Doctor of Philosophy

DissertationHealth information technology (HIT) in conjunction with quality improvement (QI) methodologies can promote higher quality care at lower costs. Unfortunately, most inpatient hospital settings have been slow to adopt HIT and QI methodologies. Successful adoption requires close attention to workflow. Workflow is the sequence of tasks, processes, and the set of people or resources needed for those tasks that are necessary to accomplish a given goal. Assessing the impact on workflow is an important component of determining whether a HIT implementation will be successful, but little research has been conducted on the impact of eMeasure (electronic performance measure) implementation on workflow. One solution to addressing implementation challenges such as the lack of attention to workflow is an implementation toolkit. An implementation toolkit is an assembly of instruments such as checklists, forms, and planning documents. We developed an initial eMeasure Implementation Toolkit for the heart failure (HF) eMeasure to allow QI and information technology (IT) professionals and their team to assess the impact of implementation on workflow. During the development phase of the toolkit, we undertook a literature review to determine the components of the toolkit. We conducted stakeholder interviews with HIT and QI key informants and subject matter experts (SMEs) at the US Department of Veteran Affairs (VA). Key informants provided a broad understanding about the context of workflow during eMeasure implementation. Based on snowball sampling, we also interviewed other SMEs based on the recommendations of the key informants who suggested tools and provided information essential to the toolkit development. The second phase involved evaluation of the toolkit for relevance and clarity, by experts in non-VA settings. The experts evaluated the sections of the toolkit that contained the tools, via a survey. The final toolkit provides a distinct set of resources and tools, which were iteratively developed during the research and available to users in a single source document. The research methodology provided a strong unified overarching implementation framework in the form of the Promoting Action on Research Implementation in Health Services (PARIHS) model in combination with a sociotechnical model of HIT that strengthened the overall design of the study

Transcutaneous Immunization with Toxin-Coregulated Pilin A Induces Protective Immunity against Vibrio cholerae O1 El Tor Challenge in Mice

Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V. cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], 50 mug) on days 0, 19, and 40. Mice immunized with TcpA alone did not develop anti-TcpA responses. Mice that received transcutaneously applied TcpA and CT developed prominent anti-TcpA immunoglobulin G (IgG) serum responses but minimal anti-TcpA IgA. Transcutaneous immunization with CT induced prominent IgG and IgA anti-CT serum responses. In an infant mouse model, offspring born to dams transcutaneously immunized either with TcpA and CT or with CT alone were challenged with 10(6) CFU (one 50% lethal dose) wild-type V. cholerae O1 El Tor strain N16961. At 48 h, mice born to females transcutaneously immunized with CT alone had 36% +/- 10% (mean +/- standard error of the mean) survival, while mice born to females transcutaneously immunized with TcpA and CT had 69% +/- 6% survival (P \u3c 0.001). Our results suggest that transcutaneous immunization with TcpA and an immunoadjuvant induces protective anti-TcpA immune responses. Anti-TcpA responses may contribute to an optimal cholera vaccine

‘It Brings it all Back, all those Good Times; it Makes Me Go Close to Tears’. Creating Digital Personalised Stories with People who have Dementia

The purpose of these three case studies was to analyse and theoretically explain the contribution of digital multimedia personalisation to stimulate and share long-term memories of people who live with mild to moderate dementia. We investigated how the use of a freely available iPad app can, in a supporting context, facilitate the creation of personalised multimedia stories, including the participants’ audio recordings, texts and photos of items, places or people important to them. Three people who were recruited from a club for people living with dementia created personalised multimedia stories using their own photographs and/or pictures downloaded from the internet, with written captions and audio-recorded voiceovers. Our analysis focuses on the themes and symbols across the three final stories of the participants and the process of creating stories with the Our Story iPad app. The discussion concerns the theoretical value of multimedia and the practical value of story-making apps for people with dementia. We conclude that the multimedia features available with the Our Story app offer a unique opportunity for people living with dementia to store, access and generate memories, capture them in writing and audio; and the ability to continue adding to the original stories

GLUCAGONOMA SYNDROME-A CASE REPORT

ABSTRACT : The glucagonoma syndrome is characterized by dermatitis, glucose intolerance, hypoaminoacidemia, and hyperglucagonemia secondary to an alpha-cell tumor of the pancreas. The classical symptoms are associated with alpha-cell pancreatic islet cell tumor or 'glucagonoma'. Other clinical features include anemia, glossitis, and weight loss. A 65-year-old woman with the syndrome came for medical attention for a skin rash, glossitis, and weight loss. A skin biopsy was suggestive of necrolytic migratory erythema. Necrolytic migratory erythema is considered to be a paraneoplastic dermatosis. To our knowledge, it is rarely reported in the literature. Skin symptoms are important; often they are the clue to the diagnosis of glucagonoma syndrome. On ultrasound there was hypoechoic mass in the distal pancreas so she was advised CT scan of the mass. CT scan showed high density area 4.5 cms in diameter with calcification in the tail of the pancreas. She later on passed away because of late presentation, delayed diagnosis and delayed treatment. The diagnosis of necrolytic migratory erythema is a matter of great importance, since it might be an auxiliary tool for the early detection of glucagonoma

Evaluation in Mice of a Conjugate Vaccine for Cholera Made from Vibrio cholerae O1 (Ogawa) O-Specific Polysaccharide

Background: Protective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children. Methodology Here we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc) made from V. cholerae O1 Ogawa O-Specific Polysaccharide–core (OSP) and recombinant tetanus toxoid heavy chain fragment (TThc). We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli. Principal Findings We detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model. Conclusion: We describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens

Trauma and psychotic experiences:Transnational data from the World Mental Health survey

Background: Traumatic events are associated with increased risk of psychotic experiences, but it is unclear whether this association is explained by mental disorders prior to psychotic experience onset. Aims: To investigate the associations between traumatic events and subsequent psychotic experience onset after adjusting for post-traumatic stress disorder and other mental disorders. Method: We assessed 29 traumatic event types and psychotic experiences from the World Mental Health surveys and examined the associations of traumatic events with subsequent psychotic experience onset with and without adjustments for mental disorders. Results: Respondents with any traumatic events had three times the odds of other respondents of subsequently developing psychotic experiences (OR=3.1, 95% CI 2.7-3.7), with variability in strength of association across traumatic event types. These associations persisted after adjustment for mental disorders. Conclusions: Exposure to traumatic events predicts subsequent onset of psychotic experiences even after adjusting for comorbid mental disorders