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In 2010, the government of British Columbia (B.C.) dedicated $48 million to stop the spread of HIV. The STOP HIV/AIDS pilot project promotes the uptake of HIV testing in the general population, and the use of antiretroviral therapy amongst those living with HIV/AIDS. This project operates with the rationale of ‘treatment as prevention’ (TasP), meaning that antiretroviral therapy is beneficial for the person living with HIV/AIDS, and has the secondary benefit of reducing the spread of HIV in the general population. Public health discourses are constructed via particular worldviews and involve the creation and delineation of societal problems. Undertaking a discourse analysis, I identify eight dominant discourses of TasP and STOP HIV/AIDS that include: provincial and international support for TasP and lack of federal leadership in HIV/AIDS; TasP, a ‘paradigm shift’ and a ‘game changer;’ TasP as beneficial to the individual and society; human rights and harm reduction; proof and certainty; failure of current prevention efforts; risk discourses; and, finally, universal treatment. I also identify five alternative discourses: holistic understanding/social determinants of health; stigma and discrimination; rights discourse: GIPA, informed consent and self-determination; coercion/criminalization and alternative risk discourse. Through a lens of governmentality, I explicate two overarching and simultaneous discursive strategies in realizing the objective of decreasing the spread of HIV in B.C. The first strategy acts on individuals living with HIV/AIDS, encouraging individuals to take up antiretroviral therapy. The second strategy acts on the general population, informing the population that HIV is a problem, and that treating people living with HIV/AIDS is the best way to protect society as a whole. There are various techniques within these two strategies. These discursive events have immense consequences for the uptake of health policies and programs by the public. The dominant and alternative discourses of TasP impact HIV policy and practice and specifically the individuals living with HIV and AIDS who are the subjects and targets of these initiatives. / Graduate

This is a Straussian grounded theory study about the impact of nurses’ values on pressure ulcer prevention. Semi-structured interviews were used to gather data from participants (n=16) who were recruited from the non-acute adult medical wards of 14 hospitals in one NHS Trust and a local university. The participants were asked to talk about their experiences of preventing and managing pressure ulcers and their values were elicited from their accounts. The data were analysed and interpreted with Straussian grounded theory. Nurses were found to work according to the value that they placed on pressure ulcer prevention, as this value influenced the manner in which they prioritised and delivered skin care to their patients. Similar links between nurses’ values and their delivery of care with regards to other aspects of nursing were also identified. The delivery of care to prevent pressure ulcers was found to be subject to clinical priorities and other factors. As a result, the majority of care to maintain skin integrity was delivered by nursing auxiliaries and students because nurses were busy doing other things. Despite this, nurses who place a high value on pressure ulcer prevention appear to be more proactive and determined to deliver care that protects the integrity of their patients’ skin than their peers. This is highlighted by the participants’ accounts of how their prioritisation and delivery of care to prevent pressure ulcers changed when the value that they placed on pressure ulcer prevention increased from low to high. This study also identified the manner in which the value that nurses place on pressure ulcer prevention is formed and evolves. The recommendations that arise from this study are: further testing of this grounded theory in other settings to increase its generalisability and a greater awareness of the impact that the value that nurses place on different aspects of patient care has on their delivery of care to patients, especially with regards to pressure ulcer prevention. Nurse education and training must also take into account some of the factors that help to form and change the value that nurses place on pressure ulcer prevention. Greater attention needs to be paid to the value that nurses place on different aspects of nursing in view of the relationship between nurses’ values and care delivery, if patients are to receive the best possible care.

Hospital-acquired pressure ulcers (HAPUs) represent a significant challenge in the care provided for hospitalized patients. HAPUs impact morbidity, mortality, and quality of life. At the local practice site, the incidence of HAPUs increased in the perioperative setting. The practice-focused question for this project asked if an education program for staff nurses working in a perioperative care setting with high HAPU incidence can advance nurse knowledge regarding prevention, early assessment, symptoms, and treatment of HAPUs. The purpose of this educational project was to develop a pretest and posttest designed education program on HAPU prevention and care for perioperative nurses. The Iowa model was used to guide content development with application of the content to nursing practice, and Watson’s theory of caring was used to align with the organizational core values. Information on the prevention and treatment of HAPUs was obtained from national and international guidelines. A presentation was developed to address the practice guidelines for assessment, prevention, and treatment of HAPUs. A standardized pretest from NetCE was given to 15 nurses and 5 medical assistants prior to the education program and again after the education program. NetCE score results indicated improvement in nursing staff members’ knowledge from 65 on the pretest to 100 on the posttest; medical assistants’ scores increased from 35 to 65. For patients who undergo surgical procedures, the results of this project may improve assessment, prevention, and treatment of HAPUs and thereby promote positive social change because patients have a reduced risk of HAPUs and HAPU-associated complications.

Despite a rise in breast cancer incidence, mortality rates have fallen. This improvement in mortality is due to the success of anti-cancer treatments such as chemotherapy and radiotherapy. Such treatments, however, are known to be associated with a range of symptoms. A number of studies exploring patients’ chemotherapy-related symptom experiences have shown that patients consistently rate nausea and fatigue highly, not only in relation to severity, but also in relation to the associated distress they experience. The subjective and non-observable nature of both nausea and fatigue complicates their assessment. While a range of assessment tools exists to evaluate patients’ experiences of these two symptoms, there is currently no gold standard assessment tool for assessing either symptom. Moreover, while a range of pharmacological and non-pharmacological interventions have been developed for both symptoms, further evaluation is often needed to provide the level of evidence required to recommend their implementation in real life clinical environments. The SNA↔P (structured nursing assessment into practice) study arose in response to this clinical situation. The SNA↔P study was a longitudinal study that evaluated the impact of a complex evidence-based intervention, incorporating structured multidimensional symptom assessment and multiple symptom management techniques, on patients’ experiences of nausea and fatigue during a course of chemotherapy for breast cancer. Using complementary quantitative and qualitative research methods not only allowed in-depth understanding of patients’ experiences and patterns of nausea and fatigue during a course of chemotherapy, but also facilitated a rounded evaluation of the intervention, incorporating both statistical elements and those of personal significance. The use of these methods showed that the implementation of the SNA↔P intervention in routine clinical practice has significant potential for improving patients’ symptom experiences during a course of chemotherapy. In so doing, it also highlighted a number of areas in which clinical practice can be influenced, and research conducted, to further improve patients’ symptom experiences.

This diploma thesis is focused on the prevention and monitoring of healthcare-associated infections at the Hospital Prachatice, a.s. The main objective was to describe current situation in the field of prevention of nosocomial infections in this hospital. I focused on verification of medical personnel knowledge of nosocomial infections, the work of cleaners and the quality of hand hygiene of medical personnel. Diploma thesis is focused on the 4 selected departments of the hospital department of internal medicine, gynecology-obstetric department, surgical department and ARO and ICU. Thesis is divided into theoretical and practical part. The present knowledge about the healthcare-associated infections are processed in the theoretical part. To obtain all needed information was used domestic and foreign professional literature. The practical part was about the observation and the short research in the Hospital Prachatice, a.s. The research part was combined. The qualitative method including short interviews with the cleaners was combined with a quantitative method. Within this quantitative method have been used short questionnaires, which were intended for nurses. With these questionnaires I tried to find out their basic knowledge about nosocomial diseases and how they prevent them. The microbiological department of the Hospital Prachatice, a.s. was helpful in monitoring the quality of hand hygiene through method of microbiological fingerprinting. The questionnaires were handed out to nurses which worked on shift in that time on four mentioned departments of hospital. I return total 32 questionnaires back. Questionnaire had 11 questions and my plan was find out the basic knowledge of nurses about the issue. Interviews were conducted with cleaners working on focused departments where the research took place. The microbial fingerprints of hands were collected from medical staff on current work shift including doctors and cleaners. The fingerprints were made on blood agar where after 24-hours of incubation the colonies of bacteria were evaluated. None of the fingerprints was completely negative. I determined totaly 4 research questions: 1. Are all workers of selected hospital departments well informed about nosocomial diseases? 2. What is the hygiene quality of hands among medical staff? 3. On what hygienic level is job of cleaners how often they are cleaning, which way and how often they are changing the working equipment and are the all hygiene criterions followed? 4. How is manipulated with laundry? The results of the questionnaires was surprised for me because most of the medical personnel correctly answered all the asked questions. It was found a total 16 kinds of gram+ and gram microorganisms during a hand hygiene by microbial fingerprints. Most occurred findings was Staphylococcus epidermidis and Microccocus species. In two cases occurred a epidemiologically significant Staphylococcus aureus, which in both cases was found among cleaners. From my observation, investigation and interviews with cleaners I can infer that the work they are doing, they do really conscientiously and normally the health regulations are not violated. Further was found that the manipulation with laundry in Hospital Prachatice, a.s. is in accordance with the hygiene requirements for medical devices. What is important is the effective education of personnel in the prevention of infections and supervision of compliance of mandated procedures.

Trinucleotide repeat (TNR) instability including repeat expansions and repeat deletions is the cause of more than 40 inherited incurable neurodegenerative diseases and cancer. TNR instability is associated with DNA damage and base excision repair (BER). In this dissertation research, we explored the mechanisms of BER-mediated TNR instability via biochemical analysis of the BER protein activities, DNA structures, protein-protein interaction, and protein-DNA interaction by reconstructing BER in vitro using synthesized oligonucleotide TNR substrates and purified human proteins. First, we evaluated a germline DNA polymerase β (pol β) polymorphic variant, pol βR137Q, in leading TNR instability-mediated cancers or neurodegenerative diseases. We find that the pol βR137Q has slightly weaker DNA synthesis activity compared to that of wild-type (WT) pol β. Because of the similar abilities between pol βR137Q and WT pol β in bypassing a template loop structure, both pol βR137Q and WT pol β induces similar amount of repeat deletion. We conclude that the slightly weaker DNA synthesis activity of pol βR137Q does not alter the TNR instability compared to that of WT pol β, suggesting that the pol βR137Q carriers do not have an altered risk in developing TNR instability-mediated human diseases. We then investigated the role of DNA synthesis activities of DNA polymerases in modulating TNR instability. We find that pol βY265C and pol ν with very weak DNA synthesis activities predominantly promote TNR deletions. We identify that the sequences of TNRs may also affect DNA synthesis and alter the outcomes of TNR instability. By inhibiting the DNA synthesis activity of pol β using a pol β inhibitor, we find that the outcome of TNR instability is shifted toward repeat deletions. The results provide the direct evidence that DNA synthesis activity of DNA polymerases can be utilized as a potential therapeutic target for treating TNR expansion diseases. Finally, we explored the role of post-translational modification (PTM) of proliferating cell nuclear antigen (PCNA) on TNR instability. We find that ubiquitinated PCNA (ub-PCNA) stimulates Fanconi associated nuclease 1 (FAN1) 5’-3’ exonucleolytic activities directly on hairpin structures, coordinating flap endonuclease 1 (FEN1) in removing difficult secondary structures, thereby suppressing TNR expansions. The results suggest a role of mono-ubiquitination of PCNA in maintaining TNR stability by regulating nucleases switching. Our results suggest enzymatic activities of DNA polymerases and nucleases and the regulation of the activities by PTM play important roles in BER-mediated TNR instability. This research provides the molecular basis for future development of new therapeutic strategies for prevention and treatment of TNR-mediated neurodegenerative diseases.

Uganda is using a strategy called treatment as prevention where as many individuals as possible that are infected with HIV receive treatment. As a result, the number of newly infected individuals has decreased significantly. However, there is a discussion about a potential problem regarding transmitted drug resistance. This work aims to investigate if this in fact will be a problem in the future, and to estimate the costs for different scenarios. Through developing a population-based mathematical model that describes transmission dynamics of HIV in Uganda, stochastic simulations are made for different conditions. Through analysing our simulations, we can see that Uganda may have to change their approach to HIV treatment. / För att minska smittoriskerna av HIV nyttjar Uganda en strategi som syftar till att behandla så många smittade personer som möjligt. Detta har lett till en signifikant minskning av antalet smittade personer. Det har dock uppstått en diskussion angående om läkemedels-resistent smitta kan komma att utgöra ett problem. Detta arbete syftar till att undersöka om detta kan utgöra ett problem i framtiden samt till att uppskatta de kostnader som kan uppstå i olika typer av scenarion. Under olika förutsättningar genomförs stokastiska simuleringar med hjälp av en matematisk populationsmodell framtagen för att beskriva spridningen av HIV i Uganda. Genom att analysera resultaten från olika simuleringar dras slutsatsen att Uganda kan behöva omvärdera sitt tillvägagångssätt gällande behandling av HIV.