Baylor Research Institute

Cooper-DeHoff, R. M., V. Fontil, T. Carton, A. M. Chamberlain, J. Todd, E. C. O’Brien, K. M. Shaw, M. Smith, S. Choi, E. K. Nilles, D. Ford, K. M. Tecson, P. E. Dennar, F. Ahmad, S. Wu, J. C. McClay, K. Azar, R. Singh, M. Faulkner Modrow, C. M. Shay, M. Rakotz, G. Wozniak and M. J. Pletcher (2021). “Tracking Blood Pressure Control Performance and Process Metrics in 25 US Health Systems: The PCORnet Blood Pressure Control Laboratory.” J Am Heart Assoc 10(21): e022224.

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Background The National Patient-Centered Clinical Research Network Blood Pressure Control Laboratory Surveillance System was established to identify opportunities for blood pressure (BP) control improvement and to provide a mechanism for tracking improvement longitudinally. Methods and Results We conducted a serial cross-sectional study with queries against standardized electronic health record data in the National Patient-Centered Clinical Research Network (PCORnet) common data model returned by 25 participating US health systems. Queries produced BP control metrics for adults with well-documented hypertension and a recent encounter at the health system for a series of 1-year measurement periods for each quarter of available data from January 2017 to March 2020. Aggregate weighted results are presented overall and by race and ethnicity. The most recent measurement period includes data from 1 737 995 patients, and 11 956 509 patient-years were included in the trend analysis. Overall, 15% were Black, 52% women, and 28% had diabetes. BP control (<140/90 mm Hg) was observed in 62% (range, 44%-74%) but varied by race and ethnicity, with the lowest BP control among Black patients at 57% (odds ratio, 0.79; 95% CI, 0.66-0.94). A new class of antihypertensive medication (medication intensification) was prescribed in just 12% (range, 0.6%-25%) of patient visits where BP was uncontrolled. However, when medication intensification occurred, there was a large decrease in systolic BP (≈15 mm Hg; range, 5-18 mm Hg). Conclusions Major opportunities exist for improving BP control and reducing disparities, especially through consistent medication intensification when BP is uncontrolled. These data demonstrate substantial room for improvement and opportunities to close health equity gaps.

Shimura, T., R. Kandimalla, Y. Okugawa, M. Ohi, Y. Toiyama, C. He and A. Goel (2021). “Novel evidence for m(6)A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.” Br J Cancer.

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BACKGROUND: While emerging evidence indicates that N(6)-methyladenosine (m(6)A) regulators play crucial roles in cancer progression, their clinical significance in gastric cancer (GC) has thus far not been elucidated. METHODS: We investigated the expression of the m(6)A regulator genes and their prognostic potential in a large clinical cohort of 173 GC patients using qRT-PCR assays. In addition, we undertook a series of in-vitro and in-vivo functional studies to investigate the oncogenic role of FTO. RESULTS: GC patients with low expression of METTL3, METTL14, ALKBH5, WTAP and YTHDF1 demonstrated significantly poor OS, while patients with high FTO expression exhibited markedly worse OS. Furthermore, the cumulative risk-score derived from these gene panel also significantly associated with poor OS, with a corresponding hazard ratio of 5.47 (95% CI: 3.18-9.41, p < 0.0001). We observed that FTO expression was frequently upregulated in GC cell lines, with epithelial-mesenchymal-transition (EMT) features. FTO knockdown in HGC27 and AGS cells inhibited cell proliferation and migratory potential, while its overexpression in MKN28 cells resulted in enhanced proliferation and migration. Finally, confirming our in-vitro findings, FTO suppression led to significant tumour growth inhibition in a HGC27 xenograft model. CONCLUSIONS: We demonstrate that m(6)A regulators may serve as promising prognostic biomarkers in GC. Our functional studies reveal that FTO is an important oncogene and may be a promising therapeutic target associated with EMT-alterations in gastric cancer.

Shimura, T., S. Toden, R. Kandimalla, Y. Toiyama, Y. Okugawa, M. Kanda, H. Baba, Y. Kodera, M. Kusunoki and A. Goel (2021). “Genomewide Expression Profiling Identifies a Novel miRNA-based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer.” Ann Surg 274(5): e425-e434.

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OBJECTIVE: This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC). SUMMARY BACKGROUND DATA: Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis. METHODS: We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC. RESULTS: Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann’s type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively). CONCLUSIONS: We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.

Cengiz, A., L. H. Yoder and V. Danesh (2021). “A Concept Analysis of Role Ambiguity Experienced by Hospital Nurses Providing Bedside Nursing Care.” Nurs Health Sci Oct 24. [Epub ahead of print].

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The concept of role ambiguity, despite its wide application in nursing research, lacks a clear definition and conceptualization, resulting in inconsistencies about how it is defined, operationalized, and applied in research. The purpose of this paper was to analyze and define the concept of role ambiguity among hospital nurses providing nursing care using the concept analysis method developed by Walker and Avant. The three defining attributes of role ambiguity were lack of information (information deficiency), lack of clarity, and unpredictability. Antecedents included lack of clear role definitions, lack of education/training, communication problems, supervisory behaviors and support, organizational culture, practice environment conditions, experience, group cohesiveness, and preferred work setting. The consequences of role ambiguity included increased stress, lack of organizational commitment, job dissatisfaction, burnout, and increased intent to leave. This concept analysis provides a clear conceptual definition to better understand role ambiguity among hospital nurses along with implications for nurse leaders, educators, clinicians, and researchers to support nurses and guide future research. This paper further emphasizes the importance of nurse-manager relationships in reducing experience of role ambiguity among nurses in hospitals.

Jeffery, A. D., J. A. Werthman, V. Danesh, M. S. Dietrich, L. C. Mion and L. M. Boehm (2021). “Assess, Prevent, and Manage Pain; Both Spontaneous Awakening and Breathing Trials; Choice of Analgesia/Sedation; Delirium: Assess, Prevent, and Manage; Early Mobility; Family Engagement and Empowerment Bundle Implementation: Quantifying the Association of Access to Bundle-Enhancing Supplies and Equipment.” Crit Care Explor 3(9): e0525.

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Describe the physical environment factors (i.e., availability, accessibility) of bundle-enhancing items and the association of physical environment with bundle adherence. DESIGN: This multicenter, exploratory, cross-sectional study used data from two ICU-based randomized controlled trials that measured daily bundle adherence. Unit- and patient-level data collection occurred between 2011 and 2016. We developed hierarchical logistic regression models using Frequentist and Bayesian frameworks. SETTING: The study included 10 medical and surgical ICUs in six academic medical centers in the United States. PATIENTS: Adults with qualifying respiratory failure and/or septic shock (e.g., mechanical ventilation, vasopressor use) were included in the randomized controlled trials. INTERVENTIONS: The Awakening and Breathing trial Coordination, Delirium assessment/management, Early mobility bundle was recommended standard of care for randomized controlled trial patients and adherence tracked daily. MEASUREMENTS AND MAIN RESULTS: The primary outcome was adherence to the full bundle and the early mobility bundle component as identified from daily adherence documentation (n = 751 patient observations). Models included unit-level measures such as minimum and maximum distances to bundle-enhancing items and patient-level age, body mass index, and daily mechanical ventilation status. Some models suggested the following variables were influential: unit size (larger associated with decreased adherence), a standard walker (presence associated with increased adherence), and age (older associated with decreased adherence). In all cases, mechanical ventilation was associated with decreased bundle adherence. CONCLUSIONS: Both unit- and patient-level factors were associated with full bundle and early mobility adherence. There is potential benefit of physical proximity to essential items for Awakening and Breathing trial Coordination, Delirium assessment/management, Early mobility bundle and early mobility adherence. Future studies with larger sample sizes should explore how equipment location and availability influence practice.