ASSESSMENT OF POST-DISCHARGE HEALTH CARE UTILIZATION IN INFANTS WITH NEONATAL OPIOID WITHDRAWAL SYNDROME

Background/Objectives: Children born to mothers with opioid use disorder often show withdrawal effects characterized by increased stress, hyperirritability, tremors, tachycardia, sleep deprivation, and gastrointestinal discomfort, commonly known as “neonatal opioid withdrawal syndrome” (NOWS). Studies have shown that the effect of NOWS can lead to several health-related disorders later in life leading to increased health care utilization. However, detailed study of post-discharge health care utilization, specifically focusing on encounters with the health care system is currently lacking in the literature. Our objective was to evaluate health care utilization in infants who were diagnosed with NOWS during a one-year follow-up period after their discharge from the hospital. Secondly, we wanted to assess the relationship between NOWS related severity measures and post-discharge health care utilization during a one-year follow-up period. Methods: Health Facts® data, collected from over 800 contributing CERNER hospitals across the United States, was used to identify infants who were diagnosed with NOWS. Health care utilization during a follow-up period of 365 days after the index period (discharge date) was evaluated. As comparators, two groups were utilized: late preterm (gestational age: 33 weeks up to 36 6/7 weeks) and uncomplicated birth infants. Outcomes measured were rehospitalization, emergency department visits, and outpatient visits. We used logistic regression model to assess the impact of NOWS on health care utilization after discharge. Poisson and Zero-inflated Poisson regression were used to quantify the incidence rates of the health care utilization event. Finally, Cox proportional-hazards regression was used to estimate time to first event related to health care utilization after discharge from the hospital. Results: We identified our study cohort as infants who had birth related discharges between the period of January 1, 2011, and October 31, 2016 which included 3,526 infants with NOWS, 24,474 infants who had late preterm birth, and 88,452 infants who had uncomplicated births (representing a 25% sample of the births recorded). Mirroring the opioid epidemic in the U.S. there was an increasing trend in the incidence rate of NOWS. Infants with NOWS had significantly longer length of stay (14.9 days vs. 2.1 days, p\u3c0.001), and higher cost (Median: $24,944 vs.$3,129, p\u3c0.001) compared to uncomplicated birth group. Infants diagnosed with NOWS had significantly higher odds of one-year rehospitalization (Adjusted odds ratio: 1.7, 95% C.I.: 1.3-2.2) and 30-day rehospitalization (Adjusted odds ratio: 1.9, 95% C.I.: 1.3-2.6) compared to uncomplicated birth infants. There was no statistical difference in the risk of emergency department visits in the NOWS group compared to uncomplicated birth group after adjustment for confounders. Infants in the NOWS group had higher odds of any 30-day composite visit (emergency department visit or rehospitalization) compared to the uncomplicated birth group (Adjusted odds ratio: 1.4, 95% C.I.: 1.2-1.6). The results from logistic regression models closely aligned with the findings from the Poisson, Zero-inflated Poisson, and Cox proportional-hazards regression models. Infants with NOWS had similar rates of post-discharge healthcare utilization when compared to late preterm infants. In examining the impact of NOWS severity measures on post-discharge health care utilization, we found that some of the measures, such as pharmacological management of NOWS, length of stay, receiving medications (e.g., benzodiazepines), and presence of respiratory conditions were associated with higher probability of post-discharge health care utilization. While the results from logistic regression models were inconsistent, results from principal component analysis, which combined NOWS severity measures, showed that NOWS severity was associated with post-discharge health care utilization. Conclusions/Implications: Our study shows that the higher rates of health care utilization of infants who were diagnosed with NOWS is not just limited to a period of hospitalization for NOWS treatment but can also manifest for an extended period of time post-discharge. Hospital readmissions and emergency department visits could lead to additional physical, mental, and financial stress to the families of the affected infants. Furthermore, they signal presence of an underlying medical condition that could lead to poor health and even infant mortality. The findings of our study suggest that closer follow-up and management of infants may be necessary. Additional support to the infant-maternal dyad may help in improving health outcomes in these infants in the early years of their lives

Assessment of nutritional status in pregnant women on opioid maintenance therapy

Objectives: Patients who use substances or those who are on opioid maintenance therapy could be at risk of inadequate nutrition. These inadequacies could translate to adverse outcomes during pregnancy. The objective of this study was to determine differences in dietary macro and micronutrient intake in pregnant women on OMT compared to healthy controls. Methods: Participants from a parent prospective cohort study ENRICH\u27 were classified into two groups: OMT users and healthy controls. Inclusion into the nutritional analysis was based on eligibility criteria of completion of food frequency questionnaire administered during hospital stay after delivery, absence of heavy drinking and adequate energy intake. Crude differences in energy, macro (carbohydrate, protein and total fat) and micronutrient (vitamin A, B1, B2, B6, B12, C, D, E, beta-carotenes, folate, iron and choline) intake between the study groups were compared using student\u27s t-test which was repeated after adjustment by total energy intake. To control for multiple comparisons MANOVA was used. Multivariate regression was used to control for confounders. Results: A total of 54 subjects (34 OMT and 20 controls) were included in the nutritional analyses. No significant effect of OMT status on energy intake was observed. It was observed that OMT group had lower energy adjusted protein intake (p=0.03). Analysis of the dietary micronutrient intake showed that the subjects on OMT had significantly lower Vitamin E (-0.9a-TE/1000Kcal/day, 95%CI:-1.8, 0.1, p=0.03) and folate (-45.9 DFE/1000Kcal/day, 95%CI:-87.1,-4.6, p=0.03) intake compared to controls after controlling for marital status, insurance type, age and BMI. There was a significant effect of ethnicity on energy-adjusted carbohydrate intake (p=0.02) and employment (p\u3c0.01) on energy-adjusted protein intake after controlling covariates. It was observed that diet alone was not able to meet the requirements of several micronutrients in both the OMT and control group. Conclusion: It was observed that pregnant women on OMT had lower intake of several micronutrients compared to healthy controls which could lead to adverse pregnancy outcomes. The results of this study reinforces the requirement of micronutrient supplementation during pregnancy. Future studies should focus on investigating the effect of these differences in pregnancy outcomes and implement policies to promote healthy diet

Increased Incidence of Asthma in Children with Prenatal Opioid Exposure

Prenatal opioid exposure (POE) has increased dramatically in the last 10 years, with nearly 100 babies born daily in the United States with Neonatal Opioid Withdrawal Syndrome (NOWS). The impact on long-term outcomes continues to be investigated. Given the proinflammatory state that results from POE, we hypothesized that infants with POE or NOWS diagnoses during the newborn hospitalization would have an altered immune reactivity that persisted into childhood, defined by asthma diagnosis within the first 8 years. A retrospective cohort design utilizing a comprehensive CERNER HealthFacts U.S. national database was completed, which accesses clinical data from 800 hospitals across the country. ICD-9-CM and ICD-10-CM diagnosis codes were used to identify infants born at term with known POE or NOWS and were compared to healthy control infants with no diagnoses at birth other than normal newborn codes. The incidence of asthma during the first 8 years of life was determined. Descriptive statistics of frequencies and percentages were calculated for all variables. A Chi-Square test was used to examine the association between asthma diagnosis and POE. A total of 3128 infants were included in the analysis. Approximately 41% were identified as male and 38% identified as female; the remainder were not specified with coding. Almost 52% of subjects were identified as Caucasian. Asthma diagnosis differed significantly by group, X2 (3, n = 3,128) = 12.93 with a p \u3c 0.001. These emerging results suggest infants with POE may have altered immune reactivity that not only impacts the newborn period but persists into childhood. Those with POE were more likely to be diagnosed with asthma by 8 years of age than infants in the healthy control group. Additional investigations are needed to further characterize the impact POE has on the immune system, so that potential follow up strategies and/or interventions can be established

Spatial Epidemiology: an Empirical Framework For Syndemics Research

Syndemics framework describes two or more co-occurring epidemics that synergistically interact with each other and the complex structural social forces that sustain them leading to excess disease burden. The term syndemic was first used to describe the interaction between substance abuse, violence, and AIDS by Merrill Singer. A broader range of syndemic studies has since emerged describing the framework\u27s applicability to other public health scenarios. With syndemic theory garnering significant attention, the focus is shifting towards developing robust empirical analytical approaches. Unfortunately, the complex nature of the disease-disease interactions nested within several social contexts complicates empirical analyses. In answering the call to analyze syndemics at the population level, we propose the use of spatial epidemiology as an empirical framework for syndemics research. Spatial epidemiology, which typically relies on geographic information systems (GIS) and statistics, is a discipline that studies spatial variations to understand the geographic landscape and the risk environment within which disease epidemics occur. GIS maps provide visualization aids to investigate the spatial distribution of disease outcomes, the associated social factors, and environmental exposures. Analytical inference, such as estimation of disease risks and identification of spatial disease clusters, can provide a detailed statistical view of spatial distributions of diseases. Spatial and spatiotemporal models can help us to understand, measure, and analyze disease syndemics as well as the social, biological, and structural factors associated with them in space and time. In this paper, we present a background on syndemics and spatial epidemiological theory and practice. We then present a case study focused on the HIV and HCV syndemic in West Virginia to provide an example of the use of GIS and spatial analytical methods. The concepts described in this paper can be considered to enhance understanding and analysis of other syndemics for which space-time data are available

Assessment of nutritional status in pregnant women on opioid maintenance therapy

Objectives: Patients who use substances or those who are on opioid maintenance therapy could be at risk of inadequate nutrition. These inadequacies could translate to adverse outcomes during pregnancy. The objective of this study was to determine differences in dietary macro and micronutrient intake in pregnant women on OMT compared to healthy controls. Methods: Participants from a parent prospective cohort study “ENRICH” were classified into two groups: OMT users and healthy controls. Inclusion into the nutritional analysis was based on eligibility criteria of completion of food frequency questionnaire administered during hospital stay after delivery, absence of heavy drinking and adequate energy intake. Crude differences in energy, macro (carbohydrate, protein and total fat) and micronutrient (vitamin A, B1, B2, B6, B12, C, D, E, beta-carotenes, folate, iron and choline) intake between the study groups were compared using student’s t-test which was repeated after adjustment by total energy intake. To control for multiple comparisons MANOVA was used. Multivariate regression was used to control for confounders. Results: A total of 54 subjects (34 OMT and 20 controls) were included in the nutritional analyses. No significant effect of OMT status on energy intake was observed. It was observed that OMT group had lower energy adjusted protein intake (p=0.03). Analysis of the dietary micronutrient intake showed that the subjects on OMT had significantly lower Vitamin E (-0.9a-TE/1000Kcal/day, 95%CI:-1.8, 0.1, p=0.03) and folate (-45.9 DFE/1000Kcal/day, 95%CI:-87.1,-4.6, p=0.03) intake compared to controls after controlling for marital status, insurance type, age and BMI. There was a significant effect of ethnicity on energy-adjusted carbohydrate intake (p=0.02) and employment (p<0.01) on energy-adjusted protein intake after controlling covariates. It was observed that diet alone was not able to meet the requirements of several micronutrients in both the OMT and control group. Conclusion: It was observed that pregnant women on OMT had lower intake of several micronutrients compared to healthy controls which could lead to adverse pregnancy outcomes. The results of this study reinforces the requirement of micronutrient supplementation during pregnancy. Future studies should focus on investigating the effect of these differences in pregnancy outcomes and implement policies to promote healthy diet.This work has been supported by the R01 AA021771 research grant from NIAAA/NIH.Pharmaceutical SciencesMastersUniversity of New Mexico. College of PharmacyBakhireva, Ludmila N.Raisch, Dennis W.Pribis, Pete

Barriers and facilitators to dispensing of intranasal naloxone by pharmacists.

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\u27 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\u27 concerns, include education to multiple audiences, and address provider-level, system-level, and society-level barriers

The effect of prenatal substance use and maternal contingent responsiveness on infant affect.

BACKGROUND: The effects of prenatal substance exposure on neurobehavioral outcomes are inherently confounded by the effects of the postnatal environment, making it difficult to disentangle their influence. The goal of this study was to examine the contributing effects of prenatal substance use and parenting style (operationalized as contingent responding during the play episodes of the Still-face paradigm [SFP]) on infant affect. METHODS: A prospective cohort design was utilized with repeated assessment of substance use during pregnancy and the administration of the SFP, which measures infant response to a social stressor, at approximately 6months of age. Subjects included 91 dyads classified into four groups: 1) Control (n=34); 2) Medication assisted therapy for opioid dependence (MAT; n=19); 3) Alcohol (n=15); 4) Alcohol+MAT (n=23). Mean % of positive infant affect and mean % of maternal responsiveness (watching, attention seeking, and contingent responding) was compared among the five SFP episodes across the four study groups by MANOVA. Mixed effects modelling was used to estimate the contributing effects of the study groups and maternal responsiveness on infant affect. RESULTS: Maternal contingent responding was associated with increase (β̂=0.84; p CONCLUSIONS: Higher maternal responsiveness was a much stronger predictor of infant behavior than prenatal exposures, providing the basis for future intervention studies focusing on specific parenting strategies

Dietary Intake Among Opioid- and Alcohol-Using Pregnant Women.

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