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  • Ovid Technologies (Wolters Kluwer Health)  (5)
  • 1
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 145, No. 5 ( 2022-02), p. 357-370
    Abstract: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 2
    In: Journal of Trauma and Acute Care Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 92, No. 2 ( 2022-2), p. 398-406
    Abstract: The National Academies of Sciences, Engineering, and Medicine 2016 trauma system report recommended a National Trauma Research Action Plan to strengthen and guide future trauma research. To address this recommendation, 11 expert panels completed a Delphi survey process to create a comprehensive research agenda, spanning the continuum of trauma care. We describe the gap analysis and high-priority research questions generated from the National Trauma Research Action Plan panel on prehospital and mass casualty trauma care. METHODS We recruited interdisciplinary national experts to identify gaps in the prehospital and mass casualty trauma evidence base and generate prioritized research questions using a consensus-driven Delphi survey approach. We included military and civilian representatives. Panelists were encouraged to use the Patient/Population, Intervention, Compare/Control, and Outcome format to generate research questions. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the questions on a 9-point Likert scale to low-, medium-, and high-priority items. We defined consensus as ≥60% agreement on the priority category and coded research questions using a taxonomy of 118 research concepts in 9 categories. RESULTS Thirty-one interdisciplinary subject matter experts generated 490 research questions, of which 433 (88%) reached consensus on priority. The rankings of the 433 questions were as follows: 81 (19%) high priority, 339 (78%) medium priority, and 13 (3%) low priority. Among the 81 high-priority questions, there were 46 taxonomy concepts, including health systems of care (36 questions), interventional clinical trials and comparative effectiveness (32 questions), mortality as an outcome (30 questions), prehospital time/transport mode/level of responder (24 questions), system benchmarks (17 questions), and fluid/blood product resuscitation (17 questions). CONCLUSION This Delphi gap analysis of prehospital and mass casualty care identified 81 high-priority research questions to guide investigators and funding agencies for future trauma research.
    Type of Medium: Online Resource
    ISSN: 2163-0763 , 2163-0755
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2651313-4
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  • 3
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_2 ( 2021-11-16)
    Abstract: Objective: Compared with traditional out-of-hospital cardiac arrest (OHCA) trial outcomes such as hospital survival, alternative outcomes such as intensive care unit-free (IFD) and ventilator-free days (VFD) have potential advantages including requiring smaller sample sizes to detect significant differences. Few studies have evaluated these outcomes in OHCA. We sought to evaluate the utility and validity of IFD and VFD as candidate outcomes for OHCA trials. Methods: We analyzed data from the Pragmatic Airway Resuscitation Trial (PART), which tested laryngeal tube (LT) vs. endotracheal intubation (ETI) airway strategies in adult OHCA. We defined IFD as the number of days alive and permanently out of ICU during the first 30 days after the OHCA event. We examined IFD distribution and correlation with Modified Rankin Scale (MRS). To test associations with trial interventions, we applied a range of analytic strategies, including modeling IFD as continuous (Generalized Estimating Equations - GEE), non-parametric (Wilcoxon Rank-Sum test - WRS) and count (zero-inflated negative binomial regression - ZINB) data. We also modeled time-to-ICU discharge using a survival model with death as a competing risk. We repeated the analysis assessing VFD. Results: IFD was available for 2,898 of 3,004 patients. IFD was skewed and J-shaped; 91% IFD=0 and 5.3% IFD≥22. Mean (±SD) IFD was 2.0±6.6 days; 21.2±7.5 days for survivors. IFD varied by intervention (LT 2.4±7.2, ETI 1.6±5.8 days). IFD and VFD strongly correlated with MRS (ρ= -0.88, -0.89). LT was associated with increased IFD using GEE, WRS, and ZINB, but not competing risks model. (Table) LT was associated with increased VFD using GEE and WRS, but not ZINB or competing risks models. Conclusion: IFD and VFD differentiated OHCA interventions, suggesting their utility. IFD and VFD were highly correlated with MRS, suggesting validity. IFD and VFD have important features that may influence OHCA trial design.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
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  • 4
    In: Pharmacogenetics and Genomics, Ovid Technologies (Wolters Kluwer Health), Vol. 26, No. 5 ( 2016-05), p. 235-242
    Type of Medium: Online Resource
    ISSN: 1744-6872
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2048376-4
    SSG: 15,3
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  • 5
    In: Anesthesia & Analgesia, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. 5 ( 2020-05), p. 1425-1434
    Abstract: Surgical safety has advanced rapidly with evidence of improved patient outcomes through structural and process interventions. However, knowledge of how to apply these interventions successfully and sustainably at scale is often lacking. The 2019 Global Ministerial Patient Safety Summit called for a focus on implementation strategies to maintain momentum in patient safety improvements, especially in low- and middle-income settings. This study uses an implementation framework, knowledge to action, to examine a model of nationwide World Health Organization (WHO) Surgical Safety Checklist implementation in Cameroon. Cameroon is a lower-middle-income country, and based on data from high- and low-income countries, we hypothesized that more than 50% of participants would be using the checklist (penetration) in the correct manner (fidelity) 4 months postintervention. METHODS: A collaboration of 3 stakeholders (Ministry of Health, academic institution, and nongovernmental organization) used a prospective observational design. Based on knowledge to action, there were 3 phases to the study implementation: problem identification (lack of routine checklist use in Cameroonian hospitals), multifaceted implementation strategy (3-day multidisciplinary training course, coaching, facilitated leadership engagement, and support networks), and outcome evaluation 4 months postintervention. Validated implementation outcomes were assessed. Primary outcomes were checklist use (penetration) and fidelity; secondary outcomes were perioperative teams’ reactions, learning and behavior change; and tertiary outcomes were perioperative teams’ acceptability of the checklist. RESULTS: Three hundred and fifty-one operating room staff members from 25 hospitals received training. Median time to evaluation was 4.5 months (interquartile range [IQR]: 4.5–5.5, range 3–7); checklist use (penetration) increased from 20% (95% confidence interval [CI] , 16–25) to 56% (95% CI, 49–63); fidelity for adherence to 6 basic safety processes was high: verification of patient identification was 91% (95% CI, 87–95); risk assessment for difficult intubation was 79% (95% CI, 73–85): risk assessment for blood loss was 88% (95% CI, 83–93) use of pulse oximetry was 93% (95% CI, 90–97); antibiotic administration was 95% (95% CI, 91–98); surgical counting was 89% (95% CI, 84–93); and fidelity for nontechnical skills measured by the WHO Behaviorally Anchored Rating Scale was 4.5 of 7 (95% CI, 3.5–5.4). Median scores for all secondary outcomes were 10/10, and 7 acceptability measures were consistently more than 70%. CONCLUSIONS: This study shows that a multifaceted implementation strategy is associated with successful checklist implementation in a lower-middle-income country such as Cameroon, and suggests that a theoretical framework can be used to practically drive nationwide scale-up of checklist use.
    Type of Medium: Online Resource
    ISSN: 0003-2999
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2018275-2
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