The purpose of the study The purpose of this research project was to develop and test an educational program for preparing Taiwanese nursing students for clinical practice. Study background The SARS outbreak revealed that health care professionals were ill-prepared for coping with the disease epidemic in terms of the rapid transmission of the infection, the high mortality and morbidity rate among health care workers, and the significant impacts on the public and health care personnel. Frontline nurses were the group at highest risk of becoming infected, as they are the health care personally that provide direct health care to infected patients. However, to date the ability of Taiwanese frontline nurses to respond to such a disease epidemic has not been examined. Study design This research project incorporated a three phase design, presented in the form of two separate studies. A small qualitative exploratory study was undertaken to validate the assumptions emerging from international literature regarding the preparedness nurses in managing an infection outbreak. The information gained was used to construct an infection control education program (Study I). A quasi-experimental design, using pre- and post-tests and experimental and control groups was then used to test the effectiveness of the education intervention (Study II). Participants A purposive sampling technique was used in the qualitative exploratory study, whereby six Taiwanese nurses who had provided direct nursing care to patients with SARS were interviewed. A convenience sampling approach was utilised in the quantitative study, which aimed to test the effectiveness of educational intervention. This, second study, had 175 participants in total, 80 in the experimental group and 95 in the control group. All participants were enrolled in the first semester of their fourth year in a five-year nursing program in two selected junior nursing colleges. The education intervention The purpose-designed standard and additional precautions (SnAP) program was the intervention. The experimental group received a SnAP program which consisted of 16 hours of classes over 16 weeks. The control group received a conventional education program. Data collection and instrument Data were collected at three time points during the study (baseline, four months, six month) using validated instrument. The reliability and validity of the instrument was established in a pilot study with a Taiwanese population prior to the present study. Data analysis t-tests and chi-square analyses were performed to assess any differences across demographic variables and baseline outcome variables between the experimental and control groups. Two-way repeated measures ANOVAs were used to examine the scores of the intervention and control groups across three time points. Results The data revealed that, at six months following the education program, there was a statistically significant improvement in the knowledge (F [2,180] =13.53, p=0.001) and confidence (F [2,94] =4.88, p= 0.01) of infection precautions in the intervention group compared to the control group. Also, the means of knowledge and confidence in intervention group showed a consistently increased across three time points; whereas, the mean of confidence relating infection control management in the control group resulted a drop at time 3. Although the application skills relating to infection control procedures did not show a statistically significant change during this period (F [2, 174] = 2.54, p=0.081), there were minor improvements in these scores at the six-month follow-up assessment. Conclusion The SnAP program had a positive impact on Taiwanese nursing students' readiness for clinical placement and potential outbreak of disease epidemics. Participation increased their knowledge about infection control precautions, their ability to properly use these specific precautions, and their confidence in solving infection-related issues in clinical practice.

The Diploma thesis provides basic information about the incidence of nosocomial infections, especially about the process of spreading infections, their subdivision according various aspects, major means of nosocomial infections, and about methods of surveillance. Investigative part of the thesis is aimed to describe the incidence of nosocomial infection, which can be used as quality indicator of hospital care, including the spectrum of the most frequent etiological microbial agents and their resistance against antibiotic treatment. There were used mixed research methods to process the investigative part of the thesis because the methods were quantitative and qualitative. The analysis of the data represents main part of the thesis. The research was carried out in the district hospital, namely in The Hospital Strakonice, a.s.. There were monitored infections at operation sites, between Jan 1, 2011 and Dec 31, 2011 at the surgical and gynaecology units. There were also monitored infections of the blood stream between Jan 1, 2009 and Dec 31, 2011 at all departments. The research group was formed by inpatients staying in The Hospital Strakonice, a.s., who were after surgical procedure or those, who were catheterized central blood stream in defined time period.

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No. of bitstreams: 2 Dissertação - Jessyca Rodrigues Braga - 2017.pdf: 4744453 bytes, checksum: 900a3d7f082db5d208a086c58466aa61 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-04-04 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Surgical Site Infection (SSI), besides being an indicator of the quality of care, is one of the main healthcare-associated infection (HAI). SSI caused by non-tuberculous mycobacteria (NTM) has become increasingly frequent, increasing the prevalence of SSI in clinical practice. OBJECTIVE: To analyze the epidemiological and clinical aspects of SSI by MNT in the city of Goiânia-Goiás. METHODS: Retrospective cross-sectional study, carried out from the Municipal Coordination of Infection Control and Patient Safety in Health Services (Comciss), of the Municipality of Goiânia - Goiás (Brazil). The population consisted of clinical cases of SSI by probable MNT notified to Comciss, by public and private health institutions of the city of Goiânia-Goiás, in the period from 2006 to 2015. Data were collected during the months of October to December 2015 and March 2016. The source of the data consisted of the notification/investigation forms of SSI cases by MNT stored in Comciss. The data were organized, processed and analyzed in SPSS software version 20.0 and estimated by means of simple frequency and measures of central tendency (average, fashion and median). Chi-square test or Fisher's exact test were used to assess the differences between proportions, and Odds Ratio to estimate the chance of positivity for each outcome. The level of significance was considered p <0.05. RESULTS: One hundred twenty two specimens were positive for MNT and 9 were negative. The average age of the patients was 38.15 years (SD: 13.8, min: 19 and max: 86 years). The female sex predominated in 77.1% of the cases. Comciss was the main responsible (67.1%) for the notifications. The private healthcare institutions accounted for 92.3% of the surgeries performed. Aesthetic surgeries were the most prevalent (51.9%), with mammoplasty being the most frequent. The conventional route stood out with 44.2%, compared to those made by video. The species M. abscessus and M. fortuitum prevailed. Orthopedic surgery (p = 0.002) and general surgery (p <0.001) presented a statistical association for M. abscessus infection. The use of prosthesis (p <0.001, OR 95%: 6.12) and plastic surgery (p <0.001; OR 95%: 5.90) showed statistical difference for M. fortuitum infection, but were not associated in regression. Signs / symptoms were present in 119 patients, including fever, secretion, abscess, nodules, hyperemia, among others. Clarithromycin was the most commonly used antimicrobial for the treatment of SSI by M. abscessus, and amikacin-associated clarithromycin was the most commonly used antimicrobial therapy for M. fortuitum. Resistance to 12 (80%) different antimicrobials was found for M. abscessus, and 15 (88.2%) for M. fortuitum. CONCLUSIONS: Females predominated, with mammoplasty being the main surgery. M. abscessus and M. fortuitum were the most prevalent species, being resistant to up to 15 (88,2%) antimicrobials. Being submitted to orthopedic and general surgery was a factor associated with ISC by M. abscessus. / A Infecção de Sítio Cirúrgico (ISC), além de ser um indicador da qualidade da assistência, é uma das principais infecções relacionadas à assistência à saúde (IRAS). As ISC causadas pelas Micobactérias Não Tuberculosas (MNT) têm se tornado cada vez mais frequentes, aumentando a prevalência de ISC na prática clínica. OBJETIVO: Analisar os aspectos epidemiológicos e clínicos das ISC por MNT no município de Goiânia-Goiás. MÉTODO: Estudo retrospectivo do tipo transversal, realizado a partir do banco de dados da Coordenação Municipal de Controle de Infecção e Segurança do Paciente em Serviços de Saúde (Comciss) do Município de Goiânia – Goiás (Brasil). A população constituiu-se de casos clínicos de ISC por provável MNT notificados à Comciss por instituições de saúde pública e privadas do município de Goiânia-Goiás, no período de 2006 à 2015. Os dados foram coletados durante os meses de outubro a dezembro de 2015 e março de 2016. A fonte dos dados constituiu-se das fichas de notificação/investigação dos casos de ISC por MNT armazenadas na Comciss. Os dados foram organizados, processados e analisados no software SPSS versão 20.0 e estimados por meio de frequência simples e medidas de tendência central (média, moda e mediana). Teste de Qui- quadrado ou exato de Fischer foram utilizados para avaliar as diferenças entre proporções, e Odds Ratio para estimar a chance de positividade para cada desfecho. O nível de significância foi considerado p<0,05. RESULTADOS: Foram positivas 122 espécimes para MNT e 9 negativos. A média de idade dos pacientes foi 38,15 anos (DP: 13,8; min:19 e máx: 86 anos). Predominou o sexo feminino em 77,1% dos casos. A Comciss foi a principal responsável (67,1%) pelas notificações. As instituições de saúde da rede privada foram responsáveis por 92,3% das cirurgias realizadas. As cirurgias estéticas foram as mais prevalentes (51,9%), sendo a mamoplastia a mais frequente. A via convencional se sobressaiu, com 44,2% em relação às realizadas por vídeo. Predominaram as espécies M. abscessus e M. fortuitum. Cirurgia ortopédica (p=0,002) e cirurgia geral (p<0,001) apresentaram associação estatística para infecção pelo M. abscessus. O uso de prótese (p<0,001; OR 95%: 6,12) e cirurgia plástica (p<0,001; OR 95%: 5,90) mostraram diferença estatística para infecção por M. fortuitum, porém não apresentaram associação nos modelos de regressão. Cento de dezenove pacientes apresentaram sinais/sintomas, verificou-se febre, secreção, abscesso, nódulos, hiperemia, dentre outros. Claritromicina foi o antimicrobiano mais utilizado para tratamento de ISC por M. abscessus, e claritromicina associada à amicacina foi terapêutica antimicrobiana mais utilizada para M. fortuitum. Encontrou-se resistência a 12 (70,0%) diferentes antimicrobianos para M. abscessus, e a 15 (88,2%) para M. fortuitum. CONCLUSÕES: Predominou o sexo feminino, sendo a mamoplastia a principal cirurgia envolvida. M. abscessus e M. fortuitum foram as espécies mais prevalentes, sendo as mesmas resistentes à até 15 (88,2%) antimicrobianos. Ser submetido à cirurgia ortopédica e geral foi fator associado à ISC por M. abscessus.

Introdução: As infecções relacionadas à assistência à saúde (IRAS) constituem um problema de interesse global por seu impacto para a segurança dos cuidados em saúde. Consequentemente, demandam a implantação de políticas públicas eficazes para sua prevenção e controle. Uma manifestação concreta das políticas públicas é o estabelecimento e manutenção de programas nacionais específicos para a prevenção e controle de IRAS. Objetivo: O objetivo do estudo foi analisar e comparar a implantação dos programas nacionais de prevenção e controle de IRAS no Brasil, Chile e Israel. Métodos: Trata-se de um estudo de caso descritivo e exploratório que utilizou o modelo do triângulo de análise de políticas de saúde para comparar o contexto, o processo, o conteúdo e os atores destes programas governamentais. Os dados foram coletados entre 2014 e 2017 em três fases: Fase I acesso às páginas eletrônicas dos programas nos países selecionados; Fase II visita à sede do programa nacional e Fase III - construção do modelo teórico explicativo. Resultados: Elementos comuns entre os três países foram identificados permitindo a proposição de um modelo teórico explicativo constituído de dois núcleos: núcleo de formação - composto por três componentes estratégicos (gerador de necessidade, formador de alternativas e promotor do interesse social); e núcleo de desenvolvimento e sustentabilidade dos programas composto por outros quatro componentes estratégicos (gerador de decisão, gerador de sustentação, gerador de renovação e patrocinadores do processo). Conclusão: O modelo proposto contribui na compreensão dos fatores que podem influenciar o progresso de um programa nacional de IRAS, fornecendo reflexões sobre elementos para o estabelecimento de programas em países nos quais ainda estão incipientes. / Background: Healthcare-associated infections (HAIs) are a global concern due to the impact on healthcare safety. Consequently, they demand the implementation of effective public policies for their prevention and control. A concrete manifestation of public policies is the establishment and maintenance of specific national programs for the prevention and control of IRAS. Aim: The objective of this study was to analyze and compare the implementation of national programs for the prevention and control of HAIs in Brazil, Chile, and Israel. Methods: It is a descriptive and exploratory case study that used the triangle of health policy analysis to compare the context, the process, the content and the actors of these government programs. Data were collected between 2014 and 2017 in three phases: Phase I - access to the electronic pages of the programs in the selected countries; Phase II - visit to the headquarters of the national program and Phase III - construction of the theoretical explanatory model. Results: The triangle of health policy analysis was used to compare the context, process, and content of national HAI prevention and control programs. Common elements identified among the three countries led to the proposal of an explanatory theoretical model constituted of two nuclei: formation nuclei - composed of three strategic components (necessity generator, alternatives generator and promoter of social interest); and development & sustainability nuclei - composed of four other strategic components (decision generator, sustainability generator, renewal generator and process sponsors). Conclusion: The proposed model contributes to understanding the factors that can influence the progress of a national HAI program, providing insights into the elements for establishing programs in countries where they are still inceptive.

Abstract Viral infections are common in childhood and a usual cause for hospitalization. Viruses are easily transmitted among children both in pediatric wards and in other child care facilities, like child day-care centers. Hand hygiene is an important part of prevention of the transmission of viruses. Since hospitalization times are getting shorter, hospital-associated infections often manifest after discharge. The aim of the study was to evaluate the magnitude of hospital-associated infections during and after hospitalization in pediatric wards with a focus on the effect of the ward structure. Data were collected during two periods of two years in the pediatric infectious diseases ward in Oulu University Hospital; data collection in the latter period was done using electronic follow-up methods. A two-year study period was also carried out in University Children’s hospital in Basel and in North Karelia Central Hospital in Joensuu. Paper questionnaires and electronic questionnaires were compared as methods of doing continuous surveillance of hospital-associated infections during and after hospitalization. The safety of alcohol-based hand gels in children’s use was studied using alcometer measurements after hand rub. Experiences on the use of alcohol-based hand gels in child day-care centers were collected by interviewing the personnel with questionnaires. Altogether 5.8 to 17.5% of hospitalized children (N=7046) got a hospital-associated infection; 65 to 93% of the infections became evident after discharge. The number of hospital-associated infections was lowest in wards where single rooms and cohorting based on infection etiology were used. Increased risk for hospital-associated infection was associated with young age, longer hospitalization time and a shared room. A higher response rate was achieved with electronic follow-up compared with questionnaires on paper, 84 vs. 61%. The costs of follow-up were €13.61 and €15.07 per patient in electronic and conventional follow-up, respectively. Electronic follow-up decreased annual expenses by 17.1%. Alcohol-based hand gels were found to be safe in children’s use, as no absorption was detected despite several contacts between hands and mucous membranes. Personnel in child day-care centers were active in using hand rubs and found them useful and easy to use. Earlier, there had been one incident with fire when using matches while hands were still wet with alcohol. The majority of hospital-associated infections in children become evident after discharge, and electronic follow-up is useful in evaluating their magnitude. The number of hospital-associated infections can be decreased with single room bedding and careful infection control. Alcohol-based hand gels are safe in children’s hand hygiene. / Tiivistelmä Lapset sairastavat usein virusinfektioita, jotka ovat yleinen sairaalahoidon syy. Virukset leviävät herkästi lasten keskuudessa, lastentautien osastoilla ja lapsiryhmissä, kuten päiväkodeissa. Virusten leviämistä voidaan estää hyvällä käsihygienialla. Lyhyiden hoitoaikojen vuoksi osa virusten aiheuttamista sairaalainfektioista ilmenee vasta kotona. Tutkimuksen tarkoituksena oli selvittää sairaalainfektioiden määrä hoidon aikana ja kotiutuksen jälkeen sekä osastorakenteen vaikutus sairaalainfektioihin lastentautien osastoilla. Sairaalainfektioaineisto kerättiin Oulun yliopistollisen sairaalan lasten infektio-osastolla kahtena kahden vuoden jaksona, joista jälkimmäisessä käytettiin sähköistä seurantajärjestelmää. Lisäksi kahden vuoden aineistot kerättiin Pohjois-Karjalan keskussairaalan lastentautien osastolla ja Baselin yliopistollisen sairaalan lastenosastoilla. Paperikyselylomakkeilla ja sähköisesti tehdyn sairaalainfektioseurannan toteutusta verrattiin. Lisäksi tutkittiin alkoholikäsihuuhteiden käytön turvallisuutta lapsilla päiväkotiolosuhteissa. Alkoholin imeytymistä tutkittiin poliisin tarkkuusalkometrillä käsihuuhteen käytön jälkeen. Oulun kaupungin päiväkodeista kysyttiin käsihuuhteiden käyttökokemuksista kyselylomakkeilla. Sairaalainfektion sai 5,8-17,1&#160;% sairaalassa hoidetuista lapsista (N=7046). Infektioista 65-93&#160;% tuli oireisiksi kotiutuksen jälkeen. Sairaalainfektioiden määrä oli pienin osastoilla, jossa käytettiin yhden hengen huoneita ja potilaiden kohortointia taudinaiheuttajan mukaan. Sairaalainfektion riskiä lisäsivät lapsen nuori ikä, pitkä sairaalahoitoaika ja jaettu potilashuone. Sähköisessä sairaalainfektioseurannassa oli parempi kotiutuksen jälkeinen vastausprosentti kuin paperilomakkeilla, 84&#160;% vrt. 61&#160;%. Potilasta kohden kuluja tuli sähköisessä seurannassa 13,61 euroa ja paperilomakkeilla tehdyssä seurannassa 15,07 euroa. Sähköisen seurannan käyttö laski vuosikuluja 17,1&#160;%. Alkoholikäsihuuhteiden käyttö todettiin turvalliseksi lapsilla. Useista limakalvokontakteista huolimatta käsihuuhteen käytön jälkeen alkoholia ei imeytynyt verenkiertoon. Käsihuuhteiden käyttö päiväkodeissa on aktiivista, ja henkilökunta koki sen helpoksi ja hyödylliseksi. Aiemmin oli tapahtunut yksi vaaratilanne tulen kanssa tulitikkua sytytettäessä käsien ollessa vielä käsihuuhteesta märät. Lasten sairaalainfektioista suuri osa ilmenee kotiutuksen jälkeen, ja näiden infektioiden määrää voidaan arvioida sähköisellä seurantajärjestelmällä. Sairaalainfektioiden määrää voidaan vähentää käyttämällä yhden hengen huoneita ja huolehtimalla hyvästä hygieniasta. Alkoholihuuhteiden käyttö lasten käsihygieniassa on turvallista.

Since the Morris worm was released in 1988, Internet worms continue to be one of top security threats. For example, the Conficker worm infected 9 to 15 million machines in early 2009 and shut down the service of some critical government and medical networks. Moreover, it constructed a massive peer-to-peer (P2P) botnet. Botnets are zombie networks controlled by attackers setting out coordinated attacks. In recent years, botnets have become the number one threat to the Internet. The objective of this research is to characterize spatial-temporal infection structures of Internet worms, and apply the observations to study P2P-based botnets formed by worm infection. First, we infer temporal characteristics of the Internet worm infection structure, i.e., the host infection time and the worm infection sequence, and thus pinpoint patient zero or initially infected hosts. Specifically, we apply statistical estimation techniques on Darknet observations. We show analytically and empirically that our proposed estimators can significantly improve the inference accuracy. Second, we reveal two key spatial characteristics of the Internet worm infection structure, i.e., the number of children and the generation of the underlying tree topology formed by worm infection. Specifically, we apply probabilistic modeling methods and a sequential growth model. We show analytically and empirically that the number of children has asymptotically a geometric distribution with parameter 0.5, and the generation follows closely a Poisson distribution. Finally, we evaluate bot detection strategies and effects of user defenses in P2P-based botnets formed by worm infection. Specifically, we apply the observations of the number of children and demonstrate analytically and empirically that targeted detection that focuses on the nodes with the largest number of children is an efficient way to expose bots. However, we also point out that future botnets may self-stop scanning to weaken targeted detection, without greatly slowing down the speed of worm infection. We then extend the worm spatial infection structure and show empirically that user defenses, e.g., patching or cleaning, can significantly mitigate the robustness and the effectiveness of P2P-based botnets. To counterattack, we evaluate a simple measure by future botnets that enhances topology robustness through worm re-infection.

There are an estimated 2 billion individuals infected with Mtb, and 37.7 million people living with HIV (PLWH) worldwide. HIV/Mtb co-infection increases the risk of developing active tuberculosis by over 20-fold, and 210,000 of 1.5 million deaths from TB were among co-infected PLWH in 2020. Therefore, development of effective TB vaccination, particularly within the vulnerable PLWH population, is an urgent global issue. With limited in vivo models to study co-infection, humanized NRG (huNRG) mice and humanized DRAG-A2 mice (a next-generation of huNRG mice expressing HLA class I and II transgenes with improved human immune reconstitution, huDRAG-A2) are promising tools for HIV and TB reserach as they develop robust human immune cell populations and recapitulate many aspects of HIV or TB clinical disease. HIV/Mtb co-infection was investigated using huNRG and hu-DRAG-A2 mice in separate experiments where intravaginal (with DMPA pre-treatment) or intraperitoneal HIV-1 infection was administered, respectively, and intranasal infection of Mtb was administered 3.5 weeks later. Both huNRG and huDRAG-A2 mice recapitulated hallmark features of HIV/Mtb co-infection such as severe granuloma pathology, hCD4+ T cell depletion in lung and spleen tissue, and human like lung pathology such as Mtb-infected foamy macrophages in the granuloma. Co-infected huDRAG-A2 mice also displayed significantly higher bacterial burden in the lungs, increased extrapulmonary dissemination into spleen and liver, and significantly lower hCD4+ T cells in the peripheral blood post-Mtb infection when compared to the Mtb-only infected group. To investigate TB vaccine immunogenicity, huNRG and huDRAG-A2 mice were immunized with a novel trivalent vaccine, AdCh68MV. Upon intranasal immunization, both models showed trends of developing higher Mtb antigen-specific hCD4+ T cell responses in the lung and spleen. Overall, this project sets the initial stages of a pre-clinical HIV/Mtb co-infection model in huNRG and huDRAG-A2 mice appropriate for immune investigations, therapeutic and vaccination development. / Thesis / Master of Science in Medical Sciences (MSMS) / There are over 2 billion individuals infected with TB and 37.7 million people living with HIV (PLWH) worldwide. When someone is co-infected with both diseases, the risk of death is greatly increased. Research in co-infection and developing effective TB vaccination for PLWH are urgent global issues. Animal studies are currently limited because studying HIV requires human immune cells. Our lab has established humanized mice (hu-mice) that develop many different human immune cells and are useful for HIV/Mtb co-infection research. When hu-mice were co-infected, they showed more dying lung tissue, immune cell loss, and bacteria in the lungs. Hu-mice were also used to study human immune responses to a novel TB vaccine delivered to the lungs. Trends of higher immune responses towards TB were observed in the lung and spleen of immunized hu-mice. Overall, this project shows the utility of hu-mice as pre-clinical models of HIV/Mtb co-infection and Mtb vaccine studies.

Orientador: Marileda Boanfim Carvalho / Banca: Alessandre Hataka / Banca: Marcia Mery Kogika / Banca: Fábio Nelson Gava / Banca: Andrigo Barboza De Nardi / Resumo: O objetivo do presente estudo foi padronizar a metodologia de citologia de lavado vesical preparado pelo método de citocentrifugação, avaliar o padrão das células epiteliais de transição em cães e aplicabilidade clínica da citopatologia esfoliativa como método complementar de diagnóstico de doenças vesicais em cães. O estudo foi realizado em duas fases. A primeira incluiu 34 pacientes sem anormalidade ou doença vesical (cães adultos, machos e fêmeas), para padronização da metodologia e caracterização da celularidade normal. Na segunda fase foram avaliados 95 pacientes (cães adultos, machos e fêmeas), com ou sem sinais do trato urinário inferior. Em ambas as fases os cães foram avaliados por meio de exames de rotina, com destaque para sedimentoscopia de urina, urocultura e exame ultrassonográfico da bexiga, além da citologia de lavado vesical preparada pelo método de citocentrifugação (colorações de Papanicolaou, Giemsa, Rosenfeld modificado e Gram - somente na segunda fase). Os resultados obtidos indicaram que a técnica empregada no estudo para recuperação celular realizada com barbotagens de três ciclos utilizando 1mL/kg de solução salina, se mostrou eficaz para avaliação de células uroteliais de cães sadios. Com o segundo estudo, que incluiu pacientes com doença vesical, concluiu-se que o conjunto de avaliações para o diagnóstico de doença vesical empregado são complementares e as contribuições de cada exame variam de acordo com o tipo de enfermidade a ser diagnosticada. A ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of this study was to standardize the methodology for cytology bladder washing prepared by cytospin method to evaluate the pattern of epithelial transition cells in dogs and the clinical applicability of exfoliative cytology as a complementary method for of bladder diseases diagnosis in dogs. The study was conducted in two phases. The first one included 34 patients without bladder abnormality or disease (adult dogs, male and female), for standardization of the methodology and characterization of the typical cellularity. In the second phase it was evaluated a group of 95 patients (adult dogs, male and female), with or without lower urinary tract signs. In both phases the dogs were evaluated by routine tests, especially sediment of urine, urine culture and ultrasound bladder examination, as well as cytology of bladder washing prepared by cytospin (stains of Papanicolaou, Giemsa, Rosenfeld modified and Gram - only in the second phase). The results indicated that the technique used in the study for cell recovery, performed with three barbotage cycles using 1 mL/kg of saline, was effective for urothelial cells evaluation from healthy dogs. In the second study, which included patients with bladder disease, it is concluded that the employed set of evaluations for bladder disease diagnosis are complementary and the contributions of each test vary with the type of disease to be diagnosed. The cytology of bladder washing showed was as relevant as the sediment, considering the sensitivity and specificity to detect healthy and sick patients, but with the advantages of giving refinement to enable diagnosis or the diagnosis not completed by previous tests / Doutor

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor and a prodrug of tenofovir (TFV). It is the currently recommended first line combination treatment of human immunodeficiency virus (HIV) infection in adults. Various clinical studies have associated treatment with a TDF-containing antiretroviral therapy (ART) regimen with reduced bone mineral density (BMD) and renal dysfunction. Hardly any studies to date have correlated plasma TFV concentration with markers of renal function and bone turnover (BTM). This knowledge is also unavailable in the South African public health care system. Hence, the correlations between plasma TFV concentration and renal function markers and BTM in HIV-infected women were investigated. Renal function markers and BTM in HIV-infected women were compared with those in HIV-uninfected control women. A pilot cross-sectional sub-study within the Prospective Urban and Rural Epidemiology (PURE) South Africa study was conducted. Sixty women participated, of which 30 HIV-infected women were matched for age and body mass index with 30 HIV-uninfected ones. Ethics approval was obtained from the North-West University, Human Research Ethics committee (NWU-00016-10-A1) on 12 April 2013 to conduct this sub-study and the North West Department of Health, Mmabatho on 08 August 2013 to access patient health information. A validated high-performance liquid chromatography tandem mass spectrometry method was developed to analyse TFV in plasma. Renal markers measured were the estimated glomerular filtration rate (eGFR), creatinine clearance (CrCl), albuminuria, serum creatinine (SCr), serum urea, serum uric acid, glucosuria, urine sodium (UNa) and maximum tubular reabsorption of phosphate (TmPO4/GFR). The BTM markers measured included C-terminal telopeptide (CTx), alkaline phosphatase (ALP), parathyroid hormone (PTH), total vitamin D (VitD), serum calcium (SrCa), serum phosphate (SrP) and BMD. BMD was assessed using the DTX-200 peripheral DXA system (Osteometer MediTech, Hawthorn, California, USA). Renal and bone markers were analysed on Elecsys® 2010 and COBAS INTERGRA® 400 plus (Roche Diagnostics, Switzerland). Baseline data for HIV-infected participants with regard to CD4+ cell count, SCr prior to TDF initiation, time since TDF initiation, weight prior to TDF initiation and time since HIV diagnosis were collected retrospectively from participants’ public health care files. Statistical analyses applied were linear regression, analysis of covariance, the Mann-Whitney U test, paired t-test and unpaired t-test. IBM® SPSS® Statistics software 22 was used to perform all the statistical analyses. The median and interquartile range of plasma TFV concentration was 113 (74-139.4) ng/mL (n=25) and no TFV was detected in five participants’ plasma. Adjusted analyses showed TFV concentration to be associated with albuminuria (adjusted r2 = 0.339; p = 0.001). Values of CrCl, eGFR and albuminuria (p = 0.032; p = 0.038; p = 0.048, respectively) were significantly higher in HIV-infected women compared to HIV-uninfected women. CrCl [112 (84-137) mL/min] and eGFR [134 (93-153) mL/min/1.73m2] values were abnormally high in HIV-infected women. There was also an increase in both CrCl and eGFR (p = 0.008; p < 0.001, respectively) from baseline to median follow-up of 16.6 (8.8-23.4) months in HIV-infected women. At a TFV plasma concentration of ≥ 120 ng/mL, CTx and ALP correlated positively (r = 0.704; p = 0.016). ALP (112 ± 28 U/L; p < 0.001), CTx (0.68 ± 0.4 ng/mL; p = 0.027) and PTH (56.3 ± 32 pg/mL; p = 0.050) were higher in HIV-infected women compared to HIV-uninfected women. CD4+ cell count increased from baseline to follow-up in HIV-infected women (+250 cells/mm3; p = 0.001). In HIV-infected women on a TDF-based regimen, TFV plasma concentration is associated with an increase in albuminuria, while perturbations in BTM equilibrium occur at ≥ 120 ng/mL of TFV plasma concentration. Abnormally higher CrCl and eGFR are present in HIV-infected women, seen as glomerular hyperfiltration compared with HIV-uninfected women. There was immunological improvement with TDF-based ART in HIV-infected women. Longitudinal studies with larger sample sizes are needed to confirm these findings. / MSc (Pharmacology), North-West University, Potchefstroom Campus, 2015

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor and a prodrug of tenofovir (TFV). It is the currently recommended first line combination treatment of human immunodeficiency virus (HIV) infection in adults. Various clinical studies have associated treatment with a TDF-containing antiretroviral therapy (ART) regimen with reduced bone mineral density (BMD) and renal dysfunction. Hardly any studies to date have correlated plasma TFV concentration with markers of renal function and bone turnover (BTM). This knowledge is also unavailable in the South African public health care system. Hence, the correlations between plasma TFV concentration and renal function markers and BTM in HIV-infected women were investigated. Renal function markers and BTM in HIV-infected women were compared with those in HIV-uninfected control women. A pilot cross-sectional sub-study within the Prospective Urban and Rural Epidemiology (PURE) South Africa study was conducted. Sixty women participated, of which 30 HIV-infected women were matched for age and body mass index with 30 HIV-uninfected ones. Ethics approval was obtained from the North-West University, Human Research Ethics committee (NWU-00016-10-A1) on 12 April 2013 to conduct this sub-study and the North West Department of Health, Mmabatho on 08 August 2013 to access patient health information. A validated high-performance liquid chromatography tandem mass spectrometry method was developed to analyse TFV in plasma. Renal markers measured were the estimated glomerular filtration rate (eGFR), creatinine clearance (CrCl), albuminuria, serum creatinine (SCr), serum urea, serum uric acid, glucosuria, urine sodium (UNa) and maximum tubular reabsorption of phosphate (TmPO4/GFR). The BTM markers measured included C-terminal telopeptide (CTx), alkaline phosphatase (ALP), parathyroid hormone (PTH), total vitamin D (VitD), serum calcium (SrCa), serum phosphate (SrP) and BMD. BMD was assessed using the DTX-200 peripheral DXA system (Osteometer MediTech, Hawthorn, California, USA). Renal and bone markers were analysed on Elecsys® 2010 and COBAS INTERGRA® 400 plus (Roche Diagnostics, Switzerland). Baseline data for HIV-infected participants with regard to CD4+ cell count, SCr prior to TDF initiation, time since TDF initiation, weight prior to TDF initiation and time since HIV diagnosis were collected retrospectively from participants’ public health care files. Statistical analyses applied were linear regression, analysis of covariance, the Mann-Whitney U test, paired t-test and unpaired t-test. IBM® SPSS® Statistics software 22 was used to perform all the statistical analyses. The median and interquartile range of plasma TFV concentration was 113 (74-139.4) ng/mL (n=25) and no TFV was detected in five participants’ plasma. Adjusted analyses showed TFV concentration to be associated with albuminuria (adjusted r2 = 0.339; p = 0.001). Values of CrCl, eGFR and albuminuria (p = 0.032; p = 0.038; p = 0.048, respectively) were significantly higher in HIV-infected women compared to HIV-uninfected women. CrCl [112 (84-137) mL/min] and eGFR [134 (93-153) mL/min/1.73m2] values were abnormally high in HIV-infected women. There was also an increase in both CrCl and eGFR (p = 0.008; p < 0.001, respectively) from baseline to median follow-up of 16.6 (8.8-23.4) months in HIV-infected women. At a TFV plasma concentration of ≥ 120 ng/mL, CTx and ALP correlated positively (r = 0.704; p = 0.016). ALP (112 ± 28 U/L; p < 0.001), CTx (0.68 ± 0.4 ng/mL; p = 0.027) and PTH (56.3 ± 32 pg/mL; p = 0.050) were higher in HIV-infected women compared to HIV-uninfected women. CD4+ cell count increased from baseline to follow-up in HIV-infected women (+250 cells/mm3; p = 0.001). In HIV-infected women on a TDF-based regimen, TFV plasma concentration is associated with an increase in albuminuria, while perturbations in BTM equilibrium occur at ≥ 120 ng/mL of TFV plasma concentration. Abnormally higher CrCl and eGFR are present in HIV-infected women, seen as glomerular hyperfiltration compared with HIV-uninfected women. There was immunological improvement with TDF-based ART in HIV-infected women. Longitudinal studies with larger sample sizes are needed to confirm these findings. / MSc (Pharmacology), North-West University, Potchefstroom Campus, 2015