Search

Robust assessment of potential adverse outcomes is needed to determine a safe cannabidiol (CBD) intake level for consumer use. To assist in identifying knowledge gaps and inform future decision making regarding systematic development of health-based benchmarks, we have developed the first systematic map of the safety-related information available for CBD in the peer-reviewed literature. Literature searching conducted according to a published protocol yielded a total of 4186 unique titles and abstracts published through 2020. These were screened using DistillerSR for studies that evaluated at least one potential health outcome following exposure to CBD and/or other hemp-derived substances. Additional categorization was conducted for a subset of 1001 studies in which CBD was administered alone. Studies that investigated CBD most frequently reported on neurological outcomes (532), carcinogenic outcomes (129), and pharmacokinetics (118). Less frequently studied categories included developmental and reproductive, hepatic, and gastrointestinal outcomes. The primary outcomes associated with the most adverse events reported in the literature were neurological (13) and developmental and reproductive (12). Based on the studies identified, reproductive and developmental toxicity was identified as a data gap that warrants conducting a well-designed, guideline-compliant reproductive toxicity study on CBD. In addition, immune outcomes were noted as a potential emerging research area for CBD. This systematic map provides an important baseline from which to identify topics that may be suitable for further research related to the safe use of CBD. Implications for future potential work and limitations of the mapping exercise are discussed.

Refereed/Peer-reviewed Background: The objective is to determine whether body mass index is associated with patient-reported expectations and well-being before primary total hip or total knee arthroplasty, and patient-reported outcomes 6 months after surgery. Methods: Data were obtained from the Australian Orthopaedic Association National Joint Replacement Registry. Outcome measures included pre-operative expectations for post-operative mobility, joint pain and health, pre- and post-operative EQ-5D-5L, EQ-VAS, Oxford Hip/Knee Scores and joint pain scales, and post-operative perceived change and perceived satisfaction. Associations with BMI were assessed using chi-square tests, analysis of variance and Linear Mixed Models equations. Results: Data were available for 12 816 primary THA patients and 20 253 primary TKA patients. Pre-operatively, patients in higher BMI categories were significantly more likely to expect ongoing problems with mobility, more joint pain and poorer health following surgery (P

Predictions of total water levels, the elevation of combined tides, surge, and wave runup at the shoreline, are necessary to provide guidance on potential coastal erosion and flooding. Despite the importance of early warning systems for these hazards, existing real-time meteorological and oceanographic forecast systems at regional and national scales, until now, have lacked estimates of runup necessary to predict wave-driven overwash and erosion. To address this need, we present an approach that includes wave runup in an operational, national-scale modeling system. Using this system, we quantify the contribution of waves to potential dune erosion events along 4,700 km of U.S. Atlantic and Gulf of Mexico sandy coastlines for a one-year period. Dune erosion events were predicted to occur at over 80% of coastal locations, where waves dominated shoreline total water levels, representing 73% of the signal. This shows that models that neglect the wave component underestimate the hazard. This new, national-scale operational modeling system provides communities with timely, local-scale (0.5 km resolution) coastal hazard warnings for all wave conditions, allowing for rapid decision-making related to safety and emergency management. The modeling system also enables continued research into wave-driven processes at a broad range of coastal areas.

New modulator therapies have markedly improved the health of people with cystic fibrosis (CF), allowing an increased focus on quality-of-life improvements for men with CF, including those related to sexual and reproductive health (SRH). This study explored CF providers' attitudes and experiences with addressing men's health in CF.We interviewed geographically diverse adult and pediatric United States (U.S.) CF program directors via semi-structured telephone interviews exploring their perspectives and practices related to men's SRH in CF. Two coders analyzed transcribed interviews and created a codebook to identify key themes.We interviewed 20 providers and identified the following themes: 1) Men's SRH is important to address within CF care, but there is no standardization around this aspect of care; 2) There is no consensus about the recommendation or utilization of semen analysis to assess men's infertility; 3) There are many barriers to men's SRH care provision in CF centers, including the low priority of SRH concerns and provider discomfort and lack of expertise in SRH; 4) Providers desire clear evidence-based guidelines and patient resources related to men's SRH in CF; and 5) Providers believe future research should focus on testosterone and the impact of modulators on men's SRH.CF center directors acknowledge the importance of addressing SRH with men with CF, but there is a lack of standardization and research in this aspect of care. Existing barriers to optimal SRH care and identified facilitators in this study can serve as targets for interventions in the CF care model.

In response to immune pressure, influenza viruses evolve, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response capable of recognizing multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the efficacy and immunogenicity of mRNA vaccines encoding either the conserved stem domain of a group 1 hemagglutinin (HA), a group 2 nucleoprotein (NP), or a combination of the two antigens in mice, as well as evaluated immunogenicity in naïve and influenza seropositive nonhuman primates (NHPs). HA stem-immunized animals developed a robust anti-stem antibody binding titer, and serum antibodies recognized antigenically distinct group 1 HA proteins. These antibodies showed little to no neutralizing activity in vitro but were active in an assay measuring induction of antibody-dependent cellular cytotoxicity. HA-directed cell-mediated immunity was weak following HA stem mRNA vaccination; however, robust CD4 and CD8 T cell responses were detected in both mice and NHPs after immunization with mRNA vaccines encoding NP. Both HA stem and NP mRNA vaccines partially protected mice from morbidity following lethal influenza virus challenge, and superior efficacy against two different H1N1 strains was observed when the antigens were combined. In vivo T cell depletion suggested that anti-NP cell-mediated immunity contributed to protection in the mouse model. Taken together, these data show that mRNA vaccines encoding conserved influenza antigens, like HA stem and NP in combination, induce broadly reactive humoral responses as well as cell-mediated immunity in mice and NHPs, providing protection against homologous and heterologous influenza infection in mice.

Writing strategies are important in the development of writing pedagogy and learning. Consequently, it is crucial to develop writing in the new modality of education. The current systematic review investigated the writing strategies employed in teaching writing in an online distance learning and the perceptions of students regarding these writing strategies. Thirteen studies were analysed for the employment of and students' views about writing strategies. The results of the study revealed four areas that were further categorized into Practice, Action, Tool, and Help (PATH) strategies, while the perceptions were grouped into two areas - the right path and the lost track. Also, the results revealed that strategies were thought to be essential, effective, enhancing, and pleasurable. The findings imply that by providing the PATH Strategies to learners, students will be able to maintain the interest in learning and will greatly help in the development of the writing pedagogy and acquisition.

Many higher-education administrative processes have transitioned to the online environment due to the COVID-19 pandemic. Nursing program accreditation site visits were not spared from this shift. This article describes the step-by-step online, interactive, and collaborative process one nursing department used for program re-accreditation. Kotter's 8-step process for accelerating change informed this work. Positive outcomes included increased faculty engagement and knowledge in the accreditation process and an ongoing accreditation readiness team. Recommendations include forming an accreditation committee, appointing program champions, utilizing a learning management system and a cloud-based storage system, and celebrating successes. This process could be replicated by other nursing programs undergoing accreditation.

Background Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies. Methods This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index). Results For the 74 children (median age 10.3 years; range 3–18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1–100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment. Conclusions With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues.

The development of highly effective antiretroviral treatment has significantly decreased the disease burden and increased the life expectancy of people living with HIV. As people with HIV live longer, they will require ongoing HIV specialty and primary care, which will increase the demand for specialty-trained nurse practitioners and other health care workers. This report describes the emerging HIV provider shortage and offers models to expand nurse practitioner training in HIV primary care as an approach to addressing the HIV provider shortage.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

BackgroundExpandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage Systemexpandable distal femur endoprosthesis have not been reported.MethodsWe conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis.ResultsThirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI,5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvagefailures requiring 63 unplanned surgeries. Periprosthetic joint infectionoccurred in six patients (16.7%). Limb preservation rate was 91% at 10years.ConclusionsThere is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery.Level of evidenceLevel IV, therapeutic study.

Background VRE (Vancomycin Resistant Enterococci)-associated infections are prevalent in healthcare settings and pose a significant therapeutic challenge. The lipopeptide antimicrobial daptomycin (DAP) is one of the last resort options to treat these organisms. Among VRE, mutations that confer DAP resistance (DAP-R) arise in proteins in the three-component signaling system LiaFSR, which is highly conserved in other Gram-positive pathogens. Similar to Enterococcus faecalis (Efs), LiaFSR in Bacillus subtilis (Bsu) is specifically activated by DAP and, thus, serves as a proxy for studying mechanisms of DAP-R. In Bsu, LiaF inhibits LiaR phosphorylation; however, the current model for DAP-R in Efs positions LiaF as an activator of LiaFSR directly regulated by the enterococcal-specific protein LiaX. We postulate that the intimate association between LiaX and LiaF is crucial for DAP-R in enterococci. Using an in silico approach, we compared LiaF from Efs and Bsu and searched for LiaX-like proteins in Bsu. Methods Protein predictions were determined by the RoseTTAFold algorithm (RoBetta, David Baker, UW). Structural comparisons were conducted using MatchMaker in UCSF Chimera. Paired sequence alignments were assembled through EMBOSS Needle. Results Efs and Bsu LiaF are arranged similarly with 4 transmembrane helices (TMH) in the N-terminal domain (NTD) and a β-sheet (βS) C-terminal domain (CTD). We identified LiaX-like gene products upstream from Bsu LiaFSR. Analysis of the predicted structures of LiaIHG showed that LiaI is a peptide with 4 TMH and structurally like the N-terminus of Bsu LiaF. Also, LiaH contains 3 putative α-helices akin to the N-terminus of LiaX. LiaG has 1 TMH connected to a large βS domain-like the C-terminus of LiaX. Each protein shared structural and sequence similarity that was not identified through BLAST searches. Conclusion We identified Bsu LiaIHG as structural homologs to Efs LiaX, which was not previously known due to lack of sequence identity and empirical structural data. The findings further supports our model for LiaX and LiaF as core pieces in DAP-R development. Disclosures Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support.

Background Daptomycin (DAP) resistance in enterococci is regulated by the LiaFSR three-component regulatory system. Mutations in liaF have been linked to activation of this system, with increased expression of the protein LiaX, and resistance to DAP in clinical isolates. LiaX functions by recognizing DAP in the extracellular medium, and serves as a signal transduction molecule. However, the role of LiaF in signaling and its relationship with LiaX are unknown. Methods We generated a liaF null mutant in E. faecalis OG117 by adding four stop codons at amino acid positions 11–14 (OG117liaF*11-14) using a CRISPR-Cas9 system. The mutant was complemented by restoring wild-type liaF in its chromosomal location (OG117liaF*11-14::liaF). Mutants were confirmed with whole genome sequencing (WGS). Anionic phospholipid (AP) microdomain distribution was assessed on microscopy using 10-N-nonyl-acridine-orange (NAO). LiaFSR activation was assessed by surface expression of LiaX via ELISA. DAP MICs were performed by broth microdilution in the presence/absence of exogenous LiaX (eLiaX). LL37 (50µg/ml) and DAP (1.5µg/ml) killing assays with eLiaX were also performed in triplicate. Results Truncation of liaF did not have any effect on DAP MICs, AP microdomain distribution or LiaX surface expression compared to OG117. No additional mutations were observed by WGS in the mutants. In the presence eLiaX, DAP MIC increased 8-fold in wild-type OG117 but remained the same (1 µg/mL) in OG117liaF*11-14. Complementation of liaF restored the increase in DAP MIC in the presence of eLiaX. In the LL37 killing assay, survival of OG117 was significantly increased on the addition of eLiaX (2.9% vs 11.8%, respectively, P < .002). Addition of eLiaX was unable to rescue OG117liaF*11-14 in the presence of LL-37 (2.4% vs 2.5% respectively, P=0.51), but was able to increase survival in the complemented strain (2.8% vs 7.6%, respectively, P < .002). A similar trend was seen in the DAP killing assay, with increased survival for OG117 (8.7% vs 20%) and OG117liaF*11-14::liaF (11.6% vs 17%), but not OG117liaF*11-14 (0.38% vs 1%). Conclusion LiaF is required for full tolerance to the cathelicidin LL37 and DAP in E. faecalis OG1RF. These results suggest that LiaF may interact with LiaX as a part of the LiaFSR stress response. Disclosures William R. Miller, MD, Entasis: Grant/Research Support|UpToDate: Honoraria Cesar A. Arias, MD, PhD, Entasis: Grant/Research Support|MeMed Diagnostics Ltd: Grant/Research Support|Merck: Grant/Research Support.

Background: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship. Methods: The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests. Results: 151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants’ comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship. Conclusion: An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.

One to two-thirds of all medically admitted patients have comorbid psychiatric concerns. To address the cognitive, behavioral, and emotional factors that affect medical hospitalization, psychological or psychiatric consultation-liaison (CL) services are consulted. The current study was designed to understand patient satisfaction with a CL psychology service and how it was associated with satisfaction with overall hospitalization, taking into consideration relevant factors. Adults medically admitted to an academic teaching hospital (N = 220), who were seen at least once by the CL psychology service, completed satisfaction and demographic questionnaires. Most patients reported being satisfied with the CL psychology service, with women reporting higher satisfaction than men. Satisfaction with the CL psychology service was associated with satisfaction with overall hospitalization, but did not differ based on age, race/ethnicity, education, income, length of stay, number of visits, or presence of psychiatric diagnosis. The results suggest that CL psychology services may contribute to improving overall patient experience.

(1) To describe changes in arterial stiffness and heart rate variability (HRV) over a 5-year interval, (2) examine changes by sex and race–ethnicity, and (3) evaluate the risk factors associated with the longitudinal changes in arterial stiffness and HRV. Participants with youth-onset type 2 diabetes enrolled in the observational follow-up phase of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial had arterial stiffness [(pulse wave velocity, augmentation index, brachial distensibility] and six indices of HRV measured 5 years apart. Multivariable linear regression models assessed risk factors associated with changes in the outcomes over time. At initial vascular assessment, the 304 participants were a mean age of 21 years, 34% male, and had a mean diabetes duration of 8 years. In more than half the cohort pulse wave velocity, augmentation index and HRV increased over 5 years (p

Urban, low-income, African American children and parents report lower quality primary care and face negative social determinants of health. High-quality well-child care is critical for this population. The purpose of this qualitative study was to compare and contrast parent and health care provider experiences of well-child care for urban, low-income, African American families to better understand the complex factors involved in care quality and health outcomes. Two data sets were analyzed using conventional content analysis, parent focus group data, and provider interviews. After analysis, results were sorted into similar categories, and convergence coding was completed to identify areas of agreement, partial agreement, dissonance, and silence. Thirty-five parents took part in four focus groups, and nine providers were interviewed. Following convergence coding, five categories and 31 subcategories were identified. The five categories included: social determinants of health, sources of advice and support, challenges with the healthcare system, parent-provider relationships, and anticipatory guidance topics. Triangulation demonstrated convergence between parents and providers understanding of the concepts and functions of well-child care, however the prominence and meaning varied within each category and sub-category. The variance in agreement, areas of silence, and dissonance shed light on why the population reports lower overall quality primary care.

Introduction:Paediatric cardiology fellows, tasked with studying a large and dynamic field, may benefit from a quick-access digital resource that reflects contemporary practice. The objective of this study was to evaluate the effectiveness of a paediatric cardiology handbook smartphone app in enhancing the accessibility of information such as guidelines and recommendations for paediatric cardiology fellows.Materials and methods:The Peds Cardiology Handbook app (iOS) was designed using XCode and Swift programming. A pre-app survey and download instructions were sent to the US paediatric cardiology fellows, followed by a post-app survey. Fellows were asked to rate the ease of rapid access to various types of information. Responses were compared pre- and post-app using McNemar’s test and Wilcoxon signed-rank test.Results:Two-hundred and thirty paediatric cardiology fellows were contacted; 23% (n = 53) completed both the pre- and post-app surveys and were included for analysis. After using the app, fellows found it easier to quickly access information in eight out of nine domains evaluated (p < 0.05). All fellows found the app easy to use (100%), most felt that the app was well-organised (98%), contained reliable information (92%), and was useful for finding quick answers to clinical questions (87%).Discussion:The Peds Cardiology Handbook iPhone app is a useful, reliable tool that provides quick access to high-yield information, including guidelines and references. Overall, paediatric cardiology fellows found it easier to rapidly access clinically relevant information after using the app. Future studies may be necessary to evaluate long-term use and impact on evidence-based practice.

Women living with HIV have a higher burden of non-AIDS comorbidities and prevalence of chronic conditions. The Adaptive Leadership Framework for Chronic Illness clarifies living with complex health challenges by delineating the technical work of health care providers as well as the adaptive work and leadership behaviors of patients and their providers. We conducted a descriptive, qualitative study of women residing in the Southern United States who were participating in the Women's Interagency HIV Study in North Carolina. Twenty-two participants (mean age = 52.2 years; 90.9% self-identifying as Black or African American) completed semi-structured qualitative interviews. We identified adaptive challenges (e.g., affective and disclosure challenges) and adaptive work and leadership behaviors. Women learned skills to care for their health and support their families and to work with their providers to manage their care. Findings support the importance of identifying leadership behaviors for the purpose of developing person-centered interventions.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

Despite the meteoric rise of social media, little is known about how clinical social workers and other mental health professionals respond to this new form of communication. This study used classic (Glaserian) grounded theory methodology to explore the experiences and concerns of mental health professionals on social networking websites such as Facebook, Twitter, and LinkedIn. The main concern that emerged out of research interviews with 26 mental health professionals was a loss of control over others’ perceptions and the loss of ability to compartmentalize the different parts of identities associated with personal and professional selves. Participants resolved these concerns through the author-identified basic social process of “managing digital identities.” This study highlights practice implications for professionals as they manage online identity.

Nursing program accreditation often has limited faculty engagement. This quality improvement project, implemented at a private university in the Midwestern United States, utilized innovative solutions including accreditation program champions and a learning management system to enhance faculty engagement in the accreditation process. Accreditation encompassed seven programs at three program degree levels: undergraduate, masters and doctorate. A survey measured overall engagement as well as the usefulness of accreditation program champions and the learning management system to improve engagement. Results showed increased faculty knowledge, professional development, and motivation in the accreditation process. Increased engagement not only accomplishes the work more efficiently, but also improves faculty knowledge of the process and preparation for the accreditation site visit.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development. This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.

Curiosity and intent to use alcohol in pre-adolescence is a risk factor for later experimentation and use, yet we know little of how curiosity about use develops. Here, we examine factors that may influence curiosity about alcohol use, as it may be an important predictor of later drinking behavior. Cross-sectional data on youth ages 10–11 from the ongoing Adolescent Brain Cognitive Development℠ (ABCD) Study Year 1 follow-up were used (n = 2,334; NDA 2.0.1). All participants were substance-naive at time of assessment. Group factor analysis identified latent factors across common indicators of risk for early substance use (i.e., psychopathology and trait characteristics; substance use attitudes/behaviors; neurocognition; family and environment). Logistic mixed-effect models tested associations between latent factors of risk for early substance use and curiosity about alcohol use, controlling for demographics and study site. Two multidimensional factors were significantly inversely and positively associated with greater curiosity about alcohol use, respectively: 1) low internalizing and externalizing symptomatology coupled with low impulsivity, perceived neighborhood safety, negative parental history of alcohol use problems, and fewer adverse life experiences and family conflict; and 2) low perceived risk of alcohol use coupled with lack of peer disapproval of use. When assessing all risk factors in an overall regression, lack of perceived harm from trying alcohol once or twice was associated with greater likelihood of alcohol curiosity. Taken together, perceptions that alcohol use causes little harm and having peers with similar beliefs is related to curiosity about alcohol use among substance-naive 10–11-year-olds. General mental health and environmental risk factors similarly increase the odds of curiosity for alcohol. Identification of multidimensional risk factors for early alcohol use may point to novel prevention and early intervention targets. Future longitudinal investigations in the ABCD cohort will determine the extent to which these factors and curiosity predict alcohol use among youth.

This process evaluation of the Rural Elder Awareness of Medication Safety (REAMS) program provided identification of successful and unsuccessful elements along with barriers to and facilitators of this home-based pilot program. The REAMS program was developed to assist rural older adults aged >65 years and community health care organizations with strategies to improve health literacy related to medications. Recruitment of older adults, rurality of the program's setting, time constraints, and the onset of the COVID-19 pandemic were the greatest barriers. The collaborative relationship developed with community health care partners was the greatest facilitator. This relationship promoted shared ideas and adjustments in program design to achieve the outcome goals. The lessons learned from process evaluation may benefit future researchers or community health promotion planners with designing community-based programs for older adults in rural areas. Future research should focus on expanding recruitment opportunities in acute care, primary care, and home health with the inclusion of all established health care providers in the community. [ Journal of Gerontological Nursing, 47 (4), 7–12.]

Women are important contributors in the United States military yet historically struggle for equality and equity. As women’s military service increases, literature has failed to keep up with the ch...

Expandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported.We conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis.Thirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years.There is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery.Level IV, therapeutic study.

Content analysis of language research is one of the very widely researched topics worldwide. However, in the Philippine context, few studies and systematic reviews on the content analysis of language theses and dissertations are published. The current study examinedthe features of 25 studies that looked at the content of language theses and dissertations published from 2016 to 2021. Thematic focus, study design, data analysis methodologies, and research outcomes were all investigated. The findings show that research trends, research parts, rhetorical structures, and linguistic structures are the most commonly discussed topics. Content analysis is the most widely used methodology and data analysis approach. It is worth noting thatonly one of the reviewed studies produced a research output. Recommended topics and areas for future language research are offered.

The recently discovered insecticidal protein Mpp75Aa1.1 from Brevibacillus laterosporus is a member of the ETX_MTX family of beta-pore forming proteins (β-PFPs) expressed in genetically modified (GM) maize to control western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte). In this manuscript, bioinformatic analysis establishes that although Mpp75Aa1.1 shares varying degrees of similarity to members of the ETX_MTX2 protein family, it is unlikely to have any allergenic, toxic, or otherwise adverse biological effects. The safety of Mpp75Aa1.1 is further supported by a weight of evidence approach including evaluation of the history of safe use (HOSU) of ETX_MTX2 proteins and Breviballus laterosporus. Comparisons between purified Mpp75Aa1.1 protein and a poly-histidine-tagged (His-tagged) variant of the Mpp75Aa1.1 protein demonstrate that both forms of the protein are heat labile at temperatures at or above 55°C, degraded by gastrointestinal proteases within 0.5 min, and have no adverse effects in acute mouse oral toxicity studies at a dose level of 1920 or 2120 mg/kg body weight. These results support the use of His-tagged proteins as suitable surrogates for assessing the safety of their non-tagged parent proteins. Taken together, we report that Mpp75Aa1.1 is the first ETX-MTX2 insecticidal protein from B. laterosporus and displays a similar safety profile as typical Cry proteins from Bacillus thuringiensis.

Background Cytomegalovirus (CMV) can cause congenital infection and is the leading cause of nongenetic newborn disabilities. V160, a conditionally replication-defective virus, is an investigational vaccine under evaluation for prevention of congenital CMV. The vaccine was well tolerated and induced both humoral and cellular immunity in CMV-seronegative trial participants. T-cell–mediated immunity is important for immune control of CMV. Here we describe efforts to understand the quality attributes of the T-cell responses induced by vaccination. Methods Using multicolor flow cytometry, we analyzed vaccine-induced T cells for memory phenotype, antigen specificity, cytokine profiles, and cytolytic potential. Moreover, antigen-specific T cells were sorted from 4 participants, and next-generation sequencing was used to trace clonal lineage development during the course of vaccination using T-cell receptor β-chain sequences as identifiers. Results The results demonstrated that vaccination elicited polyfunctional CD4 and CD8 T cells to 2 dominant antigens, pp65 and IE1, with a predominantly effector phenotype. Analysis of T-cell receptor repertoires showed polyclonal expansion of pp65- and IE1-specific T cells after vaccination. Conclusion V160 induced a genetically diverse and polyfunctional T-cell response and the data support further clinical development of V160 for prevention of CMV infection and congenital transmission. Clinical Trials Registration NCT01986010.

Background Few studies have examined long-term outcomes among persons who initiate preexposure prophylaxis (PrEP) in the South, including PrEP discontinuation and sexually transmitted infection (STI) rates. Methods Care discontinuation (>6 months without a PrEP appointment) and incident STIs were evaluated for patients at 2 PrEP clinics in Durham, NC. We tested for predictors of discontinuation as a binary variable using logistic regression. Model covariates included age, race/ethnicity, sex, known HIV-positive partner, commercial sex work, men who have sex with men (MSM) versus not MSM, type of insurance, and clinic site. A similar analysis was completed for STI incidence, controlling for days in the study. Results Among 271 patients, mean age was 33.2 years, 46.9% were Black and 11.1% were Latino, 81.2% were MSM, and 32% were uninsured. Preexposure prophylaxis was discontinued in 47%, and another 11% had intermittent care. Sexually transmitted infection incidence was 45.4/100 person-years, and 5 patients were diagnosed with HIV at baseline or in follow-up. Men who have sex with men were less likely to discontinue PrEP relative to non-MSM (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.10-0.64). Baseline STI was associated with a higher likelihood of incident STI (OR, 8.19; 95% CI, 3.69-19.21), whereas care discontinuation was associated with a lower likelihood of STI (OR, 0.28; 95% CI, 0.11-0.65). Conclusions Preexposure prophylaxis programs in the Southern United States are reaching uninsured and predominantly Black and Latino MSM, but discontinuation rates are high despite elevated rates of incident STI and HIV. Further work is required to elucidate causes of PrEP discontinuation and encourage persistence in care.

OBJECTIVES To analyze the impact of discharge before noon (DBN) on length of stay (LOS) and readmission of adult inpatients. STUDY DESIGN Retrospective analysis of 78,826 patients from a single tertiary care center between January 1, 2016, and December 31, 2018. METHODS The patient population was divided between patients discharged before and after noon. Outcomes were analyzed with univariate and multivariate analyses. RESULTS DBN was independently associated with higher likelihood of LOS above the median (odds ratio [OR], 1.26; 95% CI, 1.18-1.35; P

OBJECTIVES The aim of this study was to evaluate penetration of antiretrovirals into compartments and efficacy of a dual, NRTI-sparing regimen in acute HIV infection (AHI). DESIGN Single-arm, open-label pilot study of participants with AHI initiating ritonavir-boosted darunavir 800 mg once daily and etravirine 400 mg once daily or 200 mg twice daily within 30 days of AHI diagnosis. METHODS Efficacy was defined as HIV RNA less than 200 copies/ml by week 24. Optional sub-studies included pharmacokinetics analysis from genital fluids (weeks 0-4, 12, 48), cerebrospinal fluid (CSF) (weeks 2-4, 24 and 48) and endoscopic biopsies (weeks 4-12 and 36-48). Neuropsychological performance was assessed at weeks 0, 24 and 48. RESULTS Fifteen AHI participants were enrolled. Twelve (80%) participants achieved HIV RNA less than 200 copies/ml by week 24. Among 12 participants retained through week 48, nine (75%) remained suppressed to less than 50 copies/ml. The median time from ART initiation to suppression less than 200 and less than 50 copies/ml was 59 and 86 days, respectively. The penetration ratios for etravirine and darunavir in gut associated lymphoid tissue were 19.2 and 3.05, respectively. Most AHI participants achieving viral suppression experienced neurocognitive improvement. Of the three participants without overall improvement in neurocognitive functioning as measured by impairment ratings (more than two tests below 1 SD), two had virologic failure. CONCLUSION NRTI-sparing ART started during AHI resulted in rapid viral suppression similar to NRTI-based regimens. More novel and compact two-drug treatments for AHI should be considered. Early institution of ART during AHI appears to improve overall neurocognitive function and may reduce the risk of subsequent neurocognitive impairment. CLINICALTRIALS.GOV:: NCT00855413.

BACKGROUND: Family violence has been shown to have a dramatic impact on individual and family life in the United States and other countries. Numerous studies have assessed the influence that exposure to violence can have on family dynamics and parent-child relationships. However, less is known about the association between family violence and parent-child relationships with Mexican families. OBJECTIVE: Guided by social interaction learning theory, the purpose of this study was to explore the role of exposure to family violence on PTSD and mother-child interaction patterns. METHODS: Eighty-seven mother-child dyads from Mexico completed assessments for exposure to family violence, PTSD, and observational tasks were analyzed to assess prosocial parent-child interactions (i.e., positive communication and problem solving). We conducted an actor-partner independence model (APIM) to examine the association between exposure to family violence, PTSD and mother-child relationship dynamics. RESULTS: As expected, higher exposure to family violence was linked to higher PTSD symptoms for mothers. Unexpectedly, higher maternal PTSD symptoms were associated with better communication during dyadic interaction tasks with their children. CONCLUSIONS: The present study suggests that individuals from certain cultures (i.e., Mexico) may respond differently to experiencing family violence. The use of multiple measurement methods to assess the relational effects of trauma on family dynamics can advance the scientific understanding of trauma affected families.

Solution focused brief therapy (SFBT) facilitates movement of problems toward solutions, requiring a delicate process of attentive observational skills and use of language; qualities that may be similar to Ericksonian hypnotherapy. In this deep examination, we utilized discourse analysis (Gee in How to do discourse analysis toolkit, Routledge, New York, 2011) to explore the influences of Ericksonian hypnotherapy in two commercially available videos of SFBT sessions facilitated by Insoo Kim Berg. We noted both SFBT features and Ericksonian features in these sessions, commonalities between the approaches were identified, and Ericksonian resemblances in SFBT were distinguished. Our deep examination suggests that Berg worked in recursive clusters with a figured world that attends to strength and resilience; Berg was fully attentive and observational throughout, intentional in her use of language, utilized bridging and building, and attended to exceptions. These features are common in Ericksonian hypnotherapy and appear significant in a relational style of training beginning therapists to effectively utilize the SFBT approach.

OBJECTIVE Although levetiracetam is used for the prevention of early Post-traumatic seizures (EPTS) after traumatic brain injury (TBI), limited data exist describing the incidence of seizures in pediatric patients receiving levetiracetam prophylaxis. The objective of this research is to evaluate the prevalence of EPTS in children given prophylactic levetiracetam after severe TBI. METHODS This study was conducted at a Level 1 pediatric trauma center and included pediatric patients with severe TBI who received levetiracetam for EPTS prophylaxis. Demographics and clinical information were retrospectively collected and evaluated. The primary outcome was prevalence of clinical or electrographic seizures within 7 days of initial injury as noted in the EMR. RESULTS In 4 of 44 patients (9%), seizures developed despite levetiracetam prophylaxis. Concurrent use of other medications with antiepileptic properties was common (91%). There were no differences in demographic or baseline clinical characteristics between the group of patients experiencing seizures and those who did not. However, craniotomy was significantly more common in the seizure group (75% vs. 18%, p = 0.03). CONCLUSIONS Children receiving prophylaxis with levetiracetam after severe TBI had a lower incidence of seizures (9%) than had previously been reported in the literature (18%). Given the limited literature available supporting the use of levetiracetam for the prevention of EPTS in children experiencing severe TBI, further study is needed to support routine use.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK-1654, a half-life extended RSV neutralizing monoclonal antibody, is in clinical development for the prevention of RSV disease in infants. This was a phase I, randomized, placebo-controlled, single-site, double-blind trial of MK-1654 in 44 healthy Japanese adults. The safety, tolerability, pharmacokinetics, antidrug antibodies (ADAs), and serum neutralizing antibody (SNA) titers against RSV were evaluated for 1 year after a single intramuscular (i.m.) or intravenous (i.v.) dose of MK-1654 or placebo in five groups (100 mg i.m., 300 mg i.m., 300 mg i.v., 1000 mg i.v., or placebo). MK-1654 was generally well-tolerated in Japanese adults. There were no serious drug-related adverse events (AEs) reported in any MK-1654 recipient and no discontinuations due to any AEs in the study. The half-life of MK-1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability was 86% for 100 mg i.m. and 77% for 300 mg i.m. One participant out of 33 (3.0%) developed detectable ADA with no apparent associated AEs. The RSV SNA titers increased in a dose-dependent manner among participants who received MK-1654. These data support the development of MK-1654 for use in Japanese infants.

Sudden cardiac arrest (SCA) is a prevailing cause of mortality after pediatric heart transplant (HT) but remains understudied. We analyzed the incidence, outcomes, and risk factors for SCA at our center.Retrospective review of all pediatric HT patients at our center from January 1, 2009 to January 1, 2021. SCA was defined as an abrupt loss of cardiac function requiring cardiopulmonary resuscitation and/or mechanical circulatory support (MCS). Events that occurred in the setting of limited resuscitative wishes, or while on MCS were excluded. Patient characteristics and risk factors were analyzed.Fourteen of 254 (6%) experienced SCA at a median of 3 (1, 4) years post-HT. Seven (50%) events occurred out-of-hospital. Eleven (79%) died from their initial event, 2 (18%) after failure to separate from extracorporeal membrane (ECMO). In univariate analysis, black race, younger donor age, prior acute cellular rejection (ACR) episode, pacemaker and/or ICD in place, and pre-mortem diagnosis of allograft vasculopathy were associated with SCA (P = .003-0.02). In multivariable analysis, history of ACR, younger donor age, and black race retained significance. [OR = 6.3, 95% CI: 1.6-25.4, P = .01], [OR = 0.9, 95% CI: 0.8-1, P = .04], and [OR = 7.3, 95% CI: 1.1-49.9, P = .04], respectively. SCA occurred in 3 patients with a functioning ICD or pacemaker, which failed to restore a perfusing rhythm.SCA occurs relatively early after pediatric HT and is usually fatal. Half of events happen at home. Those who received younger donors, have a history of ACR, or are of black race are at increased risk. ICDs/pacemakers may offer limited protection.

The recently discovered insecticidal protein Mpp75Aa1.1 from Brevibacillus laterosporus is one member of the ETX_MTX family of beta-pore forming proteins (β-PFPs) expressed in genetically modified (GM) maize to control western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte). In this paper, bioinformatic analysis establishes that although Mpp75Aa1.1 shares varying degrees of similarity to members of the ETX_MTX2 protein family, it is unlikely to contribute to any allergenic, toxic, or otherwise adverse biological effects. The safety of Mpp75Aa1.1 is further supported by a weight of evidence including evaluation of history of safe use (HOSU) of ETX_MTX2 proteins. Assessments using either purified Mpp75Aa1.1 protein or a poly-histidine-tagged (His-tagged) variant of the Mpp75Aa1.1 protein demonstrate that both forms of the protein are heat labile at temperatures at or above 55 °C, degraded by gastrointestinal proteases within 0.5 min, and have no adverse effects in acute mouse oral toxicity studies at a dose level of 1920 or 2120 mg/kg body weight. Results also indicate that the domain-based protein characterization should be considered as part of the weight of evidence for the safe consumption of food or feed. Furthermore, these results support the use of His-tagged proteins as suitable surrogates for assessing the safety of their non-tagged parent proteins.

Dengue (DENV) is a mosquito-borne virus with four serotypes causing substantial morbidity in tropical and subtropical areas worldwide. V181 is an investigational, live, attenuated, quadrivalent dengue vaccine. In this phase 1 double-blind, placebo-controlled study, the safety, tolerability, and immunogenicity of V181 in baseline flavivirus-naïve (BFN) and flavivirus-experienced (BFE) healthy adults were evaluated in two formulations: TV003 and TV005. TV005 contains a 10-fold higher DENV2 level than TV003. Two-hundred adults were randomized 2:2:1 to receive TV003, TV005, or placebo on Days 1 and 180. Immunogenicity against the 4 DENV serotypes was measured using a Virus Reduction Neutralization Test (VRNT

Black women living with HIV (WLWH) face individual and sociostructural challenges. Despite these challenges, many exemplify remarkable levels of resilience and coping. Yet, research on resilience and coping in this population is limited. Twenty Black WLWH in the Southern United States completed semi-structured interviews that explored challenges facing WLWH. We identified six themes related to resilience and coping: self-acceptance, disclosure, self-compassion, social support, will to live, and service. Of these, social support was a driving protective element and an essential component to building and sustaining resilience and coping. Women who experienced positive support often expressed a will to live as well as a desire to support other WLWH. Resilience and social support were characterized by patterns of reciprocity, in that they were mutually sustaining, stabilizing, and strengthening.

Background and Aims Screen media activity (SMA) may impact neurodevelopment in youth. Cross-sectionally, SMA has been linked to brain structural patterns including cortical thinning in children. However, it remains unclear whether specific brain structural co-variation patterns are related to SMA and other clinically relevant measures such as psychopathology, cognition and sleep in children. Methods Adolescent Brain Cognitive Development (ABCD) participants with useable baseline structural imaging (N = 10,691; 5,107 girls) were analyzed. We first used the Joint and Individual Variation Explained (JIVE) approach to identify cortical and subcortical covariation pattern(s) among a set of 221 brain features (i.e., surface area, thickness, or cortical and subcortical gray matter (GM) volumes). Then, the identified structural covariation pattern was used as a predictor in linear mixed-effect models to investigate its associations with SMA, psychopathology, and cognitive and sleep measures. Results A thalamus-prefrontal cortex (PFC)-brainstem structural co-variation pattern (circuit) was identified. The pattern suggests brainstem and bilateral thalamus proper GM volumes covary more strongly with GM volume and/or surface area in bilateral superior frontal gyral, rostral middle frontal, inferior parietal, and inferior temporal regions. This covariation pattern highly resembled one previously linked to alcohol use initiation prior to adulthood and was consistent in girls and boys. Subsequent regression analyses showed that this co-variation pattern associated with SMA (β = 0.107, P = 0.002) and externalizing psychopathology (β = 0.117, P = 0.002), respectively. Discussion and Conclusions Findings linking SMA-related structural covariation to externalizing psychopathology in youth resonate with prior studies of alcohol-use initiation and suggest a potential neurodevelopmental mechanism underlying addiction vulnerability.