Accelerating improvement: The Pediatric Acute Care Cardiology Collaborative data timeliness project.

BACKGROUND: The Pediatric Acute Care Cardiology Collaborative (PAC3) is a learning network focused on improving acute care cardiology patient outcomes. Data submission timeliness is a vulnerability for PAC3 and most clinical registries, directly affecting collaborative benchmarking, quality improvement (QI) and research projects. OBJECTIVE: PAC3 conducted a collaborative-wide QI project addressing data timeliness and efficiency. Data analysis of submitted cases from September 2019 to February 2020 revealed nine 'High Performer' centers who submitted cases within 67 days of hospital discharge (the limit for timeliness) >90% of the time and eight 'High Potential' sites who submitted timely cases <75% of the time. The primary aim was to increase case submission timeliness in 'High Potential' centers from 41% to 80% by December 2020. The secondary aim was to maintain timeliness in 'High Performer' sites. METHOD: During the intervention phase (March-December 2020), plan-do-study-act (PDSA) cycles included webinars, facilitated exploratory conversations, data review and development of a best practice guide ('Getting Started Toolkit'). On-boarded 'New Centers' starting in 2020 were also invited to test intervention effectiveness. Balancing measures included data collector job satisfaction and stress and resubmission rates. RESULTS: 'High Performer' and 'High Potential' centers submitted 11 358 cases from November 2019 to December 2020. Timely submission rates for 'High Potential' centers improved from 40.6% to 74.6% and were maintained at >90% for 'High Performer' centers. 'New Centers' averaged 92.6% timely case submissions during their first 6 months. Data collector job satisfaction and stress were not impacted, and the resubmission rates did not increase. CONCLUSION: PAC3's multicenter QI project increased data submission timeliness in a large pediatric subspecialty registry. The lessons learned and the Toolkit developed can be applied in other registries to improve data submission efficiency, with resultant improvement in benchmarking, QI, research, length of stay and outcomes.

Retinoids and retinol differentially regulate steroid biosynthesis in ovarian theca cells isolated from normal cycling women and women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is characterized by ovarian androgen excess and infertility. Recent experiments have suggested that several genes involved in retinoic acid synthesis may be differentially expressed in PCOS theca cells and may contribute to excessive theca-derived androgen production. OBJECTIVE: The study was performed to examine whether there are differential effects of retinol and retinoids on normal and PCOS theca cell function. DESIGN: We used in vitro assays. SETTING: The study was conducted at the university laboratory. PATIENTS: We studied theca interna cells isolated from normal-cycling women and women with PCOS. INTERVENTIONS: Theca cells were treated with all-trans-retinoic acid (atRA), 9-cis retinoic acid (9-cis RA), or the retinoic acid precursor retinol. MAIN OUTCOME MEASURE(S): We measured dehydroepiandrosterone, testosterone, and progesterone biosynthesis as well as cytochrome P450 17alpha-hydroxylase (CYP17), cytochrome P450 cholesterol side-chain cleavage, and steroidogenic acute regulatory protein mRNA abundance and promoter function. RESULTS: Dehydroepiandrosterone production was increased by atRA and 9-cis RA in normal cells and by atRA, 9-cis RA, and retinol in PCOS. Testosterone production was increased by atRA in normal and by atRA, 9-cis RA, and retinol in PCOS. Progesterone production was not altered by retinoid treatment. Retinoids stimulated mRNA abundance and promoter function for CYP17 and steroidogenic acute regulatory protein in both cell types and cytochrome P450 cholesterol side-chain cleavage in normal cells. Retinol stimulated CYP17 mRNA accumulation and promoter function in PCOS but not normal theca cells. P < 0.05 was considered statistically significant. CONCLUSIONS: Differential responses to retinol and retinoids in normal and PCOS theca suggest that altered retinoic acid synthesis and action may be involved in augmented CYP17 gene expression and androgen production in PCOS.

Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome.

We have investigated the involvement of the MAPK signaling pathway in increased androgen biosynthesis and CYP17 gene expression in women with polycystic ovary syndrome (PCOS). A comparison of MAPK kinase (MEK1/2) and ERK1/2 phosphorylation in propagated normal and PCOS theca cells, revealed that MEK1/2 phosphorylation was decreased more than 70%, and ERK1/2 phosphorylation was reduced 50% in PCOS cells as compared with normal cells. Infection with dominant-negative MEK1 increased CYP17 mRNA and dehydroepiandrosterone (DHEA) abundance, whereas constitutively active MEK1 reduced DHEA production and CYP17 mRNA abundance. Similarly, the MEK inhibitor, PD98059, increased CYP17 mRNA accumulation and CYP17 promoter activity to levels observed in PCOS cells. Remarkably, in theca cells maintained in the complete absence of insulin, ERK1/2 phosphorylation was decreased in PCOS theca cells as compared with normal theca cells, and CYP17 mRNA and DHEA synthesis were increased in PCOS theca cells. These studies demonstrate that in PCOS cells reduced levels of activated MEK1/2 and ERK1/2 are correlated with increased androgen production, irrespective of the insulin concentration. These findings implicate alterations in the MAPK pathway in the pathogenesis of excessive ovarian androgen production in PCOS.