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Epidemiologists face a unique challenge in measuring risk relationships involving time-varying exposures in early pregnancy. Each week in early pregnancy is distinct in its contribution to fetal development, and this period is commonly characterized by shifts in maternal behavior and, consequently, exposures. In this simulation study, we used alcohol as an example of an exposure that often changes during early pregnancy and miscarriage as an outcome affected by early exposures. Data on alcohol consumption patterns from more than 5,000 women in the Right From the Start cohort study (United States, 2000–2012) informed measures of the prevalence of alcohol exposure, the distribution of gestational age at cessation of alcohol use, and the likelihood of miscarriage by week of gestation. We then compared the bias and precision of effect estimates and statistical power from 5 different modeling approaches in distinct simulated relationships. We demonstrate how the accuracy and precision of effect estimates depended on alignment between model assumptions and the underlying simulated relationship. Approaches that incorporated data about patterns of exposure were more powerful and less biased than simpler models when risk depended on timing or duration of exposure. To uncover risk relationships in early pregnancy, it is critical to carefully define the role of exposure timing in the underlying causal hypothesis. [ABSTRACT FROM AUTHOR]

This randomized controlled trial (NCT03889821) examined Mindfulness Based Stress Reduction (MBSR) in conjunction with the Parent-implemented Early Start Denver Model (P-ESDM). A previous report described improved metrics of parental distress (Weitlauf et al. in Pediatrics 145(Supplement 1):S81–S92, 2020). This manuscript examines child outcomes. 63 children with ASD (< 36 months) and their parents received 12 P-ESDM sessions. Half of parents also received MBSR. Longitudinal examination of whole sample means revealed modest improvements in autism severity, cognitive, and adaptive skills. There was not a significant time × group interaction for children whose parents received MBSR. Future work should examine more proximal markers of child or dyadic change to enhance understanding of the impact of providing direct treatment for parents as part of early intervention initiatives. [ABSTRACT FROM AUTHOR]

Objective: Despite enthusiasm for low carbohydrate diets (LCDs) among patients with type 1 diabetes (T1DM), no prospective study has investigated outcomes in adolescent T1DM. We aimed to quantify a pragmatic LCD intervention's impact on glycemia, lipidemia, and quality of life (QOL) in adolescents with T1DM. Research Design and Methods: At an academic center, we randomized 39 patients with T1DM aged 13–21 years to one of three 12‐week interventions: an LCD, an isocaloric standard carbohydrate diet (SCD), or general diabetes education without a prescriptive diet. Glycemic outcomes included glycosylated hemoglobin (HbA1c) and continuous glucose monitoring. Results: There were no significant differences in glycemic, lipidemic, or QOL parameters between groups at any timepoint. Median HbA1c was similar at baseline between groups and did not change appreciably (7.9%–8.4% in LCDs, 7.9%–7.9% in SCDs, and 8.2%–7.8% in controls). Change in carbohydrate consumption was minimal with only one participant reaching target carbohydrate intake. Conclusions: This pragmatic LCD intervention did not alter carbohydrate consumption or glycemia. Although this study was unable to evaluate a highly controlled LCD, it indicates that adolescents are unlikely to implement an educational LCD intervention in routine clinic settings. Thus, this approach is unlikely to effectively mitigate hyperglycemia in adolescents. [ABSTRACT FROM AUTHOR]

Introduction. Antimicrobial use is decreasing across freestanding children's hospitals, predominantly in institutions with antimicrobial stewardship programs (ASPs) in place. A highly effective ASP should effect a greater decrease in use than predicted by existing trends. Antimicrobial stewardship programs depend on clinician adherence to program recommendations, but little is known about factors associated with adherence. Methods. Parenteral antimicrobial-use data for our institution and 43 additional freestanding children's hospitals were obtained and normalized for patient census. Segmental linear regression was used to compare rates of change of parenteral antimicrobial use before and after ASP implementation. Time-series models were developed to predict use in the absence of intervention. The odds of adherence to ASP recommendations were determined based on provider characteristics and recommendation type. Results. In the 38 months before ASP implementation, parenteral antimicrobial use was decreasing at our hospital by 3.7%/year, similar to the 3.4%/year found across children's hospitals. The rate of change after implementation of the ASP at our hospital was 11.1%/year, compared to 5.6%/year for other hospitals over the same period. Of 643 interventions, teams adhered with recommendations in 495 cases (77.0%). According to adjusted analysis, primary service was not associated with adherence (P = .356). There was an association between adherence and the role of the clinician receiving a recommendation (P = .009) and the recommendation type (P = .009). Conclusions. Understanding factors associated with adherence to ASP recommendations can help those who administer such programs to strategize interventions for maximizing efficacy. Our findings reveal the value of a formal ASP in reducing use when controlling for secular trends. [ABSTRACT FROM AUTHOR]

Objective To quantify the daily risk of unplanned extubation (UE) in newborns based on developmental and anatomical factors. Methods Prospective cohort of ventilated newborns over an 18-month period in a level IV neonatal intensive care unit (NICU). We captured UEs through four data streams. We generated multivariable logistic regression models to assess the association of UE with chronological age, birth weight, and postmenstrual age. Results During the study, 718 infants were ventilated for 5,611 patient days with 117 UEs in 81 infants. The daily risk of UE had a significant, nonlinear relationship (p < 0.01) with chronological age, decreasing until day 7 (odds ratio [OR]: 0.5; 95% confidence interval [CI]: 0.17-1.47) and increasing after day 7 (day 7-28, OR: 1.36, 95% CI: 1.06-1.75; and >28 days, OR: 1.06, 95% CI: 1.0-1.14). Birth weight and postmenstrual age were not associated with UE. Adverse events occurred in 83/117 (71%) UE events. Iatrogenic causes of UE were more common in younger, smaller infants, whereas older, larger infants were more likely to self-extubate. Conclusion The daily risk and causes of UE change over the course of an infant's NICU hospitalization. These data can be used to identify infants at the highest risk of UE for whom targeted proactive interventions can be developed. document was downloaded for personal use only. Unauthorized distribution [ABSTRACT FROM AUTHOR]

Background: Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. The hypothesis of this study is that T1 and extracellular volume fraction (ECV) mapping using cardiovascular magnetic resonance (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without myocardial late gadolinium enhancement (LGE). Methods: Thirty-one DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed in all participants before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test. Results: The DMD participants had significantly higher mean native T1 compared with controls (1045 ms vs 988 ms, p = 0.001). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1039 ms vs 988 ms, p = 0.002, and 1038 ms vs 988 ms, p = 0.011). DMD participants had a significantly greater mean ECV than controls (0.31 vs 0.24, p < 0.001), even in the settings of normal LVEF (0.28 vs 0.24, p < 0.001) and negative LGE (0.29 vs 0.24, p =0.001). Conclusions: DMD participants have elevated LV myocardial native T1 and ECV, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials. [ABSTRACT FROM AUTHOR]

BACKGROUND: The OxiMax N-600x containing SatSeconds alarm management software was designed to assist clinicians in discriminating nuisance alarms from those that are clinically relevant. Instead of sounding an alarm the moment the oxygen saturation reading violates the upper or lower limit settings, a magnitude and duration of tolerance can be set. The primary objective was to study the proportion of nuisance alarms relative to the proportion of clinically relevant alarms being filtered under 4 different SatSeconds alarm settings (ie, 10, 25, 50, and 100) in the neonatal intensive care environment. METHODS: This is an observational prospective study of 50 infants cared for in 3 large neonatal ICUs. Infants were monitored for 4 continuous h each by a study observer with the study monitor, in addition to standard multiparameter monitors. The performance of the SatSeconds alarm was compared with nursing intervention. RESULTS: The area under the receiver operating characteristic curve (95% CI) for SatSeconds alarm settings when compared with nursing intervention were as follows: 0.61 (0.57-0.66) when the SatSeconds alarm setting was off, 0.63 (0.59-0.68) for the 10 SatSeconds alarm setting, 0.64 (0.59-0.69) for the 25 SatSeconds alarm setting, 0.64 (0.59-0.69) for the 50 SatSeconds alarm setting, and 0.63 (0.58-0.68) for the 100 SatSeconds alarm setting, respectively. CONCLUSIONS: The SatSeconds feature of the OxiMax N-600x pulse oximeter reduced some nuisance alarms; however, its specificity to nurse-identified desaturation events does not significantly improve with lengthening SatSeconds alarm settings. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We conducted a randomized trial to test the hypothesis that mother's voice played through a pacifier-activated music player (PAM) during nonnutritive sucking would improve the development of sucking ability and promote more effective oral feeding in preterm infants. METHODS: Preterm infants between 34 0/7 and 35 6/7 weeks' postmenstrual age, including those with brain injury, who were taking at least half their feedings enterally and less than half orally, were randomly assigned to receive 5 daily 15-minute sessions of either PAM with mother's recorded voice or no PAM, along with routine nonnutritive sucking and maternal care in both groups. Assignment was masked to the clinical team. RESULTS: Ninety-four infants (46 and 48 in the PAM intervention and control groups, respectively) completed the study. The intervention group had significantly increased oral feeding rate (2.0 vs 0.9 mL/min, P< .001), oral volume intake (91.1 vs 48.1 mL/kg/d, P= .001), oral feeds/ day (6,5 vs 4.0, P < .001), and faster time-to-full oral feedings (31 vs 38 d, P = .04) compared with controls. Weight gain and cortisol levels during the 5-day protocol were not different between groups. Average hospital stays were 20% shorter in the PAM group, but the difference was not significant {P = .07). CONCLUSIONS: A PAM using mother's voice improves oral feeding skills in preterm infants without adverse effects on hormonal stress or growth. [ABSTRACT FROM AUTHOR]

Abstract: Neonatal intensive care unit (NICU) patients are at high risk for developmental disabilities such as cerebral palsy (CP). Early identification of CP is essential to effective rehabilitation, but diagnosis is often delayed, especially in preterm infants. We hypothesized that through the longitudinal evaluation of motor trajectories in the NICU follow-up clinic, we could distinguish infants who develop CP by 3years of age. Study design and subjects: This was a retrospective study of 606 patients in the NICU Follow-up Clinic at Vanderbilt University with birth weight <1500g or a diagnosis of hypoxic ischemic encephalopathy. Outcomes measures: Assessments included neurologic exams, the Developmental Assessment of Young Children (DAYC), the Bayley Scales of Infant Development (BSID) and the Gross Motor Function Classification Scale. Results: A decrease in DAYC scores between 6 and 12months was present in preterm and term infants later diagnosed with CP, but not in children without CP (−23 vs. +1.5, p <0.001). DAYC score decreases in infancy were highly predictive of later CP (p <0.001). BSID scores quantified severe motor delays but did not add to prediction of CP diagnosis. Conclusion: Standardized assessments of motor milestones quantitatively predict the risk of CP in former NICU patients by 12months, allowing for timely diagnosis, counseling and therapy in high-risk infants. [Copyright &y& Elsevier]

Background & Aims: Diagnostic tests for gastroesophageal reflux disease (GERD) are constrained because measurements are made at a single time point, so the long-term effects on the mucosa cannot be determined. We developed a minimally invasive system to assess changes in esophageal mucosal impedance (MI), a marker of reflux. We measured the extent of changes in MI along the esophagus and show that the device to assess MI can be used to diagnose patients with GERD. Methods: A single-channel MI catheter composed of a unique sensor array was designed to easily traverse the working channel of an upper endoscope. We performed a prospective longitudinal study of patients with erosive esophagitis (n = 19), nonerosive but pH-positive GERD (n = 23), and those without GERD (n = 27). MI was measured at the site of esophagitis as well as 2, 5, and 10 cm above the squamocolumnar junction. The MI values were compared among groups, at different levels along the esophageal axis. Results: Median MI values were significantly lower at the site of erosive mucosa (811 Ω; range, 621–1272 Ω) than other nonerosive regions (3723 Ω; range, 2421–4671 Ω; P = .001), and were significantly lower at 2 cm above the squamocolumnar junction in patients with GERD (2096 Ω; range, 1415–2808 Ω), compared with those without GERD (3607 Ω; range, 1973–4238 Ω; P = .008). There was a significant and graded increase in MI along the axis of the distal to proximal esophagus in patients with GERD that was not observed in individuals without reflux (P = .004). Conclusions: Measurements of MI along the esophagus can be used to identify patients with GERD. ClinicalTrials.gov, number NCT01194323. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) vaccination disparities between urban and rural regions may moderate the vaccine's impact on reducing cervical precancer (CIN2+) and cancer incidence. We assessed population-level trends in CIN2+ incidence (2008–2018) in urban and rural areas among Medicaid-enrolled women aged 18–39 years in Tennessee, United States. A sub-group analysis among women screened for cervical cancer was conducted to control for changing screening trends. CIN2+ incidence among young women aged 18–20 and 21–24 years, who most likely benefited from the HPV vaccine, declined similarly between urban and rural areas, although significant declines began earlier in urban versus rural areas. Our results suggest evidence of HPV vaccine impact regardless of urbanicity but demonstrate lagged impact in rural areas. These findings emphasize the importance of reducing barriers to HPV vaccination, particularly in rural areas, to improve the reduction of cervical precancer and cancer incidence, toward the World Health Organization's goals of eliminating cervical cancer. Disparities in human papillomavirus (HPV) vaccination exist between urban (metropolitan statistical areas (MSAs)) and rural (non-MSAs) regions. To address whether the HPV vaccine's impact differs by urbanicity, we examined trends in cervical intraepithelial neoplasia grades 2 or 3 and adenocarcinoma in situ (collectively, CIN2+) incidence in MSAs and non-MSAs among Tennessee Medicaid (TennCare)-enrolled women aged 18–39 years and among the subset screened for cervical cancer in Tennessee, United States. Using TennCare claims data, we identified annual age-group-specific (18–20, 21–24, 25–29, 30–34, and 35–39 years) CIN2+ incidence (2008–2018). Joinpoint regression was used to identify trends over time. Age–period–cohort Poisson regression models were used to evaluate age, period, and cohort effects. All analyses were stratified by urbanicity (MSA versus non-MSA). From 2008–2018, 11,243 incident CIN2+ events (7956 in MSAs; 3287 in non-MSAs) were identified among TennCare-enrolled women aged 18–39 years. CIN2+ incident trends (2008–2018) were similar between women in MSAs and non-MSAs, with largest declines among ages 18–20 (MSA average annual percent change (AAPC): −30.4, 95% confidence interval (95%CI): −35.4, −25.0; non-MSA AAPC: −30.9, 95%CI: −36.8, −24.5) and 21–24 years (MSA AAPC: −14.8, 95%CI: −18.1, −11.3; non-MSA AAPC: −15.1, 95%CI: −17.9, −12.2). Significant declines for ages 18–20 years began in 2008 in MSAs compared to 2010 in non-MSAs. Trends were largely driven by age and cohort effects. These patterns were consistent among screened women. Despite evidence of HPV vaccine impact on reducing CIN2+ incidence regardless of urbanicity, significant declines in CIN2+ incidence were delayed in non-MSAs versus MSAs. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Unplanned extubations (UEs) in adult and pediatric populations are associated with poor clinical outcomes and increased costs. In-hospital outcomes and costs of UE in the NICU are not reported. Our objective was to determine the association of UE with clinical outcomes and costs in very-low-birth-weight infants. METHODS: We performed a retrospective matched cohort study in our level 4 NICU from 2014 to 2016. Very-low-birth-weight infants without congenital anomalies admitted by 72 hours of age, who received mechanical ventilation (MV), were included. Cases (1UE) were matched 1:1 with controls (2UE) on the basis of having an equivalent MV duration at the time of UE in the case, gestational age, and Clinical Risk Index for Babies score. We compared MV days after UE in cases or the equivalent date in controls (postmatching MV), in-hospital morbidities, and hospital costs between the matched pairs using raw and adjusted analyses. RESULTS: Of 345 infants who met inclusion criteria, 58 had $1 UE, and 56 out of 58 (97%) were matched with appropriate controls. Postmatching MV was longer in cases than controls (median: 12.5 days; interquartile range [IQR]: 7 to 25.8 vs median 6 days; IQR: 2 to 12.3; adjusted odds ratio: 4.3; 95% confidence interval: 1.9-9.5). Inflation-adjusted total hospital costs were higher in cases (median difference: $49 587; IQR: 215 063 to 119 826; adjusted odds ratio: 3.8; 95% confidence interval: 1.6-8.9). CONCLUSIONS: UEs in preterm infants are associated with worse outcomes and increased hospital costs. Improvements in UE rates in NICUs may improve clinical outcomes and lower hospital costs. [ABSTRACT FROM AUTHOR]

Objective: To examine whether premenopausal reproductive age, as indicated by serum antimüllerian hormone (AMH), is associated with leukocyte aging biomarkers.Design: Prospective cohort analysis.Setting: The Coronary Artery Risk Development in Young Adults study, a population-based study of Black and White adults from four US communities (Birmingham, AL; Chicago, IL; Minneapolis, MN; Oakland, CA).Patient(s): Premenopausal women with serum AMH measures at examination year 15 as well as leukocyte aging markers.Intervention(s): None.Main Outcome Measure(s): Telomere length, mitochondrial deoxyribonucleic acid (mtDNA) copy number, and intrinsic and extrinsic epigenetic age acceleration (EAA) at examination years 15, 20, and 25 as well as change between examination years.Result(s): Women were 40.2 (standard deviation, 3.7) years of age at examination year 15 when the AMH and initial measures of telomere length and mtDNA copy number (n = 386) were obtained and EAA occurred. After adjustment for chronological age, race, and smoking history, AMH quartile at examination year 15 was not associated with telomere length at examination years 15 and 25 or telomere length change between these years, mtDNA copy number at examination years 15 and 25 or change between these years, or intrinsic EAA at examination years 15 and 20 or change between these years. Women in the second AMH quartile had faster extrinsic EAA than women in the lowest AMH quartile (β-coefficient, 1.84; 95% confidence interval, 0.20-3.49).Conclusion(s): In a population-based cohort, AMH did not have associations with leukocyte telomere length, mtDNA copy number, or intrinsic EAA. [ABSTRACT FROM AUTHOR]