Association of a Simplified Finnegan Neonatal Abstinence Scoring Tool With the Need for Pharmacologic Treatment for Neonatal Abstinence Syndrome

Importance: Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment. Objectives: To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision. Design, Setting, and Participants: This multisite cohort study included 424 neonates with opioid exposure who had a gestational age of at least 36 weeks with follow-up from birth to hospital discharge in the derivation cohort and 109 neonates with opioid exposure from the Maternal Opioid Treatment: Human Experimental Research Study in the validation cohort. Neonates in the derivation cohort were included in a medical record review at the Universities of Louisville and Kentucky or in a randomized clinical trial and observational study conducted at Tufts University (2014-2018); the Maternal Opioid Treatment: Human Experimental Research was conducted from 2005 to 2008. Data analysis was conducted from May 2017 to August 2019. Exposures: Prenatal opioid exposure. Main Outcomes and Measures: All FNAST items were dichotomized as present or not present, and logistic regression was used to identify binary items independently associated with pharmacologic treatment. The final model was validated with an independent cohort of neonates with opioid exposure. Results: Among 424 neonates (gestational age, ≥36 weeks; 217 [51%] female infants), convulsions were not observed, and high-pitched cry and hyperactive Moro reflex had extremely different frequencies across cohorts. Therefore, these 3 FNAST items were removed from further analysis. The 2 tremor items were combined, and 8 of the remaining 17 items were independently associated with pharmacologic treatment, with an area under the curve of 0.86 (95% CI, 0.82-0.89) compared with 0.90 (95% CI, 0.87-0.94) for the 21-item FNAST. External validation of the 8 items resulted in an area under the curve of 0.86 (95% CI, 0.79-0.93). Thresholds of 4 and 5 on the simplified scale yielded the closest agreement with FNAST thresholds of 8 and 12 (weighted κ = 0.55; 95% CI, 0.48-0.61). Conclusions and Relevance: The findings of this study suggest that 8 signs of NAS may be sufficient to assess whether a neonate meets criteria for pharmacologic therapy. A focus on these signs could simplify the FNAST tool and may enhance its clinical utility

A Brief Report of Caregiver Needs and Resource Utilization During Pediatric Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) is used to eradicate disease and restore normal hematopoietic, immunologic, and/or metabolic functioning. HSCT is a complex treatment that is physiologically and psychologically demanding on the recipient, caregiver, and family. The purpose of this study was to identify needs and resources of family caregivers of pediatric HSCT recipients during the first year after transplant. Parental caregivers (n = 161) completed an online survey. The most cited sources of information were the HSCT team (87.7%), books and other print materials (83.1%), and the Internet (81.5%). However, more than half of the respondents reported that finding resources and services was a problem. More than half identified managing the emotional and social impact of the transplant on their child, posttransplant and follow-up care, practical strategies for caregiving, maintaining the family, and taking care of themselves during this first year as important topics to address. Adequately and regularly assessing caregiver and family needs and providing resources to meet those needs, especially during transitions in care, are important components of transplant care

CTSA Consortium Consensus Scientific Review Committee (SRC) Working Group Report on the SRC Processes

Human research projects must have a scientifically valid study design, analytic plan, and be operationally feasible in order to be successfully completed and thus to have translational impact. To ensure this, institutions that conduct clinical research should have a scientific review process prior to submission to the Institutional Review Committee (IRB). This paper reports the Clinical and Translational Science Award (CTSA) Consortium Scientific Review Committee (SRC) Consensus Working Group's proposed framework for a SRC process. Recommendations are provided for institutional support and roles of CTSAs, multisite research, criteria for selection of protocols that should be reviewed, roles of committee members, application process, and committee process. Additionally, to support the SCR process effectively, and to ensure efficiency, the Working Group recommends information technology infrastructures and evaluation metrics to determine outcomes are provided

Convergence to a Gaussian limit as the normalization exponent tends to

Certain quadratic forms with long-range dependence, normalized by Nd with , have a non-Gaussian limit, but under further normalization, as , the limit becomes Gaussian.Self-similar processes long-range dependence Wiener--Ito integrals

An asymptotic Wiener-Itô representation for the low frequency ordinates of the periodogram of a long memory time series

We consider a general long memory time series, assumed stationary and linear, but not necessarily Gaussian or generated by a finite-parameter model. For such a process, we derive the asymptotic joint distribution of the normalized periodogram at a fixed, finite collection of Fourier frequencies. The limiting distribution is represented in terms of Wiener-Itô integrals, and, for a single periodogram ordinate, it is an unequally weighted linear combination of independent [chi]21 random variables. This result was previously known only in the Gaussian case. Our theorem may be useful for generalizing, beyond the Gaussian case, the applicability of a semiparametric method of estimating the long memory parameter based on log-periodogram regression.Long-range dependence Spectral density Fractional ARMA

Hepatitis B Virus Reactivation and Prophylaxis During Solid Tumor Chemotherapy

Background: Solid tumor chemotherapy regimens pose a riskfor hepatitis B virus (HBV) reactivation, but screening and antiviralprophylaxis remains controversial because of insufficientevidence.Purpose: To determine the risk for HBV reactivation with andwithout antiviral prophylaxis and the effectiveness of prophylaxisin adults with solid tumors and chronic or resolved HBV infection.Data Sources: MEDLINE through 1 July 2015 and Web of Science,Cochrane Central Register of Controlled Trials, TOXNET,and Scopus through 1 March 2015.Study Selection: 26 English-language observational studiesand randomized, controlled trials in patients with chronic or resolvedHBV receiving chemotherapy for solid tumors.Data Extraction: Study characteristics, quality, and risk of biaswere assessed by 1 researcher and verified by another independentresearcher.Data Synthesis: Random-effects model meta-analyses wereused to estimate the risk and odds ratio (OR) of reactivation withversus without antiviral prophylaxis. Reactivation in chronic HBVwithout prophylaxis ranged from 4% to 68% (median, 25%) withsubstantial heterogeneity. Prophylaxis reduced the risk for HBVreactivation (OR, 0.12 [95% Cl, 0.06 to 0.22]), HBV-related hepatitis(OR, 0.18 [Cl, 0.10 to 0.32]), and chemotherapy interruption(OR, 0.10 [Cl, 0.04 to 0.27]). In 3 studies of patients with resolvedHBV infection, none received HBV prophylaxis and reactivationrisk ranged from 0.3% to 9.0%.Limitations: Significant heterogeneity in underlying study populationsand treatment regimens, incomplete baseline data, possibilityof publication bias, and limited study quality. Most studieswere observational and from Asia.Conclusion: In patients with chronic HBV receiving solid tumorchemotherapy, the risk for HBV reactivation is similar to the riskwith other types of immunosuppressive therapy. Results supportHBV screening and antiviral prophylaxis before initiation of chemotherapyfor solid tumors.Primary Funding Source: National Center for AdvancingTranslational Sciences and National Institutes of Health

Cell-free DNA fragmentation patterns in amniotic fluid identify genetic abnormalities and changes due to storage

Circulating cell-free DNA (cfDNA) has become a promising biomarker in prenatal diagnosis. However, despite extensive studies in different body fluids, cfDNA predictive value is uncertain owing to the confounding factors that can affect its levels, such as gestational age, maternal weight, smoking status, and medications. Residual fresh and archived amniotic fluid (AF) supernatants were obtained from gravid women (mean gestational age 17 wk) carrying euploid (N=36) and aneuploid (N=29) fetuses, to characterize cfDNA-fragmentation patterns with regard to aneuploidy and storage time (-80 degrees C). AF cfDNA was characterized by the real-time quantitative polymerase chain reaction amplification of glyceraldehyde-3-phosphate dehydrogenase, gel electrophoresis, and pattern recognition of the DNA fragmentation. The distributions of cfDNA fragment lengths were compared using 6 measures that defined the locations and slopes for the first and last peaks, after elimination of the confounding variables. This method allowed for the unique classification of euploid and aneuploid cfDNA samples in AF, which had been matched for storage time. In addition, we showed that archived euploid AF samples gradually lose long cfDNA fragments: this loss accurately distinguishes them from the fresh samples. We present preliminary data using cfDNA-fragmentation patterns, to uniquely distinguish between AF samples of pregnant women with regard to aneuploidy and storage time, independent of gestational age and initial DNA amount. In addition to potential applications in prenatal diagnosis, these data suggest that archived AF samples consist of large amounts of short cfDNA fragments, which are undetectable using standard real-time polymerase chain reaction amplification

Longitudinal Analysis of Gender Differences in Academic Productivity Among Medical Faculty Across 24 Medical Schools in the United States

PurposeTo examine gender differences in academic productivity, as indicated by publications and federal grant funding acquisition, among a longitudinal cohort of medical faculty from 24 U.S. medical schools, 1995 to 2012-2013.MethodData for this research were taken from the National Faculty Survey involving a survey with medical faculty recruited from medical schools in 1995, and followed up in 2012-2013. Data included surveys and publication and grant funding databases. Outcomes were number of publications, h-index, and principal investigator on a federal grant in the prior two years. Gender differences were assessed using negative binomial regression models for publication and h-index outcomes, and logistic regression for the grant funding outcome; analyses adjusted for race/ethnicity, rank, specialty area, and years since first academic appointment.ResultsData were available for 1,244 of the 1,275 (98%) subjects eligible for the follow-up study. Men were significantly more likely than women to be married/partnered, have children, and hold the rank of professor (P < .0001). Adjusted regression models documented that women had a lower rate of publication (relative number = 0.71; 95% CI = 0.63, 0.81; P < .0001) and h-index (relative number = 0.81; 95% CI = 0.73, 0.90; P < .0001) relative to men, but there was no gender difference in grant funding.ConclusionsWomen faculty acquired federal funding at similar rates as male faculty, yet lagged behind in terms of publications and their impact. Medical academia must consider how to help address ongoing gender disparities in publication records