BACKGROUND AND OBJECTIVES: Treatment of suspected infection is a mainstay of the daily work in the NICU. We hypothesized that NICU antibiotic prescribing practice variation correlates with rates of proven infection, necrotizing enterocolitis (NEC), mortality, inborn admission, and with NICU surgical volume and average length of stay. METHODS:In a retrospective cohort study of 52 061 infants in 127 NICUs across California during 2013, we compared sample means and explored linear and nonparametric correlations, stratified by NICU level of care and lowest/highest antibiotic use rate quartiles.RESULTS: Overall antibiotic use varied 40-fold, from 2.4% to 97.1% of patient-days; median = 24.5%. At all levels of care, it was independent of proven infection, NEC, surgical volume, or mortality. Fifty percent of intermediate level NICUs were in the highest antibiotic use quartile, yet most of these units reported infection rates of zero. Regional NICUs in the highest antibiotic quartile reported inborn admission rate 218% higher (0.24 vs 0.11, P = .03), and length of stay 35% longer (90.2 days vs 66.9 days, P = .03) than regional NICUs in the lowest quartile.CONCLUSIONS: Forty-fold variation in NICU antibiotic prescribing practice across 127 NICUs with similar burdens of proven infection, NEC, surgical volume, and mortality indicates that a considerable portion of antibiotic use lacks clear warrant; in some NICUs, antibiotics are overused. Additional study is needed to establish appropriate use ranges and elucidate the determinants and directionality of relationships between antibiotic and other resource use.

BACKGROUND Differences in neonatal intensive care unit (NICU) quality of care provided to very-low-birth-weight (VLBW; <1500g) infants may contribute to the persistence of racial/ethnic disparity. An examination of such disparities in a population-based sample across multiple dimensions of care and outcomes is lacking. METHODS Prospective observational analysis of 18,616 VLBW infants in 134 California NICUs between January 1, 2010 to December 31, 2014. We assessed quality of care delivery via the Baby-MONITOR, a composite indicator consisting of nine process and outcome measures of quality. For each NICU we calculated a risk adjusted composite and individual component quality score for each race/ethnicity. We standardized each score to the overall population to compare quality of care between and within NICUs. RESULTS We found clinically and statistically significant racial/ethnic variation in quality of care delivery between NICUs as well as within NICUs. Composite quality scores ranged by 5.26 standard units (range −2.30 to 2.96). Adjustment of Baby-MONITOR scores by race/ethnicity had only minimal effect on comparative assessments of NICU performance. Among subcomponents of the Baby-MONITOR, non-Hispanic White infants scored higher on measures of process compared with non-Hispanic Blacks and Hispanics. Compared with Whites, non-Hispanic Blacks scored higher on measures of outcome; Hispanics scored lower on seven of the nine Baby-MONITOR subcomponents. CONCLUSION Significant racial/ethnic variation in quality of care delivery exists between and within NICUs. Providing feedback of disparity scores to NICUs could serve as an important starting point for promoting improvement and reducing disparities.

Rationale Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction (LVEF). However, the mechanism underlying the functional benefit is unclear. Objective To evaluate whether the transplantation of cardiac lineage differentiated derivatives enhance myocardial viability and restore LVEF more effectively than undifferentiated pluripotent stem cells after a myocardial injury (MI). Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine MI model. Methods and Results Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intra-myocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14) and (5) PBS control (n=10). LVEF and myocardial viability, measured by cardiac-MRI and manganese-enhanced MRI (MEMRI), respectively, was significantly improved in hCM- and iCM-treated mice compared to pluripotent stem cell- or control-treated mice. Bioluminescence imaging (BLI) revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant up-regulation of the pro-migratory, pro-angiogenic, and anti-apoptotic targets in groups treated with cardiac lineage cells compared to pluripotent stem cell and control groups. Conclusions This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium more effectively than undifferentiated stem cells through their differential paracrine effects.

Objective. Nonsteroidal antiinflammatory drug (NSAID)-associated gastropathy is a major cause of hospitalization and death. This study was undertaken to examine whether recent preventive approaches have been associated with a declining incidence of NSAID gastropathy, and, if so, what measures may have caused the decline.Methods. We studied 5,598 patients with rheumatoid arthritis (RA) over 31,262 patient-years at 8 sites. We obtained standardized longitudinal information on the patients that had been previously used to establish the incidence of NSAID gastropathy, and also information on patient risk factors and differences in toxicity between NSAIDs. Consecutive patients were followed up with biannual Health Assessment Questionnaires and medical record audits between 1981 and 2000. The major outcome measure was the annual rate of hospitalization involving bleeding, obstruction, or perforation of the gastrointestinal (GI) tract and related conditions.Results. Rates of GI-related hospitalizations rose from 0.6% in 1981 to 1.5% in 1992 (P < 0.001), and then declined to 0.5% in 2000 (P < 0.001). The fitted spline curve fit the data well (R 2 ‫؍‬ 0.70). The period of rise was mainly associated with increasing patient age and the GI risk propensity score. The period of decline was associated with lower doses of ibuprofen and aspirin, a decline in the use of "more toxic" NSAIDs from 52% to 42% of patients, a rise in the use of "safer" NSAIDs from 19% to 48% of patients, and increasing use of proton-pump inhibitors, but not with change in age, NSAID exposure, or GI risk propensity score.Conclusion. The risk of serious NSAID gastropathy has declined by 67% in these cohorts since 1992. We estimate that 24% of this decline was the result of lower doses of NSAIDs, while 18% was associated with the use of proton-pump inhibitors and 14% with the use of less toxic NSAIDs. These declines in the incidence of NSAID gastropathy are likely to continue.

IMPORTANCE Most neonates admitted to a neonatal intensive care unit (NICU) are born at gestational age (GA) of 34 weeks or more. The degree of uniformity of admission criteria for these infants is unclear, particularly at the low-acuity end of the range of conditions warranting admission.OBJECTIVES To describe variation in NICU admission rates for neonates born at GA of 34 weeks or more and examine whether such variation is associated with high illness acuity or designated facility level of care. DESIGN, SETTING, AND PARTICIPANTSCross-sectional study of 35 921 NICU inborn admissions of GA at 34 weeks or more during calendar year 2015, using a population database of inborn NICU admissions at 130 of the 149 hospitals in California with a NICU. The aggregate service population comprised 358 453 live births. The individual NICU was the unit of observation and analysis. The analysis was stratified by designated facility level of care and correlations with the percentage admissions with high illness acuity were explored. The hypothesis at the outset of the study was that inborn admission rates would correlate positively with the percentage of admissions with high illness acuity.EXPOSURES Live birth at GA of 34 weeks or more. MAIN OUTCOMES AND MEASURES Inborn NICU admission rate.RESULTS Of the total of 358 453 live births at GA of 34 weeks or more, 35 921 infants were admitted to a NICU and accounted for 79.2% of all inborn NICU admissions; 4260 (11.9%) of these admissions met high illness acuity criteria. Inborn admission rates varied 34-fold, from 1.1% to 37.7% of births (median, 9.7%; mean [SD], 10.6% [5.8%]). Percentage with high illness acuity varied 40-fold, from 2.4% to 95% (median, 11.3%; mean, 13.2% [9.9%]). Inborn admission rate correlated inversely with percentage of admissions with high illness acuity (Spearman ρ = −0.3034, P < .001). Among regional NICUs capable of caring for patients with the highest degree of illness and support needs, inborn admission rate did not significantly correlate with percentage of admissions with high illness acuity (Spearman ρ = −0.21, P = .41). CONCLUSIONS AND RELEVANCEPercentage of admissions with high illness acuity does not explain 34-fold variation in NICU inborn admission rates for neonates born at GA of 34 weeks or more. The findings are consistent with a supply-sensitive care component and invite future investigation to clarify the lower-acuity end of the range of conditions considered to warrant neonatal intensive care.

Background Delayed gadolinium (Gd) enhancement MRI (DEMRI) identifies non-viable myocardium, but is non-specific and may overestimate nonviable territory. Manganese (Mn2+)-enhanced MRI (MEMRI) denotes specific Mn2+ uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI will identify viable infarct border zone (BZ) myocardium in vivo. Methods and Results Sixty-minute LAD ischemia-reperfusion injury (IR) was induced in 13 adult swine. Twenty-one days post-IR, 3T cardiac MRI was performed. MEMRI was obtained after injection (0.7 cc/kg) of Mn2+ contrast agent (EVP1001-1, Eagle Vision Pharmaceutical Corp.). DEMRI was then acquired after 0.2mmol/kg Gd injection. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured border zone myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride (TTC) stain and tissue electron microscopy (TEM) to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with TTC (MEMRI: r=0.78; DEMRI: r=0.75; p<0.004). MEMRI infarct volume percentage was significantly lower than DEMRI (14±4%* vs. 23±4%; *p<0.05). BZ MEMRI SNR was intermediate to remote and core infarct SNR (7.5±2.8* vs. 13.2±3.4 and 2.9±1.6; *p<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct (8.4±5.4 vs. 3.3±0.6 and 14.3±6.6; p>0.05). TEM analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement. Conclusions Dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.

ObjectiveTo develop a length of stay (LOS) model for extremely low birth weight (ELBW) infants.Study DesignWe included infants from the California Perinatal Quality Care Collaborative with birth weight 401–1,000 grams who were discharged to home. Exclusion criteria were congenital anomalies, surgery, and death. LOS was defined as days from admission to discharge. As patients who died or were transferred to lower level of care were excluded, we assessed correlation of hospital mortality rates and transfers torisk adjusted LOS.ResultsThere were 2,012 infants with median LOS 79 days (range 23–219). Lower birth weight, lack of antenatal steroids, and lower Apgar score were associated with longer LOS. There was negligiblecorrelation between risk-adjusted LOS and hospital mortality rates (r = 0.0207) and transfer-out rates (r = 0.121).ConclusionParticularly because ELBW infants have extended hospital stays, identification of unbiased and informative risk-adjusted LOS for these infants is an important step in benchmarking best practice and improving efficiency in care.

Quantification of core and border zones and their percentages of myocardium through CMR is associated with future CVE and might assist in the management of patients with ICM.