Incidental Findings Suggestive of COVID-19 in Asymptomatic Patients Undergoing Nuclear Medicine Procedures in a High-Prevalence Region

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An exploration of evaluation approaches for community based interventions for people living with HIV (PLHIV) with results applied to the ‘HOPE’ programme in Ghana

Background: The increase in the number of people living with HIV (PLHIV), especially in sub-Saharan Africa, is a major public health concern. To date, most attention has been paid to prevention strategies and clinical trials of therapy. In comparison, there have been very few studies of care and support programmes. The ‘HOPE’ programme is a major community-based care and support programme in Ghana. ‘HOPE’ provides nutritional support, skills training for employment, health education and psychological support for PLHIV and for those orphaned through AIDS. Therefore, it was seen by policy makers in the country as desirable that it should be evaluated. A PhD scholarship was funded and the researcher presenting this thesis was appointed. Broad Aims The overall aim was to carry out an evaluation of the ‘HOPE’ programme in Ghana in order to make wider recommendations for evaluation of community-based interventions (CBIs) in Ghana and Africa generally. The timing was less than ideal as many of the major decisions about the intervention had already been made and baseline data had been collected. Therefore, the preliminary aim was to explore a range of possible evaluation methods so that the most suitable approach could be selected. Thereafter, a range of more specific aims, objectives and research questions was identified. Methods: A ‘mixed methods’ approach was adopted. The first component was a desk-based analysis of the literature on the various evaluation approaches that might, at least in theory, be applied to an HIV/AIDS intervention like ‘HOPE’. From this, a decision was made to evaluate ‘HOPE’ in terms of structure, process and outcome. The second component operationalised this decision by reviewing HOPE’s working documents and conducting two pieces of field work: a quantitative and a qualitative study. The quantitative study was a structured questionnaire administered to 200 PLHIV on the ‘HOPE’ programme. The qualitative study consisted of 14 interviews with stakeholders directly involved in the programme implementation and 8 focus group discussions with the programme beneficiaries. Results: The desk-based analysis achieved three main outcomes. First, it set out in a systematic manner the different approaches to evaluation that could in theory have been applied to ‘HOPE’. It identified strengths and weaknesses and the perspectives behind each approach. Second, it set out and then summarised a detailed description of the ‘HOPE’ programme and the national context in which it operated. Third, it set the above within the context of global literature on HIV, community-based interventions and nutritional support programmes. The analysis of the quantitative data showed that beneficiaries were being provided with soy-fortified wheat and vegetable fortified oil at the time of the evaluation. On average, beneficiaries gained weight (Mean difference in weight was 2kg with 95% CI (1.1, 2.9), p-value < 0.001) and increased Body Mass Index (BMI) (Mean difference in BMI was 0.8units with 95% CI (0.4, 1.2), P-value < 0.001). Over a third of the beneficiaries (37.5%) was currently unemployed and only one in five of the beneficiaries had been trained in a skill that might have been useful to find employment: this, despite skills training for all being a programme goal. Multivariate analysis showed that the support group to which the beneficiary belonged was the most important determinant of a positive outcome. Qualitative components demonstrated perceived successes and challenges. Beneficiaries indicated that the anti-retroviral drugs were making them hungry and the food helped to alleviate that effect. They further indicated that the food was nutritious and contributed to their weight gain. Support groups have been sustained and membership increased. Some indicated that food should be more varied and some mentioned selling food to earn money to pay for their medications. Most of the beneficiaries indicated they were unemployed having lost their jobs as a result of stigmatisation. Only a few benefited from skills training leading to employment because of inadequate budgeting. Some who had been trained could not use their newly acquired skills because of lack of capital to start a business. To compound these weaknesses, most reported that they preferred petty trading to the skills offered. The monthly education and the training workshops generated hope, and improved knowledge of HIV/AIDS, promoted drug adherence and helped to reduce stigmatisation. The training of the PLHIV as peer educators is an effective method for HIV education and counselling since PLHIV listen to their peers more than health workers. Respondees predicted dissolution of the support groups when the programme ends. This is because they were not adequately involved in the decision making. Beneficiaries identified participation and cooperation as key prerequisites for sustainability but they also identified important weaknesses in ‘HOPE’ with respect to these criteria. Discussion: Despite the challenges presented by the timing and context of this study, it has been possible to carry out an evaluation that provides important learning. A mixed methods approach was appropriate and is likely to be useful in many similar evaluations. Beneficial outcomes were identified but these cannot be attributed, without qualification, to the intervention. Nonetheless, the findings indicated that participants were highly satisfied with the food support and monthly education. They were dissatisfied with the numbers trained in new skills and in other aspects of the skills training components. Also, the sustainability of the food component when the funding stops was a concern. However, the educational component could be sustained because peer educators could continue at very low cost. Most importantly, community involvement, using locally available resources, inter-sectoral collaboration and harnessing the motivation of local people were seen as key but underutilised ingredients. So, the results of the evaluation are encouraging but not conclusive. Nonetheless, care for people living with HIV is such an important problem that the desirability of conducting a cluster randomised controlled trial among a large number of support groups to assess the programme effectiveness on health, nutrition and economic status should be seriously considered despite the practical and ethical challenges implicit in such a recommendation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Hepatocyte-specific deletion of HIF2&#945; prevents NASH-related liver carcinogenesis by decreasing cancer cell proliferation

Background & aims: Hypoxia and hypoxia-inducible factors (HIFs) are involved in chronic liver disease progression. We previously showed that hepatocyte HIF-2\u3b1 activation contributed significantly to nonalcoholic fatty liver disease progression in experimental animals and human patients. In this study, using an appropriate genetic murine model, we mechanistically investigated the involvement of hepatocyte HIF-2\u3b1 in experimental nonalcoholic steatohepatitis (NASH)-related carcinogenesis. Methods: The role of HIF-2\u3b1 was investigated by morphologic, cellular, and molecular biology approaches in the following: (1) mice carrying hepatocyte-specific deletion of HIF-2\u3b1 (HIF-2\u3b1-/- mice) undergoing a NASH-related protocol of hepatocarcinogenesis; (2) HepG2 cells stably transfected to overexpress HIF-2\u3b1; and (3) liver specimens from NASH patients with hepatocellular carcinoma. Results: Mice carrying hepatocyte-specific deletion of HIF-2\u3b1 (hHIF-2\u3b1-/-) showed a significant decrease in the volume and number of liver tumors compared with wild-type littermates. These effects did not involve HIF-1\u3b1 changes and were associated with a decrease of cell proliferation markers proliferating cell nuclear antigen and Ki67. In both human and rodent nonalcoholic fatty liver disease-related tumors, HIF-2\u3b1 levels were strictly associated with hepatocyte production of SerpinB3, a mediator previously shown to stimulate liver cancer cell proliferation through the Hippo/Yes-associated protein (YAP)/c-Myc pathway. Consistently, we observed positive correlations between the transcripts of HIF-2\u3b1, YAP, and c-Myc in individual hepatocellular carcinoma tumor masses, while HIF-2\u3b1 deletion down-modulated c-Myc and YAP expression without affecting extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and AKT-dependent signaling. In\ua0vitro data confirmed that HIF-2\u3b1 overexpression induced HepG2 cell proliferation through YAP-mediated mechanisms. Conclusions: These results indicate that the activation of HIF-2\u3b1 in hepatocytes has a critical role in liver carcinogenesis during NASH progression, suggesting that HIF-2\u3b1-blocking agents may serve as novel putative therapeutic tools

Post-coital intra-cerebral venous hemorrhage in a 78-year-old man with jugular valve incompetence: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spontaneous intra-cerebral hemorrhage can occur in patients with venous disease due to obstructed venous outflow.</p> <p>Case presentation</p> <p>We report the case of a 78-year-old Caucasian man with jugular valve incompetence who experienced an intra-cerebral temporo-occipital hemorrhage following sexual intercourse. He had no other risk factors for an intra-cerebral hemorrhage.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first case of intra-cerebral hemorrhage due to jugular valve incompetence in association with the physical exertion associated with sexual intercourse.</p

Oncostatin M is overexpressed in NASH-related hepatocellular carcinoma and promotes cancer cell invasiveness and angiogenesis

: Oncostatin M (OSM) is a pleiotropic cytokine of the interleukin (IL)-6 family that contributes to the progression of chronic liver disease. Here we investigated the role of OSM in the development and progression of hepatocellular carcinoma (HCC) in NAFLD/NASH. The role of OSM was investigated in: a) selected cohorts of NAFLD/NASH HCC patients; b) liver cancer cells exposed to human recombinant OSM or stably transfected to overexpress human OSM; c) murine HCC xenografts; d) a murine NASH-related model of hepatic carcinogenesis. OSM was found to be selectively overexpressed in HCC cells of NAFLD/NASH patients, depending on tumor grade. OSM serum levels, barely detectable in patients with simple steatosis or NASH, were increased in patients with cirrhosis, and more evident in those carrying HCC. In this latter group, OSM serum levels were significantly higher in the subjects with intermediate/advanced HCCs and correlated with poor survival. Cell culture experiments indicated that OSM upregulation in hepatic cancer cells contributes to HCC progression by inducing epithelial-to-mesenchymal transition and increased invasiveness of cancer cells as well as by inducing angiogenesis, which is of critical relevance. In murine xenografts, OSM overexpression was associated with slower tumor growth, but an increased rate of lung metastases. Overexpression of OSM and its positive correlation with the angiogenic switch were also confirmed in a murine model of NAFLD/NASH-related hepatocarcinogenesis. Consistent with this, analysis of liver specimens from human NASH-related HCCs with vascular invasion showed that OSM was expressed by liver cancer cells invading hepatic vessels. In conclusion, OSM up-regulation appears to be a specific feature of HCC arising on a NAFLD/NASH background, and it correlates with clinical parameters and disease outcome. Our data highlight a novel pro-carcinogenic contribution for OSM in NAFLD/NASH, suggesting a role of this factor as a prognostic marker and a putative potential target for therapy. This article is protected by copyright. All rights reserved

Clinical and prognostic role of detection timing of distant metastases in patients with differentiated thyroid cancer

Distant metastases (DM) from DTC occur in 5-25% of cases and are correlated to lower survival; the prognostic significance of the temporal onset of DM is unclear. Our aim was to retrospectively analyze the prevalence of DM and to assess the prognostic role of the timing of manifestation of DM regarding the outcome