Health-related quality of life outcomes in pediatric patients with cardiac rhythm devices: a cross-sectional study with case-control comparison.

BACKGROUND: Little is known about health-related quality of life (HRQoL) in pediatric patients with cardiac rhythm devices. This study aims to compare self- and proxy-reported HRQoL in patients with pacemaker (PM) and implantable cardioverter-defibrillator (ICD) to that in sex- and age-matched healthy controls and to examine predictors for generic and disease-specific HRQoL. METHODS: The study included 72 PM and ICD patients (39% females) and 72 sex- and age-matched healthy controls from 3 to 18 years of age. HRQoL data was obtained by the PedsQL 4.0 Generic Core Scales and Pediatric Cardiac Quality of Life Inventory. Medical data was collected retrospectively from medical records. RESULTS: Patients had significantly lower self- and proxy-reported generic overall HRQoL and lower physical health than healthy controls, and ICD patients also had lower psychosocial health. On multivariate analyses, generic overall HRQoL and physical health was significantly predicted by current cardiac medication (ß = -.39, p = .02 for overall HRQoL, respectively ß = -.44, p = .006 for physical health). Disease-specific overall HRQoL was only marginally predicted by child age, device type, and the presence of a structural congenital heart disease (p < .10). CONCLUSIONS: This study shows that PM and ICD patients have lower HRQoL than healthy controls and that patients who need cardiac medication are seen by their parents at great risk for lower generic overall HRQoL. Our study also indicates a trend towards higher risk for low disease-specific HRQoL in younger patients, ICD patients, and patients with a structural congenital heart disease. Special attention should be given to these patients as they may benefit from a timely clinical evaluation in order to provide supportive interventions.

Impact of Empowering Leadership on Antimicrobial Stewardship: A Single Center Study in a Neonatal and Pediatric Intensive Care Unit and a Literature Review.

Background: Antimicrobial stewardship (AMS) is an important strategy of quality improvement for every hospital. Leadership is an important factor for implementation of quality improvement and AMS programs. Recent publications show successful AMS programs in children's hospitals, but successful implementation is often difficult to achieve and literature of AMS in neonatal and pediatric intensive care units (NICU/PICU) is scarce. Lack of resources and prescriber opposition are reported barriers. A leadership style focusing on empowering frontline staff to take responsibility is one approach to implement changes in health care institutions. Aim: Literature review regarding empowering leadership and AMS in health care and assessment of the impact of such a leadership style on AMS in a NICU/PICU over 3 years. Methods: Assessment of the impact of a leadership change September 1, 2015 from control-driven to an empowering leadership style on antibiotic use and hospital acquired infections. Prospective analysis and annual comparison of antibiotic use, rate of suspected and confirmed ventilator-associated pneumonia (VAP) and central-line associated blood stream infection (CLABSI) including antibiotic use overall, antibiotic therapy for culture-negative and culture-proven infections including correct initial choice and streamlining of antibiotics in the NICU/PICU of the Children's Hospital of Lucerne between January 1, 2015 and December 31, 2017. Results: Five articles were included in the literature review. All five studies concluded that an empowering leadership style may lead to a higher engagement of physicians. Three out of five studies reported improved AMS as reduced rate in hospital-acquired infections and improved prevention of MRSA infections. From 2015 to 2017, antibiotic days overall and antibiotic days for culture-negative situations (suspected infections and prophylaxis) per 1000 patient days declined significantly from 474.1 to 403.9 and from 418.2 to 309.4 days, respectively. Similar, the use of meropenem and vancomycin declined significantly. Over the 3 years, suspected and proven VAP- and CLABSI-episodes decreased with no confirmed episodes in 2017. Conclusion: An empowering leadership style which focuses on enabling frontline physicians to take direct responsibilities for their patients may be a successful strategy of antimicrobial stewardship allowing to overcome reported barriers of AMS implementation.

Combinatorial interactions of p53, activating protein-2, and YB-1 with a single enhancer element regulate gelatinase A expression in neoplastic cells.

Gelatinase A, also denoted matrix metalloproteinase 2, plays multiple critical roles in the neoplastic process, including facilitation of neoangiogenesis and formation of distal metastases. The transcriptional regulation of the gelatinase A gene is under the control of strong, evolutionarily conserved cis-acting enhancer elements, designated the r2 (human) or RE-1 (rat), that harbor contiguous binding motifs for the transcription factors activating protein-2 (AP2), p53, and YB-1. Using recombinant transcription factors, complex patterns of RE-1 binding were observed by electrophoretic mobility shift assay. Increased complex formation was detected with the AP2/YB-1 and AP2/p53 combinations, while YB-1 competed with p53 for binding. The combination of AP2, p53, and YB-1 yielded novel ternary complexes, particularly when binding to single-stranded RE-1 probes. Transient transfection of hepatocellular carcinoma cell lines with a series of gelatinase A luciferase reporter constructs were in accordance with the binding patterns determined by electrophoretic mobility shift assay. Combined AP2 and p53 increased gelatinase A luciferase reporter activity significantly, and the inclusion of YB-1 yielded further increase in both reporter activity and secreted levels of gelatinase A protein. YB-1 and p53 expression are increased following multiple genotoxic stresses, including irradiation, and the synergistic interactions of these induced transcription factors with the widely expressed AP2 protein provide a probable pathophysiologic mechanism for the enhanced tumor cell synthesis of gelatinase A induced by radiation.