Epigenetic processes associated with neonatal spinal transection.

In early development, the spinal cord in healthy or disease states displays remarkable activity-dependent changes in plasticity, which may be in part due to the increased activity of brain derived neurotrophic factor (BDNF). Indeed, BDNF delivery has been efficacious in partially ameliorating many of the neurobiological and behavioral consequences of spinal cord injury (SCI), making elucidating the role of BDNF in the normative developing and injured spinal cord a critical research focus. Recent work in our laboratory provided evidence for aberrant global and locus-specific epigenetic changes in methylation of the Bdnf gene as a consequence of SCI. In the present study, animals underwent thoracic lesions on P1, with cervical and lumbar tissue being later collected on P7, P14, and P21. Levels of Bdnf expression and methylation (exon IX and exon IV), in addition to global methylation levels were quantified at each timepoint. Results indicated locus-specific reductions of Bdnf expression that was accompanied by a parallel increase in methylation caudal to the injury site, with animals displaying increased Bdnf expression at the P14 timepoint. Together, these findings suggest that epigenetic activity of the Bdnf gene may act as biomarker in the etiology and intervention effort efficacy following SCI.

Psychostimulant Misuse Among American Indian, Alaskan Native, or Native Hawaiian College Students in the U.S. From 2015 to 2019.

Introduction: This study examines factors associated with psychostimulant misuse, including polysubstance use and social factors, among the understudied American Indian/Alaska Native/Native Hawaiian (AI/AN/NH) college student population. Methods: Data were from the 2015 to 2019 American College Health Association-National College Health Assessment IIc (ACHA-NCHA IIc) survey. Multivariable logistic regression models and odds ratios were used to estimate associations between psychostimulant misuse and potential risk and protective factors among AI/AN/NH college students, including licit and illicit substance use, social support, relationship factors, exposure to violence or abuse, mental health symptoms, drug and alcohol education, and sample demographics. Results: Opioid misuse among AI/AN/NH college students significantly increased the odds of using psychostimulants. Specifically, for cocaine use, the adjusted odds ratio (aOR) was 3.17 with a 95% confidence interval (C.I.) of 2.17 to 4.63; for methamphetamine use, the aOR was 38.87 (95% C.I. 19.24-78.52). For amphetamine misuse among non-Tobacco users, the aOR was 5.47 (95% C.I. 3.49-8.55), while among Tobacco users, the aOR was 2.65 (95% C.I. 2.07-3.41). For cocaine and other stimulant misuse, the aOR was 3.64 (95% C.I. 2.30-5.67). Additionally, the use of other types of licit and illicit substances was associated with greater odds of psychostimulant use and misuse. Conversely, factors such as age, living on campus, and residing in parental/guardian housing were linked with lower odds of psychostimulant use and misuse. Conclusion: Substance use prevention and treatment interventions targeting AI/AN/NH college students should address polysubstance use, including the combined use of opioids and psychostimulants. Substance use interventions should not be siloed to focus narrowly on single substances but rather should leverage potential protective factors against substance use, such as promoting supportive campus and family living conditions and other social support networks, in broad efforts to reduce multiple forms of substance use among AI/AN/NH students.

Nasal airway inflammatory responses and pathogen detection in infants with cystic fibrosis.

BACKGROUND: Detecting airway inflammation non-invasively in infants with cystic fibrosis (CF) is difficult. We hypothesized that markers of inflammation in CF [IL-1ß, IL-6, IL-8, IL-10, IL-17A, neutrophil elastase (NE) and tumor necrosis factor (TNF-α)] could be measured in infants with CF from nasal fluid and would be elevated during viral infections or clinician-defined pulmonary exacerbations (PEx). METHODS: We collected nasal fluid, nasal swabs, and hair samples from 34 infants with CF during monthly clinic visits, sick visits, and hospitalizations. Nasal fluid was isolated and analyzed for cytokines. Respiratory viral detection on nasal swabs was performed using the Luminex NxTAG® Respiratory Pathogen Panel. Hair samples were analyzed for nicotine concentration by reverse-phase high-performance liquid chromatography. We compared nasal cytokine concentrations between the presence and absence of detected respiratory viruses, PEx, and smoke exposure. RESULTS: A total of 246 samples were analyzed. Compared to measurements in the absence of respiratory viruses, mean concentrations of IL-6, IL-8, TNF-α, and NE were significantly increased while IL-17A was significantly decreased in infants positive for respiratory viruses. IL-17A was significantly decreased and NE increased in those with a PEx. IL-8 and NE were significantly increased in infants with enteric pathogen positivity on airway cultures, but not P. aeruginosa or S. aureus. Compared to those with no smoke exposure, there were significantly higher levels of IL-6, IL-10, and NE in infants with detectable levels of nicotine. CONCLUSIONS: Noninvasive collection of nasal fluid may identify inflammation in infants with CF during changing clinical or environmental exposures.

The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial.

IMPORTANCE: Scalable deprescribing interventions may reduce polypharmacy and the use of potentially inappropriate medications (PIMs); however, few studies have been large enough to evaluate the impact that deprescribing may have on adverse drug events (ADEs). OBJECTIVE: To evaluate the effect of an electronic deprescribing decision support tool on ADEs after hospital discharge among older adults with polypharmacy. DESIGN, SETTING, AND PARTICIPANTS: This was a cluster randomized clinical trial of older (≥65 years) hospitalized patients with an expected survival of more than 3 months who were admitted to 1 of 11 acute care hospitals in Canada from August 22, 2017, to January 13, 2020. At admission, participants were taking 5 or more medications per day. Data analyses were performed from January 3, 2021, to September 23, 2021. INTERVENTIONS: Personalized reports of deprescribing opportunities generated by MedSafer software to address usual home medications and measures of prognosis and frailty. Deprescribing reports provided to the treating team were compared with usual care (medication reconciliation). MAIN OUTCOMES AND MEASURES: The primary outcome was a reduction of ADEs within the first 30 days postdischarge (including adverse drug withdrawal events) captured through structured telephone surveys and adjudicated blinded to intervention status. Secondary outcomes were the proportion of patients with 1 or more PIMs deprescribed at discharge and the proportion of patients with an adverse drug withdrawal event (ADWE). RESULTS: A total of 5698 participants (median [range] age, 78 [72-85] years; 2858 [50.2%] women; race and ethnicity data were not collected) were enrolled in 3 clusters and were adjudicated for the primary outcome (control, 3204; intervention, 2494). Despite cluster randomization, there were group imbalances, eg, the participants in the intervention arm were older and had more PIMS prescribed at baseline. After hospital discharge, 4989 (87.6%) participants completed an ADE interview. There was no significant difference in ADEs within 30 days of discharge (138 [5.0%] of 2742 control vs 111 [4.9%] of 2247 intervention participants; adjusted risk difference [aRD] -0.8%; 95% CI, -2.9% to 1.3%). Deprescribing increased from 795 (29.8%) of 2667 control to 1249 (55.4%) of 2256 intervention participants [aRD, 22.2%; 95% CI, 16.9% to 27.4%]. There was no difference in ADWEs between groups. Several post hoc sensitivity analyses, including the use of a nonparametric test to address the low cluster number, group imbalances, and potential biases, did not alter study conclusions. CONCLUSIONS AND RELEVANCE: This cluster randomized clinical trial showed that providing deprescribing clinical decision support during acute hospitalization had no demonstrable impact on ADEs, although the intervention was safe and led to improvements in deprescribing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03272607.

COVID-SAFER: Deprescribing Guidance for Hydroxychloroquine Drug Interactions in Older Adults.

BACKGROUND/OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes high morbidity and mortality in older adults with chronic illnesses. Several trials are currently underway evaluating the antimalarial drug hydroxychloroquine as a potential treatment for acute infection. However, polypharmacy predisposes patients to increased risk of drug-drug interactions with hydroxychloroquine and may render many in this population ineligible to participate in trials. We aimed to quantify the degree of polypharmacy and burden of potentially inappropriate medications (PIMs) that older hospitalized adults are taking that would interact with hydroxychloroquine. METHODS: We reanalyzed data from the cohort of patients 65 years and older enrolled in the MedSafer pilot study. We first identified patients taking medications with potentially harmful drug-drug interactions with hydroxychloroquine that might exclude them from participation in a typical 2019 coronavirus disease (COVID-19) therapeutic trial. Next, we identified medications that were flagged by MedSafer as potentially inappropriate and crafted guidance around medication management if contemplating the use of hydroxychloroquine. RESULTS: The cohort contained a total of 1,001 unique patients with complete data on their home medications at admission. Of these 1,001 patients, 590 (58.9%) were receiving one or more home medications that could potentially interact with hydroxychloroquine, and of these, 255 (43.2%) were flagged as potentially inappropriate by the MedSafer tool. Common classes of PIMs observed were antipsychotics, cardiac medications, and antidiabetic agents. CONCLUSION: The COVID-19 pandemic highlights the importance of medication optimization and deprescribing PIMs in older adults. By acting now to reduce polypharmacy and use of PIMs, we can better prepare this vulnerable population for inclusion in trials and, if substantiated, pharmacologic treatment or prevention of COVID-19. J Am Geriatr Soc 68:1636-1646, 2020.

In children, the microbiota of the nasopharynx and bronchoalveolar lavage fluid are both similar and different.

RATIONALE: Sputum and bronchoalveolar lavage fluid (BALF) are often obtained to elucidate the lower airway microbiota in adults. Acquiring sputum samples from children is difficult and obtaining samples via bronchoscopy in children proves challenging due to the need for anesthesia and specialized procedural expertise; therefore nasopharyngeal (NP) swabs are often used as surrogates when investigating the pediatric airway microbiota. In adults, the airway microbiota differs significantly between NP and BALF samples however, minimal data exist in children. OBJECTIVES: To compare NP and BALF samples in children undergoing clinically indicated bronchoscopy. METHODS: NP and BALF samples were collected during clinically indicated bronchoscopy. Bacterial DNA was extracted from 72 samples (36 NP/BALF pairs); the bacterial V1-V3 region of the 16S rRNA gene was amplified and sequenced on the Illumina Miseq platform. Analysis was performed using mothur software. RESULTS: Compared to NP samples, BALF had increased richness and diversity. Similarity between paired NP and BALF (intra-subject) samples was greater than inter-subject samples (P = 0.0006). NP samples contained more Actinobacteria (2.2% vs 21%; adjusted P = 1.4 × 10-6 ), while BALF contained more Bacteroidetes (29.5% vs 3.2%; adjusted P = 1.2 × 10-9 ). At the genus level several differences existed, however Streptococcus abundance was similar in both sample types (NP 37.3% vs BAL 36.1%; adjusted P = 0.8). CONCLUSION: Our results provide evidence that NP samples can be used to distinguish differences between children, but the relative abundance of organisms may differ between the nasopharynx and lower airway in pediatric patients. Studies utilizing NP samples as surrogates for the lower airway should be interpreted with caution.

Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia.

BACKGROUND: Little is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics. METHODS: Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI). Single nucleotide polymorphism (SNP) analysis of genes in the glucocorticoid pathway was also performed. RESULTS: Nine prepubertal subjects aged 8.1 ± 2.3 years completed the study. Mean ACTH, androstenedione, and 17-hydroxyprogesterone (17-OHP) values were lower following the DEX arm of the study than after subjects received HC (p ≤ 0.016) or PDN (p ≤ 0.002). 17-OHP was also lower after HC than PDN (p < 0.001). There was no difference in IGF-1, GH, or change in BMI. SNP analysis revealed significant associations between hormone concentrations, pharmacokinetic parameters, and variants in several glucocorticoid pathway genes (ABCB1, NR3C1, IP013, GLCCI1). CONCLUSIONS: DEX resulted in marked adrenal suppression suggesting that its potency relative to hydrocortisone and prednisone was underestimated. SNPs conferred significant differences in responses between subjects. Although preliminary, these pilot data suggest that incorporating pharmacogenetics has the potential to eventually lead to targeted therapy in children with CAH.

Identifying Genetic Variants in Adolescents With Oppositional Defiant Disorders and/or Conduct Disorders: A Brief Report.

PROBLEM: To add to diversity in our state biobank, we explored the feasibility of collecting genetic material from adolescents with oppositional defiant disorder (ODD) and/or conduct disorder (CD) and their family members. We also preliminarily explored genetic factors associated with ODD and/or CD by comparing participant data to 1000 Genome Project data on minor allele frequencies. METHODS: Adolescents with ODD and/or CD and family members provided saliva samples for genetic testing. We evaluated five single-nucleotide polymorphisms (SNPs), respectively, in the dopamine receptor subtype D2, dopamine receptor subtype D3, dopamine beta-hydroxylase, dopamine transporter gene SLC6A3, and alpha-2-adrenergic receptor genes. Fisher's exact tests were used to examine differences in minor allele frequencies for each SNP. FINDINGS: Thirty-one viable samples were genotyped from 15 affected adolescents and 16 unaffected family members; the 60% consent rate reflected high feasibility. Compared with the 1000 Genome Project frequencies, affected adolescents had higher frequencies of the genetic variant in the dopamine receptor subtype D2 (p = .05) and dopamine beta-hydroxylase (p = 0.03), but not of the other three SNPs examined. CONCLUSIONS: Collecting genetic materials from an ethnically diverse sample of affected adolescents and their families is feasible. We offer practical suggestions to strengthen the integrity of future research studies.

Raising the Level of Nursing Involvement in the National Precision Medicine Initiative: An Example.

PURPOSE: The Precision Medicine Initiative (PMI) goal of ushering in a new and more effective era of health care that benefits all Americans requires two critical and interdependent components: a cohort assembly of 1 million or more Americans who reflect the diversity of the United States of America and an interdisciplinary workforce that includes nursing. The purpose of this article is to provide an example of nursing involvement in PM, specifically as related to gathering biospecimens (saliva) from vulnerable, understudied adolescents with disruptive behavior disorders and their family members. SOURCE(S): First, we provide a brief description of important concepts related to PM as well as current roles of nurses in PM. Then, we share lessons learned from our feasibility study aimed at increasing the diversity of our statewide cohort assembly that has provided biospecimens for the Indiana Biobank. CONCLUSION: Nurses can definitely contribute to biobanks in support of the PMI. This article is a call to action for nurses to take their rightful place in PM.