Substance Exposure and Adverse Neonatal Outcomes: A Population-Based Cohort Study.

OBJECTIVE: To estimate the independent and combined effects of in utero exposures on birth outcomes in a rural population. STUDY DESIGN: The study used population-level data (2020-2022) from a state-wide surveillance tool (Working in Appalachia to identify at-risk infants, Critical congenital heart disease, and Hearing loss) in West Virginia. Outcomes included low birth weight, preterm birth, small for gestational age, and birth weight in grams. Exposure included a composite variable with 8 levels of 3 exposure (opioids, stimulants, and cannabis) categories. Analyses were adjusted for sociodemographic covariates using multiple logistic and linear regression analyses. RESULTS: Of the 34 412 singleton live births, 1 in 8 newborns (12.2%) had in utero exposure(s) to opioids, stimulants, and/or cannabis, 11.5% were preterm, 7.9% had low birthweight, 9.6% were small for gestational age, and mean birth weight was 3249 ± 563.6 g. Preterm birth was associated with stimulant alone exposure (aOR, 1.40; 95% CI, 1.03-1.89) and stimulant and cannabis concurrent exposure (aOR, 1.69; 95% CI, 1.16, 2.47). Low birthweight was associated with opioids alone (aOR, 1.34; 95% CI, 1.10, 1.63), cannabis alone (aOR, 1.31; 95% CI, 1.13 to -1.52), opioid and cannabis (aOR, 1.61; 95% CI, 1.12 to -2.31), and opioids, stimulants, and cannabis concurrent exposures (aOR, 2.27; 95% CI, 1.43-3.61). Five exposure categories were associated with lower birth weights (adjusted mean difference range. -72 to -211 g). Small for gestational age was associated with opioids alone (aOR, 1.48; 95% CI, 1.24-1.78), cannabis alone (aOR, 1.49; 95% CI, 1.31-1.69), and opioids and cannabis concurrent exposures (aOR, 1.91; 95% CI, 1.36-2.67). CONCLUSIONS: We showed complex associations between in utero substance exposures, preterm birth, birth weight, and sociodemographic factors in a rural population. The results may inform policy efforts to improve maternal and child health in socioeconomically disadvantaged and underserved rural populations.

Training in the art and science of facilitation to scale research mentor training in low and middle income countries.

Advancing biomedical research in low and middle income countries (LMICs) to expand the capacity for LMICs to integrate biomedical research into their health care systems and education has been the focus of many programs in global health over the past two decades. Central to the success of these programs is effective research mentoring, characterized by academic, career and psychosocial support through culturally appropriate practices. Research mentoring is a learned skill, developed through training, mutual discussions, practice and feedback. The majority of extant training programs are designed and delivered by US partners, so the next stage in building capacity is to train facilitators within the LMIC partner institutions to contextualize and advance mentoring specifically within their cultural and institutional norms by co-developing, delivering and evaluating semi-annual research mentoring training. To this end, we describe the development, delivery and outcome evaluation of a 5-week course in the art and skill of facilitation. Care was taken to explicitly distinguish between concepts of "teaching" and "facilitation," since "teaching" is closely connected to a transmission or banking model of education, which is characterized by "top-down," hierarchical relationship. The course discussed power and positionality, themes that resonate with partners in Nigeria and Tanzania. These themes provided unique entry into deeper conversations core to advancing mentoring practice away from the traditional dyadic power structure that remains from colonization. Evaluation findings indicate significant advances in awareness of differences between teaching and facilitating, increased confidence in facilitation skills, especially in the area of structured planning and organization, as well as improved communication and interpersonal skills. All respondents felt that students in Nigeria and Tanzania would respond well to the facilitation approach conveyed during the course and they found value in participating in the course as a cohort.

A review of executive functioning challenges and strengths in autistic adults.

Objective: There has been a steady rise in research characterizing executive functioning (EF) impairments in autistic individuals but limited research investigating EF strengths. This review provides a summary of current EF research in autistic adults with a focus on EF challenges and strengths and potential sources of heterogeneity in research findings. New avenues for addressing gaps in our understanding of EF strengths are proposed.Method: A review of the EF literature was conducted. One hundred twenty-four studies of inhibition, working memory, cognitive flexibility, fluency, planning, decision-making, and subjective measures of EF in autistic adults were included.Results: Autistic adults with average intellectual functioning demonstrate difficulties with cognitive flexibility, phonemic fluency, and working memory. Strengths in planning, decision-making, and semantic verbal fluency were evident in some but not all studies. Findings regarding inhibition are inconclusive. Key findings across each EF domain are discussed and sources of potential heterogeneity across studies were evaluated. The type of measure used appears to contribute to heterogeneous findings. Subjective EF measures revealed more consistent findings of deficits in autistic adults than objective EF measures.Conclusions: Research reveals areas of EF weaknesses as well as strengths in autistic adults. Unlike EF challenges, EF strengths are not well understood. Future research identifying EF strengths is needed to improve services and supports for autistic adults. Further investigation of potential factors that interact with or constrain EF such as comorbid disorders, verbal ability, sensory processing, and other factors specific to autism will be critical to move the field forward and increase understanding of how EF is related to everyday functioning in autistic adults.

A Feasibility Study to Increase Chronic Hepatitis C Virus RNA Testing and Linkage to Care among Clients Attending Homeless Services in Amsterdam, The Netherlands.

People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV) infections and are frequently homeless. To improve HCV case finding in these individuals, we examined the feasibility of rapid HCV RNA testing in homeless services in Amsterdam. In 2020, we provided a comprehensive service to homeless facilities, which included workshops on HCV for personnel, a "hepatitis ambassador" at each facility, a rapid, onsite HCV RNA fingerstick test service, and assistance with linkage to care. Risk factors for HCV RNA-positive status were examined using Bayesian logistic regression. Of the 152 participants enrolled, 150 (87% men; median age: 47 years) accepted rapid HCV testing. Seven tested HCV RNA positive (4.7%, 95%CrI = 1.31-8.09; 7/150). Of these, five (71%) were linked to care, of whom four (57%, 4/7) initiated treatment and one (14%, 1/7) delayed treatment due to a drug-drug interaction. Of these four people, two completed treatment (50%), of whom one (25%) achieved sustained virologic response after 12 weeks. HCV RNA-positive individuals were more likely to originate from Eastern Europe (posterior-odds ratio (OR) = 3.59 (95% credible interval (CrI) = 1.27-10.04)) and to inject drugs (ever: posterior-OR = 3.89 (95% CrI = 1.37-11.09); recent: posterior-OR = 3.94 (95% CrI = 1.29-11.71)). We identified HCV RNA-positive individuals and linkage to care was relatively high. Screening in homeless services with rapid testing is feasible and could improve HCV case finding for PWID who do not regularly attend primary care or other harm reduction services for people who use drugs.

Assessment of the FilmArray® multiplex PCR system and associated meningitis/encephalitis panel in the diagnostic service of a tertiary hospital.

Rapid and accurate diagnosis of meningitis/encephalitis (M/E) is essential for successful patient outcomes. The FilmArray® meningitis/encephalitis Panel (MEP) is a multiplexed PCR test for simultaneous, rapid detection of pathogens directly from cerebrospinal fluid (CSF) samples. 94 prospectively collected CSF specimens from patients with clinical suspicion of infective M/E underwent testing for 14 pathogens simultaneously, including Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, and Varicella zoster. MEP demonstrated 95% agreement with current PCR methods, resulting in 16 diagnosed cases of M/E. Typically, the FilmArray® MEP results were delivered within approximately one hour, contrasting with current practices taking up to 5.6 days. Given the significant morbidity and mortality associated with delayed diagnosis of central nervous system infections, the FilmArray® MEP is a useful addition to the diagnostic capabilities of a clinical microbiology department.

From opiates to methamphetamine: building new harm reduction responses in Jakarta, Indonesia.

BACKGROUND: Despite the rise of stimulant use, most harm reduction programs still focus on people who inject opioids, leaving many people who use methamphetamine (PWUM) underserviced. In Asia, especially, where methamphetamine prevalence has overtaken opioids prevalence, harm reduction programs assisting PWUM are rare. The few existing innovative practices focusing on methamphetamine use lie underreported. Understanding how these programs moved their focus from opiates to methamphetamine could help inspire new harm reduction responses. Hence, this paper analyzes a newly implemented outreach program assisting methamphetamine users in Jakarta, Indonesia. It addresses the program's critical learning points when making the transition to respond to stimulant use. METHODS: This case study is part of a more extensive research on good practices of harm reduction for stimulant use. For this case study, data was collected through Indonesian contextual documents and documents from the program, structured questionnaire, in-depth interviews with service staff and service users, a focus group discussion with service users, and in-loco observations of activities. For this paper, data was reinterpreted to focus on the key topics that needed to be addressed when the program transitioned from working with people who use opioids to PWUM. RESULTS: Four key topics were found: (1) getting in touch with different types of PWUM and building trust relationships; (2) adapting safer smoking kits to local circumstances; (3) reframing partnerships while finding ways to address mental health issues; and (4) responding to local law enforcement practices. CONCLUSIONS: The meaningful involvement of PWUM was essential in the development and evaluation of outreach work, the planning, and the adaptation of safer smoking kits to local circumstances. Also, it helped to gain understanding of the broader needs of PWUM, including mental health care and their difficulties related to law enforcement activities. Operating under a broad harm reduction definition and addressing a broad spectrum of individual and social needs are preferable to focusing solely on specific interventions and supplies for safer drug use. Since many PWUM smoke rather than inject, securing funding for harm reduction focused on people who do not inject drugs and/or who do not use opioids is fundamental in keeping programs sustainable.

Developing a mouse model of chronic ankle instability.

INTRODUCTION: Ankle sprains are the most common orthopedic pathology experienced during sport and physical activity and often result in chronic ankle instability (CAI). Understanding how to prevent CAI is difficult because of the costs and logistics associated with clinical trials aimed at preventing the heterogeneous symptoms associated with CAI. Thus, a need exists to develop an animal model that presents similar long-term consequences as CAI to assess preclinical data. Thus, the purpose was to determine whether surgically transecting the lateral ligaments of a mouse hind limb results in the development of CAI-like symptoms 12 months after injury. METHODS: Thirty male mice (CBA/J) were randomly placed into a SHAM (control), CFL (calcaneofibular ligament; mild ankle sprain), or ATFL/CFL (anterior talofibular ligament/CFL; severe) ankle sprain group and housed individually. Three days after surgically transecting the respective lateral ligaments, mice were given a solid surface running wheel and daily running wheel measurements were recorded. Outcome measures of balance and gait were obtained before and at 4, 48, 54, and 60 wk after injury. RESULTS: The ATFL/CFL group had significantly more hind foot slips than the CFL and SHAM groups (P < 0.05). The CFL also had more hind foot slips relative to the SHAM group (P < 0.05). The ATFL/CFL group was significantly less physically active relative to the SHAM and CFL groups (P < 0.05). A cut score of 4.75 foot slips had a sensitivity of 0.68 and specificity of 1.00 and indicates that 70% (14/20) of mice with an ankle sprain had developed CAI. CONCLUSIONS: The results of this study indicate that an acute ankle sprain in mice can result in the development of CAI-like symptoms 12 months after injury.

Activated eosinophils in association with enteric nerves in inflammatory bowel disease.

Enteric neural dysfunction leads to increased mucous production and dysmotility in inflammatory bowel disease (IBD). Prior studies have shown that tissue eosinophilia is related to disease activity. We hypothesized that interactions between eosinophils and nerves contribute to neural dysfunction in IBD. Tissue from patients with intractable IBD, endoscopic biopsies from patients with steroid responsive IBD, both when active and quiescent, and control tissue were studied. Immunohistochemical studies showed that eosinophils localize to nerves in the mucosal layer of patients with Crohn's disease (CD) (p<0.001) and ulcerative colitis (UC), (p<0.01). Eosinophils localized to substance P and choline acetyltransferase (ChAT) immunostained nerves. Real time PCR of laser capture micro-dissected enteric ganglia demonstrated Intercellular Adhesion Molecule 1 (ICAM-1) mRNA was increased 7-fold in UC (n = 4), (p = 0.03), and 10-fold in CD (n = 3), (p = 0.05). Compared with controls, eotaxin-3 (CCL-26) mRNA was increased 9-fold in UC (p = 0.04) and 15-fold in CD (p = 0.06). Eosinophil numbers correlated with disease activity, while deposition of major basic protein (MBP) and eosinophil Transforming Growth Factor ß-1 (TGFß-1) expression were seen in therapeutically responsive disease. These data indicate a significant localization of eosinophils to nerves in IBD, mediated through neurally expressed ICAM-1 and eotaxin-3. This cell/neural interaction may influence the function of nerves and contribute to symptoms in IBD.