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To determine whether neurodevelopmental biomarkers at 2 years of age are already present in the newborns' EEG at birth.Low-risk term newborns were enrolled and studied utilizing EEG prior to discharge from the birth hospital. A 14-channel EEG montage (scalp-level) and source signals were calculated using the EEG. Their spectral power was calculated for each of the five frequency bands. Cognitive, language and motor skills were assessed using the Bayley Scales of Infant Development-III at age 2 years. The relationship between the spectral power in each frequency band and neurodevelopmental scores were quantified using the Spearman's r. The role of gender, gestational age (GA) and delivery mode, if found significant (P 0.05), were controlled by analyzing partial correlation.We studied 47 newborns and found a significant association between gender, and delivery mode with EEG power. Scalp- and source-level spectral powers were positively associated with cognitive and language scores. At the source level, significant associations were identified in the parietal and occipital regions.Electrophysiological biomarkers of neurodevelopment at age 2 years are already present at birth in low-risk term infants.Low-risk newborns' EEG utility as a screening tool to optimize neurodevelopmental outcome warrants further evaluation.

Overdoses continue to increase in the US, but the contribution of methamphetamine use is understudied in rural communities.To estimate the prevalence of methamphetamine use and its correlates among people who use drugs (PWUD) in rural US communities and to determine whether methamphetamine use is associated with increased nonfatal overdoses.From January 2018 through March 2020, the National Rural Opioid Initiative conducted cross-sectional surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin). Participants included rural PWUD who reported any past-30-day injection drug use or noninjection opioid use to get high. A modified chain-referral sampling strategy identified seeds who referred others using drugs. Data analysis was performed from May 2021 to January 2022.Use of methamphetamine alone, opioids alone, or both.Unweighted and weighted prevalence of methamphetamine use, any past-180-day nonfatal overdose, and number of lifetime nonfatal overdoses.Among the 3048 participants, 1737 (57%) were male, 2576 (85%) were White, and 225 (7.4%) were American Indian; the mean (SD) age was 36 (10) years. Most participants (1878 of 2970 participants with any opioid or methamphetamine use [63%]) reported co-use of methamphetamine and opioids, followed by opioids alone (702 participants [24%]), and methamphetamine alone (390 participants [13%]). The estimated unweighted prevalence of methamphetamine use was 80% (95% CI, 64%-90%), and the estimated weighted prevalence was 79% (95% CI, 57%-91%). Nonfatal overdose was greatest in people using both methamphetamine and opioids (395 of 2854 participants with nonmissing overdose data [22%]) vs opioids alone (99 participants [14%]) or methamphetamine alone (23 participants [6%]). Co-use of methamphetamine and opioids was associated with greater nonfatal overdose compared with opioid use alone (adjusted odds ratio, 1.45; 95% CI, 1.08-1.94; P = .01) and methamphetamine use alone (adjusted odds ratio, 3.26; 95% CI, 2.06-5.14; P .001). Those with co-use had a mean (SD) of 2.4 (4.2) (median [IQR], 1 [0-3]) lifetime overdoses compared with 1.7 (3.5) (median [IQR], 0 [0-2]) among those using opioids alone (adjusted rate ratio, 1.20; 95% CI, 1.01-1.43; P = .04), and 1.1 (2.9) (median [IQR], 0 [0-1]) among those using methamphetamine alone (adjusted rate ratio, 1.81; 95% CI, 1.45-2.27; P .001). Participants with co-use most often reported having tried and failed to access substance use treatment: 827 participants (44%) for both, 117 participants (30%) for methamphetamine alone, and 252 participants (36%) for opioids alone (χ22 = 33.8; P .001). Only 66 participants (17%) using methamphetamine alone had naloxone.These findings suggest that harm reduction and substance use disorder treatment interventions must address both methamphetamine and opioids to decrease overdose in rural communities.

BACKGROUND Previous studies have described an association between preterm birth and maturation of the autonomic nervous system (ANS); however, this may be impacted by multiple factors, including prematurity-related complications. Our aim was to evaluate for the effect of prematurity-related morbidity on ANS development in preterm infants in the NICU. METHODS We compared time and frequency domains of heart rate variability (HRV) as a measure of ANS tone in 56 preterm infants from 2 NICUs (28 from each). One cohort was from a high-morbidity regional referral NICU, the other from a community-based inborn NICU with low prematurity-related morbidity. Propensity score matching was used to balance the groups by a 1:1 nearest neighbor design. ANS tone was analyzed. RESULTS The two cohorts showed parallel maturational trajectory of the alpha 1 time-domain metric, with the cohort from the high-morbidity NICU having lower autonomic tone. The maturational trajectories between the two cohorts differed in all other time-domain metrics (alpha 2, RMS1, RMS2). There was no difference between groups by frequency-domain metrics. CONCLUSIONS Prematurity-associated morbidities correlate with autonomic development in premature infants and may have a greater impact on the extrauterine maturation of this system than birth gestational age. IMPACT Autonomic nervous system development measured by time-domain metrics of heart rate variability correlate with morbidities associated with premature birth. This study builds upon our previously published work that showed that development of autonomic tone was not impacted by gestational age at birth. This study adds to our understanding of autonomic nervous system development in a preterm extrauterine environment. Our study suggests that gestational age at birth may have less impact on autonomic nervous system development than previously thought.

Background Illicit fentanyl has contributed to a drastic increase in overdose drug deaths. While fentanyl has subsumed the drug supply in the Northeastern and Midwestern USA, it has more recently reached the Western USA. For this study, we explored perspectives of people who use drugs (PWUD) on the changing drug supply in Oregon, experiences of and response to fentanyl-involved overdose, and recommendations from PWUD to reduce overdose risk within the context of illicit fentanyl’s dramatic increase in the recreational drug supply over the past decade. Methods We conducted in-depth interviews by phone with 34 PWUD in Oregon from May to June of 2021. We used thematic analysis to analyze transcripts and construct themes. Results PWUD knew about fentanyl, expressed concern about fentanyl pills, and were aware of other illicit drugs containing fentanyl. Participants were aware of the increased risk of an overdose but remained reluctant to engage with professional first responders due to fear of arrest. Participants had recommendations for reducing fentanyl overdose risk, including increasing access to information, harm reduction supplies (e.g., naloxone, fentanyl test strips), and medications for opioid use disorder; establishing drug checking services and overdose prevention sites; legalizing and regulating the drug supply; and reducing stigma enacted by healthcare providers. Conclusion PWUD in Oregon are aware of the rise of fentanyl and fentanyl pills and desire access to tools to reduce harm from fentanyl. As states in the Western USA face an inflection point of fentanyl in the drug supply, public health staff, behavioral health providers, and first responders can take action identified by the needs of PWUD.

Background The CHOICES study randomized participants with HIV and opioid use disorder (OUD) to HIV clinic-based extended-release naltrexone (XR-NTX), which requires complete cessation of opioid use, versus treatment-as-usual (i.e., buprenorphine, methadone). Study participants randomized to XR-NTX were interviewed to assess their experiences with successful and unsuccessful XR-NTX induction. Methods Semi-structured qualitative interviews were completed with a convenience sample of study participants with HIV and OUD (n = 37) randomized to XR-NTX in five HIV clinics between 2018 and 2019. All participants approached agreed to be interviewed. Interviews were digitally recorded, professionally transcribed, and analyzed using thematic analysis. Results Participants included women (43%), African Americans (62%) and Hispanics (16%), between 27 to 69 years of age. Individuals who completed XR-NTX induction (n = 20) reported experiencing (1) readiness for change, (2) a supportive environment during withdrawal including comfort medications, and (3) caring interactions with staff. Four contrasting themes emerged among participants (n = 17) who did not complete induction: (1) concern and anxiety about withdrawal including past negative experiences, (2) ambivalence about or reluctance to stop opioids, (3) concerns about XR-NTX effects, and (4) preferences for other medications. Conclusions The results highlight opportunities to improve initiation of XR-NTX in high-need groups. Addressing expectations regarding induction may enhance XR-NTX initiation rates. Trial Registration ClinicalTrials.gov: NCT03275350. Registered September 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03275350?term=extended+release+naltrexone&cond=Opioid+Use.

Background Residential treatment is a common approach for treating opioid use disorder (OUD), however, few studies have directly compared it to outpatient treatment. The objective of this study was to compare OUD outcomes among individuals receiving residential and outpatient treatment. Methods A retrospective cohort study used linked data from a state Medicaid program, vital statistics, and the Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Episodes Dataset (TEDS) to compare OUD-related health outcomes among individuals treated in a residential or outpatient setting between 2014 and 2017. Multivariable Cox proportional hazards and logistic regression models examined the association between treatment setting and outcomes (i.e., opioid overdose, non-overdose opioid-related and all-cause emergency department (ED) visits, hospital admissions, and treatment retention) controlling for patient characteristics, co-morbidities, and use of medications for opioid use disorders (MOUD). Interaction models evaluated how MOUD use modified associations between treatment setting and outcomes. Results Of 3293 individuals treated for OUD, 957 (29%) received treatment in a residential facility. MOUD use was higher among those treated as an outpatient (43%) compared to residential (19%). The risk of opioid overdose (aHR 1.39; 95% CI 0.73–2.64) or an opioid-related emergency department encounter or admission (aHR 1.02; 95% CI 0.80–1.29) did not differ between treatment settings. Independent of setting, MOUD use was associated with a significant reduction in overdose risk (aHR 0.45; 95% CI 0.23–0.89). Residential care was associated with greater odds of retention at 6-months (aOR 1.71; 95% CI 1.32–2.21) but not 1-year. Residential treatment was only associated with improved retention for individuals not receiving MOUD (6-month aOR 2.05; 95% CI 1.56–2.71) with no benefit observed in those who received MOUD (aOR 0.75; 95% CI 0.46–1.29; interaction p = 0.001). Conclusions Relative to outpatient treatment, residential treatment was not associated with reductions in opioid overdose or opioid-related ED encounters/hospitalizations. Regardless of setting, MOUD use was associated with a significant reduction in opioid overdose risk.

Delivery of the newborn occurs either vaginally or via caesarean section. It is not known whether the mode of delivery and exposure to labor affects early autonomic nervous system (ANS) function, as measured by heart rate variability (HRV), or cortical electroencephalogram (EEG) activity. The objective of the study was to determine if autonomic function in newborns differs by mode of delivery. Simultaneous recording of EEG and electrocardiogram were collected in low-risk term newborns at

Purpose To compare early changes in autonomic nervous system (ANS) tone between newborns with complex congenital heart disease (CHD) and newborns without CHD. Methods We performed a case–control study of heart rate variability (HRV) in newborns with complex CHD [transposition of the great arteries (TGA) or hypoplastic left heart syndrome (HLHS)] and low-risk control newborns without CHD. Cases with CHD were admitted following birth to a pediatric cardiac intensive care unit and had archived continuous ECG data. Control infants were prospectively enrolled at birth. ECG data in cases and controls were analyzed for HRV in the time and frequency domains at 24 h of age. We analyzed the following HRV metrics: alpha short (αs), alpha long (αL), root mean square short and long (RMSs and RMSL), low-frequency (LF) power, normalized LF (nLF), high-frequency (HF) power, and normalized HF (nHF). We used ANOVA to compare HRV metrics between groups and to control for medication exposures. Results HRV data from 57 infants with CHD (TGA, n = 33 and HLHS, n = 24) and from 29 controls were analyzed. The HRV metrics αS, RMSL, LF, and nLF were significantly lower in infants with CHD than in the controls. Due to the effect of normalization, nHF was higher in CHD infants (P

PURPOSE: The mature central autonomic network includes connectivity between autonomic nervous system brainstem centers and the cerebral cortex. The study objective was to evaluate the regional connectivity between the cerebral cortex and brainstem autonomic centers in term newborns by measuring coherence between high-density electroencephalography and heart rate variability as measured by electrocardiography. METHODS: Low-risk term newborns with birth gestational age 39–40 weeks were prospectively enrolled and studied using time-synced electroencephalography and electrocardiography for up to 60 minutes before discharge from the birth hospital. The cortico-autonomic nervous system association was analyzed using coherence between electroencephalography-delta power and heart rate variability. Heart rate variability measured parasympathetic tone (root mean square of successive differences of heart rate) and sympathetic tone (standard deviation of heart rate). RESULTS: One hundred and twenty-nine low-risk term infants were included. High coherence delta(-)root mean square of successive differences was found in central, bi-temporal, and occipital brain regions with less robust coherence delta-standard deviation in the central region and bi-temporal areas. CONCLUSIONS: Our findings describe a topography of cortico-autonomic connectivity present at term in low-risk newborns, which was more robust to parasympathetic than sympathetic brainstem centers and was independent of newborn state.

OBJECTIVES: The objective of this study was to investigate methamphetamine use among people who use opioids in rural Oregon communities to explore reasons for use and perceptions of methamphetamine consequences. METHODS: We conducted interviews and surveys with participants who inject drugs or misuse prescription opioids in 2 rural Oregon counties with high opioid overdose rates. Survey participants were identified through participant-driven sampling initiated in syringe service programs and field outreach (n = 144). Semi-structured interviews with participants were recruited from the same locations (n = 52). RESULTS: Of 144 surveys completed, 112 reported using opioids in the past 30 days; 96% of the 112 also report methamphetamine use. Among the 124 reporting injection drug use, 50% indicated they injected both methamphetamine and heroin in the past 30 days. Interview participants reported early exposure to methamphetamine and indicated that methamphetamine was more widely available, less expensive, and less stigmatized compared to heroin. Participants reported using methamphetamine to improve work-life functioning and because they enjoy the high produced from simultaneous use. Several participants reported a conscious effort to shift to methamphetamine from heroin as a harm reduction strategy. Some participants reported being involuntarily discharged from treatment for opioid use disorder due to methamphetamine use. Several participants perceived methamphetamine as conveying overdose prevention or reversal benefits, while fentanyl contamination in methamphetamine was reported or suspected. CONCLUSION: As rural communities respond to evolving drug supply and demand, there is increasing need for public health efforts to address the emerging issue of concurrent methamphetamine and opioid use.

Parenteral nutrition-associated cholestasis (PNAC) causes serious morbidity in the neonatal intensive care unit. Infection with gut-associated bacteria is associated with cholestasis, but the role of intestinal microbiota in PNAC is poorly understood. We examined the composition of stool microbiota from premature twins discordant for PNAC as a strategy to reduce confounding from variables associated with both microbiota and cholestasis. Eighty-four serial stool samples were included from 4 twin sets discordant for PNAC. Random Forests was utilized to determine genera most discriminatory in classifying samples from infants with and without PNAC. In infants with PNAC, we detected a significant increase in the relative abundance of Klebsiella, Veillonella, Enterobacter, and Enterococcus (P < 0.05). Bray-Curtis dissimilarities in infants with PNAC were significantly different (P < 0.05) from infants without PNAC. Our findings warrant further exploration in larger cohorts and experimental models of PNAC to determine if a microbiota signature predicts PNAC, as a basis for future interventions to mitigate liver injury.

In premature infants, we investigated whether the duration of extrauterine development influenced autonomic nervous system (ANS) maturation.We performed a longitudinal cohort study of ANS maturation in preterm infants. Eligibility included birth gestational age (GA) 37 weeks, NICU admission, and expected survival. The cohort was divided into three birth GA groups: Group 1 (≤29 weeks), Group 2 (30-33 weeks), and Group 3 (≥34 weeks). ECG data were recorded weekly and analyzed for sympathetic and parasympathetic tone using heart rate variability (HRV). Quantile regression modeled the slope of ANS maturation among the groups by postnatal age to term-equivalent age (TEA) (≥37 weeks).One hundred infants, median (Q1-Q3) birth GA of 31.9 (28.7-33.9) weeks, were enrolled: Group 1 (n = 35); Group 2 (n = 40); and Group 3 (n = 25). Earlier birth GA was associated with lower sympathetic and parasympathetic tone. However, the rate of autonomic maturation was similar, and at TEA there was no difference in HRV metrics across the three groups. The majority of infants (91%) did not experience significant neonatal morbidities.Premature infants with low prematurity-related systemic morbidity have maturational trajectories of ANS development that are comparable across a wide range of ex-utero durations regardless of birth GA.Heart rate variability can evaluate the maturation of the autonomic nervous system. Metrics of both the sympathetic and parasympathetic nervous system show maturation in the premature extrauterine milieu. The autonomic nervous system in preterm infants shows comparable maturation across a wide range of birth gestational ages. Preterm newborns with low medical morbidity have maturation of their autonomic nervous system while in the NICU. Modern NICU advances appear to support autonomic development in the preterm infant.

The study examines impacts of delivery system reforms and Medicaid expansion on treatment for alcohol use disorders within the Oregon Health Plan (Medicaid). Diagnoses, services and pharmacy claims related to alcohol use disorders were extracted from Medicaid encounter data. Logistic regression and interrupted time series analyses assessed the percent with alcohol use disorder entering care and the percent receiving pharmacotherapy before (January 2010 – June 2012) and after (January 2013 – June 2015) the initiation of Oregon’s Coordinated Care Organization (CCO) model (July 2012 – December 2012). Analyses also examined changes in access following Medicaid expansion (January 2014). Treatment entry rates increased from 35% in 2010 to 41% in 2015 following the introduction of CCOs and Medicaid expansion. The number of Medicaid enrollees with a diagnosed alcohol use disorder increased about 150% from 10,360 (2013) to 25, 454 (2014) following Medicaid expansion. Individuals with an alcohol use disorder who were prescribed a medication to support recovery increased from 2.3% (2010) to 3.8% (2015). In Oregon, Medicaid expansion and health care reforms enhanced access and improved treatment initiation for alcohol use disorders.

Objective To examine the influence of Oregon's coordinated care organizations (CCOs) and pay-for-performance incentive model on completion of screening and brief intervention (SBI) and utilization of substance use disorder (SUD) treatment services. Data Sources/Study Setting Secondary analysis of Medicaid encounter data from 2012 to 2015 and semiannual qualitative interviews with stakeholders in CCOs. Study Design Longitudinal mixed-methods design with simultaneous data collection with equal importance. Data Collection/Extraction Methods Qualitative interviews were recorded, transcribed, and coded in ATLAS.ti. Quantitative data included Medicaid encounters 30 months prior to CCO implementation, a 6-month transition period, and 30 months following CCO implementation. Data were aggregated by half-year with analyses restricted to Medicaid recipients 18–64 years of age enrolled in a CCO, not eligible for Medicare coverage or Medicaid expansion. Principal Findings Quantitative analysis documented a significant increase in SBI rates coinciding with CCO implementation (0.1 to 4.6 percent). Completed SBI was not associated with increased initiation in treatment for SUD diagnoses. Qualitative analysis highlighted importance of aligning incentives, workflow redesign, and leadership to facilitate statewide SBI. Conclusions Results provide modest support for use of a performance metric to expand SBI in primary care. Future research should examine health reform efforts that increase initiation and engagement in SUD treatment.

Background The CTN-0067 CHOICES trial tests implementation of extended-release naltrexone (XR-NTX) versus treatment-as-usual (TAU) for opioid use disorders (OUD) in HIV clinics to improve HIV viral suppression. The study team investigated recruitment strategies to elucidate the barriers and facilitators to recruitment and enrollment in the study. Main text Methods: Semi-structured, in-depth, digitally recorded interviews were completed with study recruitment-related staff and medical providers (n = 26) from six participating HIV clinics in the fall of 2018. Interviews probed 1) factors that might prevent prospective participants from engaging in study recruitment and enrollment procedures and 2) strategies used by study staff that encourage eligible patient participation. Interviews were transcribed and thematically analyzed using a content analysis approach. Results: All respondents reported that barriers to recruitment and enrollment included challenging patient social and structural factors (e.g., homelessness or living environments with high substance use, criminal justice involvement), difficulty locating patients with unsuppressed HIV viral load and OUD within the HIV clinic, time-consuming study enrollment processes, and stigma around HIV and OUD which inhibited treatment seeking. Some respondents observed that distrust of research and researchers impeded recruitment activities in the community. A specific medication-related barrier was patient fear of opioid abstinence required prior to XR-NTX induction. Facilitators of recruitment included use of trusted peer outreach/recruitment workers in the community, hospitalizations that offered windows of opportunities for screening and XR-NTX induction, providing participant transportation, and partnerships with harm reduction organizations for referrals. Conclusions Though study personnel encountered barriers to recruitment in the CHOICES study, persons with untreated HIV and OUD can be enrolled in multisite clinical trials by using enhanced recruitment strategies that extend outside of the HIV clinic. Employing peer outreach workers and collaborating with syringe service programs may be especially helpful in facilitating recruitment and merit inclusion in similar study protocols.

Objective To establish whether fetal cerebral vasoreactivity (CVRO2 ), following maternal hyperoxia, is predicted by fetal cerebral and uteroplacental Doppler pulsatility indices (PI) at baseline, fetal pulmonary vasoreactivity to oxygen (PVRO2 ), gestational age (GA), or sex. Methods Pulsatility index of middle (MCA), anterior (ACA), posterior cerebral (PCA), umbilical (UA), uterine (UtA), and branch of the pulmonary arteries (PA) were obtained, by ultrasound, before (baseline), during (hyperoxia) and after 15 minutes of maternal administration of 8 L/min of 100% oxygen, through a non-rebreathing face mask, in normal singleton pregnancies within 20 to 38 weeks' gestation. CVRO2 was defined as changes greater than zero in z score of PI of the cerebral arteries from baseline to hyperoxia. Logistic modeling was applied to identify CVRO2 predictors. Results A total of 97 pregnancies were eligible. In the overall population, median z scores of PI of MCA, ACA, and PCA did not differ between study phases. Based on the logistic model, baseline z scores for cerebral PI and GA were the best predictors of CVRO2 . Conclusions In low-risk pregnancies, fetal CVRO2 to hyperoxia does not occur uniformly but depends on cerebral PI and GA at baseline. These findings may provide useful reference points when oxygen is administered in high-risk pregnancies.

Multiple myeloma (MM) is a slow-growing malignancy characterized by a low proliferation rate of plasma cells and a relatively rare incidence of tumour lysis syndrome (TLS). Three myeloma patients developed TLS following cytotoxic therapy (two after radiation treatment) that was associated with an abrupt increase of serum free light chains (FLC). All three patients demonstrated extramedullary plasmacytomas that exhibited aggressive features compared to the original myeloma. The findings suggested that an abrupt liberation (rather than slow secretion) of FLC from myeloma cells may trigger a fulminant cast nephropathy and present an unrecognized risk factor and potentially aggravating component of TLS.

Significance Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. The genetic and molecular characteristics of PTB and related disorders remain unclear. In this study, a family-based cohort of 791 family trios, including 270 PTB and 521 control families, was investigated by using whole-genome sequencing, RNA sequencing, and DNA methylation data. Integrative analysis identified 160 genomic variants associated with PTB-related phenotypes and led to the discovery of 72 candidate biomarker genes for very early PTB (VEPTB). The genes associated with VEPTB involve growth signaling and inflammation- and immunity-related pathways. With these data, and by stratifying PTB by subphenotype, we have identified PTB genes and pathways that can be used as a starting point in further clinical studies., Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. By using whole blood samples, we integrated whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation data for 270 PTB and 521 control families. We analyzed this combined dataset to identify genomic variants associated with PTB and secondary analyses to identify variants associated with very early PTB (VEPTB) as well as other subcategories of disease that may contribute to PTB. We identified differentially expressed genes (DEGs) and methylated genomic loci and performed expression and methylation quantitative trait loci analyses to link genomic variants to these expression and methylation changes. We performed enrichment tests to identify overlaps between new and known PTB candidate gene systems. We identified 160 significant genomic variants associated with PTB-related phenotypes. The most significant variants, DEGs, and differentially methylated loci were associated with VEPTB. Integration of all data types identified a set of 72 candidate biomarker genes for VEPTB, encompassing genes and those previously associated with PTB. Notably, PTB-associated genes RAB31 and RBPJ were identified by all three data types (WGS, RNA-seq, and methylation). Pathways associated with VEPTB include EGFR and prolactin signaling pathways, inflammation- and immunity-related pathways, chemokine signaling, IFN-γ signaling, and Notch1 signaling. Progress in identifying molecular components of a complex disease is aided by integrated analyses of multiple molecular data types and clinical data. With these data, and by stratifying PTB by subphenotype, we have identified associations between VEPTB and the underlying biology.

Background It is important to understand patterns and predictors of initiation and engagement in treatment for Medicaid-covered individuals with substance use disorders because Medicaid is a major source of payment for addiction treatment in the United States. Our analysis examined similarities and differences in predictors between adults and adolescents. Methods An analysis of Oregon Medicaid claims data for the time period January 2010 through June 2015 assessed rates of substance use and of treatment initiation and engagement using the Healthcare Effectiveness Data and Information Set (HEDIS) definitions. The analysis included individuals aged 13–64 with a new alcohol and other drug dependence diagnosis who met the HEDIS enrollment criteria and did not have cancer. We created 4 logistic regression models to assess treatment initiation and engagement, separately for adults (ages 18–64) and adolescents (ages 13–17). Independent predictors included age, gender, race, the interaction of gender and race, urban/rural residence, presence of any chronic disease, a psychiatric diagnosis, or a pain diagnosis. Results Among adults, odds of initiation were lower in white males than in nonwhite males, white females, and nonwhite females. Conversely, among adolescents, odds of initiation were higher in white males than in the other gender/race groups. Predictors of initiation also went in opposite directions for presence of a psychiatric diagnosis (negative in adults, positive in adolescents) and urban residence (positive in adults, negative in adolescents). We found similar patterns in models of engagement, although for engagement those with a psychiatric diagnosis had lower odds of engagement in both adults and adolescents. Conclusions Predictors of treatment initiation and engagement for alcohol and drug use disorders differed between adults and adolescents on Medicaid. A better understanding of these differences will enable development of targeted treatment programs that are effective within age groups.

Background Premature infants are vulnerable to destructive brain injury and disturbed neurological development. Prematurity may alter maturation of the central autonomic nervous system (ANS). Aims To compare ANS function (using heart rate variability; HRV) between preterm infants with normal neuroimaging at term equivalent age and low-risk term controls. Study design, subjects. We performed a case-control study of preterm infants born ≤28 weeks gestational age that had normal brain imaging and archived continuous EKG data at term equivalent age. We documented other factors thought to influence ANS maturation (e.g. infection, ventilation days, and postnatal steroids). Controls were low-risk term gestational age newborns from uncomplicated pregnancies/deliveries. We characterized HRV metrics using frequency-(Welch periodogram) and time-domain (detrended fluctuation) analyses. Sympathetic tone was characterized by α1, root mean square analysis (RMS1 and RMS2), low-frequency (LF) power, and normalized LF (nLF) and parasympathetic tone was characterized by high-frequency (HF) power and normalized HF (nHF). α2 characterized ultraslow changes in heart rate. We used ANCOVA to compare HRV metrics between groups. Outcome measures, results. HRV from 26 preterm infants were compared to 55 controls. Analyzed HRV data for preterm infants were recorded at median (range) gestational age of 39 (36–39) weeks and for controls at 39 (37–41) weeks gestational age. α1, RMS2, LF and HF were significantly higher in control infants and remained significant after controlling for infection, ventilator days, and postnatal steroids (P Conclusions Autonomic maturation is impaired in a premature extrauterine environment. In the absence of destructive brain injury, our data suggest an important role for disturbed programming in this impaired autonomic development.

Objective Health system reform is largely dependent upon the transformation of primary care in addition to the alignment of incentives that mediate the allocation of resources. The Patient-Centered Medical Home (PCMH) is a model of enhanced primary care that encourages coordination, patient-centered care, integration of public health services, and innovative methods for improving population health-all critical elements of health system reform. Because it changes the way primary care is organized and delivered, the PCMH model has been adopted as a foundational component of Oregon's health system transformation. This article presents insights drawn from an evaluation of the implementation of Oregon's Patient-Centered Primary Care Home (PCPCH) program and the adoption of the model by primary care providers. Design We used a mixed-methods approach consisting of 2 surveys of recognized PCPCH practices, qualitative document analysis, and key informant interviews. Evaluation research findings were triangulated with findings from PCPCH clinic site visits conducted as part of a regulatory verification process. Results Survey results describe a broad range of strategies and practices adopted by recognized PCPCH clinics within 6 defined core attributes: (1) access to care; (2) accountability; (3) comprehensive whole-person care; (4) continuity; (5) coordination and integration; and (6) person- and family-centered care. We also identify 4 key factors that influenced the conceptualization, development, and implementation of the PCPCH program: (1) support and motivations; (2) administrative barriers and resource constraints; (3) alignment of short- and long-term financial incentives; and (4) leadership and interpersonal relationships. Conclusions This evaluation provides insights into the factors that influence implementation of a primary care home program as public policy; the strategies and challenges associated with implementation of the model; and the implications of both for other states that are engaged in-or considering-similar system reform efforts.

Objectives The phrase “level of sperm competition” is used only vaguely in the primate literature. There is also little distinction between the important elements of frequency and intensity of sperm competition, largely because the two current forms of measurement (socio-sexual system and relative testes size) are both proxies which allow neither precision nor fine distinctions. Both measures have critics, socio-sexual system in particular being branded subjective, misleading, and changeable. Testes size is considered the more reliable despite its validation resting on correlations with the other, less reliable, proxy. Recently, genetic paternity studies have been mooted to provide a potentially superior third measure of sperm competition but so far lack a formal interpretive framework. Here we use the published and relatively comprehensive genetic field studies of the Hominoidea to develop such a framework. Materials and methods Formulae are derived to convert paternity data into a direct measure of the frequency, intensity, and overall level of sperm competition. We then compare these measures with relative testes size at the study, species, and phylogenetic levels. Results A significant correlation between level of sperm competition and relative testes size was obtained at each level. These correlations provide independent support for the continuing use of testes size as a proxy measure when such a measure is sufficient. However, they also suggest that paternity data and our formulae yield a viable alternative measure. Discussion This alternative measure based on paternity data has a number of advantages. Not only is it a potentially direct measure of the level of sperm competition but it also allows the roles of frequency and intensity to be studied separately when of interest.

OBJECTIVE To examine whether a one-factor executive function (EF) model fit data for three groups of children differing in birth criteria (extremely low birth weight [ELBW], late preterm [LPT], and Term) at each of two chronological ages, 3 and 6 years, and whether the latent mean amount of EF differed. METHODS A retrospective observational cohort study of 1,079 participants; 668 aged 3 years born 2000-2009 (93 ELBW, 398 LPT, and 177 Term) and 411 aged 6 years born 1998-2006 (126 ELBW, 102 LPT, and 183 Term). Latent means analysis was conducted using five indicators for EF: noun fluency, action-verb fluency, similarities reasoning, matrices reasoning, and working memory. RESULTS A one-factor model had acceptable fit for all groups (RMSEA 0.95, SRMR

Community-based participatory research (CBPR) is increasingly being used to better understand and improve the health of diverse communities. A key strength of this research orientation is its adaptability to community contexts and characteristics. To date, however, few studies explicitly discuss adaptations made to CBPR principles and processes in response to community context and partners' needs. Using data from our CBPR study, the San Francisco Chinatown Restaurant Worker Health and Safety Project, and drawing from literature on immigrant political incorporation, we examine the links between the contexts of the Chinese immigrant worker community, adaptations made by our collaborative, and study outcomes. In particular, we explore the concepts of contexts of reception and participatory starting points, which may be especially relevant for partnerships with immigrant communities whose members have historically had lower rates of civic and political participation in the US. We discuss contextual findings such as worker partner accounts of language barriers, economic and social marginalization, and civic skills and participation, as well as subsequent adaptations made by the partnership. We also describe the relative effectiveness of these adaptations in yielding equitable participation and building partners' capacity. We conclude by sharing lessons learned and their implications for CBPR and partnerships with immigrant communities more broadly.

Germline mutations are the source of evolution and contribute substantially to many health-related processes. Here we use whole-genome deep sequencing data from 693 parents–offspring trios to examine the de novo point mutations (DNMs) in the offspring. Our estimate for the mutation rate per base pair per generation is 1.05 × 10−8, well within the range of previous studies. We show that maternal age has a small but significant correlation with the total number of DNMs in the offspring after controlling for paternal age (0.51 additional mutations per year, 95% CI: 0.29, 0.73), which was not detectable in the smaller and younger parental cohorts of earlier studies. Furthermore, while the total number of DNMs increases at a constant rate for paternal age, the contribution from the mother increases at an accelerated rate with age.These observations have implications related to the incidence of de novo mutations relating to maternal age., The study of germline mutations has been greatly enhanced by massive parallel sequencing technologies. Here the authors use deep sequencing data from nearly 700 parent-child trios to show maternal age has a small but significant correlation with the number of de novo mutations in the offspring.

Preterm (PT) birth is an established risk factor for high mortality and morbidity rates. Infants and school-aged children have been well-studied, but few have described neuropsychological and behavioral outcomes at preschool age. We compared a 2004-2006 preterm/extremely low birth weight (ELBW) cohort (PT/ELBW; N = 60) born ≤ 33 weeks gestation and

Objective: Motor impairments are prevalent in children born at extremely low birth weight (ELBW; < 1,000 g). Rarely studied are subtle motor deficits that indicate dysfunction or delay in neural systems critical for optimal cognitive, academic, and behavioral function. We aimed to examine quantifiable signs of subtle neuromotor dysfunction in an early school-aged ELBW cohort that coincidentally had age-appropriate cognition and design copying. Method: We studied 97 participants born between 1998 and 2001; 74 ELBW (6.7 years ± 0.75) compared with 23 term-born (6.6 years ± 0.29). Neuromotor outcomes were assessed using the Physical and Neurological Examination of Subtle Signs-Revised, and measures of dexterity/coordination and visual-motor integration. Results: ELBW participants performed worse than term-born on design-copying and dexterity, were age-appropriate compared to normative data, and had slower timed movements and more subtle overflow movements. Those ELBW born

Background Restaurant workers have among the highest rates of work-related illness and injury in the US, but little is known about the working conditions and occupational health status of Chinese immigrant restaurant workers. Methods Community-based participatory research (CBPR) was employed to study restaurant working conditions and worker health in San Francisco’s Chinatown. A community/academic/health department collaborative was formed and 23 restaurant workers trained on research techniques and worker health and safety. A worker survey instrument and a restaurant observational checklist were collaboratively developed. The checklist was piloted in 71 Chinatown restaurants, and the questionnaire administered to 433 restaurant workers. Results Restaurantworkers,togetherwithotherpartners,madesubstantialcontributions to construction of the survey and checklist tools and improved their cultural appropriateness. The utility of the checklist tool for restaurant-level data collection was demonstrated. Conclusions CBPR holds promise for both studying worker health and safety among immigrantChineserestaurantworkersanddevelopingculturallyappropriateresearchtools. A new observational checklist also has potential for restaurant-level data collection on worker health and safety conditions. Am. J. Ind. Med. 2010 Wiley-Liss, Inc.

Background Late-preterm children constitute a majority of all preterm deliveries (75%). Their immature brain development at birth has been associated with an increased risk for morbidities. Data have been sparse regarding neuropsychological outcomes in the preschool years. Aim To examine general cognition, attention/working memory, language, manual coordination/motor dexterity, visuomotor, visuospatial, and executive functions in preschoolers born late-preterm (LPT; 34–36 gestational weeks) who required NICU admission compared to term-born participants. Design Single-center retrospective cohort study of 95 three-year-old children; 60 born LPT in 2004–2005 and admitted to the NICU compared to 35 healthy term-born participants born ≥ 37 gestational weeks and ≥ 2500 g. Results LPT birth was associated with visuospatial (p = .005), visuomotor (p = .012), and executive function (noun [p = .018] and action-verb [p = .026] fluency) relative deficits, but not attention/working memory, receptive or expressive language, nonverbal reasoning, or manual coordination/dexterity deficit. Conclusions Late-preterm birth is likely to be associated with negative neuropsychological sequelae, although subtle and selective compared to effects reported for children born at an earlier gestational age. Visuospatial function appears to be especially vulnerable to disruption even at preschool age, and verbal fluency may be useful as an early predictor of executive dysfunction in childhood. Routine preschool neuropsychological evaluation is recommended to identify delay or deficit in LPT children preparing for school entry, and may highlight underlying vulnerable neural networks in LPT children.

The restaurant and food service industry in California employs one million workers, largely low-paid, vulnerable workers, including many immigrant and young workers. Ninety percent of these businesses have fewer than 50 employees (half have fewer than 10 employees)1 and often lack the health and safety information and resources typically available to larger businesses.2,3 In addition, the fast-paced nature of restaurant and food service work and the tight profit margins for many small restaurants pose challenges for integrating effective health and safety training. In response to this need, the California Commission on Health and Safety and Workers' Compensation (CHSWC) funded the development of a health and safety training program for owners/managers of small restaurants as part of its Worker Occupational Safety and Health Training and Education Program (WOSHTEP). WOSHTEP is administered by CHSWC in the Department of Industrial Relations through interagency agreements with the Labor Occupational Health Program (LOHP) at the University of California, Berkeley (UC Berkeley), and the Labor Occupational Safety and Health Program (LOSH) at the University of California, Los Angeles. Research has indicated that work culture issues, including management's commitment to and employees' engagement in health and safety, may be more important than training per se in actually preventing injuries.4–6 Yet, previously developed educational tools on restaurant health and safety did not provide employers with specific activities to support this approach.7–9 The focus of the Small Business Restaurant Supervisor Safety Training program was to encourage restaurant owners/managers to train their employees in a way that actively engages them in identifying hazards as well as solutions, and demonstrates management's commitment to making the workplace changes that are identified (including physical and work practice changes). To develop the program, LOHP reviewed existing materials, held discussions with owners of small restaurants in an informal focus group, field-tested training activities with workers in several restaurants, and pilot-tested a training workshop for managers and supervisors. Feedback from restaurateurs emphasized that training time is very limited; resources must be brief, user-friendly, and adaptable to their own restaurants; and any materials for employees must also be available in Spanish. As a result, the program's materials included a training guide for two short activities that owners/managers could conduct with their employees: (1) a walk-through or hazard-mapping activity to identify hazards in their workplace, and (2) an activity to encourage employees to generate possible solutions for specific problems using hazard-specific tip sheets. The training packet also contained other resources including a model shoe policy, fact sheets on employing teen workers, and an employee orientation checklist. Several of these resources were adapted from the “Teen-worker Restaurant Safety Program” materials developed previously by the Washington State Department of Labor and Industries.9 The entire packet was available in both Spanish and English. The training program for the owners/managers consisted of two hours of interactive training that included a demonstration of the hazard-mapping and tip sheet activities. During 2006, in partnership with the California State Compensation Insurance Fund and the California Restaurant Association, trainers from LOHP and LOSH conducted 17 two-hour training workshops for more than 200 restaurant and food service owners/managers. The training program was evaluated at the end of the first year of implementation as part of an independent evaluation of WOSHTEP. The goal of the evaluation was to assess the effects of the program and whether it helped small business managers to (1) conduct effective health and safety training for their employees, (2) involve employees in identifying and addressing workplace hazards, and (3) make changes in the physical workplace and work practices to improve workplace safety. The evaluation was modestly funded as part of a service delivery program and not as a formal research activity. Its primary purpose was to inform program stakeholders and provide a basis to decide whether to modify, abolish, or continue the program. This article summarizes the results of the evaluation.

An observational study of neuropsychological outcomes at preschool age of tiered lowered oxygen (O2) saturation targets in extremely preterm neonates. We studied 111 three-year-olds born 2group. Comparisons were made with 52 participants born in 2007–2008 when pre-initiative saturation targets were non-tiered at 89–100%, the Non-tieredO2group. Neuropsychological domains included general intellectual, executive, attention, language, visuoperceptual, visual-motor, and fine and gross motor functioning. Descriptive and inferential analyses were conducted. Group comparisons were not statistically significant. Descriptively, the TieredO2group had better general intellectual, executive function, visual-motor, and motor performance and the Non-tieredO2group had better language performance. Cohen’sdand confidence intervals arounddwere in similar direction and magnitude across measures. A large effect size was found for recall of digits-forward in participants born at 23 and 24 weeks’ gestation,d=0.99 and 1.46, respectively. Better TieredO2outcomes in all domains except language suggests that the tiered oxygen saturation target method is not harmful and merits further investigation through further studies. Benefit in auditory attention appeared greatest in those born at 23 and 24 weeks. Participants in the tiered oxygen saturation group also had fewer ventilation days and a lower incidence of bronchopulmonary dysplasia, perhaps explanatory for these neuropsychological outcomes at age 3. (JINS, 2015,21, 322–331)

To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS). Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing. NBS genes are generally well covered by WGS. There is a median of one (range: 0–6) database-annotated pathogenic variant in the NBS genes per infant. Results of WGS and NBS in detecting 28 state-screened disorders and four hemoglobin traits were concordant for 88.6% of true positives (n = 35) and 98.9% of true negatives (n = 45,757). Of the five infants affected with a state-screened disorder, WGS identified two whereas NBS detected four. WGS yielded fewer false positives than NBS (0.037 vs. 0.17%) but more results of uncertain significance (0.90 vs. 0.013%). WGS may help rule in and rule out NBS disorders, pinpoint molecular diagnoses, and detect conditions not amenable to current NBS assays. Genet Med 18 3, 221–230.

Research translation too often relies on passive methods that fail to reach those who can impact the workplace. The need for better research to practice (r2p) approaches is especially pressing in construction, where a disproportionate number of workers suffer serious injury illness.A triage process was designed and used to systematically review completed research, assess r2p readiness, establish priorities, and launch dissemination follow-up efforts. A mixed quantitative and qualitative approach was used.The process proved effective in ensuring that significant findings and evidence-based solutions are disseminated actively. Key factors emerged in the selection of follow-up priorities, including availability of partners able to reach end users, windows of opportunity, and cross-cutting approaches that can benefit multiple dissemination efforts.Use of a systematic triage process may have an important role to play in building r2p capacity in construction safety and health.

Multi-stakeholder partnerships play a critical role in dissemination and implementation in health and safety. To better document and understand construction partnerships that have successfully scaled up effective interventions to protect workers, this case study focused on the collaborative processes of the Asphalt Paving Partnership. In the 1990s, this partnership developed, evaluated, disseminated, and achieved near universal, voluntary adoption of paver engineering controls to reduce exposure to asphalt fumes.We used in-depth interviews (n = 15) and document review in the case study.We describe contextual factors that both facilitated and challenged the formation of the collaboration, central themes and group processes, and research to practice (r2p) outcomes.The Asphalt Paving Partnership offers insight into how multi-stakeholder partnerships in construction can draw upon the strengths of diverse members to improve the dissemination and adoption of health and safety innovations and build a collaborative infrastructure to sustain momentum over time.

Falls are the leading cause of fatalities in construction. The Safety Pays, Falls Cost campaign aims to prevent falls in residential construction. A critical component of our social marketing approach was to involve 70 partners in reaching target audiences.We assessed partner engagement April 2012-August 2013 through: (1) baseline partnership quality interviews (eight partners); (2) pre-/post-partner "market" readiness in-depth interviews (three partners); (3) a pre-/post- (29/31 partners) online partner engagement survey; and (4) standardized metrics to measure partner activity.We found a high level of interest and engagement that increased with the addition of prompting to action through regular communication and new resources from organizers and formation of local partnerships that were able to tailor their activities to their own communities or regions.It is feasible to leverage government-labor-management partnerships that enjoy trust among target audiences to widely disseminate campaign materials and messages.

The nucleoside analogue 3'-azido-3'-deoxythymidine (AZT) is a weak carcinogen in adult female mice and a moderately strong carcinogen in the offspring of female mice given the drug during gestation. In addition, incorporation of AZT into DNA was observed in multiple organs of transplacentally exposed newborn mice. Here we investigate the incorporation of AZT into peripheral leukocyte DNA of HIV-1-positive adult pregnant women given AZT for variable times during gestation and cord blood of infants exposed to AZT in utero. The length of treatment varied between 10 days and 9 months. High molecular weight DNA was extracted from maternal peripheral blood mononuclear cells (PBMC) and infant cord blood. A specific AZT-DNA radioimmunoassay was used to determine the amount of AZT incorporated into leukocyte DNA. Incorporation of AZT into DNA ranged up to 183.3 and 344.5 molecules of AZT/10(6) nucleotides in the mothers and infants, respectively, and was detected in about 70% of samples. Therefore, AZT-induced mutagenic events are possible in the majority of adults and infants. No correlation was found between level of incorporation and length of AZT treatment, suggesting that the differences observed among the individuals arise from variability in AZT metabolism. These data support previous observations that a high degree of inter-individual variability in AZT phosphorylation occurs in primates.

We sought to study respiratory symptoms among automobile assembly workers.In a cross-sectional study, we compared rates of respiratory symptoms and of physician-diagnosed asthma and COPD in painters and welders to those in assembly workers.Respiratory symptom reporting was significantly increased among welders (odds ratio [OR] = 1.79-2.61) compared with painters or assembly workers, after age, race, and smoking adjustment in multiple logistic regression analyses. Welders also reported significantly more improvement in symptoms on weekends or vacation. However, no significant elevations in adjusted ORs were observed for physician-diagnosed asthma or chronic obstructive pulmonary disease for welders. In contrast, significantly more painters had physician-diagnosed chronic obstructive pulmonary disease (OR = 3.73, 95% confidence interval = 1.27, 11.0).Welders and painters in this plant appeared to have increased risk of respiratory health effects compared with assembly workers.

Leukocytes from adult peripheral blood generate HIV-inhibitory soluble factors after stimulation with influenza A virus or allogeneic leukocytes. Leukocytes from neonates and adults exhibit immunological differences, and it is not known whether cord blood leukocytes secrete antiviral molecules after these types of stimulation. Our findings that cord blood mononuclear cells can generate soluble HIV-inhibitory factor(s), after antigenic stimulation, may have implications for understanding the host defence mechanisms of HIV-1 vertical transmission and the development of potential vaccine adjuvants.

Background: The approach to and delivery of medical student education has undergone significant change within the last decade. There has been a shift away from didactic lectures to small group tutorials, facilitated by clinicians. Anecdotally there is an impression that enthusiasm for teaching is waning. The aim of this qualitative study is to assess the current attitudes of consultants, across all specialities, to teaching medical students in small group settings. Methods: A Likert scale questionnaire, relating to teaching medical students in small group tutorials, was distributed via email to all consultants working in one region. Questions considered the categories: attitudes to teaching, financial considerations, time constraints and attitudes to students. Results: 367 responses were received. 72% of responders were actively involved in teaching. 72% of respondents indicated that medical students should be taught by consultants and 80% felt that teaching medical students was enjoyable. 60% felt they were not financially remunerated for teaching and 50% indicated teaching was not included in job plans; despite this a significant proportion of these respondents remain involved in teaching (68%). Non-teachers were more likely to indicate that teaching was not paid for (p=0.003). 78% indicated consultants do not have adequate time to teach medical students. 82% felt that medical students appreciate consultant led teaching but only 55% felt students had an appropriate level of enthusiasm for learning. Conclusion: Consultants in this Deanery are actively involved in medical student teaching and enjoy it. Consultants perceive that they are not adequately financially rewarded but for the most part this is not a deterrent. Time constraints are an issue and there is a desire to have teaching included in job plans to counteract this. Most consultants are complimentary about student attitudes but there is a perception that medical students need to contribute more to their own learning.

Monocyte-derived cytokine production by cord blood mononuclear cells (CBMC) from infants born to human immunodeficiency virus (HIV)-positive and -negative women was measured to determine whether monocyte dysfunction could contribute to the accelerated HIV disease of pediatric patients. Production of interleukin (IL)-12, but not that of tumor necrosis factor-alpha and IL-10, was reduced, compared with adult peripheral blood mononuclear cells (PBMC). This deficiency was more pronounced in infants of HIV-positive women, whose IL-12 production was also deficient. CBMC IL-12 levels were increased by interferon-gamma and CD40 ligand but remained deficient, compared with PBMC. IL-12 production was undetectable in 7 of 8 HIV-positive infants, in contrast to 21 of 26 uninfected infants. Uninfected infants of infected women exhibited an intermediate profile. These findings suggest that the maternal environment and/or exposure in utero to HIV products influence the newborn's immune response and that the differences between infants born to HIV-positive and -negative women may persist.

OBJECTIVE The nucleoside analog 3'-azido-3'-deoxythymidine (ZDV) has widespread clinical use but also is carcinogenic in newborn mice exposed to the drug in utero and becomes incorporated into newborn mouse DNA. This pilot study was designed to determine ZDV incorporation into human blood cell DNA from adults and newborn infants. DESIGN In this prospective cohort study, peripheral blood mononuclear cells (PBMC) were obtained from 28 non-pregnant adults and 12 pregnant women given ZDV therapy, six non-pregnant adults with no exposure to ZDV, and six non-pregnant adults who last received ZDV > or = 6 months previously. In addition, cord blood leukocytes were obtained from 22 infants of HIV-1-positive, ZDV-exposed women and from 12 infants unexposed to ZDV. There were 11 mother-infant pairs involving HIV-1 -positive women. METHODS DNA was extracted from PBMC obtained from non-pregnant HIV-1-positive adults taking ZDV, pregnant HIV-1-positive women given ZDV during pregnancy, and from adults not taking ZDV. Cord blood leukocytes were examined from infants exposed to ZDV in utero and from unexposed controls. DNA samples were assayed for ZDV incorporation by anti-ZDV radioimmunoassay (RIA). RESULTS The majority (76%) of samples from ZDV-exposed individuals, pregnant women (8 of 12), non-pregnant adults (24 of 28), or infants at delivery (15 of 22), had detectable ZDV-DNA levels. The range of positive values for ZDV-treated adults and infants was 25-544 and 22-452 molecules ZDV/10(6) nucleotides, respectively. Analysis of 11 mother-infant pairs showed variable ZDV-DNA incorporation in both, with no correlation by pair or by duration of drug treatment during pregnancy. Two of the 24 samples from individuals designated as controls were positive by anti-ZDV RIA. The 20-fold range for ZDV-DNA values in both adults and infants suggested large interindividual differences in ZDV phosphorylation. CONCLUSIONS Incorporation of ZDV into DNA was detected in most of the samples from ZDV-exposed adults and infants. Therefore, the biologic significance of ZDV-DNA damage and potential subsequent events, such as mutagenicity, should be

Primal. Virgin Books, 2009, 384 pp., US$10.86 (e-book). Caballito. Hard Nut Books, 2012, 210 pp., US$9.99 (e-book). The Hitchhiker's Child. Hard Nut Books, 2013, 239 pp., US$9.99 (e-book).

Late preterm (LP) birth (34 0/7 - 36 6/7 weeks’ gestation) accounts for nearly three-fourths of all preterm births, making this population a sizeable public health concern. The immature fetal development associated with LP delivery increases the risk of mortality and short-term medical complications. Which combination of maternal, fetal, or neonatal risk factors may be most critical has only recently begun to be addressed, and whether LP birth’s disruptive impact on brain development will exert adverse effects on neuropsychological functioning in childhood and adolescence has been understudied. Early data have shown a graded response, with LP children often functioning better than very preterm children but worse than term children, and with subtle intellectual and neuropsychological deficits in LP children compared with healthy children born at term gestational age. Further characterization of the neuropsychological profile is required and would be best accomplished through prospective longitudinal studies. Moreover, since moderate and LP births result in disparate medical and psychological outcomes, the common methodology of combining these participants into a single research cohort to assess risk and outcome should be reconsidered. The rapidly growing LP outcomes literature reinforces a critical principle: fetal development occurs along a dynamic maturational continuum from conception to birth, with each successive gestational day likely to improve overall outcome.

Spatial location memory has rarely been assessed in young children due to a scarcity of developmentally appropriate tests. This study sought to compare nonverbal learning and recall in children born extremely low birth weight (ELBW;1000 g) and less than 33 gestational weeks (GW) with term-born children at early school age using a recently developed and adapted test. We administered a modification of the Hopkins Board to 210 children at age six; 84 born ELBW (35 born26 GW; 49 born 26-33 GW) and 126 term-born. Six measures were obtained: naming, trials-to-criterion, errors-to-criterion, delayed item recall, delayed location recall, and percent retention. After age correction, ELBW children had worse general cognition, item naming, delayed item recall, delayed location recall, and percent retention than term-born children. Delayed item recall and percent retention performances of ELBW children remained worse after correction for general cognition. ELBW groups (26 GW and 26-33 GW) groups performed worse than term-born children in naming and delayed item recall with chronological age as covariate. Those born before 26 GW, but not 26-33 GW, performed worse than term-born children in delayed location recall and percent retention. Differences remained significant after controlling for gender, maternal education, and delivery type. All three groups' performance declined from final learning trial to delayed location recall, with a decline greater for less than 26 GW than term-born children. Extreme prematurity (26 GW) and ELBW are significant risk factors for spatial location memory deficit. The modified Hopkins Board discriminated high-risk preterm and term-born children at early school age and appears to be a useful test to measure this rarely studied cognitive capacity.

To study postnatal dexamethasone treatment effects on cognitive, neuropsychological and behavioral functioning at early school age in preterm children.We recruited 222 children born between 1998 and 2003: 114 extremely low birth weight (1000 g; 60 dexamethasone-treated; 54 untreated) and 108 term-born. Data were analyzed using multivariate methods.Preterm performed below term-born on all measures. Dexamethasone-treated performed below dexamethasone-untreated in immediate visual memory, visual-motor integration, mathematical skill and motor dexterity. However, stepwise regression indicated that medical and sociodemographic factors other than dexamethasone contributed to preterm group differences.Dexamethasone alone does not explain neurocognitive impairment in preterm children. Medical and sociodemographic factors (illness severity, male gender and parental education) are influential. Prospective longitudinal neuropsychological and behavioral study from preschool to school age that considers medical and sociodemographic variables will best address effects of dexamethasone exposure.

late-preterm (LPT) birth accounts for a majority of preterm deliveries and until recently was considered low risk for poor cognitive outcome. Previously, we reported deficits in complicated LPT (cLPT) preschoolers (neonatal intensive care unit [NICU]-admitted).to extend our prior study by comparing cognitive outcome in cLPT and uncomplicated LPT (uLPT; NICU non-admitted) preschoolers.single center retrospective cohort study of 118 LPT children born in 2004-2006 at 35-36 weeks of gestation; 90 cLPT and 28 uLPT, compared with 100 term-born (≥ 37 weeks of gestation and ≥ 2500 g) participants.a well-standardized measure of general conceptual ability (GCA), the Differential Ability Scales, Second Edition.cLPT participants had average mean performances but significantly poorer GCA, Nonverbal Reasoning, and Spatial scores than term-born children, and higher rates of Nonverbal Reasoning and Spatial impairment; uLPT did not differ from TERM. Combined LPT males were at eightfold greater risk than term-born males for nonverbal deficit, and at sevenfold greater risk for GCA impairment than LPT females.finding greater risk of cognitive deficit in those NICU-admitted due to clinical instability or birth weight2 kg compared with non-admitted preschoolers indicates that neonatal morbidities contribute to subtle cognitive deficits detectable at young age, with male gender an additive risk factor. LPT gestational age alone is an insufficient predictor of long-term neurocognitive outcome. Further study should elucidate salient etiologies for early emerging cognitive weaknesses and suggest appropriate interventions to prepare at-risk LPT preschoolers for elementary school entry.

A case presentation of a newborn infant with intermittent, complete airway obstruction secondary to a pedunculated nasopharyngeal dermoid is presented. The differential diagnosis of obstructing nasopharyngeal lesions of the neonatal period is discussed, and an organized management strategy is proposed.

Despite increased knowledge and improving technology, chronic lung disease (CLD) rates in extremely low birth weight infants have remained constant for 20 years. One reason for this is an ineffective translation of research-proven improvements into practice. The Neonatal Intensive Care Quality Improvement Collaborative Year 2000 (NIC/Q 2000) was created to provide participating nurseries the tools necessary to effect change. The objective of this study was to develop and implement a process that uses quality improvement techniques to collaboratively improve CLD rates.Nine member hospitals of the NIC/Q 2000 collaborative formed a focus group aiming to decrease CLD rates. The focus group established goals and outcome measures, created a list of potentially better practices (PBPs) based on available literature, benchmarked and performed site visits, encouraged individual site implementation of PBPs, developed a database, and measured outcomes.The goal "decrease CLD rates in extremely low birth weight infants" was established. Nine PBPs were identified, and 57 PBPs were implemented by the 9 participating sites. Twelve site visits were conducted, and a 435-patient database of infants with a mean birth weight of 789 g was established.Collaborative use of quality improvement techniques resulted in creation of a logical, efficient, and effective process to improve CLD rates. Group creation of PBPs, based on literature review and reinforced with site visits, internal data analysis, and improved individual site outcomes, resulted in accelerated and effective change, unlikely to occur if attempted outside of the collaborative.

Adherence to basic quality improvement principles enhances the implementation of potentially better practices (PBPs) and requires extensive planning and education. Even after PBPs have been identified and acknowledged as desirable, effective implementation of these practices does not occur easily. The objective of this study was to identify and assess implementation strategies that facilitate quality improvements in the respiratory care of extremely low birth weight infants.The 9 members of the Neonatal Intensive Care Quality Improvement Collaborative Year 2000 Reducing Lung Injury focus group identified 9 PBPs in a evidence-based manner to decrease chronic lung disease in extremely low birth weight newborns. Each site implemented several or all PBPs based on a site-specific selection process. Each site was asked to submit 1 or more examples of experiences that highlighted effective implementation strategies. This article reports these examples and emphasizes the principles on which they are based.The 9 participating institutions implemented a total of 57 PBPs (range: 1-9; median: 5). Including previous implementation, the 9 participating institutions implemented a total of 70 of a possible 81 PBPs before or during the study period (range: 5-9; median: 8). We report 7 approaches that facilitated PBP implementation: information availability, feedback, perseverance, collaboration, imitation, recognition of implementation complexity, and tracking of process indicators.Quality improvement efforts are enhanced by identifying and then implementing PBPs. In our experience, implementation of these PBPs can be difficult. Implementation strategies, such as those identified in this article, can improve the chances that quality improvement efforts will be effective.

In vitro fertilization (IVF) is considered a generally safe procedure, although associated with a higher incidence of preterm birth. The literature is inconsistent about the psychological impact of IVF, and we found no reports about outcome in late preterm (LPT) children. Our objective was to study neuropsychological and behavioral outcomes in a cohort of preschoolers born LPT between 2004 and 2007.Participants were 397 LPT children (mean age, 3.8 years) conceived assisted by IVF (n = 105) or non-IVF (n = 292). Standardized performance-based tests of general conceptual ability (intelligence quotient), executive function, focused/selective attention, visual-spatial perception, visual-motor skill, manual dexterity, learning, and memory were administered. Parents completed behavioral and executive function questionnaires.IVF group characteristics included older maternal age (P.001), lower birthweight (P.001), and higher maternal education (P .001). No main-effect significant group differences were found for any variable after controlling for these variables. However, sex differences were demonstrated for the neuropsychological variables in copying (P.001), nonverbal reasoning (P = .001), manual dexterity (P = .001), and inhibitory capacity (P = .006), all favoring girls.Birth following IVF-assisted conception did not increase the risk of intellectual, neuropsychological, or behavioral deficit in LPT preschoolers. As shown in earlier gestational-age participants, girls have selective advantages. These findings should be reassuring for parents who conceive through IVF and deliver infants 1-3 weeks before term gestational age. Future study of these children at elementary school age may detect subtle impairments not yet apparent at age 3 years.