Developing a shared decision support framework for aortic root surgery in Marfan syndrome

OBJECTIVE: The study is an early phase of development of a decision support framework for people with Marfan syndrome who are anticipating prophylactic aortic root surgery. Implications of the timing and the nature of the operation chosen were previously elicited in focus groups. In this step, we explored the range of relative values placed by individuals on the implications of decisions made about surgery. METHODS: Following the principles of the Ottawa Decision Support Framework, eight questions in the general form 'How important is it to you …' were framed by a panel. Marfan people, families and specialist doctors answered online. Quantitative and qualitative analyses were performed. RESULTS: Worldwide, 142 responses were received including 25 specialist doctors. Respondents were 55% female and 46% had previous aortic root surgery. Overall, active lifestyle was more important to males (p=0.03). Patients placed more importance than doctors on not deferring surgery (p=0.04) and on avoidance of anticoagulation in the interests of childbearing (p=0.009). Qualitative analysis showed differing but cogently reasoned values that were sometimes polarised, and mainly driven by the wish to maintain a good quality of life and active lifestyle. CONCLUSIONS: Given the cogency of these viewpoints, people anticipating root replacement surgery should have ample opportunity to express them and to have them acknowledged ahead of a consultation when they can then be fully explored in a mutually informed forum. If they differ from local medical practice, they can then be discussed in the process of reaching shared and individualised decisions

Improving Indigenous Access to Cancer Services

BackgroundHigher cancer morbidity and mortality rates for the Indigenous population compared to the overall Australian population has underlined the critical need to improve access for Aboriginal people to cancer treatment services. This paper describes an Indigenous Women’s Cancer Support Group (IWCSG) established to support Indigenous people with cancer and their carers/relatives and to facilitate Aboriginal access to cancer screening and treatment. Preliminary findings from an evaluation of the group are presented.MethodsThe study employed qualitative research methods to describe IWCSG operations and investigate the group’s effectiveness. It included one-on-one interviews with 11 Geraldton-based health service providers, the IWCSG coordinator, and 10 women who have been linked to IWCSG support, as well as observation of group meetings.ResultsDescriptive outcomes relate to group operations, group effectiveness, group benefits and future development of the group. A cultural strength of IWCSG is its ability to operate confidentially behind the scenes, providing emotional support and practical help directly to Indigenous people concerned about privacy and shame issues. The important cultural role IWCSG plays in overcoming communication and other cultural barriers to accessing cancer treatment was unanimously recognised by health service providers.  Aboriginal women supported by IWCSG spoke about an increased sense of safety, trust and support in accessing and navigating mainstream cancer services. A critical issue emerging from the research is the need for further development of effective collaborative working relationships between IWCSG members and health service providers.ConclusionsThe IWCSG has the potential to inform an effective model for facilitating Indigenous access both to cancer treatment and to mainstream treatment for a variety of health problems. Future research is required to explore the applicability of Indigenous support groups and to focus on the development of effective collaborative partnerships between Indigenous people and non-Aboriginal health service providers

Improving Indigenous access to cancer screening and treatment services: descriptive findings and a preliminary report on the Midwest Indigenous Women's Cancer Support Group

BackgroundHigher cancer morbidity and mortality rates for the Indigenous population comparedto the overall Australian population has underlined the critical need to improve accessfor Aboriginal people to cancer treatment services. This paper describes anIndigenous Women’s Cancer Support Group (IWCSG) established to supportIndigenous people with cancer and their carers/relatives and to facilitate Aboriginalaccess to cancer screening and treatment. Preliminary findings from an evaluation ofthe group are presented.MethodsThe study employed qualitative research methods to describe IWCSG operations andinvestigate the group’s effectiveness. It included one-on-one interviews with 11Geraldton-based health service providers, the IWCSG coordinator, and 10 womenwho have been linked to IWCSG support, as well as observation of group meetings.ResultsDescriptive outcomes relate to group operations, group effectiveness, group benefitsand future development of the group. A cultural strength of IWCSG is its ability tooperate confidentially behind the scenes, providing emotional support and practicalhelp directly to Indigenous people concerned about privacy and shame issues. Theimportant cultural role IWCSG plays in overcoming communication and othercultural barriers to accessing cancer treatment was unanimously recognised by healthservice providers. Aboriginal women supported by IWCSG spoke about an increasedsense of safety, trust and support in accessing and navigating mainstream cancerservices. A critical issue emerging from the research is the need for further development of effective collaborative working relationships between IWCSGmembers and health service providers.ConclusionsThe IWCSG has the potential to inform an effective model for facilitating Indigenousaccess both to cancer treatment and to mainstream treatment for a variety of healthproblems. Future research is required to explore the applicability of Indigenoussupport groups and to focus on the development of effective collaborativepartnerships between Indigenous people and non-Aboriginal health service providers

Lentivector knockdown of CCR5 in hematopoietic stem and progenitor cells confers functional and persistent HIV-1 resistance in humanized mice

Gene-engineered CD34(+) hematopoietic stem and progenitor cells (HSPCs) can be used to generate an HIV-1-resistant immune system. However, a certain threshold of transduced HSPCs might be required for transplantation into mice for creating an HIV-resistant immune system. In this study, we combined CCR5 knockdown by a highly efficient microRNA (miRNA) lentivector with pretransplantation selection of transduced HSPCs to obtain a rather pure population of gene engineered CD34(+) cells. Low-level transduction of HSPCs and subsequent sorting by flow cytometry yielded >70% transduced cells. Mice transplanted with these cells showed functional and persistent resistance to a CCR5-tropic HIV strain: viral load was significantly decreased over months, and human CD4(+) T cells were preserved. In one mouse, viral mutations, resulting presumably in a CXCR4-tropic strain, overcame HIV resistance. Our results suggest that HSPC-based CCR5 knockdown may lead to efficient control of HIV in vivo. We overcame a major limitation of previous HIV gene therapy in humanized mice in which only a proportion of the cells in chimeric mice in vivo are anti-HIV engineered. Our strategy underlines the promising future of gene engineering HIV-resistant CD34(+) cells that produce a constant supply of HIV-resistant progeny. IMPORTANCE: Major issues in experimental long-term in vivo HIV gene therapy have been (i) low efficacy of cell transduction at the time of transplantation and (ii) transduction resulting in multiple copies of heterologous DNA in target cells. In this study, we demonstrated the efficacy of a transplantation approach with a selection step for transduced cells that allows transplantation of an enriched population of HSPCs expressing a single (low) copy of a CCR5 miRNA. Efficient maintenance of CD4(+) T cells and a low viral titer resulted only when at least 70% of the HIV target cells were genetically modified. These findings imply that clinical protocols of HIV gene therapy require a selective enrichment of genetically targeted cells because positive selection of modified cells is likely to be insufficient below this threshold. This selection approach may be beneficial not only for HIV patients but also for other patients requiring transplantation of genetically modified cells

Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia

Human cytomegalovirus (HCMV) is a widely prevalent herpes virus which establishes a state of chronic infection. The establishment of CMV-specific immunity controls viral reactivation and leads to the accumulation of very large numbers of virus-specific T cells which come to dominate the immune repertoire. There is concern that this may reduce the immune response to heterologous infections and HCMV infection has been associated with reduced survival in elderly people. Patients with chronic lymphocytic leukemia (B-CLL) suffer from a state of immune suppression but have a paradoxical increase in the magnitude of the CMV-specific T cell and humoral immune response. As such, there is now considerable interest in how CMV infection impacts on the clinical outcome of patients with B-CLL. Utilizing a large prospective cohort of patients with B-CLL (n = 347) we evaluated the relationship between HCMV seropositivity and patient outcome. HCMV seropositive patients had significantly worse overall survival than HCMV negative patients in univariate analysis (HR = 2.28, 95% CI: 1.34–3.88; P = 0.002). However, CMV seropositive patients were 4 years older than seronegative donors and this survival difference was lost in multivariate modeling adjusted for age and other validated prognostic markers (P = 0.34). No significant difference was found in multivariate modeling between HCMV positive and negative patients in relation to the time to first treatment (HR = 1.12, 95% CI: 0.68–1.84; P = 0.65). These findings in a second independent cohort of 236 B-CLL patients were validated. In conclusion no evidence that HCMV impacts on the clinical outcome of patients with B-CLL was found

Better estimates of soil carbon from geographical data:A revised global approach

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Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - What is known and what is still unknown?

Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations