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BACKGROUND: Prenatal alcohol exposure (PAE) impacts the neurodevelopment of the fetus, including the infant's ability to self-regulate. Heart rate variability (HRV), that is, the beat-to-beat variability in heart rate, is a non-invasive measurement that can indicate autonomic nervous system (ANS) function/dysfunction. METHODS: The study consisted of a subset of our ENRICH-2 cohort: 80 participants (32 PAE and 48 Controls) who had completed three visits during pregnancy. The participants completed a comprehensive assessment of PAE and other substances throughout pregnancy and assessments for stress, anxiety, and depression in the third trimester. At 24 h of age, infant HRV was assessed in the hospital during the clinically indicated heel lance; 3- to 5-min HRV epochs were obtained during baseline, heel lancing, and recovery episodes. RESULTS: Parameters of HRV differed in infants with PAE compared to Controls during the recovery phase of the heel lance (respiratory sinus arrhythmia (RSA) and high-frequency (HF), p < 0.05). Increased maternal stress was also strongly associated with abnormalities in RSA, HF, and low-frequency / high-frequency (LF/HF, p's < 0.05). CONCLUSIONS: Alterations in ANS regulation associated with PAE and maternal stress may reflect abnormal development of the hypothalamic-pituitary-adrenal axis and have long term implications for infant responsiveness and self-regulation. IMPACT: Previous studies have focused on effects of moderate to heavy prenatal alcohol exposure (PAE) on autonomic dysregulation, but little is known about the effects of lower levels of PAE on infant self-regulation and heart rate variability (HRV). Prenatal stress is another risk factor for autonomic dysregulation. Mild PAE impacts infant self-regulation, which can be assessed using HRV. However, the effect of prenatal stress is stronger than that of mild PAE or other mental health variables on autonomic dysregulation.
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Enfermedades del Sistema Nervioso Autónomo , Efectos Tardíos de la Exposición Prenatal , Lactante , Humanos , Embarazo , Femenino , Sistema Hipotálamo-Hipofisario , Efectos Tardíos de la Exposición Prenatal/etiología , Sistema Hipófiso-Suprarrenal , Sistema Nervioso Autónomo , Ansiedad , Frecuencia CardíacaRESUMEN
Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11ß-HSD1, 11ß-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (p < 0.01). In multivariable modeling, PS was associated with pCRH gene expression (ß = 0.006, p < 0.01), while PAE was associated with 11ß-HSD2 protein expression (ß = 0.56, p < 0.01). A significant alcohol-by-stress interaction was observed with respect to 11ß-HSD2 protein expression (p < 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.
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Enfermedades Fetales , Efectos Tardíos de la Exposición Prenatal , Pruebas Psicológicas , Autoinforme , Humanos , Embarazo , Femenino , Placenta/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2 , Estrés Psicológico/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Desarrollo Fetal , Biomarcadores/metabolismoRESUMEN
The prevalence of prenatal alcohol exposure (PAE) is increasing, with evidence suggesting that PAE is linked to an increased risk of infections. PAE is hypothesized to affect the innate immune system, which identifies pathogens through pattern recognition receptors, of which toll-like receptors (TLRs) are key components. We hypothesized that light-to-moderate PAE would impair immune responses, as measured by a heightened response in cytokine levels following TLR stimulation. Umbilical cord samples (10 controls and 8 PAE) from a subset of the Ethanol, Neurodevelopment, Infant and Child Health Study-2 cohort were included. Peripheral blood mononuclear cells (PMBCs) were stimulated with one agonist (TLR2, TLR3, TLR4, or TLR9). TLR2 agonist stimulation significantly increased pro-inflammatory interleukin-1-beta in the PAE group after 24 h. Pro- and anti-inflammatory cytokines were increased following stimulation with the TLR2 agonists. Stimulation with TLR3 or TLR9 agonists displayed minimal impact overall, but there were significant increases in the percent change of the control compared to PAE after 24 h. The results of this pilot investigation support further work into the impact on TLR2 and TLR4 response following PAE to delineate if alterations in levels of pro- and anti-inflammatory cytokines have clinical significance that could be used in patient management and/or attention to follow-up.
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Sangre Fetal , Receptores Toll-Like , Humanos , Femenino , Embarazo , Sangre Fetal/metabolismo , Proyectos Piloto , Receptores Toll-Like/metabolismo , Receptores Toll-Like/agonistas , Citocinas/metabolismo , Citocinas/sangre , Adulto , Recién Nacido , Efectos Tardíos de la Exposición Prenatal/metabolismo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Etanol/farmacología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/agonistasRESUMEN
Increasing attention has been paid to the risks and benefits of terminating large clinical trials before reaching prespecified targets, because such decisions can greatly affect the implementation of findings. The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) is a research infrastructure dedicated to conducting high-quality clinical research. A scoping review was performed to characterize barriers preventing the attainment of prespecified recruitment, statistical power, or sample-size targets in VA CSP trials. A trial was eligible for inclusion if the trial was sponsored by the VA CSP, primary findings were published within the last 10 years, and a decision was made to terminate enrollment or follow-up before meeting a priori recruitment or endpoint targets. In 11 of 29 included trials (37.9%), a decision was made to terminate the trial early. The most common reason for early termination was related to under-recruitment (n = 5). Other reasons included early detection of safety signals (n = 2), futility (n = 1), and benefit (n = 1). This review highlights recruitment as a critical facet of trial conduct that may hinder the production of high-quality data and thus warrant additional attention. Solutions to enhance recruitment now implemented by the VA CSP, including dedicated enrollment infrastructure and screening facilitated by informatics approaches, show promise in reducing this cause for early termination.
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Veteranos , Estados Unidos , Humanos , United States Department of Veterans Affairs , Tamaño de la Muestra , Exactitud de los DatosRESUMEN
OBJECTIVE: To evaluate the severity of neonatal opioid withdrawal syndrome (NOWS) in infants prenatally exposed to medications for opioid use disorder (MOUD) and serotonin reuptake inhibitors (SRI). METHODS: A prospective cohort included 148 maternal-infant pairs categorized into MOUD (n = 127) and MOUD + SRI (n = 27) groups. NOWS severity was operationalized as the infant's need for pharmacologic treatment with opioids, duration of hospitalization, and duration of treatment. The association between prenatal SRI exposure and the need for pharmacologic treatment (logistic regression), time-to-discharge, and time-to-treatment discontinuation (Cox proportional hazards modeling) was examined after adjusting for the type of maternal MOUD, use of hydroxyzine, other opioids, benzodiazepines/sedatives, alcohol, tobacco, marijuana, gestational age, and breastfeeding. RESULTS: Infants in the MOUD + SRI group were more likely to receive pharmacologic treatment for NOWS (OR = 3.58; 95% CI: 1.31; 9.76) and had a longer hospitalization (median: 11 vs. 6 days; HR = 0.54; 95% CI: 0.33; 0.89) compared to the MOUD group. With respect to time-to-treatment discontinuation, no association was observed in infants who received treatment (HR = 0.59; 95% CI: 0.26, 1.32); however, significant differences were observed in the entire sample (HR = 0.55; 95% CI: 0.34, 0.89). CONCLUSIONS: Use of SRIs among pregnant women on MOUD might be associated with more severe NOWS. IMPACT: A potential drug-drug interaction between maternal SRIs and opioid medications that inhibit the reuptake of serotonin has been hypothesized but not carefully evaluated in clinical studies. Results of this prospective cohort indicate that the use of SRIs among pregnant women on MOUD is associated with more severe neonatal opioid withdrawal syndrome. This is the first prospective study which carefully examined effect modification between the type of maternal MOUD and SRI use on neonatal outcomes. This report lays the foundation for treatment optimization in pregnant women with co-occurring mental health and substance use disorders.
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Enfermedades del Recién Nacido , Síndrome de Abstinencia Neonatal , Trastornos Relacionados con Opioides , Efectos Tardíos de la Exposición Prenatal , Síndrome de Abstinencia a Sustancias , Analgésicos Opioides/efectos adversos , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades del Recién Nacido/tratamiento farmacológico , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , Trastornos Relacionados con Opioides/complicaciones , Trastornos Relacionados con Opioides/tratamiento farmacológico , Embarazo , Estudios Prospectivos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológicoRESUMEN
BACKGROUND: With significant increases in opioid use/misuse and persistent high prevalence of prenatal alcohol exposure (PAE), identifying infants at risk for long-term developmental sequelae due to these exposures remains an urgent need. This study reports on developmental outcomes in young children from a prospective cohort, ENRICH-1, which recruited pregnant women and followed up maternal-infant pairs. METHODS: Subjects were assigned to four study groups based on prenatal use of medications for opioid use disorder (MOUD), PAE, MOUD+PAE, and unexposed controls (UC). Mixed effects modeling was used to evaluate changes in the Bayley Scales of Infant Development-III (BSID-III) Cognitive, Language, and Motor scores between 6 and 20 months. RESULTS: There was a significant three-way interaction (MOUD-by-PAE-by-Time) with respect to the BSID-III Cognitive (p = 0.045) and Motor (p = 0.033) scales. Significant changes between the two evaluations were observed for MOUD group in Cognitive and Language scores; for PAE group in Cognitive, Language, and Motor scores, and for MOUD+PAE group in Language scores after adjusting for child sex and family socio-economic status. The developmental scores for the UC remained stable. CONCLUSION: Observed decline in neurodevelopmental scores during the first 2 years of life emphasizes the importance of a longitudinal approach when evaluating children with prenatal polysubstance exposure. IMPACT: BSID-III scores were stable during the first 2 years of life for unexposed children. BSID-III scores declined for children with prenatal exposures to alcohol and/or opioids. Standard developmental tests may not be sensitive enough during the first year of life. Findings emphasize the need for repeated evaluations of children who are at high risk.
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BACKGROUND: Accurate characterization of prenatal alcohol exposure (PAE) is challenging due to inconsistent use of screening questionnaires in routine prenatal care and substantial underreporting due to stigma associated with alcohol use in pregnancy. The aim of this study was to identify self-report tools that are efficient in accurately characterizing PAE. METHODS: Participants meeting eligibility criteria for mild-to-moderate PAE were recruited into the University of New Mexico Ethanol, Neurodevelopment, Infant and Child Health cohort (N = 121) and followed prospectively. Timeline follow-back (TLFB) interviews were administered at baseline to capture alcohol use in the periconceptional period and 30 days before enrollment; reported quantity was converted to oz absolute alcohol (AA), multiplied by frequency of use and averaged across 2 TLBF calendars. The interview also included questions about timing and number of drinks at the most recent drinking episode, maximum number of drinks in a 24-hour period since the last menstrual period, and number of drinks on "special occasions" (irrespective of whether these occurred within the TLFB reported period). Continuous measures of alcohol use were analyzed to yield the number of binge episodes by participants who consumed ≥4 drinks/occasion. The proportion of women with ≥1 binge episode was also tabulated for each type of assessment. RESULTS: Average alcohol consumption was 0.6 ± 1.3 oz of AA/day (≈ 8.4 drinks/wk). Only 3.3% of participants reported ≥1 binge episode on the TLFB, 19.8% had ≥1 binge episode when asked about "special occasions," and 52.1% when asked about the number of drinks the last time they drank alcohol. An even higher prevalence (89.3%) of bingeing was obtained based on the maximum number of drinks consumed in a 24-hour period. CONCLUSIONS: Self-reported quantity of alcohol use varies greatly based on type of questions asked. Brief targeted questions about maximum number of drinks in 24 hours and total number of drinks during the most recent drinking episode provide much higher estimates of alcohol use and thus might be less affected by self-reporting bias.
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Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Consumo Excesivo de Bebidas Alcohólicas/psicología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Autoinforme/normas , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología , Consumo Excesivo de Bebidas Alcohólicas/diagnóstico , Estudios de Cohortes , Femenino , Humanos , Embarazo , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Estudios Prospectivos , Encuestas y Cuestionarios/normas , Adulto JovenRESUMEN
The rates of opioid use disorder during pregnancy have more than quadrupled in the last decade, resulting in numerous infants suffering exposure to opioids during the perinatal period, a critical period of central nervous system (CNS) development. Despite increasing use, the characterization and definition of the molecular and cellular mechanisms of the long-term neurodevelopmental impacts of opioid exposure commencing in utero remains incomplete. Thus, in consideration of the looming public health crisis stemming from the multitude of infants with prenatal opioid exposure entering school age, we undertook an investigation of the effects of perinatal methadone exposure in a novel preclinical model. Specifically, we examined the effects of opioids on the developing brain to elucidate mechanisms of putative neural cell injury, to identify diagnostic biomarkers and to guide clinical studies of outcome and follow-up. We hypothesized that methadone would induce a pronounced inflammatory profile in both dams and their pups, and be associated with immune system dysfunction, sustained CNS injury, and altered cognition and executive function into adulthood. This investigation was conducted using a combination of cellular, molecular, biochemical, and clinically translatable biomarker, imaging and cognitive assessment platforms. Data reveal that perinatal methadone exposure increases inflammatory cytokines in the neonatal peripheral circulation, and reprograms and primes the immune system through sustained peripheral immune hyperreactivity. In the brain, perinatal methadone exposure not only increases chemokines and cytokines throughout a crucial developmental period, but also alters microglia morphology consistent with activation, and upregulates TLR4 and MyD88 mRNA. This increase in neuroinflammation coincides with reduced myelin basic protein and altered neurofilament expression, as well as reduced structural coherence and significantly decreased fractional anisotropy on diffusion tensor imaging. In addition to this microstructural brain injury, adult rats exposed to methadone in the perinatal period have significant impairment in associative learning and executive control as assessed using touchscreen technology. Collectively, these data reveal a distinct systemic and neuroinflammatory signature associated with prenatal methadone exposure, suggestive of an altered CNS microenvironment, dysregulated developmental homeostasis, complex concurrent neural injury, and imaging and cognitive findings consistent with clinical literature. Further investigation is required to define appropriate therapies targeted at the neural injury and improve the long-term outcomes for this exceedingly vulnerable patient population.
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Analgésicos Opioides/efectos adversos , Inflamación/inducido químicamente , Neuroinmunomodulación/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Animales , Imagen de Difusión Tensora , Modelos Animales de Enfermedad , Femenino , Masculino , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
It has been known for over 4 decades that prenatal alcohol exposure (PAE) can adversely affect neurodevelopment and behavior (NDB). Yet, early detection of altered NDB due to PAE continues to present a major clinical challenge. Identification of altered NDB in the first 2 years of life, before higher-order cognitive processes develop, invites early interventions for affected children to improve long-term outcomes. Studies published in English from January of 1980 to July of 2018 were identified in PubMed/MEDLINE. The review focused on prospective birth cohort studies which used standardized NDB assessments in children up to 2 years of age, wherein PAE was the main exposure and NDB was the main outcome. NDB was categorized into the domains of neurocognitive, adaptive, and self-regulation based on the 2016 Updated Clinical Guidelines for Diagnosing fetal alcohol spectrum disorder. An initial search resulted in 1,867 articles for which we reviewed abstracts; 114 were selected for full-text review; and 3 additional abstracts were identified through review of references in eligible publications. Thirty-one publications met criteria and were included: of these, 24 reported neurocognitive outcomes, 24 reported adaptive behavior outcomes, and 12 reported outcomes in the domain of self-regulation. Although self-regulation was assessed in the fewest number of studies, 8/12 (75%) reported PAE-associated deficits. In contrast, results were mixed for the other 2 domains: 13/24 (54%) of the selected studies that included neurocognitive outcomes showed poorer performance following PAE, and 8/24 (33%) studies that assessed adaptive functioning found significant differences between PAE and comparison infants. There is considerable evidence to support the value of early-life assessments of infant NDB when PAE is known or suspected. More studies focusing on infant self-regulation, in particular, are needed to determine the utility of early evaluation of this critical developmental domain in infants with PAE.
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Etanol/efectos adversos , Trastornos del Espectro Alcohólico Fetal/diagnóstico , Trastornos del Neurodesarrollo/diagnóstico , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Problema de Conducta , Diagnóstico Precoz , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: Earlier identification of children with prenatal alcohol exposure (PAE) remains a challenge. The objective of this study was to identify neurobehavioral (NB) outcomes associated with PAE in infants. METHODS: This manuscript evaluates NB outcomes at 6.33±1.12 months of age in 93 infants (39 PAE and 54 No-PAE) recruited prospectively into the ENRICH cohort. PAE was assessed by prospective repeated TLFB interviews and a panel of ethanol biomarkers. NB outcomes were evaluated by the Bayley Scales of Infant Development (BSID-III), Parenting Stress Index (PSI), Infant Behavior Questionnaire (IBQ-R), and Infant Sensory Profile (ISP). RESULTS: Mean maternal age at enrollment was 28.18±5.75, and 64.52% were Hispanic/Latina. Across three TLFB calendars, absolute alcohol per day in the PAE group was 0.44±0.72, corresponding to low-moderate alcohol consumption. While no association was observed between PAE and BSID-III (P's>0.05), PAE was associated with higher scores on the PSI difficult child scale ([Formula: see text]=13.9; P=0.015), total stress ([Formula: see text]=13.9; P=0.010), and IBQ negative affect ([Formula: see text]=8.60; P=0.008) measures after adjustment for covariates. CONCLUSIONS: Caregiver-reported assessments may provide a currently unrecognized opportunity to identify behavioral deficits, point to early interventions, and should be included in clinical assessments of infants at-risk for fetal alcohol spectrum disorder.
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Consumo de Bebidas Alcohólicas/efectos adversos , Cuidadores , Desarrollo Infantil , Trastornos del Neurodesarrollo/etiología , Complicaciones del Embarazo/diagnóstico , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Adulto , Biomarcadores/sangre , Niño , Etanol , Femenino , Trastornos del Espectro Alcohólico Fetal/diagnóstico , Hispánicos o Latinos , Humanos , Lactante , Conducta del Lactante , Recién Nacido , Masculino , Edad Materna , Trastornos del Neurodesarrollo/diagnóstico , Medición de Resultados Informados por el Paciente , Embarazo , Estudios Prospectivos , Estrés Psicológico , Trastornos Relacionados con Sustancias/complicaciones , Encuestas y Cuestionarios , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Substance abuse in nonpregnant adults has been associated with increased intake in calories and decreased intake of nutrient-dense foods; however, studies examining dietary intake in opioid-using and alcohol-using pregnant women are lacking. OBJECTIVE: The objective of this study was to evaluate dietary intake in opioid-using pregnant women with or without concurrent light-to-moderate alcohol use as compared to abstaining controls. METHODS: This prospective birth cohort included 102 pregnant women classified into four study groups: controls (n = 27), medication-assisted treatment (MAT; n = 26), alcohol (ALC; n = 22), and concurrent use of both substances (MAT + ALC; n = 27). Percentage differences in macro- and micronutrient intake were estimated from the food frequency questionnaire and compared among the study groups. Proportions of participants with intakes below the estimated average requirements (EAR) based on diet and diet with supplements were estimated. RESULTS: Three exposed groups had lower prevalence of multivitamin use in periconceptional period (11.5-31.8%) than controls (44.4%). Unadjusted mean energy intake was significantly higher in the MAT + ALC group compared to controls, while micronutrient intake per 1000 kcal was the highest in the control group for almost all of the micronutrients analyzed. After adjustment for energy intake and sociodemographic characteristics, MAT group had lower estimated dietary intake of iron (-15.0%, p = 0.04) and folate (-16.8%, p = 0.04) compared to controls. A high proportion of participants in all study groups had dietary intake below the EAR for vitamin E, iron, and folate. CONCLUSION: Results highlight the need for targeted dietary interventions for opioid-using pregnant women.
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Consumo de Bebidas Alcohólicas/psicología , Analgésicos Opioides , Dieta/estadística & datos numéricos , Consumidores de Drogas/psicología , Ingestión de Energía , Tratamiento de Sustitución de Opiáceos/psicología , Mujeres Embarazadas/psicología , Adulto , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Micronutrientes , Embarazo , Adulto JovenRESUMEN
BACKGROUND: Although misuse of prescription opioids has reached epidemic proportions, pharmacy-based preventive services to combat this epidemic are limited. The aims of this study were to identify barriers and facilitators to the dispensing of intranasal naloxone (INN) by pharmacists in New Mexico. METHODS: For this mixed-methods study, a qualitative component (focus group) informed the development of a quantitative component (electronic survey) distributed to all pharmacists registered with the New Mexico Board of Pharmacy and practicing in the state. A 46-item survey included questions about pharmacists' concerns regarding dispensing INN, barriers and facilitators to dispensing INN, efforts needed to increase availability and utilization of pharmacist-dispensed INN, and characteristics of respondents and their pharmacies. RESULTS: Pharmacists from all geographical regions and all types of pharmacy settings were represented in the sample (final N = 390, participation rate 23.5%, including a subset of 182 community pharmacists). The main barriers identified were (1) out-of-pocket costs for patients; (2) time constraints for pharmacists; and (3) inadequate reimbursement for pharmacists. The main facilitators were (1) increased awareness among opioid-using patients and family members about the need for INN; (2) additional education to the general public; and (3) additional training for pharmacists on how to initiate discussions about INN with high-risk patients. Some community pharmacists were concerned that INN dispensing would promote opioid abuse (16.5%) and attract undesirable clientele (14.3%). In a multivariable logistic regression analysis of a community pharmacy subset, a higher number of concerns about INN (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.82-0.93) and a pharmacy setting in a chain grocery or a "big box" store (OR = 0.38; 95% CI: 0.16-0.92) were associated with decreased odds of dispensing INN. CONCLUSIONS: Effective intervention strategies for increasing dispensing of intranasal naloxone by pharmacists should focus on pharmacists' concerns, include education to multiple audiences, and address provider-level, system-level, and society-level barriers.
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Accesibilidad a los Servicios de Salud , Naloxona/uso terapéutico , Servicios Farmacéuticos , Farmacéuticos , Rol Profesional , Administración Intranasal , Adulto , Anciano , Femenino , Grupos Focales , Humanos , Internet , Masculino , Persona de Mediana Edad , Naloxona/administración & dosificación , New Mexico , Servicios Farmacéuticos/estadística & datos numéricosRESUMEN
BACKGROUND: While 2 to 5% of school-aged children in the United States are estimated to be affected by fetal alcohol spectrum disorders (FASD), the prevalence of prenatal alcohol exposure (PAE) might be substantially underreported. Our objective was to systematically estimate the prevalence of PAE in Texas by measuring a direct ethanol metabolite, phosphatidylethanol (PEth), in 1,000 infant residual dried blood spots (irDBSs) in the Texas Newborn Screening Repository. METHODS: All public health regions (PHRs) were represented proportional to their 2014 birth rate (~0.25% of total births). A cross-sectional study design (unit of observation: individual irDBS cards/infants) with additional ecologic subanalysis (unit of observation: aggregate measures for each Texas PHR) was utilized. The study used PEth-irDBS to estimate the prevalence of PAE within 1 month before delivery for the state of Texas and each Texas PHR. The ecologic subanalysis compared different geographical regions' aggregate prevalence of PAE with (i) retail liquor licenses, (ii) median household income by PHR, and (iii) prevalence of birth outcomes commonly associated with FASD. RESULTS: The sample included an equal number of males and females; 47.8% non-Hispanic White, 40.8% Hispanic, 6.6% African American, and 4.8% Asian infants. In the entire sample, 8.4% of irDBSs were positive for PEth (>20 ng/ml) indicative of PAE within approximately 1 month before delivery. Large regional differences were observed with mostly urban, high median-income regions demonstrating the highest prevalence. CONCLUSIONS: Results of this first systematic statewide PAE prevalence study demonstrate that PAE might be more prevalent than previously thought. Active case ascertainment efforts for FASD coupled with systematic objective assessment of PAE should expand to the national level to better estimate public health needs required to provide adequate services for children affected by PAE.
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Consumo de Bebidas Alcohólicas/sangre , Pruebas con Sangre Seca , Glicerofosfolípidos/sangre , Tamizaje Neonatal , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Biomarcadores/sangre , Estudios Transversales , Pruebas con Sangre Seca/métodos , Femenino , Humanos , Recién Nacido , Masculino , Tamizaje Neonatal/métodos , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Prevalencia , Texas/epidemiologíaRESUMEN
Background Given the large increases in opioid use among pregnant women and associations with hepatitis C virus (HCV) infection, screening pregnant women who are on (opioid agonist) pharmacotherapy for HCV infection has potential to inform medical care for these mothers as well as their newborns. We investigated the HCV testing cascade among pregnant women on pharmacotherapy in order to describe exposure and infection rates and to identify opportunities that would improve care. Methods Secondary analyses of laboratory results were performed for HCV testing, including anti-HCV, viremia (RNA) and genotype. Information was abstracted from the medical records of women who were followed at a comprehensive prenatal care clinic for women with substance use disorders at the University of New Mexico. Results The sample included 190 pregnant women, of whom 188 were on pharmacotherapy (43.7% on buprenorphine and 55.3% on methadone); the remaining two had tested positive for heroin or prescription opioids. A total of 178 (93.7%) were tested for anti-HCV, 94 (98.9%) of whom were tested for RNA, and 41 (57.7%) were genotyped. Prevalence of exposure to HCV by anti-HCV results was 53.3%, and 37.3% were positive for HCV RNA indicating chronic infection. Conclusions The high prevalence of exposure and infection with HCV in pregnant women involved in pharmacotherapy for a substance use disorder indicate a need for ongoing surveillance and testing for HCV. Identifying HCV during pregnancy is crucial because this identification would serve to enhance medical care and potentially prevent vertical transmission. Identifying HCV would also facilitate referrals to newly available curative HCV treatments following delivery.
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Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Trastornos Relacionados con Opioides/complicaciones , Complicaciones Infecciosas del Embarazo/diagnóstico , Mujeres Embarazadas , Atención Prenatal/estadística & datos numéricos , Adulto , Analgésicos Opioides/uso terapéutico , Femenino , Hepacivirus , Humanos , Tamizaje Masivo , Metadona/uso terapéutico , México/epidemiología , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Mujeres Embarazadas/etnología , Mujeres Embarazadas/psicología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: While prenatal 3D ultrasonography results in improved diagnostic accuracy, no data are available on biometric assessment of the fetal frontal lobe. This study was designed to assess feasibility of a standardized approach to biometric measurement of the fetal frontal lobe and to construct frontal lobe growth trajectories throughout gestation. STUDY DESIGN: A sonographic 3D volume set was obtained and measured in 101 patients between 16.1 and 33.7 gestational weeks. Measurements were obtained by two independent raters. To model the relationship between gestational age and each frontal lobe measurement, flexible linear regression models were fit using penalized regression splines. RESULTS: The sample contained an ethnically diverse population (7.9% Native Americans, 45.5% Hispanic/Latina). There was high inter-rater reliability (correlation coefficients: 0.95, 1.0, and 0.87 for frontal lobe length, width, and height; p-values < 0.001). Graphs of the growth trajectories and corresponding percentiles were estimated as a function of gestational age. The estimated rates of frontal lobe growth were 0.096 cm/week, 0.247 cm/week, and 0.111 cm/week for length, width, and height. CONCLUSION: To our knowledge, this is the first study to examine fetal frontal lobe growth trajectories through 3D prenatal ultrasound examination. Such normative data will allow for future prenatal evaluation of a particular disease state by 3D ultrasound imaging.
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Desarrollo Fetal/fisiología , Lóbulo Frontal/diagnóstico por imagen , Diagnóstico Prenatal/métodos , Ultrasonografía Prenatal/métodos , Adulto , Estudios de Factibilidad , Femenino , Lóbulo Frontal/patología , Edad Gestacional , Humanos , Imagenología Tridimensional , Embarazo , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
Objective: To assess the feasibility of a standardized approach to biometric measurement of the fetal frontal lobe and to construct frontal lobe growth trajectories throughout gestation. Study Design: A sonographic 3-dimensional (3D) volume set was obtained and measured in 101 patients between 16.1 and 33.7 gestational weeks. Measurements were obtained by 2 independent raters. To model the relationship between gestational age and each frontal lobe measurement, flexible linear regression models were fit using penalized regression splines. Results: The sample contained an ethnically diverse population (7.9% Native Americans, 45.5% Hispanics/Latinas). There was high interrater reliability (correlation coefficients 0.95, 1.0, and 0.87 for frontal lobe length, width, and height; p values <0.001). Graphs of the growth trajectories and corresponding percentiles were estimated as a function of gestational age. The estimated rates of frontal lobe growth were 0.096 cm/week, 0.247 cm/week, and 0.111 cm/week for length, width, and height, respectively. Conclusion: To our knowledge, this is the first study to examine fetal frontal lobe growth trajectories through 3D prenatal ultrasound examination. Such normative data will allow for future prenatal evaluation of a particular disease state by 3D ultrasound imaging.
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Desarrollo Fetal/fisiología , Lóbulo Frontal/diagnóstico por imagen , Imagenología Tridimensional/métodos , Ultrasonografía Prenatal/métodos , Adulto , Femenino , Feto/diagnóstico por imagen , Humanos , Embarazo , Atención Prenatal/métodos , Estándares de Referencia , Reproducibilidad de los Resultados , UltrasonografíaRESUMEN
BACKGROUND: Given that opioid misuse/abuse and opioid overdose have reached epidemic proportions in the United States, expansion of naloxone access programs are desperately needed. The objective of this study was to describe emerging trends in naloxone rescue kit (NRK) prescription patterns by pharmacists in New Mexico as an example of a unique health care delivery system. METHODS: The study presents cross-sectional analysis of the data on NRK prescriptions by pharmacists who received naloxone pharmacist prescriptive authority certification since 2013. Data were obtained from the Prevention of Opioid Overdose by New Mexico Pharmacists (POINt-Rx) Registry, maintained by the University of New Mexico and the New Mexico Pharmacists Association. RESULTS: Since 2013, 133 NRKs prescribed by pharmacists have been reported to the POINt-Rx Registry. The mean age of the patients was 41.5 ± 12.0 years (range: 19-67 years), and 60.2% were female participants. Only 11.3% of the prescriptions were from pharmacists practicing in rural/mixed urban-rural areas. The majority of NRKs (89.5%) were first-time prescriptions. The most common reason for a NRK prescription was patient's request (56.4%), followed by a pharmacist's prescription of NRK due to high dose of prescription opioids (28.6%) and history of opioid misuse/abuse (15.0%). In addition to opioids, other frequently reported substances included alcohol (9.2%) and benzodiazepines (10.8%). More than a third of patients (38.5%) reported polysubstance use in the previous 72 hours. CONCLUSIONS: These results indicate that patients at risk of opioid overdose might feel comfortable soliciting NRKs from a pharmacist. Participation of pharmacists in rural areas in the naloxone prescriptive authority highlight the opportunity for this novel health care delivery model in underserved areas; however, the program is clearly underutilized in these areas. Such a model can provide expanded patient access in community practices, whereas systematic efforts for uptake of the program by policy makers, communities, and pharmacists continue to be needed nationwide.
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Sobredosis de Droga/prevención & control , Prescripciones de Medicamentos/estadística & datos numéricos , Naloxona/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Servicios Farmacéuticos , Adulto , Anciano , Estudios Transversales , Sobredosis de Droga/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Narcóticos/uso terapéutico , New Mexico , Adulto JovenRESUMEN
BACKGROUND: Given the challenges of confirming prenatal alcohol exposure (PAE) during pregnancy using currently established biomarkers of alcohol consumption, we examined whether serum microRNAs (miRNAs) may serve as stable biomarkers for PAE. Alterations in the levels of specific circulating miRNAs have been associated with various disease states and in animal models of fetal alcohol spectrum disorder. METHODS: Pregnant women in this prospective study were recruited from substance abuse and general maternity clinics affiliated with the University of New Mexico. Serum was collected at the time of admission for delivery from 14 subjects who reported ≥1 binge-drinking episode or ≥3 drinks/wk during pregnancy and 16 subjects who reported abstinence during pregnancy and tested negative for 5 ethanol biomarkers. Total RNA was isolated from serum and used for microarray analysis. RESULTS: False discovery rate-corrected analyses of covariance revealed that 55 miRNAs were significantly altered between the 2 groups. Hierarchical clustering using only the significantly altered miRNAs grouped samples into alcohol-consuming and non-alcohol-consuming individuals. Discriminant analysis then identified miRs-122*, -126, -216b, -221*, -3119, -3942-5p, -4704-3p, -4743, -514-5p, and -602 as the top 10 discriminators between the 2 groups. Ingenuity Pathway Analysis of putative miRNA targets illustrated that miRNAs identified in this study are involved in biological pathways that mediate the effects of alcohol, such as brain-derived neurotrophic factor, ERK1/2, and PI3K/AKT signaling. CONCLUSIONS: This is the first report of alterations in serum miRNA expression that are associated with alcohol use during human pregnancy. These results suggest that serum miRNAs could be useful as biomarkers of alcohol exposure.
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Consumo de Bebidas Alcohólicas/sangre , Fenómenos Fisiologicos Nutricionales Maternos/fisiología , MicroARNs/sangre , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/genética , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Redes Reguladoras de Genes/fisiología , Humanos , MicroARNs/genética , Embarazo , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: The analysis of phosphatidylethanol, a promising direct ethanol metabolite, in dry blood spots (PEth-DBS) is advantageous due to ease of storage, transportation and minimal invasiveness of capillary blood collection. One potential application of PEth-DBS is to confirm prenatal alcohol exposure in newborns suspected of FASD; however, stability of PEth-DBS is largely unknown. METHODS: Phlebotomized samples from 31 adults with a history of alcoholism, admitted to the University of New Mexico Emergency Department, were analyzed for blood alcohol content and pipetted onto DBS cards (13 spots per patient). The first spot was analyzed within 2 weeks of collection for a baseline PEth; the remaining 12 spots were allocated into three temperature conditions (room temperature, 4°C, -80°C) for the repeated measures analysis. In addition, 5 newborn DBS samples with a baseline PEth>LOD were obtained from a prospective cohort at UNM and re-analyzed at 4 months after storage at -80°C. A mixed linear model was fitted to examine the effects of temperature, time and temperature-time interaction on PEth degradation over the first 9 months. RESULTS: The baseline PEth levels were 592.8 ± 86.7 ng/ml and 18.3 ± 4.8 ng/ml in adult and newborn samples, respectively. All DBS samples remained positive in successive samples in all temperature conditions. Results of mixed linear model demonstrated a significant effect of temperature (P < 0.001) on PEth degradation over 9 months. CONCLUSIONS: PEth-DBS appears to be relatively stable, especially when stored at lower temperatures. These initial results are encouraging and highlight the PEth-DBS potential in retrospective assessment of alcohol exposure.
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Consumo de Bebidas Alcohólicas/sangre , Alcoholismo/sangre , Nivel de Alcohol en Sangre , Pruebas con Sangre Seca/métodos , Glicerofosfolípidos/sangre , Glicerofosfolípidos/química , Adulto , Femenino , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Temperatura , Factores de TiempoRESUMEN
OBJECTIVES: To evaluate the effects of prenatal polydrug and exclusive opioid use on fetal growth outcomes. METHODS: This analysis relied on the data obtained from two prospective cohorts at the University of New Mexico. For both cohorts, pregnant women were recruited during one of their prenatal care visits and followed up to delivery. The merged sample included 59 polydrug users, 22 exclusive opioid users, and 278 abstinent controls. Continuous growth measures (birth weight, height, occipital frontal circumference [OFC], and corresponding sex-specific percentiles) were compared by ANOVA and ANCOVA in bivariate and multivariable analyses, respectively. Categorical outcomes (prevalence of small-for-gestational age [SGA] for weight, length, and OFC) were compared among groups by Chi-square and multivariable logistic regression analyses.. RESULTS: The sample included a large proportion of ethnic minorities (78.8% Hispanic) and patients with low educational attainment (68% ≤ high school). The risk of microcephaly (OFC<10th percentile) was significantly greater in the polydrug (OR=4.7; 95% CI: 2.0; 10.8) and exclusive opioid (OR=2.8; 95% CI: 1.0; 8.1) groups compared to abstinent controls. CONCLUSION: Given that microcephaly is often associated with serious neurocognitive and behavioral deficits later in life, our finding of 49.2% incidence of microcephaly among polydrug users is alarming and requires further investigation.