2,455 research outputs found

    Wiskott-Aldrich Syndrome (WAS) and Dedicator of Cytokinesis 8- (DOCK8) Deficiency

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    Both Wiskott-Aldrich syndrome (WAS) and dedicator of cytokinesis 8 (DOCK8) deficiency are primary immunodeficiency diseases caused by mutations in genes that result in defective organization of the cytoskeleton in hematopoietic tissues. They share some overlapping features such as a combined immunodeficiency, eczema and a predisposition to autoimmunity and malignancy, but also have some unique features that make them relatively easy to diagnose by clinical means. Both diseases can be cured by HSCT in a large proportion of patients. In WAS it is sometimes difficult to establish an indication for HSCT due to the large variability of disease severity, while HSCT is probably indicated in all patients affected by DOCK8 deficiency. There is considerably more published HSCT experience for WAS than for DOCK8 deficiency, but many open questions remain, which will be discussed in this review

    How well did experts and laypeople forecast the size of the COVID-19 pandemic?

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    Throughout the COVID-19 pandemic, social and traditional media have disseminated predictions from experts and nonexperts about its expected magnitude. How accurate were the predictions of 'experts'-individuals holding occupations or roles in subject-relevant fields, such as epidemiologists and statisticians-compared with those of the public? We conducted a survey in April 2020 of 140 UK experts and 2,086 UK laypersons; all were asked to make four quantitative predictions about the impact of COVID-19 by 31 Dec 2020. In addition to soliciting point estimates, we asked participants for lower and higher bounds of a range that they felt had a 75% chance of containing the true answer. Experts exhibited greater accuracy and calibration than laypersons, even when restricting the comparison to a subset of laypersons who scored in the top quartile on a numeracy test. Even so, experts substantially underestimated the ultimate extent of the pandemic, and the mean number of predictions for which the expert intervals contained the actual outcome was only 1.8 (out of 4), suggesting that experts should consider broadening the range of scenarios they consider plausible. Predictions of the public were even more inaccurate and poorly calibrated, suggesting that an important role remains for expert predictions as long as experts acknowledge their uncertainty

    Do colored cells in risk matrices affect decision-making and risk perception? Insights from randomized controlled studies

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    Risk matrices communicate the likelihood and potential impact of risks and are often used to inform decision-making around risk mitigations. The merits and demerits of risk matrices in general have been discussed extensively, yet little attention has been paid to the potential influence of color in risk matrices on their users. We draw from fuzzy-trace theory and hypothesize that when color is present, individuals are likely to place greater value on reducing risks that cross color boundaries (i.e., the boundary-crossing effect), leading to sub-optimal decision making. In two randomized controlled studies, employing forced-choice and willingness-to-pay measures to investigate the boundary-crossing effect in two different color formats for risk matrices, we find preliminary evidence to support our hypotheses that color can influence decision making. The evidence also suggests that the boundary-crossing effect is only present in, or is stronger for, higher numeracy individuals. We therefore recommend that designers should consider avoiding color in risk matrices, particularly in situations where these are likely to be used by highly numerate individuals, if the communication goal is to inform in an unbiased way

    Brief mindfulness training enhances cognitive control in socioemotional contexts: Behavioral and neural evidence.

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    In social contexts, the dynamic nature of others' emotions places unique demands on attention and emotion regulation. Mindfulness, characterized by heightened and receptive moment-to-moment attending, may be well-suited to meet these demands. In particular, mindfulness may support more effective cognitive control in social situations via efficient deployment of top-down attention. To test this, a randomized controlled study examined effects of mindfulness training (MT) on behavioral and neural (event-related potentials [ERPs]) responses during an emotional go/no-go task that tested cognitive control in the context of emotional facial expressions that tend to elicit approach or avoidance behavior. Participants (N = 66) were randomly assigned to four brief (20 min) MT sessions or to structurally equivalent book learning control sessions. Relative to the control group, MT led to improved discrimination of facial expressions, as indexed by d-prime, as well as more efficient cognitive control, as indexed by response time and accuracy, and particularly for those evidencing poorer discrimination and cognitive control at baseline. MT also produced better conflict monitoring of behavioral goal-prepotent response tendencies, as indexed by larger No-Go N200 ERP amplitudes, and particularly so for those with smaller No-Go amplitude at baseline. Overall, findings are consistent with MT's potential to enhance deployment of early top-down attention to better meet the unique cognitive and emotional demands of socioemotional contexts, particularly for those with greater opportunity for change. Findings also suggest that early top-down attention deployment could be a cognitive mechanism correspondent to the present-oriented attention commonly used to explain regulatory benefits of mindfulness more broadly

    Teaching clinicians shared decision making and risk communication online: an evaluation study

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    Objectives: To describe the development and initial evaluation of a brief e-learning course as a means of teaching shared decision making and risk communication skills to clinicians of all specialties. Design: Comparison pre-course and post-course of scores in subjective confidence and objective knowledge about shared decision making and risk communication. Setting: Online and open to all specialties and levels of clinical experience, including students. Participants: The course is freely available online and all who started the course from September 2018 to May 2020 were invited to participate in the evaluation study. Intervention: The self-guided e-learning course is made up of four modules and takes approximately 2 hours to complete. It is hosted on the website of the Winton Centre for Risk Communication and the UK’s National Health Service e-learning platform. Main outcome measures: Pre-course and post-course confidence in performing shared decision making (as measured by a 10-item scale adapted from the OPTION tool; total score range 10–50), and objective knowledge about basic principles of shared decision making and risk communication, as measured by performance on four knowledge questions and three calculations. At course commencement, a single item from the Berlin Numeracy Test, and the eight-item Subjective Numeracy Test were also asked. Results: Of 366 unique participants who consented and commenced the course, 210 completed all modules and the final post-course test. Participants’ mean age was 38.1 years, 69% were in current clinical practice and had a mean of 10.5 years of clinical practice. Numeracy was relatively low, with 50.7% correctly answering the Berlin Numeracy Test item pre-course. Participants who completed the course showed a significant improvement in their confidence by a mean summed score of 3.7 units (95% CI 2.9 to 4.6, p<0.0001) from a mean pre-course of 37.4 (SD 6.1) to post-course of 41.1 (SD 6.9). There was an increase in the proportion of correct answers for most knowledge questions (p<0.0001, p=0.013 for two directly compared), although no improvement in most skill questions that involved numbers (eg, calculating relative risks). Participants with higher numeracy appeared to show higher skill and confidence on most questions. Conclusions: This online, free e-learning course was successful in increasing participants’ confidence in, and some aspects of knowledge about, shared decision making and risk communication. It also highlighted the need for improvements in clinicians’ numerical skills as a vital part of training. We suggest that the course is used in combination with practical face-to-face experience and more intensive numerical skills training

    The adverse effects of bisphosphonates in breast cancer: A systematic review and network meta-analysis.

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    BACKGROUND: Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects. METHODS: We systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE. FINDINGS: We identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: 'flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies. CONCLUSIONS: This meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers
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