123 research outputs found

    PCN17: AN ANALYSIS OF RESOURCE USE IN THE TREATMENT OF ADVANCED COLORECTAL CANCER IN THE UK

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    Synthesis of guidance available for assessing methodological quality and grading of evidence from qualitative research to inform clinical recommendations: a systematic literature review

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    Objective To understand (1) what guidance exists to assess the methodological quality of qualitative research; (2) what methods exist to grade levels of evidence from qualitative research to inform recommendations within European Alliance of Associations for Rheumatology (EULAR). Methods A systematic literature review was performed in multiple databases including PubMed/Medline, EMBASE, Web of Science, COCHRANE and PsycINFO, from inception to 23 October 2020. Eligible studies included primary articles and guideline documents available in English, describing the: (1) development; (2) application of validated tools (eg, checklists); (3) guidance on assessing methodological quality of qualitative research and (4) guidance on grading levels of qualitative evidence. A narrative synthesis was conducted to identify key similarities between included studies. Results Of 9073 records retrieved, 51 went through to full-manuscript review, with 15 selected for inclusion. Six articles described methodological tools to assess the quality of qualitative research. The tools evaluated research design, recruitment, ethical rigour, data collection and analysis. Seven articles described one approach, focusing on four key components to determine how much confidence to place in findings from systematic reviews of qualitative research. Two articles focused on grading levels of clinical recommendations based on qualitative evidence; one described a qualitative evidence hierarchy, and another a research pyramid. Conclusion There is a lack of consensus on the use of tools, checklists and approaches suitable for appraising the methodological quality of qualitative research and the grading of qualitative evidence to inform clinical practice. This work is expected to facilitate the inclusion of qualitative evidence in the process of developing recommendations at EULAR level

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Alternative scenarios: harnessing mid-level providers and evidence-based practice in primary dental care in England through operational research

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    Background: In primary care dentistry, strategies to reconfigure the traditional boundaries of various dental professional groups by task sharing and role substitution have been encouraged in order to meet changing oral health needs. Aim: The aim of this research was to investigate the potential for skill mix use in primary dental care in England based on the undergraduate training experience in a primary care team training centre for dentists and mid-level dental providers. Methods: An operational research model and four alternative scenarios to test the potential for skill mix use in primary care in England were developed, informed by the model of care at a primary dental care training centre in the south of England, professional policy including scope of practice and contemporary evidence-based preventative practice. The model was developed in Excel and drew on published national timings and salary costs. The scenarios included the following: “No Skill Mix”, “Minimal Direct Access”, “More Prevention” and “Maximum Delegation”. The scenario outputs comprised clinical time, workforce numbers and salary costs required for state-funded primary dental care in England. Results: The operational research model suggested that 73% of clinical time in England’s state-funded primary dental care in 2011/12 was spent on tasks that may be delegated to dental care professionals (DCPs), and 45- to 54-year-old patients received the most clinical time overall. Using estimated National Health Service (NHS) clinical working patterns, the model suggested alternative NHS workforce numbers and salary costs to meet the dental demand based on each developed scenario. For scenario 1:“No Skill Mix”, the dentist-only scenario, 81% of the dentists currently registered in England would be required to participate. In scenario 2: “Minimal Direct Access”, where 70% of examinations were delegated and the primary care training centre delegation patterns for other treatments were practised, 40% of registered dentists and eight times the number of dental therapists currently registered would be required; this would save 38% of current salary costs cf. “No Skill Mix”. Scenario 3: “More Prevention”, that is, the current model with no direct access and increasing fluoride varnish from 13.1% to 50% and maintaining the same model of delegation as scenario 2 for other care, would require 57% of registered dentists and 4.7 times the number of dental therapists. It would achieve a 1% salary cost saving cf. “No Skill Mix”. Scenario 4 “Maximum Delegation” where all care within dental therapists’ jurisdiction is delegated at 100%, together with 50% of restorations and radiographs, suggested that only 30% of registered dentists would be required and 10 times the number of dental therapists registered; this scenario would achieve a 52% salary cost saving cf. “No Skill Mix”. Conclusion: Alternative scenarios based on wider expressed treatment need in national primary dental care in England, changing regulations on the scope of practice and increased evidence-based preventive practice suggest that the majority of care in primary dental practice may be delegated to dental therapists, and there is potential time and salary cost saving if the majority of diagnostic tasks and prevention are delegated. However, this would require an increase in trained DCPs, including role enhancement, as part of rebalancing the dental workforce

    Global, regional, and national burden of other musculoskeletal disorders, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

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    Background Musculoskeletal disorders include more than 150 different conditions affecting joints, muscles, bones, ligaments, tendons, and the spine. To capture all health loss from death and disability due to musculoskeletal disorders, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) includes a residual musculoskeletal category for conditions other than osteoarthritis, rheumatoid arthritis, gout, low back pain, and neck pain. This category is called other musculoskeletal disorders and includes, for example, systemic lupus erythematosus and spondylopathies. We provide updated estimates of the prevalence, mortality, and disability attributable to other musculoskeletal disorders and forecasted prevalence to 2050. Methods Prevalence of other musculoskeletal disorders was estimated in 204 countries and territories from 1990 to 2020 using data from 68 sources across 23 countries from which subtraction of cases of rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout from the total number of cases of musculoskeletal disorders was possible. Data were analysed with Bayesian meta-regression models to estimate prevalence by year, age, sex, and location. Years lived with disability (YLDs) were estimated from prevalence and disability weights. Mortality attributed to other musculoskeletal disorders was estimated using vital registration data. Prevalence was forecast to 2050 by regressing prevalence estimates from 1990 to 2020 with Socio-demographic Index as a predictor, then multiplying by population forecasts. Findings Globally, 494 million (95% uncertainty interval 431–564) people had other musculoskeletal disorders in 2020, an increase of 123·4% (116·9–129·3) in total cases from 221 million (192–253) in 1990. Cases of other musculoskeletal disorders are projected to increase by 115% (107–124) from 2020 to 2050, to an estimated 1060 million (95% UI 964–1170) prevalent cases in 2050; most regions were projected to have at least a 50% increase in cases between 2020 and 2050. The global age-standardised prevalence of other musculoskeletal disorders was 47·4% (44·9–49·4) higher in females than in males and increased with age to a peak at 65–69 years in male and female sexes. In 2020, other musculoskeletal disorders was the sixth ranked cause of YLDs globally (42·7 million [29·4–60·0]) and was associated with 83 100 deaths (73 600–91 600). Interpretation Other musculoskeletal disorders were responsible for a large number of global YLDs in 2020. Until individual conditions and risk factors are more explicitly quantified, policy responses to this burden remain a challenge. Temporal trends and geographical differences in estimates of non-fatal disease burden should not be overinterpreted as they are based on sparse, low-quality data.publishedVersio

    Role of Δ1-Pyrroline-5-Carboxylate Dehydrogenase Supports Mitochondrial Metabolism and Host-Cell Invasion ofTrypanosoma cruzi

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    Proline is crucial for energizing critical events throughout the life cycle of Trypanosoma cruzi, the etiological agent of Chagas disease. The proline breakdown pathway consists of two oxidation steps, both of which producereducing equivalents as follows: the conversion of proline to Δ1-pyrroline-5-carboxylate (P5C), and the subsequent conversion of P5C to glutamate. We have identified and characterized the Δ1-pyrroline-5-carboxylate dehydrogenase from T. cruzi (TcP5CDH) and report here on how this enzyme contributes to a central metabolic pathway in this parasite. Size-exclusionchromatography, two-dimensional gel electrophoresis, and small angle x-ray scattering analysis of TcP5CDH revealed an oligomericstate composed of two subunits of six protomers. TcP5CDH was found to complement a yeast strain deficient in PUT2 activity,confirming the enzyme's functional role; and the biochemical parameters (Km, kcat, and kcat/Km) of the recombinant TcP5CDH were determined, exhibiting values comparable with those from T. cruzi lysates. In addition, TcP5CDH exhibited mitochondrial staining during the main stages of the T. cruzi life cycle. mRNA and enzymatic activity levels indicated the up-regulation (6-fold change) of TcP5CDH during the infectivestages of the parasite. The participation of P5C as an energy source was also demonstrated. Overall, we propose that thisenzymatic step is crucial for the viability of both replicative and infective forms of T. cruzi
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