Meltonklausen5964
Our results should benefit the development of therapeutic approaches to cancer through targeting MALAT1.Comprehensive characterization of differentially spliced RNA transcripts with nanopore sequencing is limited by bioinformatics tools that are reliant on existing annotations. We have developed FLAME, a bioinformatics pipeline for alternative splicing analysis of gene-specific or transcriptome-wide long-read sequencing data. FLAME is a Python-based tool aimed at providing comprehensible quantification of full-length splice variants, reliable de novo recognition of splice sites and exons, and representation of consecutive exon connectivity in the form of a weighted adjacency matrix. Notably, this workflow circumvents issues related to inadequate reference annotations and allows for incorporation of short-read sequencing data to improve the confidence of nanopore sequencing reads. In this study, the Epstein-Barr virus long non-coding RNA RPMS1 was used to demonstrate the utility of the pipeline. RPMS1 is ubiquitously expressed in Epstein-Barr virus associated cancer and known to undergo ample differential splicing. To fully resolve the RPMS1 spliceome, we combined gene-specific nanopore sequencing reads from a primary gastric adenocarcinoma and a nasopharyngeal carcinoma cell line with matched publicly available short-read sequencing datasets. All previously reported splice variants, including putative ORFs, were detected using FLAME. In addition, 32 novel exons, including two intron retentions and a cassette exon, were discovered within the RPMS1 gene. .
Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.
We aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.
An electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. BTK activity inhibition Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.
We included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA-RR 1.69, 95% CI 1.09 to 2.62, I²-24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.
Current evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.
CRD42020216178.
CRD42020216178.Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is usually quantified by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Available therapeutic options include biological disease-modifying antirheumatic drugs (bDMARDs), which have been proven effective in suppressing inflammation in several randomised controlled trials (RCT), the gold standard for evaluating causal treatment effects. RCTs are, however, unfeasible for testing structural effects in axSpA mainly due to the low sensitivity to change of the mSASSS. The available literature therefore mainly includes observational research, which poses serious challenges to the determination of causality. Here, we review the studies testing the effect of bDMARDs on spinal radiographic progression, making use of the principles of causal inference. By exploring the assumptions of causality under counterfactual reasoning (exchangeability, positivity and consistency), we distinguish between studies that likely have reported confounded treatment effects and studies that, on the basis of their design, have more likely reported causal treatment effects. We conclude that bDMARDs might, indirectly, interfere with spinal radiographic progression in axSpA by their effect on inflammation. Innovations in imaging are expected, so that placebo-controlled trials can in the future become a reality. In the meantime, causal inference analysis using observational data may contribute to a better understanding of whether disease modification is possible in axSpA.
Internationally, patient and public involvement (PPI) is core policy for health service quality improvement (QI). However, authentic QI partnerships are not commonplace. A lack of patient and staff capability to deliver successful partnerships may be a barrier to meaningful QI collaboration.
The research questions for this scoping review were What is known regarding the capabilities required for healthcare staff and patients to effectively partner in QI at the service level?; and What is known regarding the best practice learning and development strategies required to build and support those capabilities?
A six-stage scoping review was completed. Five electronic databases were searched for publications from January 2010 to February 2020. The database searches incorporated relevant terms for the following concepts capabilities for PPI in healthcare QI; and best practice learning and development strategies to support those capabilities. Data were analysed using descriptive statistics and qualitative conteactice, and remote learning need to be expanded and evaluated.
The framework developed here could guide individualised development or learning plans for patient partners and staff, or could assist organisations to review learning topics and approaches such as training content, mentoring guidelines or community of practice agendas. Future directions include refining and evaluating the framework. Development approaches such as self-reflection, communities of practice, and remote learning need to be expanded and evaluated.
Using latent class analysis (LCA), two subphenotypes of acute respiratory distress syndrome (ARDS) have consistently been identified in five randomised controlled trials (RCTs), with distinct biological characteristics, divergent outcomes and differential treatment responses to randomised interventions. Their existence in unselected populations of ARDS remains unknown. We sought to identify subphenotypes in observational cohorts of ARDS using LCA.
LCA was independently applied to patients with ARDS from two prospective observational cohorts of patients admitted to the intensive care unit, derived from the Validating Acute Lung Injury markers for Diagnosis (VALID) (n=624) and Early Assessment of Renal and Lung Injury (EARLI) (n=335) studies. Clinical and biological data were used as class-defining variables. To test for concordance with prior ARDS subphenotypes, the performance metrics of parsimonious classifier models (interleukin 8, bicarbonate, protein C and vasopressor-use), previously developed in RCTtrix metalloproteinase-9 was significantly lower.
Previously described subphenotypes are generalisable to unselected populations of non-trauma ARDS.
Previously described subphenotypes are generalisable to unselected populations of non-trauma ARDS.
The number of gynaecological cancer survivors is increasing and there is a need for a more sustainable model of follow-up care. Today's follow-up model is time-consuming and patients have reported unmet needs regarding information about their cancer and strategies for managing the consequences of treatment. The main aim of this study is to assess health-related empowerment-in terms of patient education, psychosocial support, and promotion of physical activity-in a new follow-up model by comparing it to standard follow-up in a quasi-randomised study involving intervention hospitals and control hospitals.
At the intervention hospitals, patients will be stratified by risk of recurrence and late effects to either 1 or 3 years' follow-up. Nurses will replace doctors in half of the follow-up visits and focus in particular on patient education, self-management and physical activity. They will provide patients with information and guide them in goal setting and action planning. These measures will be reinforced by a smartphone application for monitoring symptoms and promoting physical activity. At the control hospitals, patients will be included in the standard follow-up programme. All patients will be asked to complete questionnaires at baseline and after 3, 6, 12, 24 and 36 months. Blood samples will be collected for biobanking at 3, 12 and 36 months. The primary outcome is health-related empowerment. Secondary outcomes include health-related quality of life, adherence to physical activity recommendations, time to recurrence, healthcare costs and changes in biomarkers. Changes in these outcomes will be analysed using generalised linear mixed models for repeated measures. Type of hospital (intervention or control), time (measurement point), and possible confounders will be included as fixed factors.
The study is approved by the Regional Committee for Medical Research Ethics (2019/11093). Dissemination of findings will occur at the local, national and international levels.
NCT04122235.
NCT04122235.
Early diagnosis and timely treatment are key elements of a successful healthcare system. We assessed the role of socioeconomic and cultural norms in accelerating or decelerating uptake and utilisation of health technologies into policy and practice.
Secondary and tertiary level healthcare facilities (HCFs) in three East African countries. Level of HCF was selected based on the WHO recommendation for implantation of tuberculosis (TB) molecular diagnostics.
Using implementation of TB diagnostics as a model, we purposively selected participants (TB patients, carers, survivors, healthcare practitioners, community members, opinion leaders and policy-makers) based on their role as stakeholders. In-depth interviews, key informant interviews and focus group discussions were held to collect the data between 2016 and 2018. The data were transcribed, translated, coded and analysed by thematic-content analysis.
A total of 712 individuals participated in the study. Socioeconomic and cultural factors such as povert system barriers.
Our findings show that socioeconomic and cultural factors are substantial 'roadblocks' to accelerating the uptake and utilisation of diagnostic and treatment tools. Resolving these barriers should be given equal attention as is to health system barriers.
To systematically review evidence on effectiveness of contact tracing apps (CTAs) for SARS-CoV-2 on epidemiological and clinical outcomes.
Rapid systematic review.
EMBASE (OVID), MEDLINE (PubMed), BioRxiv and MedRxiv were searched up to 28 October 2020.
Studies, both empirical and model-based, assessing effect of CTAs for SARS-CoV-2 on reproduction number (R), total number of infections, hospitalisation rate, mortality rate, and other epidemiologically and clinically relevant outcomes, were eligible for inclusion.
Empirical and model-based studies were critically appraised using separate checklists. Data on type of study (ie, empirical or model-based), sample size, (simulated) time horizon, study population, CTA type (and associated interventions), comparator and outcomes assessed, were extracted. The most important findings were extracted and narratively summarised. Specifically for model-based studies, characteristics and values of important model parameters were collected.
2140 studies were identified, of which 17 studies (2 empirical, 15 model-based studies) were eligible and included in this review.
