Background: Gastric cancer is the fourth most common cancer in the world. Non-curative, metastatic disease is frequent in low incidence countries; management strategies for relief of symptoms include surgery, chemotherapy and radiotherapy. The resource utilization of metastatic gastric cancer patients is unstudied in the Canadian system, and predictors of major cost drivers and end-of-life care unknown. Our purpose was to describe the resource utilization of metastatic gastric cancer patients in Ontario, compare resource utilization among Local Health Integration Networks (LHINs) and examine predictors of inpatient hospital days and receipt of homecare. Methods: This is a retrospective cohort study of metastatic gastric adenocarcinoma patients registered in the Ontario Cancer Registry between April 1, 2005 and March 31st, 2008. Chart review and administrative healthcare data were linked to describe non-therapeutic endoscopic, radiologic and surgical investigations and treatment strategies from the healthcare system perspective, using a two-year and two month time horizon. Chi square tests were used to compare proportions of resource utilization, and non-parametric one-way ANOVA compared mean per patient usage. Negative binomial regression was used to model the number of inpatient hospital days. Modified Poisson regression was used to model receipt of homecare. Results: The cohort consisted of 1433 patients with metastatic disease. Less than half of the patients received chemotherapy (43%), gastrectomy (37%) or radiotherapy (28%). Geographic variation existed in the type of health services consumed and in the frequency of their use among LHINs. Location of the primary tumour, resource utilization band, receipt of a gastrectomy and care from a high volume physician were independent predictors of inpatient hospital days. Home care use was predicted by location of the primary tumour, receipt of care from a high volume physician and the number of days survived within the study period. Conclusion: Variation in healthcare resource utilization exists between LHINs in Ontario for the care of metastatic gastric cancer patients. Whether these differences reflect differential access to iii resources, patient preference or physician preference is not known. Further research needs to examine differences and how they impact on clinical disease outcomes. Next steps include incorporating predictors of resource utilization measures into clinical and policy-level decision-making. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2012-08-30 09:49:34.731

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Antalet vuxna som lever med fetma har enligt WHO fördubblats sedan 1980. Kirurgiskt ingrepp såsom gastric bypass är den metod som leder till hållbar viktminskning. Syftet med studien var att undersöka hur patienter som genomgått viktminskningskirurgi kan uppleva stödet före, under och efter operation. Studien har en narrativ fenomenologisk ansats, berättelserna har analyserats genom meningskoncentrering, strukturering och tolkning. Studien innefattar berättelser från fem informanter som valdes genom handplockat urval. Resultatet visar att de flesta informanter upplever ett fint stöd från omgivningen under processen. Missnöjet riktar sig mot sjukvården och det först efter operationen. Informanterna upplever sig som ensamma och saknar sjukvårdens förståelse. Den bristfälliga uppföljningen genererar i svårigheter för patienterna att med tiden följa de kostrekommendationer som angavs. En samtalskontakt som stöd för hållbar viktminskning och för undvikande av bristsjukdomar är att rekommendera.

Gastric Bypass är en kirurgisk viktminskningsmetod som innebär att magsäcken förminskas.Detta sker genom att maten leds förbi större delen av magsäcken och den första delen avtunntarmen. Den Gastric Bypass opererade blir då fortare mätt och kroppens upptag avnäringsämnen och kalorier minskar. Det har gjorts en hel del medicinsk forskning kringGastric Bypass, men inte så mycket kring de opererades egna upplevelser av operationen,samt de pedagogiska aspekter som det innebär att vara tvungen att lära sig leva efter en heltny livsstil. Detta fann vi därför intressant att undersöka närmare i denna kvalitativa studie. Syfte: Syftet med studien var att undersöka hur Gastric Bypass opererade, med bloggen somredskap lär sig leva med den livsstilsförändring som operationen innebär, samt vad som skermed bloggarens sociala identitet under den snabba viktnedgången. Teoretisk utgångspunkt:Studiens utgångspunkt ligger i ett sociokulturellt perspektiv av textanalys, med inspiration avhermeneutik i analysarbetet. Datamaterial samlades in via sex bloggare, som via sina bloggarskriver om upplevelser före och efter en Gastric Bypass operation. Resultat: Ur analysenframkom att samtliga av de bloggare som vi valt att ha med i studien ser Gastric Bypass somden sista utvägen att bli fri från sin övervikt. De upplever även att de komplikationer som kanuppstå vid operationen är en mindre risk än ett fortsatt liv som överviktig. Som vi tolkar det ärdet även vanligt att bloggarna försöker hålla uppe en positiv ton kring operationen i bloggen.Detta trots att vi i analysen funnit flertalet tecken på att den livsstilsförändring som krävs avde opererade är allt annat än enkel att genomföra. Problematik kring kosten och den egnasjälvuppfattningen ser vi som vanligt förekommande, samt att omgivningens påverkan fårbetydelse för bloggaren på flera olika sätt. I vår analys har vi även sett att bloggen skullekunna fungera som ett hjälpmedel för Gastric Bypass opererade då den ger möjlighet tilllärande genom utbyte av erfarenheter mellan bloggare och läsare, samt även fungerar somskrivterapi och en sorts social gemenskap. Slutsats: Slutsatsen av vår tolkning av upplevelsenkring en Gastric Bypass, är att det är vanligt med en viss förvirring kring den socialaidentiteten och de nya rutinerna hos den opererade. Vi menar därför att Gastric Bypassopererade borde erbjudas mer pedagogisk hjälp för att ändra sitt beteende, och att fokus inteenbart bör läggas på de medicinska effekterna, utan även på de opererades egna upplevelserav operationen.

Bakgrund Övervikt och fetma är ett hälsoproblem, både globalt och i Sverige. Genetik, livsstilsfaktoreroch beroendeproblematik är bakomliggande orsaker till övervikt och fetma. Olika behandlingsmetoder används vid övervikt och fetma, varav gastric bypass är en metod. En gastric bypass kräver livsstils- och beteendeförändringar i samband med operationen. Hälso och sjukvården har ett ansvar att ge informativt och rådgivande stöd i samband med livsstilsförändringar. Syfte Syftet var att beskriva personers upplevda behov av stöd från hälso- och sjukvården i samband med en gastric bypassoperation. Metod En kvalitativ intervjustudie användes med utgångspunkt i gastric bypassopererade personers erfarenheter. En halvstrukturerad intervjuguide med följdfrågor utformades och sammanlagt genomfördes sex intervjuer. Inklusionskriterier för deltagande var att operationen skulle ha ägt rum minst två år före intervjutillfället samt att personen var svensktalande och myndig.Insamlat datamaterial analyserades med kvalitativ innehållsanalys. Resultat Medicinskt stöd samt skriftlig information upplevdes tillräckligt. Informanterna önskade insatser i form av utökat stöd vid livsstils- och beteendeförändringar, främst preoperativt,samt att få ta del av andras erfarenheter i liknande situationer. Telefonkontakt med hälso- och sjukvård och ett gott socialt stöd medförde trygghet. Tidigare kunskaper och ett personcentrerat bemötande från hälso- och sjukvården föredrogs. Slutligen upplevdesuppföljningen bristfällig från primärvården och informanterna poängterade sitt eget ansvar att följa upp och själv kontakta sjukvården vid behov. Slutsats Det finns ett behov av ytterligare stöd från hälso- och sjukvården i samband med gastricbypass, främst vad gäller det stöd som krävs vid livsstils- och beteendeförändringar.Informationsbehov föreligger både pre- och postoperativt.

Research Doctorate - Doctor of Philosophy (PhD) / A number of oncolytic picornaviruses are currently under evaluation as potential therapeutic agents for a range of human malignancies. In particular, a subset of naturally occurring human C-cluster enteroviruses; Coxsackievirus A13 (CVA13), Coxsackievirus A15 (CVA15), Coxsackievirus A18 (CVA18) and Coxsackievirus A21 (CVA21) and the human B-cluster enterovirus, Echovirus 1 (EV1), display promising pre-clinical oncolytic activity against a wide variety of neoplastic cells. CVA21 is currently under clinical evaluation for the control of melanoma, breast, prostate and head/neck cancer. The preferential targeting of cancer cells by this subset of viruses is based on extracellular capsid interactions with specific viral receptors (intercellular adhesion molecule-1 [ICAM-1], decay-accelerating factor [DAF] or integrin α2β1), on the surface of malignant cells. In the present study, the therapeutic potential of this subset of enteroviruses was evaluated as a novel treatment strategy for the control of human malignancies of the gastrointestinal system. In Chapter 3, the capacity of the aforementioned enteroviruses for oncolytic activity was assessed in a panel of in vitro human gastric cancer cell cultures. Flow cytometric analysis revealed low-to-medium levels of ICAM-1, in addition to abundant α2β1 and DAF expression on the surface of gastric cancer cell lines. Cell monolayer lytic infectivity assays demonstrated that, of the viruses under evaluation, EV1 displayed the most potent and widespread in vitro lytic activity against the gastric cancer cell lines. Monoclonal antibody blockade confirmed the specific integrin α2β1-mediated route of EV1 cell infection in the gastric cancer MKN-45 cell line. Subsequently, an in vivo dose ranging study assessing the efficacy of oncolytic EV1 was undertaken in an immune-compromised MKN-45-Luc mouse model of human gastric cancer peritoneal carcinomatosis (PC). In this model, an intra-peritoneal dose of as little as 1x103 TCID50 EV1 resulted in a significant reduction in peritoneal tumour burden. In Chapter 4, the oncolytic capacity of this enterovirus subset was further evaluated, as a potential therapeutic option for the control of colorectal cancer (CRC). Flow cytometric analysis of a panel of CRC cell lines demonstrated abundant levels of DAF and integrin α2β1, and low-to-moderate levels of ICAM-1 expression on the surface of CRC cells. Of the subset of viruses examined, a DAF-using variant of CVA21 (CVA21-DAFv) displayed the most potent and widespread oncolytic activity against in vitro CRC cell cultures. Consequently, the potential in vivo oncolytic capacity of CVA21-DAFv and the wild-type CVA21 was evaluated in three individual immune-compromised mouse sub-cutaneous xenograft models of human CRC. However, despite the immunohistochemical detection of ICAM-1/DAF on cells of the CRC xenografts, and the detection of infectious virus in the blood of treated tumour-bearing mice, a detectable reduction in tumour burden was not observed. On account of the varying degrees of oncolytic efficacy observed in colorectal and gastric cancers, global gene expression profiling was employed in Chapters 5 and 6, to further elucidate the molecular mechanisms of enterovirus-mediated tumour cell tropism and cell death. As the most extensively characterised virus in pre-clinical studies, and the only virus of this subset under current clinical evaluation, CVA21 was selected as the challenge virus for analysis of the transcriptional response to enterovirus infection. Malignant cells that displayed reproducible susceptibility to in vitro and in vivo lytic CVA21 challenge were necessary for extensive characterisation, therefore, melanoma SK-Mel-28 and breast cancer MDA-MB-231-Luc cell lines, rather than CRC cell lines, were utilised. In Chapter 5, the response of SK-Mel-28 and MDA-MB-231-Luc cell monolayers, and a supporting panel of malignant and normal cell lines, to in vitro CVA21 challenge was assessed. In Chapter 6, the transcriptional response of immune-compromised mouse SK-Mel-28 and MDA-MB-231-Luc xenograft cells to systemic CVA21 administration was characterised. The transcriptional response of cells propagated as in vitro monolayers differed markedly when compared to that of in vivo xenografts generated from the same cell lines. In Chapter 5, a delayed rate of CVA21 replication and cell lysis was observed in normal cell cultures, as compared to malignant cell lines. Gene expression profiling suggested that the normal human lung fibroblast cell line, MRC-5, mounted an interferon (IFN)-mediated innate immune response against CVA21 challenge, a phenomenon not observed following challenge of the malignant cell line panel. Such findings suggest a potential role for the functional status of the IFN-mediated innate immune system in the tumour cell tropism of oncolytic CVA21. Somewhat surprisingly, in Chapter 6, an IFN-mediated transcriptional response was observed in the SK-Mel-28/MDA-MB-231-Luc xenograft cells, potentially attributed to the ‘priming’ effects of in vivo endogenous murine IFN activity. Furthermore, in Chapters 5 and 6, the potential contributions of transcriptionally regulated genes, in respect to their biological roles in cell cycle regulation, apoptosis, oxidative stress, stimulation of anti-tumoural immunity, and inhibition of angiogenesis in CVA21-mediated oncolysis were considered. Moreover, in Chapter 6, a distinct genetic signature of infection was identified, comprising a total of 9 individual genes, significantly upregulated in response to infection in each xenograft model at 24 and 72 h following the systemic administration of CVA21. The identified genes involved in this core transcriptional response to infection may serve as effective molecular biomarkers for the evaluation of oncolytic CVA21 efficacy.

Research Doctorate - Doctor of Philosophy (PhD) / A number of oncolytic picornaviruses are currently under evaluation as potential therapeutic agents for a range of human malignancies. In particular, a subset of naturally occurring human C-cluster enteroviruses; Coxsackievirus A13 (CVA13), Coxsackievirus A15 (CVA15), Coxsackievirus A18 (CVA18) and Coxsackievirus A21 (CVA21) and the human B-cluster enterovirus, Echovirus 1 (EV1), display promising pre-clinical oncolytic activity against a wide variety of neoplastic cells. CVA21 is currently under clinical evaluation for the control of melanoma, breast, prostate and head/neck cancer. The preferential targeting of cancer cells by this subset of viruses is based on extracellular capsid interactions with specific viral receptors (intercellular adhesion molecule-1 [ICAM-1], decay-accelerating factor [DAF] or integrin α2β1), on the surface of malignant cells. In the present study, the therapeutic potential of this subset of enteroviruses was evaluated as a novel treatment strategy for the control of human malignancies of the gastrointestinal system. In Chapter 3, the capacity of the aforementioned enteroviruses for oncolytic activity was assessed in a panel of in vitro human gastric cancer cell cultures. Flow cytometric analysis revealed low-to-medium levels of ICAM-1, in addition to abundant α2β1 and DAF expression on the surface of gastric cancer cell lines. Cell monolayer lytic infectivity assays demonstrated that, of the viruses under evaluation, EV1 displayed the most potent and widespread in vitro lytic activity against the gastric cancer cell lines. Monoclonal antibody blockade confirmed the specific integrin α2β1-mediated route of EV1 cell infection in the gastric cancer MKN-45 cell line. Subsequently, an in vivo dose ranging study assessing the efficacy of oncolytic EV1 was undertaken in an immune-compromised MKN-45-Luc mouse model of human gastric cancer peritoneal carcinomatosis (PC). In this model, an intra-peritoneal dose of as little as 1x103 TCID50 EV1 resulted in a significant reduction in peritoneal tumour burden. In Chapter 4, the oncolytic capacity of this enterovirus subset was further evaluated, as a potential therapeutic option for the control of colorectal cancer (CRC). Flow cytometric analysis of a panel of CRC cell lines demonstrated abundant levels of DAF and integrin α2β1, and low-to-moderate levels of ICAM-1 expression on the surface of CRC cells. Of the subset of viruses examined, a DAF-using variant of CVA21 (CVA21-DAFv) displayed the most potent and widespread oncolytic activity against in vitro CRC cell cultures. Consequently, the potential in vivo oncolytic capacity of CVA21-DAFv and the wild-type CVA21 was evaluated in three individual immune-compromised mouse sub-cutaneous xenograft models of human CRC. However, despite the immunohistochemical detection of ICAM-1/DAF on cells of the CRC xenografts, and the detection of infectious virus in the blood of treated tumour-bearing mice, a detectable reduction in tumour burden was not observed. On account of the varying degrees of oncolytic efficacy observed in colorectal and gastric cancers, global gene expression profiling was employed in Chapters 5 and 6, to further elucidate the molecular mechanisms of enterovirus-mediated tumour cell tropism and cell death. As the most extensively characterised virus in pre-clinical studies, and the only virus of this subset under current clinical evaluation, CVA21 was selected as the challenge virus for analysis of the transcriptional response to enterovirus infection. Malignant cells that displayed reproducible susceptibility to in vitro and in vivo lytic CVA21 challenge were necessary for extensive characterisation, therefore, melanoma SK-Mel-28 and breast cancer MDA-MB-231-Luc cell lines, rather than CRC cell lines, were utilised. In Chapter 5, the response of SK-Mel-28 and MDA-MB-231-Luc cell monolayers, and a supporting panel of malignant and normal cell lines, to in vitro CVA21 challenge was assessed. In Chapter 6, the transcriptional response of immune-compromised mouse SK-Mel-28 and MDA-MB-231-Luc xenograft cells to systemic CVA21 administration was characterised. The transcriptional response of cells propagated as in vitro monolayers differed markedly when compared to that of in vivo xenografts generated from the same cell lines. In Chapter 5, a delayed rate of CVA21 replication and cell lysis was observed in normal cell cultures, as compared to malignant cell lines. Gene expression profiling suggested that the normal human lung fibroblast cell line, MRC-5, mounted an interferon (IFN)-mediated innate immune response against CVA21 challenge, a phenomenon not observed following challenge of the malignant cell line panel. Such findings suggest a potential role for the functional status of the IFN-mediated innate immune system in the tumour cell tropism of oncolytic CVA21. Somewhat surprisingly, in Chapter 6, an IFN-mediated transcriptional response was observed in the SK-Mel-28/MDA-MB-231-Luc xenograft cells, potentially attributed to the ‘priming’ effects of in vivo endogenous murine IFN activity. Furthermore, in Chapters 5 and 6, the potential contributions of transcriptionally regulated genes, in respect to their biological roles in cell cycle regulation, apoptosis, oxidative stress, stimulation of anti-tumoural immunity, and inhibition of angiogenesis in CVA21-mediated oncolysis were considered. Moreover, in Chapter 6, a distinct genetic signature of infection was identified, comprising a total of 9 individual genes, significantly upregulated in response to infection in each xenograft model at 24 and 72 h following the systemic administration of CVA21. The identified genes involved in this core transcriptional response to infection may serve as effective molecular biomarkers for the evaluation of oncolytic CVA21 efficacy.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Hong Kong, 1993.