534 research outputs found

    Disseminated adenovirus infection after allogeneic stem cell transplant and the potential role of brincidofovir - Case series and 10 year experience of management in an adult transplant cohort

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    Background Adenovirus infection is a recognized complication following haematopoietic stem cell transplantation. We present a review of our experience of these infections in our transplant cohort over 10 years including 3 patients treated with the novel antiviral brincidofovir. Objectives We aimed to describe the presentation, response to treatment and outcomes of adult stem cell transplant patients with disseminated adenovirus infection. Study design All adult cases of disseminated adenovirus infection following haematopoietic stem cell transplant in our unit between 2005 and 2015 were identified. Transplant details and data on timing of diagnosis, course of infection, viral co-infection and treatment were collected. Results Of 733 patients transplanted, 10 patients had disseminated infection, including 4 male and 6 female patients with median age of 36.5 (range 19–59) years. 6/10 received an allograft from an unrelated donor. Median post-transplant time to detection of viraemia was 67 days (range 20–1140 days). Median peak viral load was 3133 copies/ml (352–11,000,000) in survivors received cidofovir alone, one cidofovir then brincidofovir and two brincidofovir alone. 8/10 p and 1,580,000 copies/ml (41,999–3,000.000) in those who died. Five patientsatients had a decrease in viral load following antivirals and/or reduction in immunosuppression including all on brincidofovir. Three died on treatment. Conclusions Disseminated adenovirus infection is uncommon in adult transplant patients and uncertainties remain surrounding effective treatment. In our cohort, brincidofovir has shown promise in treatment of adenoviral infection. However, randomized controlled studies are required to confirm this impression

    Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations.</p> <p>Case presentation</p> <p>We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.</p> <p>Conclusion</p> <p>It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.</p

    Assessing the quality of reports of randomized trials in pediatric complementary and alternative medicine

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    OBJECTIVE: To evaluate the quality of reports of complementary and alternative medicine (CAM) randomized controlled trials (RCTs) in the pediatric population. We also examined whether there was a change in the quality of reporting over time. METHODS: We used a systematic sample of 251 reports of RCTs that used a CAM intervention. The quality of each report was assessed using the number of CONSORT checklist items included, the frequency of unclear allocation concealment, and a 5-point quality assessment instrument. RESULTS: Nearly half (40%) of the CONSORT checklist items were included in the reports, with an increase in the number of items included. The majority (81.3%) of RCTs reported unclear allocation concealment with no significant change over time. The quality of reports achieved approximately 40% of their maximum possible total score as assessed with the Jadad scale with no change over time. Information regarding adverse events was reported in less than one quarter of the RCTs (22%) and information regarding costs was mentioned in only a minority of reports (4%). CONCLUSIONS: RCTs are an important tool for evidence based health care decisions. If these studies are to be relevant in the evaluation of CAM interventions it is important that they are conducted and reported with the highest possible standards. There is a need to redouble efforts to ensure that children and their families are participating in RCTs that are conducted and reported with minimal bias. Such studies will increase their usefulness to a board spectrum of interested stakeholders

    Transmission of Hepatitis B Core Antibody and Galactomannan Enzyme Immunoassay Positivity via Immunoglobulin Products: A Comprehensive Analysis

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    BACKGROUND: Therapeutic immunoglobulins are used as replacement or immunomodulatory therapy, but can transmit clinically important molecules. We investigated hepatitis B virus (HBV) antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity. Detection of HBV core antibody may prompt antiviral prophylaxis when commencing therapy such as rituximab; a positive GM-EIA result prompts investigation or treatment for invasive fungal disease. METHODS: We performed a cross-sectional analysis of HBV serology in 80 patients established (>6 months) on immunoglobulin therapy; prospective analysis of HBV serology in 16 patients commencing intravenous immunoglobulin (IVIG); and pre- and post-infusion analysis of GM-EIA in 37 patients receiving IVIG. RESULTS: Pre-IVIG, 9 of 80 patients tested positive for HBV surface antibody and 1 of 80 tested equivocal for HBV core antibody. On IVIG, 79 of 79 tested positive for surface antibody, 37 of 80 tested positive for core antibody, and 10 of 80 tested equivocal for core antibody. There were significant differences by product, but among patients receiving products that appear to transmit core antibody, negative results correlated with lower surface antibody titers and longer time since infusion, suggesting a simple concentration effect. There was a progressive increase with each infusion in the percentage of patients testing positive for HBV core antibody among patients newly commencing IVIG. Some patients “seroreverted” to negative during therapy. Certain IVIG products tested positive for GM-EIA and there were rises in index values in corresponding patient samples from pre- to post-infusion. Overall, 5 of 37 patient samples pre-infusion and 15 of 37 samples post-infusion tested positive for GM-EIA. CONCLUSIONS: HBV antibodies and GM-EIA positivity are common in patients receiving IVIG and confound diagnostic results

    A database application for pre-processing, storage and comparison of mass spectra derived from patients and controls.

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    BACKGROUND: Statistical comparison of peptide profiles in biomarker discovery requires fast, user-friendly software for high throughput data analysis. Important features are flexibility in changing input variables and statistical analysis of peptides that are differentially expressed between patient and control groups. In addition, integration the mass spectrometry data with the results of other experiments, such as microarray analysis, and information from other databases requires a central storage of the profile matrix, where protein id's can be added to peptide masses of interest. RESULTS: A new database application is presented, to detect and identify significantly differentially expressed peptides in peptide profiles obtained from body fluids of patient and control groups. The presented modular software is capable of central storage of mass spectra and results in fast analysis. The software architecture consists of 4 pillars, 1) a Graphical User Interface written in Java, 2) a MySQL database, which contains all metadata, such as experiment numbers and sample codes, 3) a FTP (File Transport Protocol) server to store all raw mass spectrometry files and processed data, and 4) the software package R, which is used for modular statistical calculations, such as the Wilcoxon-Mann-Whitney rank sum test. Statistic analysis by the Wilcoxon-Mann-Whitney test in R demonstrates that peptide-profiles of two patient groups 1) breast cancer patients with leptomeningeal metastases and 2) prostate cancer patients in end stage disease can be distinguished from those of control groups. CONCLUSION: The database application is capable to distinguish patient Matrix Assisted Laser Desorption Ionization (MALDI-TOF) peptide profiles from control groups using large size datasets. The modular architecture of the application makes it possible to adapt the application to handle also large sized data from MS/MS- and Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry experiments. It is expected that the higher resolution and mass accuracy of the FT-ICR mass spectrometry prevents the clustering of peaks of different peptides and allows the identification of differentially expressed proteins from the peptide profiles

    The effectiveness of strategies to change organisational culture to improve healthcare performance: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>Organisational culture is an anthropological metaphor used to inform research and consultancy and to explain organisational environments. In recent years, increasing emphasis has been placed on the need to change organisational culture in order to improve healthcare performance. However, the precise function of organisational culture in healthcare policy often remains underspecified and the desirability and feasibility of strategies to be adopted have been called into question. The objective of this review was to determine the effectiveness of strategies to change organisational culture in order to improve healthcare performance.</p> <p>Methods</p> <p>We searched the following electronic databases: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Sociological Abstracts, Web of Knowledge, PsycINFO, Business and Management, EThOS, Index to Theses, Intute, HMIC, SIGLE, and Scopus until October 2009. The Database of Abstracts of Reviews of Effectiveness (DARE) was searched for related reviews. We also searched the reference lists of all papers and relevant reviews identified, and we contacted experts in the field for advice on further potential studies. We considered randomised controlled trials (RCTs) or well designed quasi-experimental studies (controlled clinical trials (CCTs), controlled before and after studies (CBAs), and interrupted time series (ITS) analyses). Studies could be set in any type of healthcare organisation in which strategies to change organisational culture in order to improve healthcare performance were applied. Our main outcomes were objective measures of professional performance and patient outcome.</p> <p>Results</p> <p>The search strategy yielded 4,239 records. After the full text assessment, two CBA studies were included in the review. They both assessed the impact of interventions aimed at changing organisational culture, but one evaluated the impact on work-related and personal outcomes while the other measured clinical outcomes. Both were at high risk of bias. Both reported positive results.</p> <p>Conclusions</p> <p>Current available evidence does not identify any effective, generalisable strategies to change organisational culture. Healthcare organisations considering implementing interventions aimed at changing culture should seriously consider conducting an evaluation (using a robust design, <it>e.g.</it>, ITS) to strengthen the evidence about this topic.</p

    Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway

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    Radiation therapy (RT) is utilised for the treatment of around half of all oncology patients during the course of their illness. Despite great clinical progress in the rational deployment of RT, the underlying molecular basis for its efficacy and toxicity are currently imperfectly understood. In this study, we took a biochemical approach to evaluate the potential role of key ionising radiation repair proteins in the treatment outcomes of patients with severe acute or late RT side effects. Lymphoblastoid cell lines were established from blood samples from 36 radiosensitive cases and a number of controls (the latter had had RT but did not develop significant toxicity). The expression level and migration of key proteins from the nonhomologous end-joining (NHEJ) pathway was evaluated by Western blot analysis on cases and controls. We did not observe any abnormalities in expression level or migration pattern of the following NHEJ proteins in radiosensitive cancer cases: Ku70, Ku80, XRCC4, DNA Ligase IV. These important negative results provide evidence that mutations that affect protein expression of these NHEJ components are unlikely to underlie clinical radiation sensitivity

    A qualitative study of the learning processes in young physicians treating suicidal patients: from insecurity to personal pattern knowledge and self-confidence

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    <p>Abstract</p> <p>Background</p> <p>Little empirical work has been done in studying learning processes among newly educated physicians in the mental health field.</p> <p>The aim of the study was to shed light on the meaning of newly educated physicians' lived experiences of learning processes related to treating suicidal patients.</p> <p>Methods</p> <p>Thirteen newly educated physicians narrated their learning experiences while treating suicidal patients in their own practice. The interview texts were transcribed and interpreted using a phenomenological-hermeneutical method inspired by Ricoeur's philosophy.</p> <p>Results</p> <p>There was one main theme, four themes and eleven sub themes. The main theme was: Being in a transitional learning process. The themes and sub themes were: Preparing for practice (Getting tools and training skills, Becoming aware of one's own attitudes); Gaining experience from treating patients (Treating and following up patients over time, Storing memories and recognizing similarities and differences in patients); Participating in the professional community (Being an apprentice, Relating clinical stories and receiving feedback, Sharing emotions from clinical experiences, Receiving support from peers); and Developing personal competence (Having unarticulated awareness, Having emotional knowledge, Achieving self-confidence). The informants gave a detailed account of the learning process; from recognising similarities and differences in patients they have treated, to accumulating pattern knowledge, which then contributed to their personal feelings of competence and confidence. They described their personal competence with cognitive and emotional elements consisting of both articulated and less articulated knowledge. The findings are interpreted in relation to different learning theories that focus on both individual factors and the interaction with the learning environment.</p> <p>Conclusion</p> <p>This study provides additional information about learning experiences of young physicians during the critical transition phase from medical school to early professional life. Peers are used for both learning and support and might represent a more powerful resource in the learning process than previously recognized. Emotional experiences do not seem to be adequately focused upon in supervision, which obviously has relevance both for learning and for the well-being of young professionals. The study indicates some areas of the educational system that could profitably be expanded including stimulating more systematically to critical reflection on and in practice, attention to feelings in the reflective process and provision of more performance feedback to young physicians.</p
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