia, podendo fornecer estimativas do canal adequadas, mesmo sob nÃveis fortes de interferÃncia e tambÃm em casos onde os sinais do usuÃrio desejado e dos interferentes sÃo altamente correlacionados espacialmente. Extensas campanhas de simulaÃÃo computacional foram realizadas, dandoum carÃter exploratÃrio a esta dissertaÃÃo no sentido de abranger diferentes cenÃrios e avaliar as tÃcnicas investigadas em comparaÃÃo com soluÃÃes jà consolidadas, permitindo assim a elaboraÃÃo de um panorama mais completo de caracterizaÃÃo dos problemas de estimaÃÃo de parÃmetros no caso VL-MIMO. / The aim of this dissertation is mainly to investigate and propose different channel estimation techniques for a multicell multiuser multiple-input multiple-output (MIMO) communication system. Particular attention is payed to the case that is referred to as very large (VL) MIMO (VL-MIMO) arrays, where the base stations are equipped with a great (or even huge) number of antenna sensors. Some of these techniques exploit properties issued from the (large) Random Matrices Theory and are therefore less affected by the so-called pilot contamination effect. In this work, the parameters of the VL-MIMO channel are estimated from the eigenvalue decomposition (EVD) of the output covariance matrix of the receive antenna array. This technique is more robust to the interference of signals from other cells compared with methods that do not exploit the specific properties of the VL-MIMO channel matrix, which is the case of the classical least squares (LS) solution. In this context, this work also proposes a simpler way to resolve the scaling ambiguity remaining from the EVD-based method using the Khatri-Rao product. The second part of this dissertation exploits the VL-MIMO properties on a source localization problem, aiming to determine the direction of arrival (DoA) of the signals impinging on the antenna array from a given desired cell. Based on the subspace representation of the outer cell interference signals, we propose a new blind MUSIC-like classification algorithm to estimate the channel matrix. The proposed technique convert the high resolution gains of the VL-MIMO arrays into ability to reduce power of undesired signals, yielding good channel estimates even under high interference power levels, and including cases where desired and undesired signals are strongly correlated. Computer simulations have been done in order to cope with different situations and propagation scenarios, thus yielding an exploratory character to our research and allowing us to evaluate and assess the investigated algorithms, comparing them to consolidated solutions in order to establish a complete overview of the parameter estimation problem in the VL-MIMO case.