Incorporating a polygenic risk score-triaged coronary calcium score into cardiovascular disease examinations to identify subclinical coronary artery disease (ESCALATE): Protocol for a prospective, nonrandomized implementation trial.

BACKGROUND: Identifying and targeting established modifiable risk factors has been a successful strategy for reducing the burden of coronary artery disease (CAD) at the population-level. However, up to 1-in-4 patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. Polygenic risk scores (PRS) have demonstrated an ability to improve risk prediction models independent of traditional risk factors and self-reported family history, but a pathway for implementation has yet to be clearly identified. The aim of this study is to examine the utility of a CAD PRS to identify individuals with subclinical CAD via a novel clinical pathway, triaging low or intermediate absolute risk individuals for noninvasive coronary imaging, and examining the impact on shared treatment decisions and participant experience. TRIAL DESIGN: The ESCALATE study is a 12-month, prospective, multicenter implementation study incorporating PRS into otherwise standard primary care CVD risk assessments, to identify patients at increased lifetime CAD risk for noninvasive coronary imaging. One-thousand eligible participants aged 45 to 65 years old will enter the study, which applies PRS to those considered low or moderate 5-year absolute CVD risk and triages those with CAD PRS ≥80% for a coronary calcium scan. The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) >0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sex-matched percentile, the use and intensity of lipid- and blood pressure-lowering therapeutics, cholesterol and blood pressure levels, and health-related quality of life (HRQOL). CONCLUSION: This novel trial will generate evidence on the ability of a PRS-triaged CACS to identify subclinical CAD, as well as subsequent differences in traditional risk factor medical management, pharmacotherapy utilization, and participant experience. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12622000436774. Trial was prospectively registered on March 18, 2022. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383134.

The status of patient portal use among Emergency Department patients experiencing houselessness: A large-scale single-center observational study.

OBJECTIVE: Patient portal (PP) use has rapidly increased in recent years. However, the PP use status among houseless patients is largely unknown. We aim to determine 1) the PP use status among Emergency Department (ED) patients experiencing houselessness, and 2) whether PP use is linked to the increase in patient clinic visits. METHODS: This is a single-center retrospective observational study. From March 1, 2019, to February 28, 2021, houseless patients who presented at ED were included. Their PP use status, including passive PP use (log-on only PP) and effective PP use (use PP of functions) was compared between houseless and non-houseless patients. The number of clinic visits was also compared between these two groups. Lastly, a multivariate logistic regression was analyzed to determine the association between houseless status and PP use. RESULTS: We included a total of 236,684 patients, 13% of whom (30,956) were houseless at time of their encounter. Fewer houseless patients had effective PP use in comparison to non-houseless patients (7.3% versus 11.6%, p < 0.001). In addition, a higher number of clinic visits were found among houseless patients who had effective PP use than those without (18 versus 3, p < 0.001). The adjusted odds ratio of houseless status associated with PP use was 0.48 (95% CI 0.46-0.49, p < 0.001). CONCLUSIONS: Houselessness is a potential risk factor preventing patient portal use. In addition, using patient portals could potentially increase clinic visits among the houseless patient population.

Cascade testing for inherited arrhythmia conditions: Experiences and attitudes of family communication approaches for a Canadian cohort.

Inherited arrhythmia conditions (IAC) can lead to sudden cardiac death at any age, and relatives of an affected person have up to a 50% chance of inheriting the condition and are at risk for developing features. Cascade testing is a stepwise approach for identifying relatives at risk for IACs through clinical screening and genetic testing. Early detection can reduce morbidity and mortality for affected individuals and determine potential risk mitigation strategies for relatives. However, cardiovascular genetic studies have reported an incomplete uptake of cascade testing in at-risk relatives. We explored patient perspectives on cascade testing for IACs and alternative approaches to family communication. Twelve semi-structured phone interviews were conducted with probands of the British Columbia Inherited Arrhythmia Program confirmed to carry a pathogenic or likely pathogenic variant in a gene associated with an IAC. Thematic analysis of transcripts through an iterative coding process revealed five main themes: (a) a stepwise approach is followed in disclosing risk to relatives, (b) relatives' autonomy in cascade testing is supported, (c) lived experience with the condition influences disclosure and uptake of cascade testing, (d) collaborative approach to informing relatives reduces negative impact of disclosure, and (e) direct contact from a healthcare provider is viewed as acceptable. The findings highlight this patient cohort's experiences and opinions with approaches to disclosure and demonstrate their understanding and acceptance of their relatives' approaches to cascade testing. In addition, while the notion of direct contact was generally accepted, a collaborative approach to contacting relatives between the proband and provider may be most effective.

Two-step predictive model for early detection of emergency department patients with prolonged stay and its management implications.

OBJECTIVE: To develop a novel model for predicting Emergency Department (ED) prolonged length of stay (LOS) patients upon triage completion, and further investigate the benefit of a targeted intervention for patients with prolonged ED LOS. MATERIALS AND METHODS: A two-step model to predict patients with prolonged ED LOS (>16 h) was constructed. This model was initially used to predict ED resource usage and was subsequently adapted to predict patient ED LOS based on the number of ED resources using binary logistic regressions and was validated internally with accuracy. Finally, a discrete event simulation was used to move patients with predicted prolonged ED LOS directly to a virtual Clinical Decision Unit (CDU). The changes of ED crowding status (Overcrowding, Crowding, and Not-Crowding) and savings of ED bed-hour equivalents were estimated as the measures of the efficacy of this intervention. RESULTS: We screened a total of 123,975 patient visits with final enrollment of 110,471 patient visits. The overall accuracy of the final model predicting prolonged patient LOS was 67.8%. The C-index of this model ranges from 0.72 to 0.82. By implementing the proposed intervention, the simulation showed a 12% (1044/8760) reduction of ED overcrowded status - an equivalent savings of 129.3 ED bed-hours per day. CONCLUSIONS: Early prediction of prolonged ED LOS patients and subsequent (simulated) early CDU transfer could lead to more efficiently utilization of ED resources and improved efficacy of ED operations. This study provides evidence to support the implementation of this novel intervention into real healthcare practice.

Initiation of the ABCD3-I algorithm for expediated evaluation of transient ischemic attack patients in an emergency department.

BACKGROUND: The use of ABCD3-I score for Transient ischemic attack (TIA) evaluation has not been widely investigated in the ED. We aim to determine the performance and cost-effectiveness of an ABCD3-I based pathway for expedited evaluation of TIA patients in the ED. METHODS: We conducted a single-center, pre- and post-intervention study among ED patients with possible TIA. Accrual occurred for seven months before (Oct. 2016-April 2017) and after (Oct. 2017-April 2018) implementing the ABCD3-I algorithm with a five-month wash-in period (May-Sept. 2017). Total ED length of stay (LOS), admissions to the hospital, healthcare cost, and 90-day ED returns with subsequent stroke were analyzed and compared. RESULTS: Pre-implementation and post-implementation cohorts included 143 and 118 patients respectively. A total of 132 (92%) patients were admitted to the hospital in the pre-implementation cohort in comparison to 28 (24%) patients admitted in the post-implementation cohort (p < 0.001) with similar 90-day post-discharge stroke occurrence (2 in pre-implementation versus 1 in post-implementation groups, p > 0.05). The mean ABCD2 scores were 4.5 (1.4) in pre- and 4.1 (1.3) in post-implementation cohorts (p = 0.01). The mean ABCD3-I scores were 4.5 (1.8) in post-implementation cohorts. Total ED LOS was 310 min (201, 420) in pre- and 275 min (222, 342) in post-implementation cohorts (p > 0.05). Utilization of the ABCD3-I algorithm saved an average of over 40% of total healthcare cost per patient in the post-implementation cohort. CONCLUSIONS: The initiation of an ABCD3-I based pathway for TIA evaluation in the ED significantly decreased hospital admissions and cost with similar 90-day neurological outcomes.

Common step-wise interventions improved primary care clinic visits and reduced emergency department discharge failures: a large-scale retrospective observational study.

BACKGROUND: It is critical to understand whether providing health insurance coverage, assigning a dedicated Primary Care Physician (PCP), and arranging timely post-Emergency Department (ED) clinic follow-up can improve compliance with clinic visits and reduce ED discharge failures. We aim to determine the benefits of providing these common step-wise interventions and further investigate the necessity of urgent PCP referrals on behalf of ED discharged patients. METHODS: This is a single-center retrospective observational study. All patients discharged from the ED over the period Jan 1, 2015 through Dec 31, 2017 were included in the study population. Step-wise interventions included providing charity health insurance, assigning a dedicated PCP, and providing ED follow-up clinics. PCP clinic compliance and ED discharge failures were measured and compared among groups receiving different interventions. RESULT: A total of 227,627 patients were included. Fifty-eight percent of patients receiving charity insurance had PCP visits in comparison to 23% of patients without charity insurance (p < 0.001). Seventy-seven percent of patients with charity insurance and PCP assignments completed post-ED discharge PCP visits in comparison to only 4.5% of those with neither charity insurance nor PCP assignments (p < 0.001). CONCLUSIONS: Step-wise interventions increased patient clinic follow-up compliance while simultaneously reducing ED discharge failures. Such interventions might benefit communities with similar patient populations.

Rutin increases the cytotoxicity of temozolomide in glioblastoma via autophagy inhibition.

The chemotherapeutic agent temozolomide (TMZ) is widely used in the treatment of glioblastoma multiforme (GBM). Rutin, a citrus flavonoid ecglycoside found in edible plants, has neuroprotective and anticancer activities. This study aimed to investigate the efficacy and the underlying mechanisms of rutin used in combination with TMZ in GBM. In vitro cell viability assay demonstrated that rutin alone had generally low cytotoxic effect, but it enhanced the efficacy of TMZ in a dose-dependent manner. Subcutaneous and orthotopic xenograft studies also showed that tumor volumes were significantly lower in mice receiving combined TMZ/Rutin treatment as compared to TMZ or rutin alone treatment. Moreover, immunoblotting analysis showed that TMZ activated JNK activity to induce protective response autophagy, which was blocked by rutin, resulting in decreased autophagy and increased apoptosis, suggesting that rutin enhances TMZ efficacy both in vitro and in vivo via inhibiting JNK-mediated autophagy in GBM. The combination rutin with TMZ may be a potentially useful therapeutic approach for GBM patient.

IDH1 mutation-associated long non-coding RNA expression profile changes in glioma.

Isocitrate dehydrogenase 1 (IDH1) mutation is an important prognostic marker in glioma. However, its downstream effect remains incompletely understood. Long non-coding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis in a number of human malignancies, including glioma. Here, we investigated whether and how lncRNA expression profiles would differ between gliomas with or without IDH1 mutation. By using our previously reported lncRNA mining approach, we performed lncRNA profiling in three public glioma microarray datasets. The differential lncRNA expression analysis was then conducted between mutant-type and wild-type IDH1 glioma samples. Comparison analysis identified 14 and 9 lncRNA probe sets that showed significantly altered expressions in astrocytic and oligodendroglial tumors, respectively (fold change ≥ 1.5, false discovery rate ≤ 0.1). Moreover, the differential expressions of these lncRNAs could be confirmed in the independent testing sets. Functional exploration of the lncRNAs by analyzing the lncRNA-protein interactions revealed that these IDH1 mutation-associated lncRNAs were involved in multiple tumor-associated cellular processes, including metabolism, cell growth and apoptosis. Our data suggest the potential roles of lncRNA in gliomagenesis, and may help to understand the pathogenesis of gliomas associated with IDH1 mutation.

Shifts in hormonal stress reactivity during adolescence are not associated with changes in glucocorticoid receptor levels in the brain and pituitary of male rats.

Preadolescent animals display protracted hormonal stress responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis compared to adults. Though the mechanisms that underlie this shift in stress reactivity are unknown, reduced glucocorticoid-dependent negative feedback on the HPA axis has been posited to contribute to this differential responsiveness. As the glucocorticoid receptors (GRs) are integral to this feedback response, we hypothesize that prior to puberty there will be fewer GRs in the neural-pituitary network that mediate negative feedback. To test this hypothesis we measured GR protein levels in the brains of preadolescent (28 days old), midadolescent (40 days old) and adult (77 days old) male rats via immunohistochemistry. Additionally, we assessed stress-induced plasma adrenocorticotropic hormone and corticosterone in prepubertal (30 days old) and adult (70 days old) male rats and examined GR protein levels via Western blot in the brain and pituitary. We found that despite substantial adolescent-related changes in hormonal responsiveness, no significant differences were found between these ages in GR protein levels in regions that are important in negative feedback, including the medial prefrontal cortex, paraventricular nucleus of the hypothalamus, hippocampal formation, and pituitary. These data indicate that the extended hormonal stress response exhibited by preadolescent animals is independent of significant pubertal changes in GR protein levels.

Effects of progesterone vs. dexamethasone on brain oedema and inflammatory responses following experimental brain resection.

BACKGROUND: Dexamethasone (DEXA) is commonly used to reduce brain swelling during neurosurgical procedures. DEXA, however, has many side-effects that can increase the risks of post-operative complications. In contrast, progesterone (PRO) has fewer side-effects and has been found to be neuroprotective on traumatic brain injury (TBI). Whether PRO may be used as an alternative to DEXA during routine procedures has not been fully explored. OBJECT: To compare the effects of DEXA and PRO on surgical brain injury (SBI). METHODS: Seventy-five adult male Sprague Dawley rats were randomized into five groups: (1) SBI + drug vehicle (peanut oil, 1 ml kg(-1)); (2) SBI + DEXA (1 mg kg(-1)); (3) SBI + low-dose PRO (10 mg kg(-1)); (4) SBI + high-dose PRO (20 mg kg(-1)); and (5) sham SBI + drug vehicle. Magnetic resonance imaging study and assessments of brain water content (BWC), blood-brain barrier (BBB) permeability, cellular inflammatory responses and matrix metalloproteinase 9 (MMP-9) expression were conducted. RESULTS: This model consistently resulted in increased BWC and BBB disruption. PRO reduced astrocyte and microglia responses and attenuated brain oedema with preservation of BBB. A significant down-regulation of MMP-9 expression occurred in the PRO 20 group. CONCLUSIONS: PRO is as effective as DEXA in reducing brain oedema and inflammation following SBI; 10 mg kg(-1) of PRO was demonstrated to be more effective in relieving acute cellular inflammatory responses.

Evaluation of an augmented reality navigational guidance platform for percutaneous procedures in a cadaver model.

Purpose: The objective of this study is to review the accuracy of an augmented reality navigational guidance system designed to facilitate improved visualization, guidance, and accuracy during percutaneous needle-based procedures including biopsies and ablations. Approach: Using the HoloLens 2, the system registers and projects 3D CT-based models of segmented anatomy along with live ultrasound, fused with electromagnetically tracked instruments including ultrasound probes and needles, giving the operator comprehensive stereoscopic visualization for intraoperative planning and navigation during procedures.Tracked needles were guided to targets implanted in a cadaveric model using the system. Image fusion registration error, the multimodality error measured as the post-registration distance between a corresponding point measured in the stereoscopic CT and tracked ultrasound coordinate systems, and target registration error, the Euclidean distance between needle tip and target after needle placement, were measured as registration and targeting accuracy metrics. A t-distribution was used for statistical analysis. Results: Three operators performed 36 total needle passes, 18 to measure image fusion registration error and 18 to measure target registration error on four targets. The average depth of each needle pass was 8.4 cm from skin to target center. Mean IFRE was 4.4 mm (H0: µ=5 mm, P<0.05). Mean TRE was 2.3 mm (H0: µ=5 mm, P<0.00001). Conclusions: The study demonstrated high registration and targeting accuracy of this AR navigational guidance system in percutaneous, needle-based procedures. This suggests the ability to facilitate improved clinical performance in percutaneous procedures such as ablations and biopsies.

Trends in Incident Prescriptions for Behavioral Health Medications in the US, 2018-2022.

Importance: The COVID-19 pandemic reportedly increased behavioral health needs and impacted treatment access. Objective: To assess changes in incident prescriptions dispensed for medications commonly used to treat depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and opioid use disorder (OUD), before and during the COVID-19 pandemic. Design, Setting, and Participants: This was a cross-sectional study using comprehensive, population-level, nationally projected data from IQVIA National Prescription Audit on incident prescriptions (prescriptions dispensed to patients with no prior dispensing from the same drug class in the previous 12 months) dispensed for antidepressants, benzodiazepines, Schedule II (C-II) stimulants, nonstimulant medications for ADHD, and buprenorphine-containing medication for OUD (MOUD), from US outpatient pharmacies. Data were analyzed from April 2018 to March 2022. Exposure: Incident prescriptions by drug class (by prescriber specialty, patient age, and sex) and drug. Main Outcomes and Measures: Interrupted time-series analysis to compare changes in trends in the monthly incident prescriptions dispensed by drug class and percentage changes in aggregate incident prescriptions dispensed between April 2018 and March 2022. Results: Incident prescriptions dispensed for the 5 drug classes changed from 51 500 321 before the COVID-19 pandemic to 54 000 169 during the pandemic. The largest unadjusted percentage increase in incident prescriptions by prescriber specialty was among nurse practitioners across all drug classes ranging from 7% (from 1 811 376 to 1 944 852; benzodiazepines) to 78% (from 157 578 to 280 925; buprenorphine MOUD), whereas for patient age and sex, the largest increases were within C-II stimulants and nonstimulant ADHD drugs among patients aged 20 to 39 years (30% [from 1 887 017 to 2 455 706] and 81% [from 255 053 to 461 017], respectively) and female patients (25% [from 2 352 095 to 2 942 604] and 59% [from 395 678 to 630 678], respectively). Trends for C-II stimulants and nonstimulant ADHD drugs (slope change: 4007 prescriptions per month; 95% CI, 1592-6422 and 1120 prescriptions per month; 95% CI, 706-1533, respectively) significantly changed during the pandemic, exceeding prepandemic trends after an initial drop at the onset of the pandemic (level changes: -50 044 prescriptions; 95% CI, -80 202 to -19 886 and -12 876 prescriptions; 95% CI, -17 756 to -7996, respectively). Although buprenorphine MOUD dropped significantly (level change: -2915 prescriptions; 95% CI, -5513 to -318), trends did not significantly change for buprenorphine MOUD, antidepressants, or benzodiazepines. Conclusions and Relevance: Incident use of many behavioral health medications remained relatively stable during the COVID-19 pandemic in the US, whereas ADHD medications, notably C-II stimulants, sharply increased. Additional research is needed to differentiate increases due to unmet need vs overprescribing, highlighting the need for further ADHD guideline development to define treatment appropriateness.

A long non-coding RNA signature in glioblastoma multiforme predicts survival.

Long non-coding RNAs (lncRNAs) represent the leading edge of cancer research, and have been implicated in cancer biogenesis and prognosis. We aimed to identify lncRNA signatures that have prognostic values in glioblastoma multiforme (GBM). Using a lncRNA-mining approach, we performed lncRNA expression profiling in 213 GBM tumors from The Cancer Genome Atlas (TCGA), randomly divided into a training (n=107) and a testing set (n=106). We analyzed the associations between lncRNA signatures and clinical outcome in the training set, and validated the findings in the testing set. We also validated the identified lncRNA signature in another two independent GBM data sets from Gene Expression Omnibus (GEO), which contained specimens from 68 and 101 patients, respectively. We identified a set of six lncRNAs that were significantly associated with the overall survival in the training set (P≤0.01). Based on this six-lncRNA signature, the training-set patients could be classified into high-risk and low-risk subgroups with significantly different survival (HR=2.13, 95% CI=1.38-3.29; P=0.001). The prognostic value of this six-lncRNA signature was confirmed in the testing set and the two independent data sets. Further analysis revealed that the prognostic value of this signature was independent of age and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. The identification of the prognostic lncRNAs indicates the potential roles of lncRNAs in GBM pathogenesis. This six-lncRNA signature may have clinical implications in the subclassification of GBM.

Modeling the Relationships Among Reading Instruction, Motivation, Engagement, and Achievement for Adolescents.

This study modeled the interrelationships of reading instruction, motivation, engagement, and achievement in two contexts, employing data from 1,159 seventh graders. In the traditional reading/language arts (R/LA) context, all students participated in traditional R/LA instruction. In the intervention R/LA context, 854 students from the full sample received Concept-Oriented Reading Instruction (CORI) while the remainder continued to receive traditional R/LA. CORI emphasizes support for reading motivation, reading engagement, and cognitive strategies for reading informational text. Seven motivation constructs were included: four motivations that are usually positively associated with achievement (intrinsic motivation, self-efficacy, valuing, and prosocial goals) and three motivations that are usually negatively associated with achievement (perceived difficulty, devaluing, and antisocial goals). Reading engagement was also represented by positive and negative constructs, namely dedication to and avoidance of reading. Gender, ethnicity, and income were statistically controlled in all analyses. In the traditional R/LA context, a total network model prevailed, in which motivation was associated with achievement both directly and indirectly through engagement. In contrast, in the intervention R/LA context, a dual-effects model prevailed, in which engagement and achievement were separate outcomes of instruction and motivation. The intervention R/LA context analyses revealed that CORI was associated with positive changes in motivation, engagement, and achievement relative to traditional R/LA instruction. The discussion explains why there were different relations in the two instructional contexts and demonstrates the importance of simultaneously examining both positive (affirming) and negative (undermining) forms of motivation and engagement.

Factors Associated with Reducing Disparities in Electronic Personal Heath Records Use Among Non-Hispanic White and Hispanic Adults.

OBJECTIVES: Personal health records (PHR) use has improved individuals' health outcomes. The adoption of PHR remains low with documented racial disparities. We aim to determine factors associated with reducing racial and ethnic disparities among Hispanic adults in PHR use. METHODS: Participants included non-Hispanic White (NHW) and Hispanic adults (age ≥ 18 years) enrolled in Health Information National Trends Survey in 2018 and 2019. We identified PHR use as online medical record access in the last 12 months. We considered three factors (1. accessing mHealth Apps on the phone, 2. having a usual source of care, and 3. electronically communicating (e-communication) with healthcare providers) as facilitating PHR use. Multivariable logistic regressions with replicate weights were analyzed to determine factors associated with racial/ethnic disparities in PHR use after controlling for general characteristics (i.e., sex, age, education, insurance status, and income). RESULTS: A lower percentage of Hispanics than NHWs used PHR (42.0% vs. 53.5%, P < .001). When adjusted for individual general characteristics, the adjusted odds ratio (AOR) of e-communication with healthcare providers associated with PHR use was 1.49 (1.19-1.86, P < .001), AOR was 2.06 (1.62-2.6, P < .001) on accessing to mHealth App, and 2.60 (1.86-3.63, P < .001) on having a usual source of care. However, the racial difference was not statistically significant after adjusting three factors promoting PHR use (AOR = 0.90, 95% CI = 0.66, 1.22, P = .48). CONCLUSIONS: Ethnic disparities were reduced when PHR use was facilitated by having a usual source of care, active e-communication, and having access to mHealth apps. Interventions focusing on these three factors may potentially reduce racial/ethnic disparities.

A Multi-Level Analysis of Individual and Neighborhood Factors Associated with Patient Portal Use among Adult Emergency Department Patients with Multimorbidity.

Background: Patient portals tethered to electronic health records (EHR) have become vital to patient engagement and better disease management, specifically among adults with multimorbidity. We determined individual and neighborhood factors associated with patient portal use (MyChart) among adult patients with multimorbidity seen in an Emergency Department (ED). Methods: This study adopted a cross-sectional study design and used a linked database of EHR from a single ED site to patients' neighborhood characteristics (i.e., zip code level) from the American Community Survey. The study population included all adults (age > 18 years), with at least one visit to an ED and multimorbidity between 1 January 2019 to 31 December 2020 (N = 40,544). Patient and neighborhood characteristics were compared among patients with and without MyChart use. Random-intercept multi-level logistic regressions were used to analyze the associations of patient and neighborhood factors with MyChart use. Results: Only 19% (N = 7757) of adults with multimorbidity used the patient portal. In the fully adjusted multi-level model, at the patient level, having a primary care physician (AOR = 5.55, 95% CI 5.07−6.07, p < 0.001) and health insurance coverage (AOR = 2.41, 95% CI 2.23−2.61, p < 0.001) were associated with MyChart use. At the neighborhood level, 4.73% of the variation in MyChart use was due to differences in neighborhood factors. However, significant heterogeneity existed in patient portal use when neighborhood characteristics were included in the model. Conclusions: Among ED patients with multimorbidity, one in five adults used patient portals. Patient-level factors, such as having primary care physicians and insurance, may promote patient portal use.

Effects of Deferasirox in Alzheimer's Disease and Tauopathy Animal Models.

The accumulation of iron may contribute to Alzheimer's disease (AD) and other tauopathies. The iron chelator desferrioxamine slows disease progression in AD patients. However, desferrioxamine requires injection, which is inconvenient and may hinder compliance. We therefore tested an oral iron chelator, desferasirox (Exjade), in transgenic animal models. Tg2576 mice overexpress the mutant human APP protein and produce the Aß peptide. JNPL3 mice (Tau/Tau) overexpress the mutant human tau protein. Crossing these produced APP/Tau mice, overexpressing both APP and tau. Treating the three models with 1.6 mg deferasirox thrice weekly from age 8 to 14 months did not affect memory as measured by contextual fear conditioning or motor function as measured by rotarod, but tended to decrease hyperphosphorylated tau as measured by AT8 immunohistochemistry and immunoblotting. Deferasirox might act by decreasing iron, which aggregates tau, or directly binding tau to inhibit aggregation.

Patient Portal Use Among Diabetic Patients With Different Races and Ethnicities.

Background: Patient portal (PP) use varies among different patient populations, specifically among those with diabetes mellitus (DM). In addition, it is still uncertain whether PP use could be linked to improved clinical outcomes. Therefore, the aim of this paper was to determine PP use status for patients, recognize factors promoting PP use, and further identify the association between PP use and clinical outcome among diabetic patients of different races and ethnicities. Methods: This was a single-center cross-section study. Patients were divided into non-Hispanic white (NHW), non-Hispanic black (NHB), and Hispanic/Latino groups. PP use was compared among these three groups. Multivariate logistic regressions were used to determine factors associated with PP use, serum glycemic control, and emergency department (ED) hospitalizations. Results: A total of 77,977 patients were analyzed. The rate of PP use among patients of NHW (24%) was higher than those of NHB (19%) and Hispanic/Latinos (18%, P < 0.0001). The adjusted odds ratio (AOR) of insurance coverage associated with PP use was 2.12 (2.02 - 2.23, P < 0.0001), and having a primary care physician (PCP) associated with PP use was 3.89 (3.71 - 4.07, P < 0.0001). In terms of clinical outcomes, the AOR of PP use associated with serum glycemic control was 0.98 (0.90 - 1.05, P = 0.547) and ED hospitalization was 0.79 (0.73 - 0.86, P < 0.0001). Conclusion: PP use disparity occurred among NHB and Hispanic/Latino patients in the ED. Having insurance coverage and PCPs seem to correlate with PP use. PP use did not seem to associate with serum glycemic control among DM patients present in the ED but could possibly reduce patient hospitalizations.

Study protocol for a randomized controlled trial comparing the effectiveness of physical exercise and melatonin supplement on treating sleep disturbance in children with autism spectrum disorders.

BACKGROUND: Previous study showed that both melatonin supplement and physical exercise intervention could improve sleep quality in children with autism spectrum disorders (ASD) with the increase in endogenous melatonin level. However, none of the studies have directly compared the effectiveness between the two interventions on treating sleep disturbance in children with ASD. Without direct comparison, we do not know which intervention is better. Thus, we designed a study to compare which intervention is more effective to treat sleep disturbance in children with ASD and to examine whether the combination of the two could be the most efficacious. We present a protocol for conducting a randomized controlled trial to compare the effectiveness of physical exercise and melatonin supplement on treating sleep disturbance in children with ASD. STUDY DESIGN: The proposed study will be a four-group randomised control trial (RCT) design, with equal allocation of participants to the three intervention groups and one control group. METHODS: All eligible participants will be randomly allocated to a morning jogging group, a melatonin supplement group, a combination group and a control group. Changes in sleep quality will be monitored through actigraphic assessment and parental sleep logs. Melatonin levels represented by 6-sulfoxymelatonin will be measured from the participants' 24-h and the first morning void urinary samples. All the assessments will be carried out before the intervention (T1), in the mid of the study (5 weeks after the commencement of the study) (T2) and after the 10-week intervention (T3). Level of statistical significance will be set at 5% (i.e. p < .05). The results of this trial will be submitted for publication in peer-reviewed journal. FINDINGS: The findings will provide evidence to determine whether physical exercise or melatonin supplement or the combination of interventions is the most effective to treat sleep disturbance in children with ASD.

Coronavirus disease 2019 pandemic associated with anxiety and depression among Non-Hispanic whites with chronic conditions in the US.

OBJECTIVES: During the coronavirus 2019 (COVID-19) pandemic, increased anxiety and depression were reported, with mixed findings among individuals of different races/ethnicities. This study examines whether anxiety and depression increased during the COVID-19 pandemic compared to the pre-COVD-19 period among different racial/ethnic groups in the US. METHODS: The Health Information National Trend Surveys 5 (HINTS 5) Cycle 4 data was analyzed. We used the time when the survey was administered as the pre-COVID-19 period (before March 11, 2020, weighted N = 77,501,549) and during the COVID-19 period (on and after March 11, 2020, weighted N = 37,222,019). The Patient Health Questionnaire (PHQ) was used to measure anxiety/depression and further compared before and during COVID-19. Separate multivariable logistic regression analyses were used to determine the association of the COVID-19 pandemic with anxiety/depression after adjusting for age, sex, insurance, income, and education. RESULT: A higher percentage of Non-Hispanic whites (NHW) with chronic conditions reported anxiety (24.3% vs. 11.5%, p = 0.0021) and depression (20.7% vs. 9.3%, p = 0.0034) during COVID-19 than pre-COVID-19. The adjusted odds ratio (AOR) of anxiety and depression for NHWs with chronic conditions during the COVID-19 pandemic was 2.02 (95% confidence interval of 1.10-3.73, p = 0.025) and 2.33 (1.17-4.65, p = 0.018) compared to NHWs who participated in the survey before the COVID-19. LIMITATIONS: Limited to the NHW US population. PHQ can only be used as the initial screening tool. CONCLUSION: The COVID-19 pandemic was associated with an increased prevalence of anxiety and depression among NHW adults with chronic conditions, but not among people of color.