88 research outputs found
Defects in swift heavy ion irradiated n-4H-SiC
Please read abstract in the article.http://www.elsevier.com/locate/nimb2020-12-01hj2020Physic
Clinical Practice Audit on the Management of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis in the Netherlands
Introduction: Managing complex and rare systemic autoimmune diseases such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) can be challenging and is often accompanied by undesirable variations in clinical practice. Adequate understanding of clinical practice can help identify essential issues to improve the care for AAV patients. Therefore, we studied the real-life management and outcomes of AAV patients in the Netherlands. Methods: In this cohort study, we investigated clinical practice in university and nonuniversity teaching hospitals with respect to patients with a clinical diagnosis of AAV. We retrospectively collected clinical data encompassing clinical variables, medication details, and outcome parameters. Results: Data of 230 AAV patients were collected in 9 Dutch hospitals. Of these, 167 patients (73%) were diagnosed with granulomatosis with polyangiitis, 54 (24%) with microscopic polyangiitis and 9 (4%) with eosinophilic granulomatosis with polyangiitis. One hundred sixty-six patients (72%) had generalized disease. The median year of diagnosis was 2013 (range 1987–2018). Besides steroids, oral cyclophosphamide was the most used drug (50%) for induction therapy and azathioprine (68%) for maintenance therapy. Adverse outcomes were major infections in 35%, major relapses in 23%, malignancy in 10%, major cardiovascular events in 8%, and end-stage renal disease in 7%. Conclusion: Oral cyclophosphamide was the most frequently used induction therapy, azathioprine for maintenance therapy; over time, the use of rituximab is increasingly employed. Major infection and relapses are the most prevalent adverse outcomes. This audit resulted in important indicators for treatment of AAV patients that can be implemented for future, national audits to improve the outcomes of AAV patients
Evaluating the Effectiveness and Cost-Effectiveness of Seizure Dogs in Persons With Medically Refractory Epilepsy in the Netherlands
__Background:__ Epilepsy is associated with a high disease burden, impacting the lives of
people with epilepsy and their caregivers and family. Persons with medically refractory
epilepsy experience the greatest burden, suffering from profound physical, psychological,
and social consequences. Anecdotal evidence suggests these persons may benefit
from a seizure dog. As the training of a seizure dog is a substantial investment,
their accessibility is limited in the absence of collective reimbursement as is seen
in the Netherlands. Despite sustained interest in seizure dogs, scientific knowledge
on their benefits and costs remains scarce. To substantiate reimbursement decisions
stronger evidence is required. The EPISODE study aims to provide this evidence
by evaluating the effectiveness and cost-effectiveness of seizure dogs in adults with
medically refractory epilepsy.
__Methods:__ The study is designed as a stepped wedge randomized controlled trial that
compares the use of seizure dogs in addition to usual care, with usual care alone. The
study includes adults with epilepsy for whom current treatment options failed to achieve
seizure freedom. Seizure frequency of participants should be at least two seizures per
week, and the seizures should be associated with a high risk of injury or dysfunction.
During the 3 year follow-up period, participants receive a seizure dog in a randomized
order. Outcome measures are taken at multiple time points both before and after receiving
the seizure dog. Seizure frequency is the primary outcome of the study and will be
recorded continuously using a seizure diary. Questionnaires measuring seizure severity,
quality of life, well-being, resource use, productivity, social participation, and caregiver
burden will be completed at baseline and every 3 months thereafter. The study is
designed to include a minimum of 25 participants.
__Discussion:__ This protocol describes the first randomized controlled trial on seizure
dogs. The study will provide comprehensive data on the effectiveness and cost effectiveness
of seizure dogs in adults with medically refractory epilepsy. Broader benefits
of seizure dogs for persons with epilepsy and their caregivers are taken into account,
as well as the welfare of the dogs. The findings of the study can be used to inform
decision-makers on the reimbursement of seizure dogs
Diagnostic accuracy of consensus diagnostic criteria for frontotemporal dementia in a memory clinic population
Background/Aims: The goal of the present study was to evaluate the diagnostic accuracy of the core diagnostic criteria for frontotemporal dementia (FTD) [Neary D, et al: Neurology 1998;51:1546-1554] within a memory clinic population. Methods: The 5 core diagnostic criteria for FTD were operationalised in an informant-based written questionnaire. For a diagnosis of FTD the total clinical picture was weighted with findings on additional investigations and possible exclusion criteria, with follow-up of at least 1 year. Results: The operationalised core criteria for FTD had a sensitivity of 79% (95% CI = 57-92) and a specificity of 90% (95% CI = 85-94). Conclusion: The core diagnostic criteria for FTD applied in a caregiver questionnaire have good diagnostic accuracy among subjects without advanced dementia attending a memory clinic. This stresses the importance of the informant-based history in the differential diagnosis of dementia. Copyrigh
Using conversation analysis to explore feedback on resident performance
Feedback on clinical performance of residents is seen as a fundamental element in postgraduate medical education. Although literature on feedback in medical education is abundant, many supervisors struggle with providing this feedback and residents experience
feedback as insufciently constructive. With a detailed analysis of real-world feedback conversations, this study aims to contribute to the current literature by deepening the understanding of how feedback on residents’ performance is provided, and to formulate recommendations for improvement of feedback practice. Eight evaluation meetings between
program directors and residents were recorded in 2015–2016. These meetings were analyzed using conversation analysis. This is an ethno-methodological approach that uses a
data-driven, iterative procedure to uncover interactional patterns that structure naturally
occurring, spoken interaction. Feedback in our data took two forms: feedback as a unidirectional activity and feedback as a dialogic activity. The unidirectional feedback activities prevailed over the dialogic activities. The two diferent formats elicit diferent types of
resident responses and have diferent implications for the progress of the interaction. Both
feedback format
A de novo substitution in BCL11B leads to loss of interaction with transcriptional complexes and craniosynostosis
Craniosynostosis, the premature ossification of cranial sutures, is a developmental disorder of the skull vault, occurring in approximately 1 in 2250 births. The causes are heterogeneous, with a monogenic basis identified in ~25% of patients. Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis. BCL11B is a transcription factor that interacts directly with the nucleosome remodelling and deacetylation complex (NuRD) and polycomb-related complex 2 (PRC2) through the invariant proteins RBBP4 and RBBP7. The p.R3S substitution occurs within a conserved amino-terminal motif (RRKQxxP) of BCL11B and reduces interaction with both transcriptional complexes. Equilibrium binding studies and molecular dynamics simulations show that the p.R3S substitution disrupts ionic coordination between BCL11B and the RBBP4-MTA1 complex, a subassembly of the NuRD complex, and increases the conformational flexibility of Arg-4, Lys-5 and Gln-6 of BCL11B. These alterations collectively reduce the affinity of BCL11B p.R3S for the RBBP4-MTA1 complex by nearly an order of magnitude. We generated a mouse model of the BCL11B p.R3S substitution using a CRISPR-Cas9-based approach, and we report herein that these mice exhibit craniosynostosis of the coronal suture, as well as other cranial sutures. This finding provides strong evidence that the BCL11B p.R3S substitution is causally associated with craniosynostosis and confirms an important role for BCL11B in the maintenance of cranial suture patency
Design and evaluation of a clinical competency committee
Introduction In postgraduate medical education, group decision-making has emerged as an essential too
Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients
Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with complex karyotype (CK) (46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity (0-2, 3- 4 and ¿5 abnormalities) was also analyzed. No significant differences in the percentage of patients in each group were detected, but only a moderate agreement was observed between methods when focusing on individual cases (kappa=0.507; P<0.001). Discordant classification was obtained in 100 patients (29.4%), including 3% classified in opposite risk groups. Most discrepancies were technique-dependent and no greater correlation in the number of abnormalities was achieved when different filtering strategies were applied for GM. Nonetheless, both methods showed a similar concordance index for prediction of time to first treatment (TTFT) (CBA: 0.67 vs. GM: 0.65) and overall survival (CBA: 0.55 vs. GM: 0.57)
TP53 abnormalities are underlying the poor outcome associated with chromothripsis in chronic lymphocytic leukemia patients with complex karyotype
Simple Summary Chromothripsis, a genomic event that generates massive chromosomal rearrangements, has been described in 1-3% of CLL patients and is associated with poor prognostic factors (e.g., TP53 abnormalities and genomic complexity). However, previous studies have not assessed its role in CLL patients with complex karyotypes. Herein, we aimed to describe the genetic characteristics of 33 CLL patients with high genomic complexity and chromothripsis. Moreover, we analyzed the clinical impact of chromothripsis, comparing these patients against a cohort of 129 patients with complex karyotypes not presenting this catastrophic event. Nine cases were also assessed via the novel cytogenomic methodology known as optical genome mapping. We confirmed that this phenomenon is heterogeneous and associated with a shorter time to first treatment. Nonetheless, our findings suggested that TP53 abnormalities, rather than chromothripsis itself, underlie the dismal outcome.
Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes. Nine cth cases were analyzed using optical genome mapping (OGM). Patterns detected by genomic ..
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