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Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
The Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic. Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways (MPs) proved successful in treating MDD. It is possible that examining polygenicity within specific MPs implicated in MDD can further refine molecular drug targets.
Using a large case–control GWAS based on low-coverage whole genome sequencing (N = 10 640) in Han Chinese women, we derived polygenic risk scores (PRS) for MDD and for MDD specific to each of over 300 MPs previously shown to be relevant to psychiatric diagnoses. We then identified sets of PRSs, accounting for critical covariates, significantly predictive of case status.
Over and above global MDD polygenic risk, polygenic risk within the GO: 0017144 drug metabolism pathway significantly predicted recurrent depression after multiple testing correction. Secondary transcriptomic analysis suggests that among genes in this pathway, CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1) might be most relevant to MDD. Within the cases, pathway-based risk was additionally associated with age at onset of MDD.
Results indicate that pathway-based risk might inform etiology of recurrent major depression. Future research should examine whether polygenicity of the drug metabolism gene pathway has any association with clinical presentation or treatment response. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
Contemporary ice stream flow is directly linked to conditions at the ice/bed interface, yet this environment is logistically difficult to access. Instead, we investigate subglacial processes important for ice stream flow by studying tills on the deglaciated Antarctic continental shelf. We test currently-accepted hypotheses surrounding subglacial processes and till properties with a Ross Sea dataset. Till shear strengths indicate a continuum of simultaneous processes acting at the bed, rather than discrete ‘deformation’ and ‘lodgement’ end-members. We identify a threshold water content representing saturated pore spaces, leading to basal sliding and meltwater channelization. Based on observations of till properties relative to glacial landforms, we challenge the assumption that low shear strength is linked to intense deformation. Spatial variability in landform morphology reflects variability in deforming processes at the sub-ice stream scale and suggests a maximum deforming bed thickness of 2 m at the grounding line. Regional till properties generally correlate with seafloor geology and deglacial history; the western Ross Sea is characterized by higher and more variable shear strengths and water contents, while lower-shear strength till was preserved in the Eastern Basin. These observations inform till interpretation and provide context for deforming beds beneath the modern ice sheet and on glaciated continental shelves.
Building on our earlier analysis of the factorial structure of bilingualism for young adults obtained from the Language and Social Background Questionnaire (LSBQ; Anderson, Mak, Keyvani Chahi & Bialystok, 2018), we analyzed responses from 675 children and 125 older adults to a similar questionnaire. Three factors accounting for 74% of the variance emerged in the analysis of children's responses: Adult Language in the Home, Non-English use for Media, Non-English use with Siblings. There were also three factors that explained the responses of older adults that accounted for 79% of the variance: Non-English Use, Non-English Proficiency, and English Proficiency. Therefore, bilingual experience is captured by different factors at different points in the lifespan. These results are discussed in conjunction with the earlier results from young adults and the implications for understanding bilingualism across the lifespan.