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    Cost-effectiveness of stereotactic large-core needle biopsy for nonpalpable breast lesions compared to open-breast biopsy

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    This paper demonstrates that the introduction of large-core needle biopsy (LCNB) replacing needle-localised breast biopsy (NLBB) for nonpalpable (screen-detected) breast lesions could result in substantial cost savings at the expense of a possible slight increase in breast cancer mortality. The cost-effectiveness of LCNB and NLBB was estimated using a microsimulation model. The sensitivity of LCNB (0.97) and resource use and costs of LCNB and NLBB were derived from a multicentre consecutive cohort study among 973 women who consented in getting LCNB and NLBB, if LCNB was negative. Sensitivity analyses were performed. Replacing NLBB with LCNB would result in approximately six more breast cancer deaths per year (in a target population of 2.1 million women), or in 1000 extra life-years lost from breast cancer (effect over 100 years). The total costs of management of breast cancer (3% discounted) are estimated at £4676 million with NLBB; introducing LCNB would save £13 million. The incremental cost-effectiveness ratio of continued NLBB vs LCNB would be £12 482 per additional life-year gained (3% discounted); incremental costs range from £-21 687 (low threshold for breast biopsy) to £74 378 (high sensitivity of LCNB)

    Example-based learning: comparing the effects of additionally providing three different integrative learning activities on physiotherapy intervention knowledge

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    BACKGROUND: Example-based learning using worked examples can foster clinical reasoning. Worked examples are instructional tools that learners can use to study the steps needed to solve a problem. Studying worked examples paired with completion examples promotes acquisition of problem-solving skills more than studying worked examples alone. Completion examples are worked examples in which some of the solution steps remain unsolved for learners to complete. Providing learners engaged in example-based learning with self-explanation prompts has been shown to foster increased meaningful learning compared to providing no self-explanation prompts. Concept mapping and concept map study are other instructional activities known to promote meaningful learning. This study compares the effects of self-explaining, completing a concept map and studying a concept map on conceptual knowledge and problem-solving skills among novice learners engaged in example-based learning.METHODS: Ninety-one physiotherapy students were randomized into three conditions. They performed a pre-test and a post-test to evaluate their gains in conceptual knowledge and problem-solving skills (transfer performance) in intervention selection. They st

    Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration

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    Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5 + crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regulation of the ISC compartment after tissue damage. Using ex vivo organoid cultures, here we show that innat

    Communicating tensions among incumbents about system innovation in the Dutch dairy sector

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    This article investigates the ways in which innovating incumbents address and deal with tensions in their daily conversations in a case of an dairy initiative aiming for sector transformation. Analysis of meetings shows that innovating incumbents employ three strategies to address and deal with tensions such as concerns about the initiative's impact: voicing concerns, questioning as starting point and questioning as response. In these ways, they address tensions at the boundaries between representative and initiative and between representative and constituency. The assigned staff members of initiatives play a key role in opening up conversations on tensions. Tensions among innovating incumbents are avoided in the formal meetings, but are addressed in the frequent bilateral contacts. The research adds to the understanding of the roles of incumbents in a 'transformation pathway', by showing how innovating incumbents in interaction question which actions contribute to a sector transformation

    Ivacaftor for the treatment of patients with cystic fibrosis and the G551D mutation: A systematic review and cost-effectiveness analysis

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    Background: Ivacaftor (Kalydeco®, Vertex Pharmaceuticals) is the first of a new class of drugs that target the underlying protein defect in cystic fibrosis (CF). It is aimed at patients with the G551D (glycine to aspartate change in nucleotide 1784 in exon 11) mutation; 5.7% of patients with CF in the UK have this mutation. Objectives: To review the clinical effectiveness and cost-effectiveness of ivacaftor for the treatment of CF in patients aged ≥ 6 years who have the G551D mutation. Methods: Ten databases, including MEDLINE and EMBASE, were searched from inception to J

    Dynamics of the serologic response in vaccinated and unvaccinated mumps cases during an epidemic

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    In the last decade, several mumps outbreaks were reported in various countries despite high vaccination coverage. In most cases,

    Access to orphan drugs in western Europe: Can more systematic policymaking really help to avoid different decisions about the same drug?

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    When the Scottish government recently launched a £21 million fund to provide patients with rare diseases access to treatment, Alex Neill, the Scottish Health Secretary, stated that 'it was only right that Scottish patients with rare conditions had access to innovative medicines which were clinically justified, and that they were not disadvantaged due to the very high cost of these treatments'. This statement raises questions about the criteria that play a role in reimbursement decisions on orphan drugs. This editorial examines the criteria that were used in the decisions about the reimbursement of an orphan drug for Pompe disease and explores methods to improve the transparency and consistency of reimbursement decisions for orphan drugs in general

    A patient with autoimmune pancreatitis type 1 with previously known lymphadenopathy, both in the context of igG4-related disease

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    Objective: Unusual clinical course Background: Autoimmune pancreatitis (AIP) is an important clinical pathologic concept of IgG-4-related disease. AIP is a rare cause of chronic pancreati

    Tumour basement membrane laminin expression predicts outcome following curative resection of pancreatic head cancer

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    Background: Although widely fragmented BMs have been associated with adverse outcome in several cancer types, comparatively little is known with respect to its effect on the prognosis of pancreatic cancer. The aim of the current study was therefore to determine the prognostic value of tumour basement membrane (BM) continuity in two anatomically closely related, however, prognostically different tumours, pancreatic head-and periampullary cancer. Methods: Tumour BM continuity was determined by immunohistochemical staining of its two major components, laminin and collagen type IV. Associations were made with recurrence free survival (RFS), cancer-specific survival (CSS), overall survival (OS) and conventional prognostic factors. Results: Fifty-nine and 61% of pancreatic head and periampullary tumours, respectively, showed limited BM laminin expression. Whereas 43% and 41% of pancreatic head and periampullary cancers, respectively, showed limited BM collagen type IV expression. Limited BM laminin was associated with poor outcome following curative resection of pancreatic head cancer (P=0.034, 0.013 and 0.017 for RFS, CSS and OS, respectively). Two and a half times as many patients with 25% BM laminin were recurrence free and alive 5 years following resection compared with those with limited BM laminin. Although staining patterns of both BM components were weakly correlated with each other, BM collagen type IV expression was not significantly associated with outcome in either tumour type.Conclusion: Discontinuous BMs, determined by laminin expression, are associated with poor outcome following curative resection of pancreatic head cancer
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