Treating Women Who Are Pregnant and Parenting for Opioid Use Disorder and the Concurrent Care of Their Infants and Children: Literature Review to Support National Guidance

The prevalence of opioid use disorder (OUD) during pregnancy is increasing. Practical recommendations will help providers treat pregnant women with OUD and reduce potentially negative health consequences for mother, fetus, and child. This article summarizes the literature review conducted using the RAND/University of California, Los Angeles Appropriateness Method project completed by the US Department of Health and Human Services Substance Abuse and Mental Health Services Administration to obtain current evidence on treatment approaches for pregnant and parenting women with OUD and their infants and children

Usability and Acceptability Testing of a Plan of Safe Care in a Mobile Health Platform

Purpose: Women who are pregnant or parenting while recovering from substance use disorder (SUD) are at risk for insufficient recovery support. With the federal mandate, implementation has been left to each state for the Plan of Safe Care (POSC), leading to challenges in providing comprehensive care coordination and meeting federal reporting requirements. Methods: This research tests the usability and acceptability of a POSC platform, called SAFE4BOTH, which combines a mobile health (mHealth) app for use by mothers with substance use disorder (MSUD) with a web-based case management system for use by stakeholders to reduce the issue of fragmented postnatal maternal and infant care. The platform was designed to enable access to services, improve reporting task workflow, and assist in improving interactions between mothers and service providers. After applying a user-centered design approach, the usability and acceptability of the SAFE4BOTH platform were evaluated using focus groups, interviews, and a System Usability Scale (SUS). The evaluation involved four staff members from a Medication for Addiction Treatment clinic (comprising of three case management workers and one peer counselor), four state employees of the Delaware Division of Family Services, and 20 mothers with MSUD who had delivered infants in need of a POSC. Features tested in the SAFE4BOTH platform included a secure, web-based POSC, a contingency management-based reward system, a micro-learning library, a resources locator, a chat messaging and videoconferencing system, a directory for contact management, a QR code reader, use of an appointment compliance system engaging geofencing, and an enhanced calendar. Family services and treatment center staff accessed SAFE4BOTH from their laptops or tablets, and MSUD accessed SAFE4BOTH from their phones. Results: Family services staff, treatment center staff, and MSUD participants rated SAFE4BOTH as usable and acceptable with average System Usability Scale scores of 68.1 (SD 8.5), 92.5 (SD 11.73), and 78.4 (SD 12.5) (respectively). Conclusion: The platform was judged both usable and acceptable by all three target populations (family services staff, treatment center staff, and MSUD). Further studies are planned to explore the efficacy of longitudinally supporting the mother’s recovery and the infant’s healthy development

Post-transcriptional regulation of androgen receptor mRNA by an ErbB3 binding protein 1 in prostate cancer

Androgen receptor (AR)-mediated pathways play a critical role in the development and progression of prostate cancer. However, little is known about the regulation of AR mRNA stability and translation, two central processes that control AR expression. The ErbB3 binding protein 1 (EBP1), an AR corepressor, negatively regulates crosstalk between ErbB3 ligand heregulin (HRG)-triggered signaling and the AR axis, affecting biological properties of prostate cancer cells. EBP1 protein expression is also decreased in clinical prostate cancer. We previously demonstrated that EBP1 overexpression results in decreased AR protein levels by affecting AR promoter activity. However, EBP1 has recently been demonstrated to be an RNA binding protein. We therefore examined the ability of EBP1 to regulate AR post-transcriptionally. Here we show that EBP1 promoted AR mRNA decay through physical interaction with a conserved UC-rich motif within the 3′-UTR of AR. The ability of EBP1 to accelerate AR mRNA decay was further enhanced by HRG treatment. EBP1 also bound to a CAG-formed stem-loop in the 5′ coding region of AR mRNA and was able to inhibit AR translation. Thus, decreases of EBP1 in prostate cancer could be important for the post-transcriptional up-regulation of AR contributing to aberrant AR expression and disease progression

Neonatal Outcomes after Combined Opioid and Nicotine Exposure in Utero: A Scoping Review

Background: The majority of women who are pregnant with opioid use disorder (OUD) also smoke tobacco but are rarely offered tobacco cessation counseling. While the effects of exposure to opioids and nicotine in utero are well-understood separately, understanding the impact of the combined exposure to these substances on neonatal outcomes is lacking. Methods: A scoping review was conducted using PubMed and Scopus databases for studies addressing the combined exposure to opioids and nicotine during pregnancy published between 1 January 1980 and 9 July 2019. A total of 29 papers met the eligibility criteria for inclusion, with nine being identified as clinical trials (three from the MOTHER study) and two as secondary data analysis of clinical trial data. Results: Neonatal outcomes for infants who had a combined exposure to opioids and nicotine in utero indicated a reduction in birth weight and birth length. Findings in infants exposed to both nicotine and opioids were mixed with regard to the duration of neonatal abstinence syndrome (NAS), the likelihood of treatment for NAS, doses of medicine used to treat NAS, and NAS scores when compared with infants who had opioid exposure without nicotine. Conclusions: The combined exposure to nicotine and opioids during pregnancy may lead to a reduction in neonatal birth weight and birth length and more severe NAS signs, compared with opioid use alone, but more research is necessary to identify the minimum dosage and length of nicotine exposure to accurately predict these outcomes

An investigation into morphological and biochemical abnormalities in the central nervous system of the mutant mouse tottering

The mutant mouse tottering carries an autosomal recessive single gene mutation on chromosome 8 that produces three distinct neurological disorders shortly before weaning: petit mal or absence-like seizures, ataxia and intermittent movement disorders. The majority of the research on the mutant mouse tottering has concentrated on investigating the petit mal component of the neurological triad while overlooking the significant motor behavior abnormalities. This dissertation compared the morphology of developing and adult cerebella and the distribution patterns of calcium binding proteins throughout the motor systems of the brain, in two related murine mutants (tottering (tg/tg) and tottering/leaner (tg/tg\sp{\rm la})) and normal age-matched mice.The first portion of the dissertation was designed to investigate whether any previously reported abnormalities in the cerebellum of the mutant mice were present prior to the onset of behavioral symptoms. By using a second mutation, Oligosyndactyly (Os), that produces fused digits, and thereby allows the identification of mutants at birth, we determined that the brain weight and the thickness of the molecular layer and the size of Purkinje cell somata in the paramedian lobule of the cerebellum were significantly reduced in both mutants after, but not prior, to the onset of the symptoms. Using unbiased, stereologically correct methods, the volume of the entire cerebellum and volume of the molecular layer per Purkinje cell, but not the Purkinje cell number and density, were found to be reduced in adult mutant mice.Evidence from the immunohistochemical analysis of the levels of three calcium binding proteins, calbindin, calretinin and parvalbumin, revealed differential staining between the mutant and wild type mice. Specifically, the motor cortex, basal ganglia and cerebellum, exhibited altered staining patterns in the mutant mice. In addition, the calcium binding proteins highlighted some structural abnormalities which had not been seen with other staining methods, namely torpedoes in the Purkinje cell axons of mutant mice.U of I OnlyETDs are only available to UIUC Users without author permissio

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used