239 research outputs found

    A Systematic Review of Literatures onFactors Associated with Educational ndAcademic Performance in Attention DeficitHyperactivity Disorder

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    __Abstract__ Attention Deficit Hyperactivity Disorder (ADHD) has been shown to impair major life activities including educational functioning. However, there is no consensus on the specific cause for the impact on this worse educational outcome. This systematic review aims to identify factors that have been associated with educational and academic underperformance of children and adolescents with ADHD. A literature search was conducted using PubMed and the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The study focused on articles presenting results of data-based analyses related to ADHD and keywords related to education. The search resulted in 376 records that were screened by title. Of these, 185 articles were screened by abstract and 35 met the eligibility criteria for inclusion in the review. These 35 articles were related to seven domains: educational training, educational environment, pharmacological treatment, ADHD symptoms, associations of ADHD with academic outcomes, self-concept, and specific skills. The main source of educational challenges seems to be related to the inattentive symptoms (or subtype) of ADHD. This outcome is different than expected, since hyperactive symptoms are pronounced more prominently and often refer children to clinical practice. Inattentive symptoms amongst others refer to difficulties in organization skills and can lead to decreased self-efficacy and development of depressive symptoms. This decreased self-efficacy and the depressive symptoms were also found to be related to influence the relation between ADHD and academic performance. Educational outcomes were shown to be improved using small group work, learning via a computer-based service and as a result of coaching and pharmacological treatment. To help children and adults achieve educational goals that now are out of reach, more attention should be spent to the inattentive symptoms of ADHD and possibilities to overcome experienced problems

    Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer

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    Background:Breast cancer anti-oestrogen resistance 4 (BCAR4) was identified in a search for genes involved in anti-oestrogen resistance in breast cancer. We explored whether BCAR4 is predictive for tamoxifen resistance and prognostic for tumour aggressiveness, and studied its function.Methods:BCAR4 mRNA levels were measured in primary breast tumours, and evaluated for association with progression-free survival (PFS) and clinical benefit in patients with oestrogen receptor (ERα)-positive tumours receiving tamoxifen as first-line monotherapy for advanced disease. In a separate cohort of patients with lymph node-negative, ERα-positive cancer, and not receiving systemic adjuvant therapy, BCAR4 levels were evaluated for association with distant metastasis-free survival (MFS). The function of BCAR4 was studied with immunoblotting and RNA interference in a cell model.Results:Multivariate analyses established high BCAR4 mRNA levels as an independent predictive factor for poor PFS after start of tamoxifen therapy for recurrent disease. High BCAR4 mRNA levels were associated with poor MFS and overall survival, reflecting tumour aggressiveness. In BCAR4-expressing cells, phosphorylation of v-erb-b2 erythroblastic leukaemia viral oncogene homolog (ERBB)2, ERBB3, and their downstream mediators extracellular signal-regulated kinase 1/2 and v-akt murine thymoma viral oncogene homolog (AKT) 1/2, was increased. Selective knockdown of ERBB2 or ERBB3 inhibited proliferation, confirming their role in BCAR4-induced tamoxifen resistance.Conclusion:BCAR4 may have clinical relevance for tumour aggressiveness and tamoxifen resistance. Our cell model suggests that BCAR4-positive breast tumours are driven by ERBB2/ERBB3 signalling. Patients with such tumours may benefit from ERBB-targeted therapy

    Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

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    INTRODUCTION: Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling. METHODS: We have measured the expression changes induced by overexpression of the BCAR1 or BCAR3 gene in ZR-75-1 cells and have made direct comparisons with the expression changes after cell stimulation with oestrogen or epidermal growth factor (EGF). A comparison with published gene expression data of cell models and breast tumours is made. RESULTS: Relatively few changes in gene expression were detected in the BCAR-transfected cells, in comparison with the extensive and distinct differences in gene expression induced by oestrogen or EGF. Both BCAR1 and BCAR3 regulate discrete sets of genes in these ZR-75-1-derived cells, indicating that the proliferation signalling proceeds along distinct pathways. Oestrogen-regulated genes in our cell model showed general concordance with reported data of cell models and gene expression association with oestrogen receptor status of breast tumours. CONCLUSIONS: The direct comparison of the expression profiles of BCAR transfectants and oestrogen or EGF-stimulated cells strongly suggests that anti-oestrogen-resistant cell proliferation is not caused by alternative activation of the oestrogen receptor or by the epidermal growth factor receptor signalling pathway

    Probabilistic markov model estimating cost effectiveness of methylphenidate osmotic-release oral system versus immediate-release methylphenidate in children and adolescents: Which information is needed?

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    Background: Incidence of attention deficit hyperactivity disorder (ADHD) in children and adolescents has been increasing. The disorder results in high societal costs. Policymakers increasingly use health economic evaluations to inform decisions on competing treatments of ADHD. Yet, health economic evaluations of first-choice medication of ADHD in children and adolescents are scarce and generally do not include broader societal effects. Objectives: This study presents a probabilistic model and analysis of methylphenidate osmotic-release oral system (OROS) versus methylphenidate immediate-release (IR). We investigate and include relevant societal aspects in the analysis so as to provide cost-effectiveness estimates based on a broad societal perspective. Methods: We enhanced an existing Markov model and determined the cost effectiveness of OROS versus IR for children and adolescents responding suboptimally to treatment with IR. Enhancements included screening of a broad literature base, updated utilit

    PCN1 COST ANALYSIS OF HLA-IDENTICAL SIBLING AND VOLUNTARY UNRELATED ALLOGENEIC BONE MARROW AND PERIPHERAL BLOOD STEM CELL TRANSPLANTATION IN ADULTS WITH ACUTE MYELOCYTIC LEUKAEMIA OR ACUTE LYMPHOBLASTIC LEUKAEMIA

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    Item does not contain fulltextAllogeneic stem cell transplantation (SCT) is one of the most expensive medical procedures. However, only a few studies to date have addressed the costs of HLA-identical sibling transplantation and only one study has reported costs of unrelated transplantation. No recent cost analysis with a proper follow-up period and donor identification expenses is available on related or voluntary matched unrelated donor (MUD) SCT for adult AML or ALL. Therefore, we calculated direct medical (hospital) costs based on 97 adults who underwent HLA-identical sibling bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT), and patients who received a graft from a MUD between 1994 and 1999. The average costs per transplanted patient were Euro 98,334 (BMT), Euro 151,754 (MUD), and Euro 98,977 (PBSCT), including donor identification expenses, 2 years follow-up and costs of patients who were not transplanted after they had been planned to receive an allograft. The majority of these costs was generated during the hospitalisation for graft infusion. For MUD transplants, nearly one-third of these costs was spent on the search for a suitable donor. For patients who were alive after 2 years, cumulative expenses were calculated to be Euro 103,509 (BMT), Euro 173,587 (MUD), and Euro 105,906 (PBSCT)

    CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer

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    Background:Endocrine therapies of breast cancer are effective but ultimately fail because of the development of treatment resistance. We have previously revealed several genes leading to tamoxifen resistance in vitro by retroviral insertion mutagenesis. To understand the manner in which these genes yield tamoxifen resistance, their effects on global gene expression were studied and those genes resulting in a distinct gene expression profile were further investigated for their clinical relevance.Methods:Gene expression profiles of 69 human breast cancer cell lines that were made tamoxifen resistant through retroviral insertion mutagenesis were obtained using oligonucleotide arrays and analysed with bioinformatic tools. mRNA levels of NCOR2 and CITED2 in oestrogen receptor-positive breast tumours were determined by quantitative RT-PCR. mRNA levels were evaluated for association with metastasis-free survival (MFS) in 620 patients with lymph node-negative primary breast cancer who did not receive systemic adjuvant therapy, and with clinical benefit in 296 patients receiving tamoxifen therapy for recurrent breast cancer.Results:mRNA expression profiles of most tamoxifen-resistant cell lines were strikingly similar, except for the subgroups of cell lines in which NCOR2 or CITED2 were targeted by the retrovirus. Both NCOR2 and CITED2 mRNA levels were associated with MFS, that is, tumour aggressiveness, independently of traditional prognostic factors. In addition, high CITED2 mRNA levels were predictive for a clinical benefit from first-line tamoxifen treatment in patients with advanced disease.Conclusions: Most retrovirally targeted genes yielding tamoxifen resistance in our cell lines do not impose a distinctive expressi
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