Research Spotlight

Douglas Lawson, T., K. M. Tecson, C. N. Shaver, S. A. Barnes and S. Kavli (2018). “The impact of informal leader nurses on patient satisfaction.” J Nurs Manag Jul 11. [Epub ahead of print].

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BACKGROUND: The relationship between informal leaders, i.e., highly competent individuals who have influence over peers without holding formal leadership positions, and organisational outcomes has not been adequately assessed in health care. AIMS: We evaluated the relationships between informal leaders and experience, job satisfaction and patient satisfaction, among hospital nurses. METHODS: Floor nurses in non-leadership positions participated in an online survey and rated colleagues’ leadership behaviours. Nurses identified as informal leaders took an additional survey to determine their leadership styles via the Multifactor Leadership Questionnaire(TM) . Six months of patient satisfaction data were linked to the nursing units. RESULTS: A total of 3,456 (91%) nurses received peer ratings and 628 (18%) were identified as informal leaders. Informal leaders had more experience (13.2 +/- 10.9 vs. 8.4 +/- 9.7 years, p < 0.001) and higher job satisfaction than their counterparts (4.8 +/- 1.2 vs. 4.5 +/- 1.1, p = 0.007). Neither the proportion of informal leaders on a unit nor leadership style was associated with patient satisfaction (p = 0.53, 0.46, respectively). CONCLUSION: While significant relationships were not detected between patient satisfaction and styles/proportion of informal leaders, we found that informal leaders had more years of experience and higher job satisfaction. More work is needed to understand the informal leaders' roles in achieving organisational outcomes. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse informal leaders are unique resources and health care organisations should utilise them for optimal outcomes.

Dellon, E. S., C. A. Liacouras, J. Molina-Infante, G. T. Furuta, J. M. Spergel, N. Zevit, S. J. Spechler . . . and A. J. Bredenoord (2018). “Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference.” Gastroenterology Jul 12. [Epub ahead of print].

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BACKGROUND AND AIMS: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE in order to develop updated international consensus criteria for EoE diagnosis. METHODS: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries utilized on-line communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences. RESULTS: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement. CONCLUSIONS: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm(2)) on esophageal biopsy, and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.

Chen, S., R. A. Bastarrachea, J. S. Shen, A. Laviada-Nagel, E. Rodriguez-Ayala, E. J. Nava-Gonzalez, P. Huang, R. A. DeFronzo, J. W. Kent, Jr. and P. A. Grayburn (2018). “Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy.” Gene Ther Aug 2. [Epub ahead of print].

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Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent. Our main findings were a robust cellular presence of mUCP-1 immunostaining (IHC), significantly higher expression levels of mUCP-1 measured by qRT-PCR, and highest temperature elevation measured by infrared thermography in the treated thigh, achieved in rats after delivering the UTMD-PRDM16/PGC-1a/BMP7/hyPB gene cocktail. Interestingly, the weight loss obtained in the treated rats with the triple gene delivery, never recovered the levels observed in the controls in spite of food intake recovery. Our results establish the feasibility of minimally invasive UTMD gene-based therapy administration in SKM, to induce overexpression of ectopic mUCP-1 after delivery of the thermogenic BAT gene program, and describe systemic effects of this intervention on food intake, weight loss, and thermogenesis.

Chaudhry, R. I., R. O. Mathew, M. S. Sidhu, P. Sidhu-Adler, R. Lyubarova, J. Rangaswami, L. Salman, A. Asif, J. L. Fleg, P. A. McCullough, F. Maddux and S. Bangalore (2018). “Detection of Atherosclerotic Cardiovascular Disease in Patients with Advanced Chronic Kidney Disease in the Cardiology and Nephrology Communities.” Cardiorenal Med 8(4): 285-295.

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BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality among patients with chronic kidney disease (CKD) with a glomerular filtration rate of < 60 mL/min/1.73 m2 body surface area. The availability of high-quality randomized controlled trial data to guide management for the population with CKD and ASCVD is limited. Understanding current practice patterns among providers caring for individuals with CKD and CVD is important in guiding future trial questions. METHODS: A qualitative survey study was performed. An electronic survey regarding the diagnosis and management of CVD in patients with CKD was conducted using a convenience sample of 450 practicing nephrology and cardiology providers. The survey was administered using Qualtrics(R) (https://www.qualtrics.com). RESULTS: There were a total of 113 responses, 81 of which were complete responses. More than 90% of the respondents acknowledged the importance of CVD as a cause of morbidity and mortality in patients with CKD. Outside the kidney transplant evaluation setting, 5% of the respondents would screen an asymptomatic patient with advanced CKD for ASCVD. Outside the kidney transplant evaluation scenario, the respondents did not opt for invasive management strategies in advanced CKD. CONCLUSIONS: The survey results reveal a lack of consensus among providers caring for patients with advanced CKD about the management of ASCVD in this setting. Future randomized controlled trials will be needed to better inform the clinical management of ASCVD in these patients. The limitations of the study include its small sample size and the relatively low response rate among the respondents.

Roy, R., R. Kandimalla, F. Sonohara, M. Koike, Y. Kodera, N. Takahashi, Y. Yamada and A. Goel (2018). “A comprehensive methylation signature identifies lymph node metastasis in esophageal squamous cell carcinoma.” Int J Cancer Jul 14. [Epub ahead of print].

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Treatment modalities in esophageal squamous cell carcinoma (ESCC) depend largely on lymph node metastasis (LNM) status. With sub-optimal detection sensitivity of existing imaging techniques, we propose a methylation signature which identifies patients with LNM with greater accuracy. This would allow precise stratification of high-risk patients requiring more aggressive treatment from low-risk ESCC patients who can forego radical surgery. An unbiased genome-wide methylation signature for LNM detection was established from an initial in-silico discovery phase. The signature was tested in independent clinical cohorts comprising 249 ESCC patients. The prognostic potential of the methylation signature was compared to clinical variables including LNM status. A 10-probe LNM associated signature (LNAS) was developed using stringent bioinformatics analyses. The area under the curve values for LNAS risk scores were 0.81 and 0.88 in training and validation cohorts respectively in association with lymphatic vessel invasion and tumor stage. High LNAS risk-score was also associated with worse overall survival [HR (95% CI) 3 (1.8 to 4.8), p < 0.0001 training and 3.9 (1.5 to 10.2), p = 0.001 validation cohort]. In conclusion, our novel methylation signature is a powerful biomarker that identifies LNM status robustly and is also associated with worse prognosis in ESCC patients.