Testosterone treatment and the risk of osteonecrosis: a pharmacovigilance analysis in Vigibase.

PURPOSE: Recent reports have raised concerns about a potential risk of osteonecrosis associated with testosterone treatment (TT). The aim of this pharmacovigilance study was to assess the risk of reporting osteonecrosis associated with the use of TT compared with use of any other medication. METHODS: We performed a disproportionality analysis to investigate the risk of reporting osteonecrosis with TT using the WHO database VigiBase®. We estimated the reporting odds ratio (ROR) and 95% confidence interval (CI) of reporting osteonecrosis with use of TT vs all other drugs, and the adjusted ROR with use of TT vs use of drugs for benign prostatic hyperplasia (BPH). RESULTS: Among men at least 18 years of age between January 1, 2000, and December 31, 2019, we identified 3479 reports of osteonecrosis, 84 of which were associated with TT use, out of a total of 4,667,754 adverse event reports. Reports of osteonecrosis in TT users occurred with both transdermal and injectable forms, and the mean age at report was 55.4 years. TT use was associated with a greater risk of reporting osteonecrosis compared to all other drugs (ROR, 5.13; 95% CI, 4.13-6.37) and compared with use of drugs for BPH (ROR, 3.00; 95% CI, 2.08-4.30). Half of the osteonecrosis reports associated with TT indicated concomitant use of corticosteroids. CONCLUSION: TT was associated with a greater risk of reports of osteonecrosis compared to use of any other drug and use of drugs for BPH. This signal should be confirmed in complementary studies.

Sources of Medications Used by Children and Adolescents for Intentional Ingestion: A Retrospective Chart Review.

INTRODUCTION: Suicide is a leading cause of death among adolescents. Oregon ranks 17th nationally for youth suicide rates, and ingestion of medications as a means of suicide is common. Despite the high prevalence of intentional poisoning among youth in Oregon, information about medications used by children and adolescents for attempted suicide, in particular the sources of medications, is not readily available. METHODS: The objective of this study is to describe types and sources of medications used for intentional ingestion among patients seen by the Doernbecher Children's Hospital Child and Adolescent Psychiatry Consultation-Liaison Service. This was a retrospective analysis of patients seen by the Child and Adolescent Psychiatry Consultation-Liaison Service for intentional ingestion from 2015 to 2017. Data on 434 total intentional ingestions were collected, including demographic information, types of medications ingested, and sources of both over-the-counter (OTC) and prescription (Rx) medications. Ingestions without intent of suicide were excluded. Descriptive analysis of ingestion data was performed. RESULTS: Intentional ingestions included Rx and OTC medications in similar frequencies. For Rx medications, 68% of ingestions included patients' own Rxs. Eighty-eight percent of ingestions that were not the patients' own Rx belonged to someone else living in their home. For OTC medications, 66% of medications were available at home. CONCLUSIONS: Intentional ingestions among adolescents most frequently involve medications that are readily available in their homes, and these include both OTC and Rx medications. This study highlights the importance of securing medications at home as a preventative measure and the importance of anticipatory guidance for primary care providers.

Nonlinear ultrasonic technique for the characterization of microstructure in additive materials.

This study employs nonlinear ultrasonic techniques to track microstructural changes in additively manufactured metals. The second harmonic generation technique based on the transmission of Rayleigh surface waves is used to measure the acoustic nonlinearity parameter, ß. Stainless steel specimens are made through three procedures: traditional wrought manufacturing, laser-powder bed fusion, and laser engineered net shaping. The ß parameter is measured through successive steps of an annealing heat treatment intended to decrease dislocation density. Dislocation density is known to be sensitive to manufacturing variables. In agreement with fundamental material models for the dislocation-acoustic nonlinearity relationship in the second harmonic generation, ß drops in each specimen throughout the heat treatment before recrystallization. Geometrically necessary dislocations (GNDs) are measured from electron back-scatter diffraction as a quantitative indicator of dislocations; average GND density and ß are found to have a statistical correlation coefficient of 0.852 showing the sensitivity of ß to dislocations in additively manufactured metals. Moreover, ß shows an excellent correlation with hardness, which is a measure of the macroscopic effect of dislocations.

Access to Outpatient Pediatric Mental Health Care After Emergency Department Discharge.

OBJECTIVES: Pediatric mental health presentations to emergency departments (EDs) have shown dramatic increases nationally. This study aimed to identify the ability of patients discharged with mental health from the ED to establish outpatient care. METHODS: This was a cross-sectional study of all mental health patients aged 7 to 19 years who were seen by a child psychiatry consult team in a tertiary care pediatric ED from September 2016 to January 2017. Patients were contacted by phone at least 6 months after discharge. Data obtained included time to follow-up, reasons for delayed follow-up, type of provider seen, and frequency of outpatient visits. RESULTS: Two hundred twenty-eight charts were reviewed and 51 were successfully interviewed. The median age was 14 years and 61% were female. Most patients (61%) reported seeing a psychiatrist or therapist, whereas 19% reported a primary care provider and 19% reporting "other." The majority were able to establish care within 1 month (73%), whereas 9% reported never obtaining outpatient follow-up. Most patients (58%) were able to be seen more than once per month. The most common reason for delayed follow-up was provider availability. CONCLUSIONS: This study found that a large number of patients were able to be seen within 1 month of discharge for mental health care. However, almost 10% of patients never established outpatient care, which is concerning and is an area needing further research.

Using the Two-Minute Assessment With Debriefing to Optimize Traditional Patient Care Clinical Experiences.

Traditional patient care clinical experiences present numerous challenges to faculty in prelicensure nursing education. This article presents an adapted nontraditional clinical activity for use in patient care clinical experiences. The Two-Minute Assessment With Debriefing incorporates peer collaboration and attributes of debriefing, including assimilation, accommodation, and anticipation. Nursing students in acute care facilities are assigned to either traditional or nontraditional care, with the group ideally split in half. The use of nontraditional clinical activities with reflection has been supported as a strategy to engage higher order thinking about patient care while allowing focused faculty time with students in traditional patient care.

Development of a modular, high-speed plenoptic-camera for 3D flow-measurement.

This paper describes the development of a Modular Plenoptic Adaptor (MPA) for rapid and reversible conversion of high-speed cameras into plenoptic imaging systems, with the primary goal of enabling single-camera, time-resolved 3D flow-measurements. The MPA consists of a regular imaging lens, a microlens array, a tilt-adjustable microlens mount and an optical relay, which are collectively installed onto a high-speed camera through a standard lens mount. Each component within the system is swappable to optimize for specific imaging applications. In this study, multiple configurations of the MPA were tested and they demonstrated the ability to refocus and shift perspectives within high-speed scenes after capture. Additionally, the MPA demonstrated 3D reconstruction of captured scenes with <1% spatial error across a volume spanning approximately 50×30×50mm3. Finally, the MPA also demonstrated reconstruction of a 3D droplets-field with sufficient quality to support qualitatively accurate plenoptic particle image velocimetry (PPIV) calculations.

In Operando Monitoring of Dynamic Recovery in 3D-Printed Thermoset Nanocomposites by XPCS.

Extrusion-based additive manufacturing methods, such as direct-write of carbon fiber-reinforced epoxy inks, have become an attractive route toward development of structural composites in recent years, because of emerging techniques such as big area additive manufacturing. The development of improved materials for these methods has been a major focus area; however, an understanding of the effects of the printing process on the structural and dynamic recovery in printed materials remains largely unexplored. The goal of this work is to capture multiscale and temporal morphology and dynamics within thermosetting composite inks to determine the parameters during the printing process that influence the recovery of the printed material. Herein, we use X-ray photon correlation spectroscopy in small-angle scattering geometry to reveal both morphology and recovery dynamics of a nanoparticle (layered-silicate Cloisite 30B) in a thermoset epoxy resin (EPON 826) during the printing process in real time. Our results show that the dynamics of the layered silicate particles during recovery are anisotropic and slow down to behavior which is characteristic of aging in colloidal clay suspensions around  tage ≈ 12 s. The dynamics and alignment of the particles during recovery were tempo-spatially mapped, and the recovery post printing was shown to be strongly influenced by the deposition onto the build plate in addition to the extrusion through the print head. Our in operando results provide insight into the parameters that must be considered when optimizing materials and methods for precisely tailored local properties during 3D printing.

Delirium in the pediatric hematology, oncology, and bone marrow transplant population.

BACKGROUND: Delirium affects 10% to 30% of patients in pediatric intensive care units (PICU) and is associated with increased length of stay and prolonged late sequela. There are no prospective trials evaluating delirium in the pediatric hematology, oncology, and bone marrow transplant (PHO) population. Hypothesizing that delirium is underrecognized in this population, our study aimed to identify the prevalence of delirium in hospitalized PHO patients and associated risk factors. PROCEDURE: PHO and PICU nurses were trained to use the Cornell Assessment for Pediatric Delirium and to record scores once every 12-hour shift. Predetermined demographic and clinical variables were collected daily on all hospitalized PHO patients during the year-long prospective study. RESULTS: Prior to initiating routine delirium screening, 1.1% of PHO admissions and 2.4% of unique patients had delirium mentioned in a progress note. This study included 807 consecutive admissions: 671 oncology, 49 hematology, and 87 bone marrow transplant (BMT) hospitalizations among 223 unique PHO patients. The prevalence of delirium among hospitalizations was 5% and among unique patients was 13%. Among BMT hospitalizations, the prevalence was 23%. Multiple logistic regression identified significant association of delirium with increased length of stay, admission to the BMT service, patient location (PICU vs PHO unit), benzodiazepine, opioid, and anticholinergic administration. CONCLUSIONS: Before routine screening, delirium was underrecognized in this PHO-hospitalized population. Patients at highest risk had prolonged hospital stays, PICU admissions, BMT, and/or frequent use of benzodiazepines, opioids, or anticholinergics. Routine screening is feasible and may improve our recognition of delirium.

Suicide Risk Screening in Pediatric Hospitals: Clinical Pathways to Address a Global Health Crisis.

BACKGROUND: Youth suicide is on the rise worldwide. Most suicide decedents received healthcare services in the year before killing themselves. Standardized workflows for suicide risk screening in pediatric hospitals using validated tools can help with timely and appropriate intervention, while attending to The Joint Commission Sentinel Event Alert 56. OBJECTIVE: Here we describe the first attempt to generate clinical pathways for patients presenting to pediatric emergency departments (EDs) and inpatient medical settings. METHODS: The workgroup reviewed available evidence and generated a series of steps to be taken to feasibly screen medical patients presenting to hospitals. When evidence was limited, expert consensus was used. A standardized, iterative approach was utilized to create clinical pathways. Stakeholders reviewed initial drafts. Feedback was incorporated into the final pathway. RESULTS: Clinical pathways were created for suicide risk screening in pediatric EDs and inpatient medical/surgical units. The pathway outlines a 3-tiered screening process utilizing the Ask Suicide-Screening Questions for initial screening, followed by a brief suicide safety assessment to determine if a full suicide risk assessment is warranted. This essential step helps conserve resources and decide upon appropriate interventions for each patient who screens positive. Detailed implementation guidelines along with scripts for provider training are included. CONCLUSION: Youth suicide is a significant public health problem. Clinical pathways can empower hospital systems by providing a guide for feasible and effective suicide risk-screening implementation by using validated tools to identify patients at risk and apply appropriate interventions for those who screen positive. Outcomes assessment is essential to inform future iterations.

Brain age in bipolar disorders: Effects of lithium treatment.

OBJECTIVE: Bipolar disorders increase the risk of dementia and show biological and brain alterations, which resemble accelerated aging. Lithium may counter some of these processes and lower the risk of dementia. However, until now no study has specifically investigated the effects of Li on brain age. METHODS: We acquired structural magnetic resonance imaging scans from 84 participants with bipolar disorders (41 with and 43 without Li treatment) and 45 controls. We used a machine learning model trained on an independent sample of 504 controls to estimate the individual brain ages of study participants, and calculated BrainAGE by subtracting chronological from the estimated brain age. RESULTS: BrainAGE was significantly greater in non-Li relative to Li or control participants, F(2, 125) = 10.22, p < 0.001, with no differences between the Li treated and control groups. The estimated brain age was significantly higher than the chronological age in the non-Li (4.28 ± 6.33 years, matched t(42) = 4.43, p < 0.001), but not the Li-treated group (0.48 ± 7.60 years, not significant). Even Li-treated participants with partial prophylactic treatment response showed lower BrainAGE than the non-Li group, F(1, 64) = 4.80, p = 0.03. CONCLUSIONS: Bipolar disorders were associated with greater, whereas Li treatment with lower discrepancy between brain and chronological age. These findings support the neuroprotective effects of Li, which were sufficiently pronounced to affect a complex, multivariate measure of brain structure. The association between Li treatment and BrainAGE was independent of long-term thymoprophylactic response and thus may generalize beyond bipolar disorders, to neurodegenerative disorders.

Exploring the relationship between threat-related changes in anxiety, attention focus, and postural control.

Individuals report directing attention toward and away from multiple sources when standing under height-related postural threat, and these changes in attention focus are associated with postural control modifications. As it is unknown whether these changes generalize to other types of threat situations, this study aimed to quantify changes in attention focus and examine their relationship with postural control changes in response to a direct threat to stability. Eighty young adults stood on a force plate fixed to a translating platform. Three postural threat conditions were created by altering the expectation of, and prior experience with, a postural perturbation: no threat of perturbation, threat without perturbation experience, and threat with perturbation experience. When threatened, participants were more anxious and reported directing more attention to movement processes, threat-related stimuli, and self-regulatory strategies, and less to task-irrelevant information. Postural sway amplitude and frequency increased with threat, with greater increases in frequency and smaller increases in amplitude observed with experience. Without experience, threat-related changes in postural control were accounted for by changes in anxiety; larger changes in anxiety were related to larger changes in sway amplitude. With experience, threat-related postural control changes were accounted for by changes in attention focus; increases in attention to movement processes were related to greater forward leaning and increases in sway amplitude, while increases in attention to self-regulatory strategies were related to greater increases in sway frequency. Results suggest that relationships between threat-related changes in anxiety, attention focus, and postural control depend on the context associated with the threat.

Free Surface Relaxations of Star-Shaped Polymer Films.

The surface relaxation dynamics of supported star-shaped polymer thin films are shown to be slower than the bulk, persisting up to temperatures at least 50 K above the bulk glass transition temperature T_{g}^{bulk}. This behavior, exhibited by star-shaped polystyrenes with functionality f=8 arms and molecular weights per arm M_{arm}

ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation.

Aberrations in chromatin dynamics play a fundamental role in tumorigenesis, yet relatively little is known of the molecular mechanisms linking histone lysine methylation to neoplastic disease. ING4 (Inhibitor of Growth 4) is a native subunit of an HBO1 histone acetyltransferase (HAT) complex and a tumor suppressor protein. Here we show a critical role for specific recognition of histone H3 trimethylated at lysine 4 (H3K4me3) by the ING4 PHD finger in mediating ING4 gene expression and tumor suppressor functions. The interaction between ING4 and H3K4me3 augments HBO1 acetylation activity on H3 tails and drives H3 acetylation at ING4 target promoters. Further, ING4 facilitates apoptosis in response to genotoxic stress and inhibits anchorage-independent cell growth, and these functions depend on ING4 interactions with H3K4me3. Together, our results demonstrate a mechanism for brokering crosstalk between H3K4 methylation and H3 acetylation and reveal a molecular link between chromatin modulation and tumor suppressor mechanisms.

Impact of an Inpatient Psychiatric Unit on Pediatric Emergency Mental Health Care.

OBJECTIVES: Mental health complaints are a frequent presentation to the pediatric emergency department (PED). It is unclear if having an on-site inpatient pediatric psychiatric unit impacts pediatric mental health care in the acute setting. The objective of this study was to compare PED mental health care between a pediatric tertiary care center with an associated inpatient child psychiatric unit (PAPED) and one that does not (NOPED) with the hypothesis that children have longer lengths of stay (LOS) at the PED without an inpatient unit. METHODS: This was a retrospective, observational study of all mental health presentations aged 1 to 18 years to 2 tertiary care PEDs from March 2012 to June 2013 with a final mental health diagnosis International Classification of Diseases, Ninth Revision code. RESULTS: A total of 1409 patient encounters comprised the study group. The PAPED had a significantly higher rate of admission 41.3% versus 18.8% (P < 0.0001). The LOS was significantly longer at the NOPED compared with the PAPED with a visit of 15.6 versus 6.3, respectively (P < 0.0001). When LOS was stratified for disposition, patients requiring admission from the NOPED had a significantly longer LOS of 33.4 compared with an emergency department LOS of 8.1 at the PAPED (P < 0.0001). CONCLUSIONS: Mental health care in the PED seems to be affected by having an associated inpatient child psychiatric unit. Further research needs to address this growing problem and ways to utilize community resources to develop safe outpatient plans and divert admission if possible.

Branched Aramid Nanofibers.

Interconnectivity of components in three-dimensional networks (3DNs) is essential for stress transfer in hydrogels, aerogels, and composites. Entanglement of nanoscale components in the network relies on weak short-range intermolecular interactions. The intrinsic stiffness and rod-like geometry of nanoscale components limit the cohesive energy of the physical crosslinks in 3DN materials. Nature realizes networked gels differently using components with extensive branching. Branched aramid nanofibers (BANFs) mimicking polymeric components of biological gels were synthesized to produce 3DNs with high efficiency stress transfer. Individual BANFs are flexible, with the number of branches controlled by base strength in the hydrolysis process. The extensive connectivity of the BANFs allows them to form hydro- and aerogel monoliths with an order of magnitude less solid content than rod-like nanocomponents. Branching of nanofibers also leads to improved mechanics of gels and nanocomposites.

Phenotypic spandrel: absolute discrimination and ligand antagonism.

We consider the general problem of sensitive and specific discrimination between biochemical species. An important instance is immune discrimination between self and not-self, where it is also observed experimentally that ligands just below the discrimination threshold negatively impact response, a phenomenon called antagonism. We characterize mathematically the generic properties of such discrimination, first relating it to biochemical adaptation. Then, based on basic biochemical rules, we establish that, surprisingly, antagonism is a generic consequence of any strictly specific discrimination made independently from ligand concentration. Thus antagonism constitutes a 'phenotypic spandrel': a phenotype existing as a necessary by-product of another phenotype. We exhibit a simple analytic model of discrimination displaying antagonism, where antagonism strength is linear in distance from the detection threshold. This contrasts with traditional proofreading based models where antagonism vanishes far from threshold and thus displays an inverted hierarchy of antagonism compared to simpler models. The phenotypic spandrel studied here is expected to structure many decision pathways such as immune detection mediated by TCRs and FCϵRIs, as well as endocrine signalling/disruption.

The Effect of a Dedicated Psychiatric Team to Pediatric Emergency Mental Health Care.

BACKGROUND: Pediatric emergency department (PED) visits among children and adolescents with acute mental health needs have increased over the past decade with long wait times in the PED awaiting disposition. OBJECTIVE: The objective of this study was to evaluate the effect of a new pediatric mental health liaison program with the hypothesis that this model reduces length of stay (LOS) and hospitalization rates among pediatric mental health patients. METHODS: This was a pre- and postintervention retrospective study of the year prior to (June 2012-June 2013) and the year after (October 2013-October 2014) implementation of a new PED psychiatric team. All patients aged 1-18 years with a mental health International Classification of Diseases-9(th) Revision code were included. Patients who did not receive a Psychiatry consult in the PED were excluded. RESULTS: There were 83 encounters in the year prior to and 129 encounters in the year after the implementation of the liaison program. There was an increase in the suicidality of mental health patients during this time. There was a significant decrease in mean PED LOS of 27% (95% confidence interval [CI] 0-46%; p = 0.05) from pre- to postintervention period. The decrease in the proportion of patients admitted/transferred to an inpatient psychiatric facility in the postintervention year was statistically significant (odds ratio 0.35; 95% CI 0.17-0.71; p < 0.01). CONCLUSIONS: The use of a dedicated child psychiatrist and mental health social worker to the PED results in significantly decreased LOS and need for admission without any change in return visit rate. Larger, multicenter studies are needed to confirm these findings.

Multi-Agent-Based Simulation of a Complex Ecosystem of Mental Health Care.

This paper discusses the creation of an Agent-Based Simulation that modeled the introduction of care coordination capabilities into a complex system of care for patients with Serious and Persistent Mental Illness. The model describes the engagement between patients and the medical, social and criminal justice services they interact with in a complex ecosystem of care. We outline the challenges involved in developing the model, including process mapping and the collection and synthesis of data to support parametric estimates, and describe the controls built into the model to support analysis of potential changes to the system. We also describe the approach taken to calibrate the model to an observable level of system performance. Preliminary results from application of the simulation are provided to demonstrate how it can provide insights into potential improvements deriving from introduction of care coordination technology.