Implementation of a Neonatal Audit Tool to Drive Quality Initiatives.

Audit tools optimize the delivery of healthcare to patients. A network of 11 neonatal intensive care units (NICUs) affiliated with a large urban pediatric care institution implemented an audit tool for use on daily patient rounds. The article reports findings collected from 2011 to 2016. METHODS: Primary drivers for implementation were (1) engagement from local providers; (2) identification of local improvement needs and improvement progress; (3) ability to customize audit questions based on local needs; (4) encouragement of information sharing between NICUs; and (5) improving measurable outcomes in neonatal care delivery. The Level IV NICU managed and refined a centralized process for managing site-specific tools, data analysis, and reporting. Each NICU customized the number and wording of action questions based on their needs. Answer choices were limited to "yes" or "no," which corresponded to favorable or unfavorable actions toward the patient. Users also answered, "Was action taken as a result of an unfavorable response?" RESULTS: Plan-Do-Study-Action cycles were completed to refine the tool and its implementation process. Adherence was variable among and within each network site. Across the network, 11.4% of actions tracked by the audit indicated improvement over time. CONCLUSION: Generalized use of the Audit Tool resulted in limited optimization of care actions addressed in the NICUs. Success depended on multi-disciplinary, multi-professional teamwork, respect for local autonomy, and leadership support. Increasing the use of the Audit Tool likely depends on the team's ability to evolve the tool's intrinsic value from a reminder to a monitoring system.

Increasing Immunization Rates in Infants with Severe Chronic Lung Disease: A Quality Improvement Initiative.

OBJECTIVES: Immunizations provide important protection from serious childhood illnesses. Infant chronic lung disease (CLD) is a serious complication of prematurity and predisposes premature infants to respiratory morbidity, rehospitalization, and mortality. This high-risk group is especially vulnerable to infections, such as invasive pneumococcal disease, influenza, and bronchiolitis. Our purpose for this project was to increase 2-, 4-, and 6-month immunization rates in eligible infants with CLD in the NICU by 30% through December 2016. METHODS: A multidisciplinary team developed weekly targeted rounds to identify eligible patients with outstanding immunizations. Exclusion criteria included the following: (1) a fraction of inspired oxygen requirement of >80%, (2) pulmonary hypertensive crisis, (3) positive blood culture results or if within 48 hours of a sepsis evaluation, (4) if within 5 days of a surgical or interventional procedure, (5) receiving steroid treatment (not including a physiologic hydrocortisone dose for adrenal insufficiency), (6) a CLD team consensus of contraindication, and (7) parental refusal. RESULTS: The project managed 60 patients from March 2016 to December 2016. Immunization of eligible patients increased from 44% to 75% and was sustained for the next 6 months. The average number of days from admission to immunization record review decreased from 71 days at baseline to 27 days. CONCLUSIONS: The implementation of (1) an in-hospital immunization record review, (2) an e-mail reminder, (3) a weekly multidisciplinary eligibility discussion, and (4) an updated rounding tool was successful in increasing and sustaining immunization rates in this population of infants with CLD. The multidisciplinary CLD meeting was a novel opportunity to discuss immunization eligibility and safety monitoring.

Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing.

Aprataxin (APTX) deficiency causes progressive cerebellar degeneration, ataxia and oculomotor apraxia in man. Cell free assays and crystal structure studies demonstrate a role for APTX in resolving 5'-adenylated nucleic acid breaks, however, APTX function in vertebrates remains unclear due to the lack of an appropriate model system. Here, we generated a murine model in which a pathogenic mutant of superoxide dismutase 1 (SOD1(G93A)) is expressed in an Aptx-/- mouse strain. We report a delayed population doubling and accelerated senescence in Aptx-/- primary mouse fibroblasts, which is not due to detectable telomere instability or cell cycle deregulation but is associated with a reduction in transcription recovery following oxidative stress. Expression of SOD1(G93A) uncovers a survival defect ex vivo in cultured cells and in vivo in tissues lacking Aptx. The surviving neurons feature numerous and deep nuclear envelope invaginations, a hallmark of cellular stress. Furthermore, they possess an elevated number of high-density nuclear regions and a concomitant increase in histone H3 K9 trimethylation, hallmarks of silenced chromatin. Finally, the accelerated cellular senescence was also observed at the organismal level as shown by down-regulation of insulin-like growth factor 1 (IGF-1), a hallmark of premature ageing. Together, this study demonstrates a protective role of Aptx in vivo and suggests that its loss results in progressive accumulation of DNA breaks in the nervous system, triggering hallmarks of premature ageing, systemically.

TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage.

Tyrosyl DNA phosphodiesterase (TDP1) is a DNA 3'-end processing enzyme that preferentially hydrolyses the bond between the 3'-end of DNA and stalled DNA topoisomerase 1. the importance of TDP1 is highlighted by its association with the human genetic disease spinocerebellar ataxia with axonal neuropathy. TDP1 comprises of a highly conserved C-terminus phosphodiesterase domain and a less conserved N-terminus tail. the importance of the N-terminus domain was suggested by its interaction with Lig3alpha. Here we show that this interaction is promoted by serine 81 that is located within a putative S/TQ site in the N-terminus domain of TDP1. Although mutation of serine 81 to alanine had no impact on TDP1 activity in vitro and had little impact on the ability of TDP1 to mediate the rapid repair of CPT- or IR-induced DNA breaks in vivo, it led to marked reduction of protein stability. Moreover, it reduced the ability of TDP1 to promote cell survival following genotoxic stress. Together, our findings highlight a novel mechanism for regulating TDP1 function in mammalian cells that is not directly related to its enzymatic activity.