163 research outputs found

    Understanding Treatment Refusal Among Adults Presenting for HIV-Testing in Soweto, South Africa: A Qualitative Study

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    HIV treatment initiatives have focused on increasing access to antiretroviral therapy (ART). There is growing evidence, however, that treatment availability alone is insufficient to stop the epidemic. In South Africa, only one third of individuals living with HIV are actually on treatment. Treatment refusal has been identified as a phenomenon among people who are asymptomatic, however, factors driving refusal remain poorly understood. We interviewed 50 purposively sampled participants who presented for voluntary counseling and testing in Soweto to elicit a broad range of detailed perspectives on ART refusal. We then integrated our core findings into an explanatory framework. Participants described feeling “too healthy” to start treatment, despite often having a diagnosis of AIDS. This subjective view of wellness was framed within the context of treatment being reserved for the sick. Taking ART could also lead to unintended disclosure and social isolation. These data provide a novel explanatory model of treatment refusal, recognizing perceived risks and social costs incurred when disclosing one’s status through treatment initiation. Our findings suggest that improving engagement in care for people living with HIV in South Africa will require optimizing social integration and connectivity for those who test positive

    A Qualitative Analysis of Factors Influencing HPV Vaccine Uptake in Soweto, South Africa among Adolescents and Their Caregivers

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    Background: In South Africa, the prevalence of oncogenic Human Papillomavirus (HPV) may be as high as 64%, and cervical cancer is the leading cause of cancer-related death among women. The development of efficacious prophylactic vaccines has provided an opportunity for primary prevention. Given the importance of psycho-social forces in vaccine uptake, we sought to elucidate factors influencing HPV vaccination among a sample of low-income South African adolescents receiving the vaccine for the first time in Soweto. Methods: The HPV vaccine was introduced to adolescents in low-income townships throughout South Africa as part of a nationwide trial to understand adolescent involvement in future vaccine research targeting human immunodeficiency virus (HIV). We performed in-depth semi-structured interviews with purposively-sampled adolescents and their care providers to understand what forces shaped HPV vaccine uptake. Interviews were recorded, transcribed, translated, and examined using thematic analysis. Results: Of 224 adolescents recruited, 201 initiated the vaccine; 192 (95.5%) received a second immunization; and 164 (81.6%) completed three doses. In our qualitative study of 39 adolescent-caregiver dyads, we found that factors driving vaccine uptake reflected a socio-cultural backdrop of high HIV endemnicity, sexual violence, poverty, and an abundance of female-headed households. Adolescents exercised a high level of autonomy and often initiated decision-making. Healthcare providers and peers provided support and guidance that was absent at home. The impact of the HIV epidemic on decision-making was substantial, leading participants to mistakenly conflate HPV and HIV. Conclusions: In a setting of perceived rampant sexual violence and epidemic levels of HIV, adolescents and caregivers sought to decrease harm by seeking a vaccine targeting a sexually transmitted infection (STI). Despite careful consenting, there was confusion regarding the vaccine’s target. Future interventions promoting STI vaccines will need to provide substantial information for participants, particularly adolescents who may exercise a significant level of autonomy in decision-making

    Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models

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    <p>Abstract</p> <p>Background</p> <p>Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood.</p> <p>Methods</p> <p>The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS).</p> <p>The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses.</p> <p>The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer.</p> <p>Results</p> <p>In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (<it>CHKA</it>, <it>CHKB</it>) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (<it>PLA2G4A</it>) and phospholipase B1 (<it>PLB1</it>) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer.</p> <p>Conclusions</p> <p>The differences in choline metabolite concentrations corresponded well with differences in gene expression, demonstrating distinct metabolic profiles in the xenograft models representing basal-like and luminal-like breast cancer. The same characteristics of choline metabolite profiles were also observed in patient material from ER+/PgR+ and triple-negative breast cancer, suggesting that the xenografts are relevant model systems for studies of choline metabolism in luminal-like and basal-like breast cancer.</p

    Party rules, party resources, and the politics of parliamentary democracies: how parties organize in the 21st Century

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    This article introduces the first findings of the Political Party Database (PPDB) project, a major survey of party organizations in parliamentary and semi-presidential democracies. The project’s first round of data covers 122 parties in 19 countries. In this paper we describe the scope of the database, then investigate what it tells us about contemporary party organization in these countries, focussing on parties’ resources, structures and internal decision-making. We examine organizational patterns by country and party family, and where possible we make temporal comparisons with older datasets. Our analyses suggest a remarkable coexistence of uniformity and diversity. In terms of the major organizational resources on which parties can draw, such as members, staff and finance, the new evidence largely confirms the continuation of trends identified in previous research: i.e., declining membership, but enhanced financial resources and more paid staff. We also find remarkable uniformity regarding the core architecture of party organizations. At the same time, however, we find substantial variation between countries and party families in terms of their internal processes, with particular regard to how internally democratic they are, and in the forms that this democratization takes

    Risk-Reducing Gynecological Surgery in Lynch Syndrome : Results of an International Survey from the Prospective Lynch Syndrome Database

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    Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome. Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT. Results: Risk-reducing hysterectomy and BSO are offered to path_MLH1 and path_MSH2 carriers in 20/21 (95%) contributing centers, to path_MSH6 carriers in 19/21 (91%) and to path_PMS2 carriers in 14/21 (67%). Regarding the involvement of stakeholders, there is global agreement (similar to 90%) that risk-reducing surgery should be offered to women, and that this discussion may involve gynecologists, genetic counselors and/or medical geneticists. Prescription of estrogen-only HRT is offered by 15/21 (71%) centers to women of variable age range (35-55 years). Conclusions: Most centers offer risk-reducing gynecological surgery to carriers of path_MLH1, path_MSH2 and path_MSH6 variants but less so for path_PMS2 carriers. There is wide variation in how, when and to whom this is offered. The Manchester International Consensus Group developed recommendations to harmonize clinical practice across centers, but there is a clear need for more research.Peer reviewe

    What Makes Entrepreneurs Happy? Determinants of Satisfaction Among Founders

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    This study empirically investigates factors influencing satisfaction levels of founders of new ventures, using a representative sample of 1,107 Dutch founders. We relate entrepreneurial satisfaction (with income, psychological burden and leisure time) to firm performance, motivation and human capital. Founders with high levels of specific human capital are more satisfied with income than those with high levels of general human capital. Intrinsic motivation and that of combining responsibilities lowers stress and leads to more satisfaction with leisure time. Women are more satisfied with their income than men, even though they have a lower average monthly turnover

    Assessment of a primary and tertiary care integrated management model for chronic obstructive pulmonary disease

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    <p>Abstract</p> <p>Background</p> <p>The diagnosis and treatment of patients with chronic obstructive pulmonary disease (COPD) in Spain continues to present challenges, and problems are exacerbated when there is a lack of coordinated follow-up between levels of care. This paper sets out the protocol for assessing the impact of an integrated management model for the care of patients with COPD. The new model will be evaluated in terms of 1) improvement in the rational utilization of health-care services and 2) benefits reflected in improved health status and quality of life for patients.</p> <p>Methods/Design</p> <p>A quasi-experimental study of the effectiveness of a COPD management model called COPD PROCESS. The patients in the study cohorts will be residents of neighborhoods served by two referral hospitals in Barcelona, Spain. One area comprises the intervention group (n = 32,248 patients) and the other the control group (n = 32,114 patients). The study will include pre- and post-intervention assessment 18 months after the program goes into effect. Analyses will be on two datasets: clinical and administrative data available for all patients, and clinical assessment information for a cohort of 440 patients sampled randomly from the intervention and control areas. The main endpoints will be the hospitalization rates in the two health-care areas and quality-of-life measures in the two cohorts.</p> <p>Discussion</p> <p>The COPD PROCESS model foresees the integrated multidisciplinary management of interventions at different levels of the health-care system through coordinated routine clinical practice. It will put into practice diagnostic and treatment procedures that are based on current evidence, multidisciplinary consensus, and efficient use of available resources. Care pathways in this model are defined in terms of patient characteristics, level of disease severity and the presence or absence of exacerbation. The protocol covers the full range of care from primary prevention to treatment of complex cases.</p

    Uptake of hysterectomy and bilateral salpingooophorectomy in carriers of pathogenic mismatch repair variants:a Prospective Lynch Syndrome Database report

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    Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants. Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years. Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery. Conclusion: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene-and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syn-drome to improve outcomes. (C) 2021 The Author(s). Published by Elsevier Ltd
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