140 research outputs found

    One Thousand Ceasarean Sections in the Modern Era of Obstetrics

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    Assessing communication quality of consultations in primary care: initial reliability of the Global Consultation Rating Scale, based on the Calgary-Cambridge Guide to the Medical Interview.

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    OBJECTIVES: To investigate initial reliability of the Global Consultation Rating Scale (GCRS: an instrument to assess the effectiveness of communication across an entire doctor-patient consultation, based on the Calgary-Cambridge guide to the medical interview), in simulated patient consultations. DESIGN: Multiple ratings of simulated general practitioner (GP)-patient consultations by trained GP evaluators. SETTING: UK primary care. PARTICIPANTS: 21 GPs and six trained GP evaluators. OUTCOME MEASURES: GCRS score. METHODS: 6 GP raters used GCRS to rate randomly assigned video recordings of GP consultations with simulated patients. Each of the 42 consultations was rated separately by four raters. We considered whether a fixed difference between scores had the same meaning at all levels of performance. We then examined the reliability of GCRS using mixed linear regression models. We augmented our regression model to also examine whether there were systematic biases between the scores given by different raters and to look for possible order effects. RESULTS: Assessing the communication quality of individual consultations, GCRS achieved a reliability of 0.73 (95% CI 0.44 to 0.79) for two raters, 0.80 (0.54 to 0.85) for three and 0.85 (0.61 to 0.88) for four. We found an average difference of 1.65 (on a 0-10 scale) in the scores given by the least and most generous raters: adjusting for this evaluator bias increased reliability to 0.78 (0.53 to 0.83) for two raters; 0.85 (0.63 to 0.88) for three and 0.88 (0.69 to 0.91) for four. There were considerable order effects, with later consultations (after 15-20 ratings) receiving, on average, scores more than one point higher on a 0-10 scale. CONCLUSIONS: GCRS shows good reliability with three raters assessing each consultation. We are currently developing the scale further by assessing a large sample of real-world consultations

    Investigating the meaning of 'good' or 'very good' patient evaluations of care in English general practice: A mixed methods study

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    This is the final version. Available from the publisher via the DOI in this record.The data set is available on request from the authors: please email Jenni Burt ( [email protected]) for details.Objective: To examine concordance between responses to patient experience survey items evaluating doctors' interpersonal skills, and subsequent patient interview accounts of their experiences of care. Design: Mixed methods study integrating data from patient questionnaires completed immediately after a video-recorded face-to-face consultation with a general practitioner (GP) and subsequent interviews with the same patients which included playback of the recording. Setting: 12 general practices in rural, urban and inner city locations in six areas in England. Participants: 50 patients (66% female, aged 19-96 years) consulting face-to-face with 32 participating GPs. Main outcome measures: Positive responses to interpersonal skills items in a postconsultation questionnaire ('good' and 'very good') were compared with experiences reported during subsequent video elicitation interview (categorised as positive, negative or neutral by independent clinical raters) when reviewing that aspect of care. Results: We extracted 230 textual statements from 50 interview transcripts which related to the evaluation of GPs' interpersonal skills. Raters classified 70.9% (n=163) of these statements as positive, 19.6% (n=45) neutral and 9.6% (n=22) negative. Comments made by individual patients during interviews did not always express the same sentiment as their responses to the questionnaire. Where questionnaire responses indicated that interpersonal skills were 'very good', 84.6% of interview statements concerning that item were classified as positive. However, where patients rated interpersonal skills as 'good', only 41.9% of interview statements were classified as positive, and 18.9% as negative. Conclusions: Positive responses on patient experience questionnaires can mask important negative experiences which patients describe in subsequent interviews. The interpretation of absolute patient experience scores in feedback and public reporting should be done with caution, and clinicians should not be complacent following receipt of 'good' feedback. Relative scores are more easily interpretable when used to compare the performance of providers.NHS Cambridgeshire and Peterborough CCGNational Institute for Health Researc

    Does evidence support the high expectations placed in precision medicine? A bibliographic review

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    Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient’s individual characteristics. However, conventional clinical trials are designed to find differences in averages, and interpreting these differences depends on untestable assumptions. Although only an ideal, a constant effect of treatment would facilitate individual management. A direct consequence of a constant effect is that the variance of the outcome measure would be the same in the treated and control arms. We reviewed the literature to explore the similarity of these variances as a foundation for examining whether and how often precision medicine is definitively required. Methods: We reviewed parallel clinical trials with numerical primary endpoints published in 2004, 2007, 2010 and 2013. We collected the baseline and final standard deviations of the main outcome measure. We assessed homoscedasticity by comparing the variance of the primary endpoint between arms through the outcome variance ratio (treated to control group). Results: The review provided 208 articles with enough information to conduct the analysis. One out of five studies (n = 40, 19.2%) had statistically different variances between groups, implying a non-constant-effect. The adjusted point estimate of the mean outcome variance ratio (treated to control group) is 0.89 (95% CI 0.81 to 0.97). Conclusions: The mean variance ratio is significantly lower than 1 and the lower variance was found more often in the intervention group than in the control group, suggesting it is more usual for treated patients to be stable. This observed reduction in variance might also imply that there could be a subgroup of less ill patients who derive no benefit from treatment. This would require further study as to whether the treatment effect outweighs the side effects as well as the economic costs. We have shown that there are ways to analyze the apparently unobservable constant effect

    Real-Time Dynamics of Ca2+, Caspase-3/7, and Morphological Changes in Retinal Ganglion Cell Apoptosis under Elevated Pressure

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    Quantitative information on the dynamics of multiple molecular processes in individual live cells under controlled stress is central to the understanding of the cell behavior of interest and the establishment of reliable models. Here, the dynamics of the apoptosis regulator intracellular Ca2+, apoptosis effector caspase-3/7, and morphological changes, as well as temporal correlation between them at the single cell level, are examined in retinal gangling cell line (differentiated RGC-5 cells) undergoing apoptosis at elevated hydrostatic pressure using a custom-designed imaging platform that allows long-term real-time simultaneous imaging of morphological and molecular-level physiological changes in large numbers of live cells (beyond the field-of-view of typical microscopy) under controlled hydrostatic pressure. This examination revealed intracellular Ca2+ elevation with transient single or multiple peaks of less than 0.5 hour duration appearing at the early stages (typically less than 5 hours after the onset of 100 mmHg pressure) followed by gradual caspase-3/7 activation at late stages (typically later than 5 hours). The data reveal a strong temporal correlation between the Ca2+ peak occurrence and morphological changes of neurite retraction and cell body shrinkage. This suggests that Ca2+ elevation, through its impact on ion channel activity and water efflux, is likely responsible for the onset of apoptotic morphological changes. Moreover, the data show a significant cell-to-cell variation in the onset of caspase-3/7 activation, an inevitable consequence of the stochastic nature of the underlying biochemical reactions not captured by conventional assays based on population-averaged cellular responses. This real-time imaging study provides, for the first time, statistically significant data on simultaneous multiple molecular level changes to enable refinements and testing of models of the dynamics of mitochondria-mediated apoptosis. Further, the platform developed and the approach has direct significance to the study of a variety of signaling pathway phenomena

    Filament Depolymerization Can Explain Chromosome Pulling during Bacterial Mitosis

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    Chromosome segregation is fundamental to all cells, but the force-generating mechanisms underlying chromosome translocation in bacteria remain mysterious. Caulobacter crescentus utilizes a depolymerization-driven process in which a ParA protein structure elongates from the new cell pole, binds to a ParB-decorated chromosome, and then retracts via disassembly, pulling the chromosome across the cell. This poses the question of how a depolymerizing structure can robustly pull the chromosome that disassembles it. We perform Brownian dynamics simulations with a simple, physically consistent model of the ParABS system. The simulations suggest that the mechanism of translocation is “self-diffusiophoretic”: by disassembling ParA, ParB generates a ParA concentration gradient so that the ParA concentration is higher in front of the chromosome than behind it. Since the chromosome is attracted to ParA via ParB, it moves up the ParA gradient and across the cell. We find that translocation is most robust when ParB binds side-on to ParA filaments. In this case, robust translocation occurs over a wide parameter range and is controlled by a single dimensionless quantity: the product of the rate of ParA disassembly and a characteristic relaxation time of the chromosome. This time scale measures the time it takes for the chromosome to recover its average shape after it is has been pulled. Our results suggest explanations for observed phenomena such as segregation failure, filament-length-dependent translocation velocity, and chromosomal compaction

    Control of adult neurogenesis by programmed cell death in the mammalian brain

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    Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities

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    Peritoneal macrophages are one of the most studied macrophage populations in the body, yet the composition, developmental origin and mechanisms governing the maintenance of this compartment are controversial. Here we show resident F4/80(hi)GATA6(+) macrophages are long-lived, undergo non-stochastic self-renewal and retain cells of embryonic origin for at least 4 months in mice. However, Ly6C(+) monocytes constitutively enter the peritoneal cavity in a CCR2-dependent manner, where they mature into short-lived F4/80(lo)MHCII(+) cells that act, in part, as precursors of F4/80(hi)GATA6(+) macrophages. Notably, monocyte-derived F4/80(hi) macrophages eventually displace the embryonic population with age in a process that is highly gender dependent and not due to proliferative exhaustion of the incumbent embryonic population, despite the greater proliferative activity of newly recruited cells. Furthermore, although monocyte-derived cells acquire key characteristics of the embryonic population, expression of Tim4 was impaired, leading to cumulative changes in the population with age

    Developing a measure of polypharmacy appropriateness in primary care: systematic review and expert consensus study.

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    BACKGROUND: Polypharmacy is an increasing challenge for primary care. Although sometimes clinically justified, polypharmacy can be inappropriate, leading to undesirable outcomes. Optimising care for polypharmacy necessitates effective targeting and monitoring of interventions. This requires a valid, reliable measure of polypharmacy, relevant for all patients, that considers clinical appropriateness and generic prescribing issues applicable across all medications. Whilst there are several existing measures of potentially inappropriate prescribing, these are not specifically designed with polypharmacy in mind, can require extensive clinical input to complete, and often cover a limited number of drugs. The aim of this study was to identify what experts consider to be the key elements of a measure of prescribing appropriateness in the context of polypharmacy. METHODS: Firstly, we conducted a systematic review to identify generic (not drug specific) prescribing indicators relevant to polypharmacy appropriateness. Indicators were subject to content analysis to enable categorisation. Secondly, we convened a panel of 10 clinical experts to review the identified indicators and assess their relative clinical importance. For each indicator category, a brief evidence summary was developed, based on relevant clinical and indicator literature, clinical guidance, and opinions obtained from a separate patient discussion panel. A two-stage RAND/UCLA Appropriateness Method was used to reach consensus amongst the panel on a core set of indicators of polypharmacy appropriateness. RESULTS: We identified 20,879 papers for title/abstract screening, obtaining 273 full papers. We extracted 189 generic indicators, and presented 160 to the panel grouped into 18 classifications (e.g. adherence, dosage, clinical efficacy). After two stages, during which the panel introduced 18 additional indicators, there was consensus that 134 indicators were of clinical importance. Following the application of decision rules and further panel consultation, 12 indicators were placed into the final selection. Panel members particularly valued indicators concerned with adverse drug reactions, contraindications, drug-drug interactions, and the conduct of medication reviews. CONCLUSIONS: We have identified a set of 12 indicators of clinical importance considered relevant to polypharmacy appropriateness. Use of these indicators in clinical practice and informatics systems is dependent on their operationalisation and their utility (e.g. risk stratification, targeting and monitoring polypharmacy interventions) requires subsequent evaluation. TRIAL REGISTRATION: Registration number: PROSPERO ( CRD42016049176 ).NIHR SPC
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