Overdose responses among rural people who use drugs: A multi-regional qualitative study.

BACKGROUND: Efforts to distribute naloxone have equipped more people with the ability to reverse opioid overdoses but people who use drugs are often reluctant to call 911 due to concerns for legal repercussions. Rural communities face unique challenges in reducing overdose deaths compared to urban communities, including limited access to harm reduction services as well as greater concerns about stigma and privacy. METHODS: The Rural Opioid Initiative was funded in 2017 to better understand the health-related harms associated with the opioid crisis in rural US communities and consists of eight studies spanning ten states and 65 counties. Each study conducted semi-structured qualitative interviews with people who use drugs to understand contextual factors influencing drug use and health behaviors. We analyzed qualitative data from seven studies with data available at the time of analysis to understand peer response to overdose. RESULTS: Of the 304 participants interviewed, 55% were men, 70% were white, 80% reported current injection drug use, and 60% reported methamphetamine use. Similar to what has been found in studies focused on urban settings, people who use drugs in rural communities use a range of strategies to reverse overdoses, including non-evidence-based approaches. Several reported that multiple doses of naloxone are needed to reverse overdose. Three themes emerged around the willingness to call 911, including (1) hesitancy to call 911 for fear of legal consequences, (2) negative perceptions or experiences with law enforcement officers, and (3) efforts to obtain medical intervention while avoiding identification/law enforcement involvement. CONCLUSION: People who use drugs employ multiple strategies to attempt overdose reversal, including non-evidence-based approaches. Greater education about the most effective and least harmful strategies is needed. Reluctance to call 911 is rooted in concerns about potential legal consequences as well as perceptions about law enforcement officers, which may be heightened in rural communities where people who use drugs are more easily identified by law enforcement. People who use drugs will go to great strides to connect their peers to needed medical services, suggesting that comprehensive interventions to reduce interactions with law enforcement officers and eliminate legal consequences for reporting overdoses are critical.

The relationship between felt stigma and non-fatal overdose among rural people who use drugs.

BACKGROUND: Drug overdose deaths in the United States exceeded 100,000 in 2021 and 2022. Substance use stigma is a major barrier to treatment and harm reduction utilization and is a priority target in ending the overdose epidemic. However, little is known about the relationship between stigma and overdose, especially in rural areas. We aimed to characterize the association between felt stigma and non-fatal overdose in a multi-state sample of rural-dwelling people who use drugs. METHODS: Between January 2018 and March 2020, 2,608 people reporting past 30-day opioid use were recruited via modified chain-referral sampling in rural areas across 10 states. Participants completed a computer-assisted survey of substance use and substance-related attitudes, behaviors, and experiences. We used multivariable logistic regression with generalized estimating equations to test the association between felt stigma and recent non-fatal overdose. RESULTS: 6.6% of participants (n = 173) reported an overdose in the past 30 days. Recent non-fatal overdose was significantly associated with felt stigma after adjusting for demographic and substance use-related covariates (aOR: 1.47, 95% CI: 1.20-1.81). The association remained significant in sensitivity analyses on component fear of enacted stigma items (aOR: 1.48, 95% CI: 1.20-1.83) and an internalized stigma item (aOR: 1.51, 95% CI: 1.07-2.14). CONCLUSIONS: Felt stigma related to substance use is associated with higher risk of non-fatal overdose in rural-dwelling people who use drugs. Stigma reduction interventions and tailored services for those experiencing high stigma are underutilized approaches that may mitigate overdose risk.

Association of brain functional connectivity with neurodevelopmental outcomes in healthy full-term newborns.

OBJECTIVE: To study the association between neurodevelopmental outcomes and functional brain connectivity (FBC) in healthy term infants. METHODS: This is a retrospective study of prospectively collected High-density electroencephalography (HD-EEG) from newborns within 72 hours from birth. Developmental assessments were performed at two years of age using the Bayley Scales of Infant Development-III (BSID-III) measuring cognitive, language, motor, and socio-emotional scores. The FBC was calculated using phase synchronization analysis of source signals in delta, theta, alpha, beta, and gamma frequency bands and its association with neurodevelopmental score was assessed with stepwise regression. RESULTS: 47/163 had both HD-EEG and BSID-III scores. The FBC of frontal region was associated with cognitive score in the theta band (corrected p, regression coefficients range: p < 0.01, 1.66-1.735). Language scores were significantly associated with connectivity in all frequency bands, predominantly in the left hemisphere (p < 0.01, -2.74-2.40). The FBC of frontal and occipital brain regions of both hemispheres was related to motor score and socio-emotional development in theta, alpha, and gamma frequency bands (p < 0.01, -2.16-2.97). CONCLUSIONS: Functional connectivity of higher-order processing is already present at term age. SIGNIFICANCE: The FBC might be used to guide interventions for optimizing subsequent neurodevelopment even in low-risk newborns.

Evaluation of the international Ki67 working group cut point recommendations for early breast cancer: comparison with 21-gene assay results in a large integrated health care system.

PURPOSE: The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2-, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut points for selecting patients for further testing with the 21-gene Recurrence Score (RS) assay. METHODS: We included 307 women aged 50+ years with node-negative, ER+PR+HER2- breast cancer and with available RS results. Slides from the diagnostic biopsy were stained for Ki67 and scored using digital image analysis (IA). Two IHC pathologists underwent IKWG training and visually scored slides, blinded to each other and IA readings. Interobserver reproducibility was examined using intraclass correlation (ICC) and Kappa statistics. RESULTS: Depending on reader, 8.8-16.0% of our cohort had Ki67 ≤ 5% and 11.4-22.5% had scores ≥ 30%. The ICC for Ki67 scores by the two pathologists was 0.82 (95% CI 0.78-0.85); it was 0.79 (95% CI 0.74-0.83) for pathologist 1 and IA and 0.76 (95% CI 0.71-0.80) for pathologist 2 and IA. For Ki67 scores ≤ 5%, the percentages with RS < 26 were 92.6%, 91.8%, and 90.9% for pathologist 1, pathologist 2, and IA, respectively. For Ki67 scores ≥ 30%, the percentages with RS ≥ 26 were 41.5%, 51.4%, and 27.5%, respectively. CONCLUSION: The IKWG's Ki67 training resulted in moderate to strong reproducibility across readers but cut points had only moderate overlap with RS cut points, especially for Ki67 ≥ 30% and RS ≥ 26; thus, their clinical utility for a 21-gene assay testing pathway remains unclear.

Shotgun metagenomic sequencing on skin microbiome indicates dysbiosis exists prior to the onset of atopic dermatitis.

BACKGROUND: While the microbiome is increasingly seen as a targetable contributor to atopic dermatitis (AD), questions remain as to whether the dysbiosis is secondary to diseased skin or if it predates symptom onset. Previous work has evaluated how the skin microbiome changes with age and established the influence of factors like delivery mode and breastfeeding on global microbiome diversity. However, these studies were unable to identify taxa which predict subsequent AD. METHODS: Skin swab samples were collected from the first week of life for 72 children in the neonatal intensive care unit (NICU) at a single site hospital. Participants were followed for 3 years to determine their health status. We applied shotgun metagenomic sequencing to assess the microbiome differences between 31 children who went on to develop AD and 41 controls. RESULTS: We identified that subsequent development of AD was associated with differential abundance of several bacterial and fungal taxa as well as several metabolic pathways, each of which have been previously associated with active AD. CONCLUSIONS: Our work provides evidence of reproducibility for the previously reported dysbiotic signatures predating AD onset while also expanding prior findings through the first use of metagenomic assessment prior to AD onset. While extrapolation of our findings beyond the pre-term, NICU cohort is limited, our findings add to the evidence that the dysbiosis associated with AD pre-dates disease onset rather than reflect a secondary consequence of skin inflammation.

"I am not a junkie": Social categorization and differentiation among people who use drugs.

BACKGROUND: Substance use stigma is a form of group-based exclusion, and delineating pathways from stigma to poor health requires a deeper understanding of the social dynamics of people who use drugs (PWUD). Outside of recovery, scant research has examined the role of social identity in addiction. Framed by Social Identity Theory/Self-Categorization Theory, this qualitative study investigated strategies of within-group categorization and differentiation among PWUD and the roles these social categories may play in shaping intragroup attitudes, perceptions, and behaviors. METHODS: Data come from the Rural Opioid Initiative, a multi-site study of the overdose epidemic in rural United States. We conducted in-depth interviews with people who reported using opioids or injecting any drug (n=355) living in 65 counties across 10 states. Interviews focused on participants' biographical histories, past and current drug use, risk behaviors, and experiences with healthcare providers and law enforcement. Social categories and dimensions along which categories were evaluated were inductively identified using reflexive thematic analysis. RESULTS: We identified seven social categories that were commonly appraised by participants along eight evaluative dimensions. Categories included drug of choice, route of administration, method of attainment, gender, age, genesis of use, and recovery approach. Categories were evaluated by participants based on ascribed characteristics of morality, destructiveness, aversiveness, control, functionality, victimhood, recklessness, and determination. Participants performed nuanced identity work during interviews, including reifying social categories, defining 'addict' prototypicality, reflexively comparing self to other, and disidentifying from the PWUD supra-category. CONCLUSION: We identify several facets of identity, both behavioral and demographic, along which people who use drugs perceive salient social boundaries. Beyond an addiction-recovery binary, identity is shaped by multiple aspects of the social self in substance use. Patterns of categorization and differentiation revealed negative intragroup attitudes, including stigma, that may hinder solidary-building and collective action in this marginalized group.

Functional brain network properties of healthy full-term newborns quantified by scalp and source-reconstructed EEG.

OBJECTIVE: Identifying the functional brain network properties of term low-risk newborns using high-density EEG (HD-EEG) and comparing these properties with those of established functional magnetic resonance image (fMRI) - based networks. METHODS: HD-EEG was collected from 113 low-risk term newborns before delivery hospital discharge and within 72 hours of birth. Functional brain networks were reconstructed using coherence at the scalp and source levels in delta, theta, alpha, beta, and gamma frequency bands. These networks were characterized for the global and local network architecture. RESULTS: Source-level networks in all the frequency bands identified the presence of the efficient small world (small-world propensity (SWP) > 0.6) architecture with four distinct modules linked by hub regions and rich-club (coefficient > 1) topology. The modular regions included primary, association, limbic, paralimbic, and subcortical regions, which have been demonstrated in fMRI studies. In contrast, scalp-level networks did not display consistent small world architecture (SWP < 0.6), and also identified only 2-3 modules in each frequency band.The modular regions of the scalp-network primarily included frontal and occipital regions. CONCLUSIONS: Our findings show that EEG sources in low-risk newborns corroborate fMRI-based connectivity results. SIGNIFICANCE: EEG source analysis characterizes functional connectivity at the bedside of low-risk newborn infants soon after birth.

Rural communities face more than an opioid crisis: Reimagining funding assistance to address polysubstance use, associated health problems, and limited rural service capacity.

PURPOSE: Rural communities in the United States face unique challenges related to the opioid epidemic. This paper explores the substances and substance-related health problems that pose the greatest concern to rural communities that received funding to address the opioid epidemic and examines their reported capacity to address these challenges. METHODS: This paper analyzed data collected as part of quarterly progress reporting from multisector consortiums across 2 cohorts of grantees funded to reduce the morbidity and mortality of opioids. Consortium project directors ranked the top 3 issues in their community in each of the following categories: (1) drugs of concern; (2) drugs with the least capacity to address; (3) related problem areas of concern (eg, neonatal abstinence syndrome [NAS]); and (4) related problem areas with the least capacity to address. FINDINGS: Methamphetamines, fentanyl, and alcohol were the substances rated as most problematic in rural communities funded to address the opioid epidemic across all reporting periods. Over 40% of respondents ranked methamphetamine as a top concern and the substance they had the least capacity to address. This was nearly double the percentage of the next highest-ranked substance (fentanyl). Overdoses, NAS, and viral hepatitis constituted the top-ranking related concerns, with limited capacity to address them. CONCLUSIONS: Multiple drug and concomitant problems coalesced on rural communities during the opioid epidemic. Funding communities to address substance use disorders and related problems of concern, rather than targeting funding toward a specific type of drug, may result in better health outcomes throughout the entire community.

A Prospective Evaluation of Arrhythmias in a Large Tertiary Neonatal Intensive Care Unit.

Arrhythmias in the neonatal period are common and can be classified as bradyarhythmias and tachyarrhythmias and as benign or non-benign. Neonatal arrhythmias are further differentiated between those with abnormalities in generation (non-sinus) and those with abnormalities in propagation. Because the neonatal myocardium is immature and operates at the peak of the Starling curve, significant changes in heart rate can result in a decline in cardiac output and compromise end-organ perfusion. This is especially true for premature neonates, those critically ill, or those with concomitant congenital heart disease. While sustained arrhythmias are frequently witnessed and recorded in tertiary neonatal intensive care units (NICU) very little data exist on the observance of non-sustained brady- or tachyarrhythmias in this cohort. No prospective study has been performed on all neonates admitted to a large tertiary NICU throughout their entire stay. The purpose of this study was to prospectively evaluate the prevalence and type of arrhythmias in a large NICU population from admission to discharge. All neonates admitted to the NICU at Inova Children's Hospital at Inova Fairfax Medical Campus between January 1, 2021 and April 1, 2021 were prospectively evaluated from admission to hospital discharge via continuous bedside monitoring reviewed every 24 h. Concerning telemetry strips were reviewed by two team members as well as the senior electrophysiologist. Two-hundred and one neonates (mean gestational age = 344/7 weeks) were enrolled in the study. Admission length ranged from 1 to 195 days (total of 5624 patient days, median 16 days). Overall, 68% (N = 137) of admissions had one or more arrhythmias, the most common of which was sinus tachycardia (65%, N = 130), followed by sinus bradycardia (30%, N = 60). Clinically relevant arrhythmias were diagnosed in 6.5% of neonates. During the study period there were four deaths, none of which were directly attributable to a primary arrhythmia. Approximately 68% of neonates exhibited at least one arrhythmia. Although the vast majority of these arrhythmias were benign, clinically relevant arrhythmias were observed in 6.5%. Patients admitted to the NICU appear to have a relatively high burden of benign arrhythmias, but a relatively low burden of pathologic arrhythmias.

Association of Methamphetamine and Opioid Use With Nonfatal Overdose in Rural Communities.

Importance: Overdoses continue to increase in the US, but the contribution of methamphetamine use is understudied in rural communities. Objective: 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. Design, Setting, and Participants: 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. Exposures: Use of methamphetamine alone, opioids alone, or both. Main Outcomes and Measures: Unweighted and weighted prevalence of methamphetamine use, any past-180-day nonfatal overdose, and number of lifetime nonfatal overdoses. Results: 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. Conclusions and Relevance: These findings suggest that harm reduction and substance use disorder treatment interventions must address both methamphetamine and opioids to decrease overdose in rural communities.

Association between treatment setting and outcomes among oregon medicaid patients with opioid use disorder: a retrospective cohort study.

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.

"It wasn't here, and now it is. It's everywhere": fentanyl's rising presence in Oregon's drug supply.

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.

Electroencephalogram in low-risk term newborns predicts neurodevelopmental metrics at age two years.

OBJECTIVE: To determine whether neurodevelopmental biomarkers at 2 years of age are already present in the newborns' EEG at birth. METHODS: 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. RESULTS: 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. CONCLUSIONS: Electrophysiological biomarkers of neurodevelopment at age 2 years are already present at birth in low-risk term infants. SIGNIFICANCE: Low-risk newborns' EEG utility as a screening tool to optimize neurodevelopmental outcome warrants further evaluation.

Fecal sphingolipids predict parenteral nutrition-associated cholestasis in the neonatal intensive care unit.

BACKGROUND: Parenteral nutrition-associated cholestasis (PNAC) in the neonatal intensive care unit (NICU) causes significant morbidity and associated healthcare costs. Laboratory detection of PNAC currently relies on elevated serum conjugated bilirubin levels in the aftermath of impaired bile flow. Here, we sought to identify fecal biomarkers, which when integrated with clinical data, would better predict risk for developing PNAC. METHODS: Using untargeted metabolomics in 200 serial stool samples from 60 infants, we applied statistical and machine learning approaches to identify clinical features and metabolic biomarkers with the greatest associative potential for risk of developing PNAC. Stools were collected prospectively from infants receiving PN with soybean oil-based lipid emulsion at a level IV NICU. RESULTS: Low birth weight, extreme prematurity, longer duration of PN, and greater number of antibiotic courses were all risk factors for PNAC (P < 0.05). We identified 78 stool biomarkers with early predictive potential (P < 0.05). From these 78 biomarkers, we further identified 12 sphingomyelin lipids with high association for the development of PNAC in precholestasis stool samples when combined with birth anthropometry. CONCLUSION: We demonstrate the potential for stool metabolomics to enhance early identification of PNAC risk. Earlier detection of high-risk infants would empower proactive mitigation with alterations to PN for at-risk infants and optimization of energy nutrition with PN for infants at lower risk.

Autonomic development in preterm infants is associated with morbidity of prematurity.

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.

Perspectives on extended-release naltrexone induction among patients living with HIV and opioid use disorder: a qualitative analysis.

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 .

Cerebral cortical autonomic connectivity in low-risk term newborns.

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 of 39-40 weeks were prospectively enrolled and studied using time-synced electroencephalography and electrocardiography for up to 60 min before discharge from the birth hospital. The ccortical autonomicc nervous system association was analyzed using coherence between electroencephalography-delta power and heart rate variability. Heart rate variability measured the 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, bitemporal, and occipital brain regions, with less robust coherence delta-standard deviation in the central region and bitemporal areas. CONCLUSIONS: Our findings describe a topography of ccortical autonomicc connectivity present at term in low-risk newborns, which was more robust to parasympathetic than sympathetic brainstem centers and was independent of newborn state.

"Like Yin and Yang": Perceptions of Methamphetamine Benefits and Consequences Among People Who Use Opioids in Rural Communities.

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.

Autonomic nervous system maturation in the premature extrauterine milieu.

BACKGROUND: In premature infants, we investigated whether the duration of extrauterine development influenced autonomic nervous system (ANS) maturation. METHODS: 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). RESULTS: 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. CONCLUSION: 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. IMPACT: 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.

Reducing overdose after release from incarceration (ROAR): study protocol for an intervention to reduce risk of fatal and non-fatal opioid overdose among women after release from prison.

BACKGROUND: Drug overdose is the leading cause of death after release from prison, and this risk is significantly higher among women compared to men. Within the first 2 weeks after release, the risk of death from drug overdose is 12.7 times higher than the general population, with risk of death further elevated among females. Although female inmates have higher rates of opioid use disorder and post-release overdose fatality, justice-involved women are under-represented in studies of medications for opioid use disorder. The Reducing Overdose After Release from Incarceration (ROAR) pilot intervention and evaluation (recruitment June 2019 through December 2020) aims to reduce opioid overdose among women released to the community following incarceration in state prison. The evaluation further assesses induction, acceptance and effectiveness of extended release naltrexone in a female post-prison population. METHODS/DESIGN: In the week prior to their release, female adults in custody with moderate to severe opioid use disorder start treatment with extended release naltrexone, an injectable opioid antagonist that blocks the effects of opioids for up to 1 month. All ROAR participants receive training to use naloxone rescue kits and are provided nasal naloxone at release. Ongoing support from a certified recovery mentor to facilitate sustained engagement with treatment for substance use disorders begins in the month prior to release from prison and continues for 6 months in community. We evaluate the association between ROAR participation and the primary outcome of opioid overdose. Using administrative data provided by the Oregon Department of Corrections and the Oregon Health Authority, we compare the odds of overdose among ROAR participants versus a comparison group of females released from prison during the study period. Evaluation activities in community includes survey and qualitative interviews for 6 months post release, as well as a review of clinic records to assess retention on medication among the pilot cohort (N = 100). DISCUSSION: ROAR is a collaboration between Oregon's public health, criminal justice, and medical communities. The ROAR intervention and evaluation provide critical information on improving interventions to prevent opioid overdose and improve retention on treatment in community in an overlooked, high-risk population: incarcerated women re-entering the community. TRIAL REGISTRATION: Clinical Trials.gov TRN: NCT03902821 .