91 research outputs found

    Vitreoretinal interface abnormalities in middle-aged adults with visual impairment in the UK Biobank study: prevalence, impact on visual acuity and associations

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    Objective: The aim of this study was to determine the prevalence of vitreoretinal interface abnormalities (VRIA), the degree of visual impairment and associations with VRIA among adults, aged 40–69 years, in the UK Biobank study. Methods and analysis: Colour fundus photographs and spectral domain optical coherence tomography images were graded for 25% of the 8359 UK Biobank participants with mild visual impairment or worse (LogMAR >0.3 or Snellen <6/12) in at least one eye. The prevalence and contribution of VRIA to visual impairment was determined and multinomial logistic regression models were used to investigate association with known risk factors and other predetermined socioeconomic, biometric, lifestyle and medical variables for cases and matched controls. Results: The minimum prevalence of any VRIA was 17.6% and 8.1% in the eyes with and without visual impairment, respectively. VRIA were identified as the primary cause of visual impairment in 3.6% of eyes. Although epiretinal membrane and vitreomacular traction were the most common VRIA, the degree of visual impairment was typically milder with these than with other VRIA. Visual impairment with a VRIA was positively associated with increasing age (relative risk ratio (RRR) 1.22 (95% CI 1.07 to 1.40)), female gender (RRR 1.28; 1.08 to 1.52) and Asian or Asian British ethnicity (RRR 1.60; 1.10 to 2.32). Conclusions: VRIA are common in middle-aged adults in the UK Biobank study, especially in eyes with visual impairment. VRIA were considered to be the primary cause of visual impairment in 3.6% of all eyes with visual impairment, although there was variation in the degree of visual impairment for each type of VRIA

    Assessing the impact of care farms on quality of life and offending: a pilot study among probation service users in England

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    OBJECTIVES: To assess the feasibility of conducting a cost-effectiveness study of using care farms (CFs) to improve quality of life and reduce reoffending among offenders undertaking community orders (COs). To pilot questionnaires to assess quality of life, connection to nature, lifestyle behaviours, health and social-care use. To assess recruitment and retention at 6 months and feasibility of data linkage to Police National Computer (PNC) reconvictions data and data held by probation services. DESIGN: Pilot study using questionnaires to assess quality of life, individually linked to police and probation data. SETTING: The pilot study was conducted in three probation service regions in England. Each site included a CF and at least one comparator CO project. CFs are working farms used with a range of clients, including offenders, for therapeutic purposes. The three CFs included one aquaponics and horticulture social enterprise, a religious charity focusing on horticulture and a family-run cattle farm. Comparator projects included sorting secondhand clothes and activities to address alcohol misuse and anger management. PARTICIPANTS: We recruited 134 adults (over 18) serving COs in England, 29% female. RESULTS: 52% of participants completed follow-up questionnaires. Privatisation of UK probation trusts in 2014 negatively impacted on recruitment and retention. Linkage to PNC data was a more successful means of follow-up, with 90% consenting to access their probation and PNC data. Collection of health and social-care costs and quality-adjusted life year derivation were feasible. Propensity score adjustment provided a viable comparison method despite differences between comparators. We found worse health and higher reoffending risk among CF participants due to allocation of challenging offenders to CFs, making risk of reoffending a confounder. CONCLUSIONS: Recruitment would be feasible in a more stable probation environment. Follow-up was challenging; however, assessing reconvictions from PNC data is feasible and a potential primary outcome for future studies

    Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register

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    Objective. Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK. This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) after 6 months of therapy in 261 patients enrolled in a national prospective observational register

    Role of potassium and calcium channels in sevoflurane-mediated vasodilation in the foeto-placental circulation

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    <p>Abstract</p> <p>Background</p> <p>Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings.</p> <p>Methods</p> <p>Quadruplicate <it>ex vivo </it>human chorionic plate arterial rings were used in all studies. <b><it>Series 1 and 2 </it></b>examined the role of the K<sup>+ </sup>channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K<sup>+ </sup>(K<sub>Ca++</sub>) channels (<b><it>Series 1A+B</it></b>) or glibenclamide, which blocks the ATP sensitive K<sup>+ </sup>(K<sub>ATP</sub>) channel (<b><it>Series 2</it></b>), modulated sevoflurane-mediated vasodilation. <b><it>Series 3 – 5 </it></b>examined the role of the Ca<sup>++ </sup>channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca<sup>++ </sup>channel (<b><it>Series 3</it></b>), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca<sup>++ </sup>channels (<b><it>Series 4A+B</it></b>), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca<sup>++ </sup>channel (<b><it>Series 5A+B</it></b>), modulated sevoflurane-mediated vasodilation.</p> <p>Results</p> <p>Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the K<sub>Ca++ </sub>and K<sub>ATP </sub>channels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K<sup>+ </sup>channels. Blockade of the voltage-operated Ca<sup>++</sup>channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca<sup>++</sup>channels did not alter sevoflurane vasodilation.</p> <p>Conclusion</p> <p>Sevoflurane appears to block chorionic arterial K<sub>Ca++ </sub>and K<sub>ATP </sub>channels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the <it>in vitro </it>foeto-placental circulation.</p

    Impact and cost-effectiveness of care farms on health and well-being of offenders on probation: a pilot study

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    Background Care farms (CFs), in which all or part of the farm is used for therapeutic purposes, show potential for improving well-being for disadvantaged groups. We assessed the feasibility of determining the cost-effectiveness of CFs in improving quality of life compared with comparator sites among probationers undertaking community orders (COs). Objectives (1) To conduct a systematic review of CF impacts and mechanisms in improving health and logic model development; (2) to inform future studies by estimating differences in quality of life and other outcomes, identifying factors driving CO allocation and ways to maximise recruitment and follow-up; and (3) to assess feasibility of cost-effectiveness analysis. Review methods A mixed-methods synthesis following Campbell Collaboration guidelines. Pilot study: three probation service regions in England, each with a CF and a comparator CO site. Participants were adult offenders (aged ≥ 18 years) serving COs. The primary outcome was quality of life [as measured via the Clinical Outcome in Routine Evaluation–Outcome Measure (CORE-OM)]. Other outcomes were health behaviours, mental well-being, connectedness to nature and reconvictions. Data sources In November 2014, we searched 22 health, education, environmental, criminal justice and social science electronic databases, databases of grey literature and care farming websites across Europe. There were no language restrictions. A full list of databases searched is given in Appendix 1; some examples include Web of Science, Cumulative Index to Nursing and Allied Health Literature (via EBSCOhost), The Campbell Library, Criminal Justice Abstracts (via EBSCOhost), MEDLINE (via Ovid) and Scopus (Elsevier B.V., Amsterdam, the Netherlands). Results Our systematic review identified 1659 articles: 14 qualitative, 12 quantitative and one mixed-methods study. Small sample sizes and poor design meant that all were rated as being at a high risk of bias. Components of CFs that potentially improve health are being in a group, the role of the farmer and meaningful work, and interaction with animals. There was a lack of quantitative evidence indicating that CFs improve quality of life and there was weak evidence of improved mental health, self-efficacy, self-esteem, affect and mood. In the pilot study we recruited 134 respondents, and only 21 declined; 37% were allocated to three CFs and the remainder to comparators. This was below our recruitment target of 300. Recruitment proved challenging as a result of the changes in probation (probation trusts were disbanded in 2014) and closure of one CF. We found significant differences between CFs and comparator users: those at CFs were more likely to be male, smokers, substance users, at higher risk of reoffending (a confounder) and have more missing CORE-OM questions. Despite these differences, the use of propensity analysis facilitated comparison. Participants consented to our team accessing, and we were able to link, probation and police reconviction data for 90% of respondents. We gained follow-up questionnaire data from 52% of respondents, including health and social care use cost data. We transformed CORE-OM into CORE-6D, allowing derivation of quality-adjusted life-years. As a pilot, our study was not powered to identify significant differences in outcomes. Qualitatively, we observed that within COs, CFs can be formally recognised as rehabilitative but in practice can be seen as punitive. Limitations Changes in probation presented many challenges that limited recruitment and collection of cost data. Conclusions Recruitment is likely to be feasible in a more stable probation environment. Retention among probationers is challenging but assessing reconvictions from existing data is feasible. We found worse health and risk of reoffending among offenders at CFs, reflecting the use of CFs by probation to manage challenging offenders. Future work A sufficiently powered natural experiment is feasible and of value. Using reconvictions (from police data) as a primary outcome is one solution to challenges with retention. Propensity analysis provides a viable method for comparison despite differences in participants at CFs and comparator sites. However, future work is dependent on stability and support for CFs within probation services. Study registration This study is registered as PROSPERO CRD42014013892 and SW2013–04 (the Campbell Collaboration). Funding details The National Institute for Health Research Public Health Research programme

    A Reliable Method for the Selection of Exploitable Melanoma Archival Paraffin Embedded Tissues for Transcript Biomarker Profiling

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    The source tissue for biomarkers mRNA expression profiling of tumors has traditionally been fresh-frozen tissue. The adaptation of formalin-fixed, paraffin-embedded (FFPE) tissues for routine mRNA profiling would however be invaluable in view of their abundance and the clinical information related to them. However, their use in the clinic remains a challenge due to the poor quality of RNA extracted from such tissues. Here, we developed a method for the selection of melanoma archival paraffin-embedded tissues that can be reliably used for transcript biomarker profiling. For that, we used qRT-PCR to conduct a comparative study in matched pairs of frozen and FFPE melanoma tissues of the expression of 25 genes involved in angiogenesis/tumor invasion and 15 housekeeping genes. A classification method was developed that can select the samples with a good frozen/FFPE correlation and identify those that should be discarded on the basis of paraffin data for four reference genes only. We propose therefore a simple and inexpensive assay which improves reliability of mRNA profiling in FFPE samples by allowing the identification and analysis of “good” samples only. This assay which can be extended to other genes would however need validation at the clinical level and on independent tumor series

    Clinicopathologic and gene expression parameters predict liver cancer prognosis

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    <p>Abstract</p> <p>Background</p> <p>The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model.</p> <p>Methods</p> <p>Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction.</p> <p>Results</p> <p>HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis.</p> <p>Conclusion</p> <p>When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome.</p
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