Evans, Laura

OBJECTIVES: This study aimed to establish a set of guiding principles for data sharing and harmonization in critical care, focusing on the use of real-world data (RWD) and real-world evidence (RWE) to improve patient outcomes and research efficacy. The principles were developed through a systematic literature review and a modified Delphi process, with the goal of enhancing data accessibility, standardization, and interoperability across critical care settings. DATA SOURCES: Data sources included a comprehensive search of peer-reviewed literature, specifically studies related to the use of RWD and RWE in healthcare, guidelines, best practices, and recommendations on data sharing and harmonization. A total of 8150 articles were initially identified through databases such as MEDLINE and Web of Science, with 257 studies meeting inclusion criteria. STUDY SELECTION: Inclusion criteria focused on publications discussing health-related informatics, recommendations for RWD/RWE usage, data sharing, and harmonization principles. Exclusion criteria ruled out non-human studies, case studies, conference abstracts, and articles published before 2013, as well as those not available in English. DATA EXTRACTION: From the 257 selected studies, 322 statements were extracted. After removing irrelevant definitions and off-topic content, 232 statements underwent content validation and thematic analysis. These statements were then consolidated into 24 candidate guiding principles after rigorous review and consensus-building among the expert panel. DATA SYNTHESIS: A three-phase modified Delphi process was employed, involving a conceptualization group, a review group, and a Delphi group. In phase 1, experts identified key themes and search terms for the systematic review. Phase 2 involved validating and refining the prospective guiding principles, while phase 3 employed a Delphi panel to rate principles on acceptability, importance, and feasibility. This process resulted in 24 guiding principles, with high consensus achieved in rounds 2 and 3 on their relevance and applicability. CONCLUSIONS: The systematic review and Delphi process resulted in 24 guiding principles to improve data sharing and harmonization in critical care. These principles address challenges across the data lifecycle, including generation, storage, access, and usage of RWD and RWE. This framework is designed to promote more effective and equitable data practices, with relevance for the development of artificial intelligence-based decision support tools and clinical research. The principles are intended to guide the responsible use of data science in critical care, with emphasis on ethics and equity, while acknowledging the variability of resources across settings.

Abstract BackgroundOverexpression of c-Myc is required for the progression of pre-malignant plasma cells in monoclonal gammopathy of undetermined significance (MGUS) to malignant plasma cells in multiple myeloma (MM). c-Myc also increases glutamine anaplerosis into the tricarboxylic acid (TCA) cycle within cancer cells. Whether increased glutamine anaplerosis is associated with the progression of pre-malignant to malignant plasma cells is unknown.MethodsHuman volunteers (N = 7) and patients with MGUS (N = 11) and MM (N = 12) were prospectively recruited to undergo an intravenous infusion of 13C-labelled glutamine followed by a bone marrow aspiration to obtain bone marrow cells and plasma.ResultsDespite notable heterogeneity, stable isotope resolved metabolomics (SIRM) revealed that the mean 13C-labelled glutamine anaplerosis into the TCA cycle was higher in malignant compared to pre-malignant bone marrow plasma cells relative to the remainder of their paired bone marrow mononuclear cells. RNA sequencing demonstrated a higher relative mRNA expression of c-Myc and glutamine transporters such as ASCT2 and SN2 in malignant compared to pre-malignant bone marrow plasma cells. Finally, higher quantitative levels of TCA cycle intermediates in the bone marrow plasma differentiated MM from MGUS patients.ConclusionMeasurement of the in vivo activity of glutamine anaplerosis into the TCA cycle provides novel insight into the metabolic changes associated with the transformation of pre-malignant plasma cells in MGUS to malignant plasma cells in MM.

Abstract The objective of this study is to compare the cyclic loading strength and ultimate failure load in suture anchor repair versus transosseous tunnel repair of patellar tendons using a cadaver model. Twelve cadaveric patella specimens were used (six matched pairs). Dual-energy X-ray absorptiometry (DXA) measurements were performed to ensure equal bone quality among groups. All right knees were assigned to the suture anchor repair group (n = 6), whereas all left knees were assigned to the transosseous bone tunnel group (n = 6). Suture type and repair configuration were equivalent. After the respective procedures were performed, each patella was mounted into a gripping jig. Tensile load was applied at a rate of 1 Hz between magnitudes of 50 and 150 N, 50 and 200 N, 50 and 250 N, and tensile load at a rate of 0.1 mm/s until failure. Failure was defined as a sharp deviation in the linear load versus displacement curve, and failure mode was recorded. DXA measurements demonstrated equivalence of bone quality between the two groups (p > 0.05). During cyclic load testing, there was only a statistically significant difference between the groups with regard to cyclic loading at the 50 to 200 N loading cycle (p = 0.010). There was no statistically significant difference between the groups with regard to ultimate load to failure (p = 0.43). Failure mode within the suture anchor cohort occurred through anchor pullout except for one, which failed through the tendon. All specimens within the transosseous cohort failed through the midsubstance of the tendon except for one, which failed through suture breakage. Suture anchor repair demonstrated a similar biomechanical profile regarding cyclic loading and ultimate load to failure when compared with “gold standard” transosseous tunnel patellar tendon repair with a trend toward less gapping in the suture anchor group. Using suture anchors for repair of the patella tendon has similar biomechanical properties to transpatellar tunnels but may provide other clinical advantages.