1,721,005 research outputs found
Novel Screening Strategies for HIV, Hepatitis B and C Infection
No full textAbstract Title: Novel Screening Strategies for HIV, Hepatitis B and C Infection.
Author: Dr Sarah O?Connell
Introduction: Despite prevention measures in place, rates of HIV infection have failed to decline in Ireland in recent years. From 2015 to 2016, a 6% increase was seen in notifications of newly diagnosed HIV infection. High numbers of chronic hepatitis B infection continue to be diagnosed in Ireland every year and rates of newly diagnosed hepatitis C infection have fallen slightly in recent years. The HIV UNAIDS 90-90-90 plan outlines a target for 2020, where 90% of those with HIV infection be diagnosed, 90% of those are linked to care and 90% of those are on effective anti-retroviral therapy. The National Hepatitis C Treatment Programme aims to see progression towards eradication of hepatitis C by 2026. Risk based screening nationally are the most common screening practices in Ireland. I proposed to undertake a research programme to understand current HIV presentation patterns and the current landscape of blood borne virus cascade of care, to introduce a pilot blood borne virus screening programme, to examine the feasibility and acceptability of such a programme and to examine the sero-prevalence of infection in a high-prevalence cohort. I aimed to understand the demographics of those diagnosed, measure linkage to care rates, monitor patients through their treatment pathways and examine ways to improve the testing and follow up service.
Methods: Retrospective cohort studies examining HIV, hepatitis B and C retention in care rates and treatment outcomes were undertaken at our centre. A nested case control study examining factors associated with non-retention in HIV care was performed. A retrospective cohort study of those who presented with late HIV infection at our centre from 2002 and 2014 was then performed. A cross sectional pilot study was then undertaken, where 10,000 patient samples in St James?s Hospital Emergency Department were tested on an opt-out basis for HIV, hepatitis B and C infection. Uptake rate of testing was recorded. Given high rates of poor engagement to hepatitis C care, a retrospective cohort study of those with known hepatitis C infection was then performed to understand factors associated with non-engagement in hepatitis C care. Success of this pilot study led to the implementation of blood-borne virus testing as routine care. Referrals to the Department of Genito-Urinary Medicine and Infectious Diseases were recorded and tracked to monitor retention in care and triage/treatment outcomes. A quality improvement programme was then undertaken to explore ways to improve hepatitis C retention in care.
Results: Patients with heterosexual mode of acquisition and of an older age were more likely to present at a late point in their HIV illness, suggesting a non-risk based HIV screening approach is necessary. In our BBV cohort, retention in HIV care rates are comparable with international standards, but can be improved upon to meet the UNAIDS 90-90-90 target. Hepatitis B and C retention in care rates are poor. No significant demographic is associated with hepatitis B disengagement from care and reasons for disengaging are poorly understood. Results of a nested case-control study showed that the non-Irish, heterosexual population are more likely to disengage from HIV care. Following the introduction of a pilot ED opt-out BBV study, a high feasibility and acceptability rate was found. High sero-prevalence for all 3 infections was found, and a high proportion of those with previously known hepatitis C were not attending care. Cases were diagnosed and linked/re-linked to care. Factors associated with non-engagement in hepatitis C care included active intravenous drug use. Success of this pilot project led to the introduction of routine testing in the ED. Results show ongoing overall high sero-prevalence rates. A quality improvement programme was introduced to find ways to improve the poor hepatitis C retention in care rate. This programme provided the team with valuable experience in Quality Improvement tools that can be used to deliver quality healthcare.
Conclusion: Patients need to be diagnosed with BBV infections they are unaware of, and linked to care. We have shown that this is possible, and the healthcare infrastructure in place can serve these patients well. We need to make improvements in our healthcare service in the areas of BBV retention in care and increased BBV testing overall. Improved healthcare staff education around the need for widespread BBV testing, the need to understand predictors of non-retention in care and the need for increased awareness of HIV clinical indicant conditions is required. Lastly, BBV screening programmes need to be expanded nationally to allow for widespread testing
The role of Ma1 in macrophage responses to tuberculosis
No full textTHESIS 10592Heterozygotes for the common S180L polymorphism in the TLR adaptor Mal (TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas homozygotes are at increased risk. We report that Mal has a hitherto unknown TLR- independent role in interferon-gamma receptor (IFNyR) signaling. This novel Mal- dependent IFNyR signalling pathway leads to MAPK p38 phosphorylation and autophagy. IFN-y signalling via Mal is is required for phagosome maturation and killing of intracellular M. tuberculosis. The S180L polymorphism and its murine equivalent reduce Mal?s affinity for the IFNyR thereby compromising IFNyR signaling in macrophages and impairing in vitro and in vivo responses to TB. These findings highlight a new role for Mal outside the TLR system and imply that genetic variation in Mal may be linked to other IFN-y related diseases including autoimmunity and cancer
Vaccination as a means of disease prevention in HIV infected individuals; successes, challenges & opportunities
No full textThis thesis is structured to systemically assess susceptibility to vaccine preventable infections in HIV-infected adults, to investigate effectiveness of an integrated vaccine programme as a model of care for vaccine delivery to a HIV-infected cohort, to investigate the burden of vaccine preventable infections (pneumococcal and human papillomavirus (HPV) infection) in HIV-infected adults and to assess immunognenicity of a prime-boost pneumococcal vaccine strategy and HPV vaccine in HIV-infected adults.
Chapter 2 investigates seroepidemiology of common vaccine preventable infections (hepatitis A virus (HAV), hepatitis B virus (HBV), varicella zoster virus (VZV), measles, mumps and rubella (MMR) in HIV-infected adults attending the department of Genito Urinary Medicine and Infectious Diseases clinic (GUIDE), the largest tertiary referral HIV specialist centre in Ireland.
Chapter 3 investigates the effectiveness of an integrated vaccine unit as a model of care for delivery of routine immunisations including seasonal influenza vaccine, pneumococcal vaccine and HBV vaccine to a cohort of HIV-infected adults.
Chapter 4 examines the burden of invasive pneumococcal disease (IPD) in HIV-infected adults attending a tertiary referral hospital (St James?s Hospital, Dublin). We then investigate immunogenicity of pneumococcal vaccine strategies in HIV-infected adults.
Chapter 5 examines the burden of anal cancer in HIV-infected adults attending the GUIDE clinic. Additionally, we investigate prevalence and persistence of HPV infection and infection with high-risk (hr) or oncogenic HPV types in HIV-infected MSM. We examine acceptability of HPV vaccine in this patient group and immunogenicity of the quadrivalent HPV vaccine in young HIV-infected MSM in whom the HPV vaccine is indicated.
Chapter 6 extends the context surrounding the research questions, discusses the main findings of the PhD, draws conclusions and alludes to future directions of research to build on findings of this thesis
The inflammatory degenerative continuum of HIV related cognitive impairment
No full textTHESIS 11057This thesis is the result of three years of research from January 2011 to December
2013 examining the role of cognition in HIV infection in an Irish specialist HIV service.
This had not previously been examined in Ireland. Four studies were undertaken which
were all linked. The first examined the prevalence of a positive screen for cognitive
impairment. The second examined the cognitive profile of HAND in Ireland in the post
highly active anti-retroviral therapy era. The third study investigated the magnetic
resonance imaging (MRI) features of HAND with voxel based morphometry (VBM) and
diffusion tensor imaging (DTI). The final study explored the immunological,
inflammatory and degenerative biomarkers of HAND in cerebrospinal fluid. All of the
studies were cross-sectional in nature
Therapeutic outcomes, immunological responses to treatment and vaccine preventative strategies for Hepatitis C in HIV seropositive individuals
No full textIntroduction:
HIV and Hepatitis C virus (HCV) represent significant causes of morbidity and mortality worldwide. Because of shared routes of transmission co-infection is common. Recent advances in treatment for both HIV and HCV look set to significantly alter the natural history of both diseases and offer long-term hope for patients. The advent of direct-acting antiviral (DAA) therapy for HCV has markedly improved therapeutic outcomes for patients engaged in care. Despite, excellent tolerability and high rates of sustained virological response (SVR) with these new agents, they are costly, associated with drug-drug interactions, do not prevent against re-infection and are not 100% effective. Additionally, HCV viral resistance may represent a challenge in the future. This DAA therapy will have a limited impact on the burden of HCV-related disease on a population level unless barriers to HCV education, screening, evaluation and treatment are addressed and treatment uptake improves. At present, no commercial vaccine exists for prevention of HCV.
Aims/Methods:
The aims of this thesis were threefold. Firstly, I looked to examine therapeutic outcomes for patients with HIV/HCV co-infection treated for HCV from 2001 to 2016. Secondly, further understanding of the complex interaction between HCV and the immune system is likely to yield benefits in terms of therapeutic and preventative strategies. We looked to examine alterations in the IFN-alpha JAK-STAT signaling pathway in primary immune cells of co-infected patients as a result of HCV treatment with a Telaprevir-based regimen. Finally, towards a preventative strategy for HCV in HIV patients, we looked to examine the safety and immunogenicity of novel vaccine candidates (AdCh3NSmut1 and MVA-NSmut) delivered in a prime-boost regimen.
Results:
Regarding therapeutic outcomes, a significant difference in mortality and liver-related morbidity was observed between patients who obtained and did not obtain a SVR with interferon-based treatment regimens. Outcomes for people who inject drugs (PWIDs) were similar to non-PWIDs. An increase in treatment uptake and SVR rates was seen with the new DAA regimens. We found that STAT1 protein levels are reduced from primary immune cells in patients with HIV/HCV co-infection and Telaprevir-based regimens resulted in on-treatment restoration of STAT1 levels in these patients. Finally, we showed that AdCh3/MVA vaccination in HIV-infected patients is safe and induced T-cell responses in the majority of antigenic pools tested by ELISpot assay in all individuals.
Discussion:
This work has chronicled the improvements in therapeutic outcomes for HCV therapy in co-infected patients and shown the benefits of obtaining a SVR in HIV/HCV co-infected patients. We have outlined a previously undescribed phenomenon in HIV/HCV co-infected patients where DAA therapy has resulted in a significant increase in STAT1 protein from primary immune cells. This work has also evaluated the safety and immunogenicity of a novel vaccine strategy in HIV-positive patients. The vaccine strategy has been shown to be safe and highly immunogenic. Data from an on-going Phase 2 study looking at efficacy of this vaccine regimen are eagerly awaited
Career choice in medicine
Full text linkBackground: Career Choice in Medicine is an important and problematic topic. Medical education has been framed as professional identity development, yet career choice has not been viewed as a matter of identity. My primary aim was to offer new insights by exploring career choice using Figured Worlds theory, a socio-cultural theory of identity. Graduate retention is a challenge for many countries, including Ireland. My secondary aim was to address a gap in the data on postgraduate trainees in Ireland and to use the Irish case to illustrate points transferable to other contexts. Methodology & Methods: This was a predominantly qualitative Mixed Methods programme of research. My qualitative studies were oriented towards social constructionism. I collated existing data from the Royal College of Physicians of Ireland (RCPI) and HSE-MET to describe trainees and their career paths. I surveyed Basic Specialist Training trainees (n=333) about their career plans. I surveyed new trainees (n=527) about their expectations of training and all RCPI trainees about their experiences of training (n=1246). I conducted semi-structured interviews with 18 medical students and doctors. A subgroup (n=6) provided longitudinal data. Figured Worlds theory and Gee’s discourse tools were used for analysis. Results: I have used the case of medical training and career choice in Ireland to explain how social, political and cultural context, and day to day experiences in the cultural world of medicine, shaped doctors’ career choices. My qualitative findings described a unifying model of career choice, consisting of priming, exposure, positioning and open-endedness, which can guide the design of interventions to shape and support career choice. Conclusion: My original contribution has been to demonstrate the fruitfulness of framing career choice in terms of identity development. This represents a turn in the conversation about career choice, which brings new starting points and moves the dialogue forward
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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