Clinical factors associated with genetic diagnosis in suspected neurogenetic disorders in a tertiary care clinic.

PURPOSE: This study aimed to identify phenotypic factors associated with genetic diagnoses in patients with neurodevelopmental disorders and generate a decision tree to assist clinicians in identifying patients most likely to receive a positive result on genetic testing. METHODS: We retrospectively reviewed the charts of 316 patients evaluated in a neurodevelopmental clinic between 2014 and 2019. Patients were categorized based on genetic test results. Analyses were performed to identify variables that discriminate between patients with and without a genetic diagnosis. RESULTS: Patients with a genetic diagnosis were more likely to be female and have a history of motor delay, hypotonia, congenital heart disease, and early intervention. Classification and regression tree analysis revealed that 75% of patients with motor delay had a genetic diagnosis. In patients without motor delay, hypotonia, age of walking, and age at initial evaluation were important indicators of a genetic diagnosis. CONCLUSION: Our findings suggest that motor delay and hypotonia are associated with genetic diagnoses in children with neurodevelopmental disorders. The decision tree highlights patient subsets at greater risk and suggests possible phenotypic screens. Future studies could develop validated decision trees based on phenotypic data to assist clinicians in stratifying patients for genetic testing.

Associations between anemia and FGF23 in the CKiD study.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in chronic kidney disease-mineral bone disorder and is associated with CKD progression and cardiovascular morbidity. Factors related to CKD-associated anemia, including iron deficiency, can increase FGF23 production. This study aimed to assess whether anemia and/or iron deficiency are associated with increased circulating concentrations of FGF23 in the large, well-characterized Chronic Kidney Disease in Children (CKiD) study cohort. METHODS: Hemoglobin concentrations, iron parameters, C-terminal (total) FGF23, intact FGF23, and relevant covariables were measured in cross-sectional analysis of CKiD study subjects. RESULTS: In 493 pediatric patients with CKD (median [interquartile range] age 13 [9, 16] years), the median estimated glomerular filtration rate was 48 [35, 61] ml/min/1.73 m2, and 103 patients (21%) were anemic. Anemic subjects had higher total FGF23 concentrations than non-anemic subjects (204 [124, 390] vs. 109 [77, 168] RU/ml, p < 0.001). In multivariable linear regression modeling, anemia was independently associated with higher total FGF23, after adjustment for demographic, kidney-related, mineral metabolism, and inflammatory covariables (standardized ß (95% confidence interval) 0.10 (0.04, 0.17), p = 0.002). In the subset of subjects with available iron parameters (n = 191), iron deficiency was not associated with significantly higher total FGF23 concentrations. In the subgroup that had measurements of both total and intact FGF23 (n = 185), in fully adjusted models, anemia was significantly associated with higher total FGF23 (standardized ß (95% CI) 0.16 (0.04, 0.27), p = 0.008) but not intact FGF23 (standardized ß (95% CI) 0.02 (-0.12, 0.15), p = 0.81). CONCLUSIONS: In this cohort of pediatric patients with CKD, anemia was associated with increased total FGF23 levels but was not independently associated with elevated intact FGF23, suggesting possible effects on both FGF23 production and cleavage. Further studies are warranted to investigate non-mineral factors affecting FGF23 production and metabolism in CKD.

Efficacy of a Multimodal Surgical Site Injection for Postoperative Pain Control in Pediatric Patients With Cerebral Palsy Undergoing Hip Reconstruction: A Randomized Controlled Trial.

BACKGROUND: One in 4 children with cerebral palsy (CP) will undergo orthopaedic surgery during their childhood. Despite its ubiquity, postoperative pain control has been poorly studied in this patient population. Moreover, poor pain management has been associated with adverse surgical outcomes. Multimodal analgesic injections have been well studied in the adult population, demonstrating safety and efficacy in reducing postoperative pain and narcotic consumption, but this modality has not been studied in pediatric patients undergoing similarly complex procedures. The objective of this study was to evaluate the efficacy of a multimodal surgical site injection for postoperative pain control following operative management of hip dysplasia in patients with CP. METHODS: After obtaining IRB approval, a multicenter, randomized double-blind placebo control trial was completed. Patients below 18 years old with a diagnosis of CP who were scheduled for varus derotation osteotomy (VDRO) of the proximal femur were randomized to receive a surgical-site injection with either a combination of ropivacaine (3 mg/kg), epinephrine (0.5 mg), and ketorolac (0.5 mg/kg) (experimental group) or normal saline (control). All included patients had identical postoperative care, including immobilization, physical therapy, and standardized, multimodal postoperative pain control. Pain scores and narcotic consumption were recorded at regular intervals and compared between groups utilizing two-tailed t test or a nonparametric Mann-Whitney test for quantitative variables and a Fischer exact test for categorical variables. RESULTS: Thirty-four patients were included, evenly divided between study arms. There were no significant differences in demographic variables, gross motor function classification system (GMFCS), comorbidities, preoperative radiographic parameters, or concomitant surgeries between groups. Patients in the experimental group required significantly lower narcotic medications at all postoperative time points from PACU until hospital discharge compared with controls (0.41 ± 0.42 vs. 1.87 ± 2.05 total morphine mEQ/kg, P=0.01). Similarly, patients in the experimental group were found to have significantly lower pain scores throughout their hospital stays compared with controls (1.0 ± 0.6 vs. 2.4 ± 1.1 mean pain score, P<0.001). There were no significant differences in operative time, OR time, blood transfusion requirements or hospital length of stay between groups. There were no adverse medication reactions or injection site complications in either group. CONCLUSIONS: In patients with CP undergoing hip reconstruction, surgical-site injection with a multimodal analgesic combination improves pain control and reduces narcotic consumption in the early postoperative period with no observed adverse effects. SIGNIFICANCE: Local multimodal analgesic injections should be adopted as part of standard multimodal pain control in this patient population for all osseous surgeries. LEVEL OF EVIDENCE: Level I-therapeutic.

Recurrent High-Grade Squamous Intraepithelial Lesion After Loop Excision Procedure Versus Loop Procedure With Top Hat.

OBJECTIVE: To evaluate single-pass loop electrosurgical excision procedure (LEEP-SP) versus LEEP with top hat (LEEP-TH) in terms of treatment failure defined as high-grade squamous intraepithelial lesion (HSIL) cytology within 2 years' follow-up. METHODS: This single-institution cohort study used a prospectively collected cervical dysplasia database including all patients who underwent LEEP-SP or LEEP-TH for biopsy-proven cervical intraepithelial neoplasia between 2005 and 2019. RESULTS: Of 340 patients included, 178 underwent LEEP-SP and 162 LEEP-TH. The LEEP-TH patients were more likely to be older (mean age, 40.4 vs 36.5 years; p < .001) and have a positive preprocedure endocervical sampling (68.5% vs 11.8%; p < .001). Positive margins were found in 23 LEEP-SP (12.9%) and in 25 LEEP-TH (15.4%; p = .507). There was no significant difference in depth of excision between LEEP-SP (13.21 ± 23.19 mm) and LEEP-TH (17.37 ± 28.26 mm; p = .138). At 2 years, there was no difference in the rates of HSIL cytology (5.2% vs 6.3%; p = .698), any positive human papillomavirus test, or HSIL cytology (25% vs 15%; p = .284). The 57 patients undergoing repeat excision were more likely to be older (mean age, 40.95 vs 37.52 years; p = .023), have had a LEEP-TH (26.3% vs 73.7%; p < .001), and have initial cytologic HSIL (64.9% vs 35.0%; p < .001). CONCLUSIONS: In this single-institution study, there is no difference in the rate of recurrent HSIL in patients undergoing LEEP-SP versus LEEP-TH. A LEEP-TH may have limited additional benefit over a LEEP-SP in the treatment of cervical HSIL.

Machine Learning-Based Epigenetic Classifiers for Axillary Staging of Patients with ER-Positive Early-Stage Breast Cancer.

BACKGROUND: In the era of molecular stratification and effective multimodality therapies, surgical staging of the axilla is becoming less relevant for patients with estrogen receptor (ER)-positive early-stage breast cancer (EBC). Therefore, a nonsurgical method for accurately predicting lymph node disease is the next step in the de-escalation of axillary surgery. This study sought to identify epigenetic signatures in the primary tumor that accurately predict lymph node status. PATIENTS AND METHODS: We selected a cohort of patients in The Cancer Genome Atlas (TCGA) with ER-positive, HER2-negative invasive ductal carcinomas, and clinically-negative axillae (n = 127). Clinicopathological nomograms from the Memorial Sloan Kettering Cancer Center (MSKCC) and the MD Anderson Cancer Center (MDACC) were calculated. DNA methylation (DNAm) patterns from primary tumor specimens were compared between patients with pN0 and those with > pN0. The cohort was divided into training (n = 85) and validation (n = 42) sets. Random forest was employed to obtain the combinations of DNAm features with the highest accuracy for stratifying patients with > pN0. The most efficient combinations were selected according to the area under the curve (AUC). RESULTS: Clinicopathological models displayed a modest predictive potential for identifying > pN0 disease (MSKCC AUC 0.76, MDACC AUC 0.69, p = 0.15). Differentially methylated sites (DMS) between patients with pN0 and those with > pN0 were identified (n = 1656). DMS showed a similar performance to the MSKCC model (AUC = 0.76, p = 0.83). Machine learning approaches generated five epigenetic classifiers, which showed higher discriminative potential than the clinicopathological variables tested (AUC > 0.88, p < 0.05). CONCLUSIONS: Epigenetic classifiers based on primary tumor characteristics can efficiently stratify patients with no lymph node involvement from those with axillary lymph node disease, thereby providing an accurate method of staging the axilla.

Randomized controlled trial of family-focused treatment for child depression compared to individual psychotherapy: one-year outcomes.

OBJECTIVE: Childhood-onset depression is associated with increased risk of recurrent depression and high morbidity extending into adolescence and adulthood. This multisite randomized controlled trial evaluated two active psychosocial treatments for childhood depression: family-focused treatment for childhood depression (FFT-CD) and individual supportive psychotherapy (IP). Aims were to describe effects through 52 weeks postrandomization on measures of depression, functioning, nondepressive symptoms, and harm events. METHODS: Children meeting criteria for depressive disorders (N = 134) were randomly assigned to 15 sessions of FFT-CD or IP and evaluated at mid-treatment for depressive symptoms and fully at roughly 16 weeks (after acute treatment), 32 weeks, and 52 weeks/one year. See clinicaltrials.gov: NCT01159041. RESULTS: Analyses using generalized linear mixed models confirmed the previously reported FFT-CD advantage on rates of acute depression response (≥50% Children's Depression Rating Scale reduction). Improvements in depression and other outcomes were most rapid during the acute treatment period, and leveled off between weeks 16 and 52, with a corresponding attenuation of observed group differences, although both groups showed improved depression and functioning over 52 weeks. Survival analyses indicated that most children recovered from their index depressive episodes by week 52: estimated 76% FFT-CD, 77% IP. However, by the week 52 assessment, one FFT-CD child and six IP children had suffered recurrent depressive episodes. Four children attempted suicide, all in the IP group. Other indicators of possible harm were relatively evenly distributed across groups. CONCLUSIONS: Results indicate a quicker depression response in FFT-CD and hint at greater protection from recurrence and suicide attempts. However, outcomes were similar for both active treatments by week 52/one year. Although community care received after acute treatment may have influenced results, findings suggest the value of a more extended/chronic disease model that includes monitoring and guidance regarding optimal interventions when signs of depression-risk emerge.

Reconnecting Homeless Adolescents and Their Families: Correlates of Participation in a Family Intervention.

Behavioral family interventions are an effective way to intervene to prevent negative developmental outcomes for adolescents. Participation in family interventions encompasses behavioral and cognitive/attitudinal dimensions, among others, indicated by retention and engagement, respectively. Two dimensions of participation, retention and engagement, in a family intervention were examined in a sample of newly homeless adolescents and their parents or guardians. Correlates of participation included parents with more income and less perceived family conflict and adolescents with higher endorsement of depression, anxiety, somatization, obsessive-compulsive, phobic, and psychotic symptoms on the Brief Symptom Inventory (BSI). Stronger therapeutic alliance was correlated with being more distressed (i.e., lower income, more hostility), being a female adolescent participant, and having greater comfort discussing sex with parents. Furthermore, parents and adolescents with greater distress and thus greater need were more apt to finish the intervention. The finding that families who were experiencing more distress had higher alliance scores suggests that there is an additional need for development of interventions for families in crisis. Both participant and provider perceptions are also important in development of a strong therapeutic alliance. This study's findings have implications for further exploration of the development of cultural humility and improving mental health literacy among facilitators of behavioral interventions.

Evolving growth hormone deficiency: proof of concept.

Introduction: We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST). Methods: We performed a retrospective chart review of children who presented for short stature (height less < 2SD for mean/mid-parental height) and/or growth failure (sustained growth velocity < 0 SD) to pediatric endocrinology at Mount Sinai Kravis Children's Hospital, New York and who had 2 GSTs. Data collected from electronic medical records were analyzed using SPSS v28.0. Results: Of 53 patients included, 42 were males. Average GH peak on initial GST was 15.48 ± 4.92 ng/ml, at 10.07 ± 2.65 years, mean height -1.68 ± 0.56SD(28% had <2SD), IGF-1 -1.00 ± 0.88SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height SDs decreased to -1.82 ± 0.63SD and IGF-1 was -1.08 ± 0.84SD. At repeat GST, average GH peak was 7.59 ± 2.12 ng/dL, with 36% ≤7 ng/dl and 32% in puberty. 12 males reached adult height of 0.08 ± 0.69 SD with a mean height gain of 1.83 ± 0.56SD(p<0.005), IGF-1 of -1.15 ± 0.81SD after 4.64 ± 1.4 years of GH. Conclusion: We offer evidence for Evolving Growth Hormone Deficiency (EGHD) through repeat GST in children with persistent growth slowdown, even with pubertal progression; emphasizing the need for careful longitudinal follow-up to make accurate diagnosis.

A Single-center Comparison of Surgical Outcomes following Prepectoral and Subpectoral Implant-based Breast Reconstruction.

Background: Prepectoral implant placement continues to gain widespread acceptance as a safe and effective option for breast reconstruction. Current literature demonstrates comparable rates of complications and revisions between prepectoral and subpectoral placement; however, these studies are underpowered and lack long-term follow-up. Methods: We performed a retrospective cohort study of patients who underwent immediate two-staged tissue expander or direct-to-implant breast reconstruction at a single center from January 2017 to March 2021. Cases were divided into prepectoral and subpectoral cohorts. The primary outcomes were postoperative complications, aesthetic deformities, and secondary revisions. Descriptive statistics and multivariable regression models were performed to compare the demographic characteristics and outcomes between the two cohorts. Results: We identified 996 breasts (570 patients), which were divided into prepectoral (391 breasts) and subpectoral (605 breasts) cohorts. There was a higher rate of complications (P < 0.001) and aesthetic deformities (P = 0.02) with prepectoral breast reconstruction. Secondary revisions were comparable between the two cohorts. Multivariable regression analysis confirmed that prepectoral reconstruction was associated with an increased risk of complications (odds ratio 2.39, P < 0.001) and aesthetic deformities (odds ratio 1.62, P = 0.003). Conclusions: This study evaluated outcomes in patients undergoing prepectoral or subpectoral breast reconstruction from a single center with long-term follow-up. Prepectoral placement was shown to have an inferior complication and aesthetic profile compared with subpectoral placement, with no difference in secondary revisions. These findings require validation with a well-designed randomized controlled trial to establish best practice for implant-based breast reconstruction.

Sexual and gender minority health-related content in geriatric fellowships.

INTRODUCTION: Despite a growing number of older lesbian, gay, bisexual transgender, and queer (LGBTQ) adults in the United States, education on care for this vulnerable population has historically been inadequate across all levels of training. This research assessed the extent of LGBTQ education in geriatric medicine fellowship curricula across the United States. METHODS: We designed a survey to anonymously collect information from geriatric medicine fellowship programs on LGBTQ curricular content. Eligible participants included all 160 fellowship directors on record with the American Geriatrics Society. The survey addressed demographics of the fellowship program, current state of inclusion of LGBTQ content in didactic curricula and in clinical settings, and other available training opportunities. RESULTS: Out of those contacted, 80 (50%) completed the survey. Of the programs surveyed, 60 (75%) were housed in internal medicine, 19 (24%) were in family medicine, and one was in their own department. Forty-seven fellowships (59%) reported some formal didactic session (e.g., lecture or case based), with the majority of these programs (72%) featuring 1-2 h of formal instruction. Forty-five programs (56%) reported offering no formal clinical experiences. There was less than 50% coverage for all surveyed topics in the required curriculum (range 46% for discrimination to 9% for gender affirming care). Time and lack of expertise were cited as the main barriers to content inclusion. CONCLUSIONS: Curricular content regarding care for LGBTQ older adults is inadequate in geriatric medicine fellowships. Faculty development of current educators and providing standardized guidelines and curricula are steps toward addressing this deficit.

Comparison of cardiac allograft vasculopathy incidence between simultaneous multiorgan and isolated heart transplant recipients in the United States.

BACKGROUND: Prior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multiorgan transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multiorgan heart transplants in the contemporary era. METHODS: We utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary end-point was the development of angiographic CAV within 5 years of follow-up. RESULTS: Among 20,591 patients included in the analysis, 1,279 (6%) underwent multiorgan heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ), and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years, and 74% were male. There were no significant between-group differences in cold ischemic time. The incidence of acute rejection during the first year after transplant was significantly lower in the multiorgan group (18% vs 33%, p < 0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multiorgan group (p < 0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multiorgan heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio = 0.76, 95% confidence interval: 0.66-0.88, p < 0.01). CONCLUSIONS: Simultaneous multiorgan heart transplantation is associated with a significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era.

Association of the COVID-19 Pandemic on Treatment Times for ST-Elevation Myocardial Infarction: Observations from the Los Angeles County Regional System.

Previous studies have documented longer treatment times and worse outcomes for patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) during the COVID-19 pandemic. The objective of the present study was to evaluate the impact of the COVID-19 pandemic on treatment times and outcomes for patients with STEMI who underwent primary PCI within a regional system of care. This was a retrospective study using data from the Los Angeles County Emergency Medical Services Agency. Data on the emergency medical service activations were abstracted for patients with STEMI from March 19, 2020 to January 31, 2021, during the COVID-19 pandemic and for the same interval the previous year. All adult patients (≥18 years) with STEMI who underwent emergent coronary angiography were included. The primary end point was the first medical contact (FMC) to device time. The secondary end points included treatment time intervals, vascular complications, need for emergent coronary artery bypass surgery, length of hospital stay, and in-hospital mortality. During the study period, 3,017 patients underwent coronary angiography for STEMI, 1,893 patients pre-COVID-19 and 1,124 patients during COVID-19 (40% lower). A total of 2,334 patients (77%) underwent PCI. During the COVID-19 period, rates of PCI were significantly lower compared with the control period (75.1% vs 78.7%, p = 0.02). FMC to device time was shorter during the COVID-19 period compared with the control period (median 77.0 vs 81.0 minutes, p = 0.004). For patients with STEMI complicated by out-of-hospital cardiac arrest, FMC to device time was similar during the COVID-19 period compared with the control period (median 95.0 [33.0] vs 100.0 [40.0] minutes, p = 0.34). Vascular complications, the need for emergent bypass surgery, length of hospital stay, and in-hospital mortality were similar between the periods. In conclusion, in this large regional system of care, we found a relatively small but significant decrease in treatment times, yet overall, similar clinical outcomes for patients with STEMI who underwent primary PCI and were treated during the COVID-19 period compared with a control period. These findings suggest that mature cardiac systems of care were able to maintain efficient care despite the challenges of the COVID-19 pandemic.

Guideline-directed medical therapy prescribing patterns and in-hospital outcomes among heart failure patients during COVID-19.

Study objective: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied. Design/setting/participants/interventions/outcome measures: Using the American Heart Association's Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19. Results: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20-3/24/21) and 26,459 patients were admitted in the year prior (2/16/19-2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p < 0.0001) and BB (56.9 % vs 62.4 %, p < 0.0001) use was lower among admitted HFrEF patients during the pandemic when compared to the year prior. Rates of ACEI/ARB/ARNI, MRA, and triple therapy (ACE/ARB/ARNI + BB + MRA) prescription at discharge were higher during the pandemic compared to the year prior. Among a subgroup of those with HFrEF and COVID-19 (n = 333), prior to admission GDMT use was not associated with in-hospital mortality or severe COVID-19. Conclusion: We found no association between prior to admission GDMT use and in-hospital mortality or severe COVID-19 among HFrEF patients admitted with ADHF and COVID-19. GDMT prescription at discharge for HFrEF patients overall has remained either similar or improved during the pandemic.

MivacunaLA (MyshotLA): A Community-Partnered Mobile Phone Intervention to Improve COVID-19 Vaccination Behaviors among Low-Income, Spanish-Speaking, and Immigrant Latino Parents or Caregivers.

We developed and tested MivacunaLA/MyshotLA, a community-informed mobile phone intervention, to increase COVID-19 vaccination among Latino parents/caretakers of minors in under-resourced areas of Los Angeles by addressing misinformation and building trust. We recruited Latino parents/caregivers with at least one unvaccinated child in East and South Los Angeles in the summer of 2021 and evaluated MivacunaLA as a randomized controlled trial with a wait-list control group. A difference-in-difference analysis showed Latino parents/caregivers that participated in MivacunaLA (n = 246), in comparison to the control group, were 15 percentage points more likely (p = 0.04) to report vaccination of minors aged 12-17 years, and 12 percentage points more likely (p = 0.03) to report a positive intention to vaccinate minors aged 2-11 years (when COVID-19 vaccines became available). Mobile phone-delivered digital interventions using videos and culturally tailored educational material to promote COVID-19 vaccine confidence can be an effective way to combat misinformation and deliver timely information to marginalized communities. Community-based participatory research approaches are crucial to advance health equity among minority communities, especially immigrant Spanish-speaking underserved communities.

Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation.

BACKGROUND: The molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. OBJECTIVES: This study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. METHODS: This retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. RESULTS: A total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-ß signaling pathway, and vasculature development. CONCLUSIONS: Patients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.

Detection of Suicidal Behavior and Self-harm Among Children Presenting to Emergency Departments: A Tree-based Classification Approach.

Suicide is the second leading cause of death of U.S. children over 10 years old. Application of statistical learning to structured EHR data may improve detection of children with suicidal behavior and self-harm. Classification trees (CART) were developed and cross-validated using mental health-related emergency department (MH-ED) visits (2015-2019) of children 10-17 years (N=600) across two sites. Performance was compared with the CDC Surveillance Case Definition ICD-10-CM code list. Gold-standard was child psychiatrist chart review. Visits were suicide-related among 284/600 (47.3%) children. ICD-10-CM detected cases with sensitivity 70.7 (95%CI 67.0-74.3), specificity 99.0 (98.8-100), and 85/284 (29.9%) false negatives. CART detected cases with sensitivity 85.1 (64.7-100) and specificity 94.9 (89.2-100). Strongest predictors were suicide-related code, MH- and suicide-related chief complaints, site, area deprivation index, and depression. Diagnostic codes miss nearly one-third of children with suicidal behavior and self-harm. Advances in EHR-based phenotyping have the potential to improve detection of childhood-onset suicidality.

Implementing depression care in under-resourced communities: a school-based family resilience skill-building pilot randomized controlled trial in the United States.

Introduction: Youth in under-resourced communities are more likely to have greater social risk factors for mental health needs yet have less access to needed care. School-based mental health services are effective in treating common disorders such as adolescent depression; however, few have a family-centered approach, which may especially benefit specific populations. Methods: Utilizing a community-partnered approach, we adapted an established, trauma-informed, resilience skill-building family intervention for adolescents with depression. We conducted a small randomized controlled feasibility pilot of an adapted intervention in a large school district that serves predominately low-income, Latinx students in the Southwest United States between 2014-2017. Youth between the ages of 12-18 years old with a Patient Health Questionnaire (PHQ-8) score of 10 or higher, who spoke English or Spanish, were recruited from 12 school mental health clinics. Twenty-five eligible adolescents with depression and their participating caregivers were enrolled and randomly assigned to receive either the adapted intervention, Families OverComing Under Stress for Families with Adolescent Depression (FOCUS-AD), or usual care, Cognitive Behavioral Therapy (CBT) only. Most of the sample was Latinx and female. We evaluated feasibility, acceptability, and preliminary effectiveness. Results: Among participants who completed standardized assessments administered at baseline and approximately five months post-randomization (n = 10 FOCUS-AD, n = 11 CBT only), effectiveness was explored by identifying significant changes over time in adolescent mental health within the FOCUS-AD and CBT only groups and comparing the magnitude of these changes between groups. Nonparametric statistical tests were used. We found the FOCUS-AD intervention to be feasible and acceptable; participant retention was high. Adolescent symptoms of depression (measured by the PHQ-8) improved significantly from baseline to follow-up for youth in both FOCUS-AD (median decrease [MD] = 10, p = 0.02) and control (MD = 6, p = 0.01) groups, with no significant difference across the two groups. Results were similar for symptoms of PTSD (measured by the Child PTSD Symptom Scale; FOCUS-AD MD = 12.5, p = 0.01; CBT only MD = 7, p = 0.04; no significant difference between groups). Conclusion: Family-centered approaches to depression treatment among adolescents living in under-resourced communities may lead to improved mental health, although further research is warranted.

Assessing Detection of Children With Suicide-Related Emergencies: Evaluation and Development of Computable Phenotyping Approaches.

BACKGROUND: Although suicide is a leading cause of death among children, the optimal approach for using health care data sets to detect suicide-related emergencies among children is not known. OBJECTIVE: This study aimed to assess the performance of suicide-related International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and suicide-related chief complaint in detecting self-injurious thoughts and behaviors (SITB) among children compared with clinician chart review. The study also aimed to examine variations in performance by child sociodemographics and type of self-injury, as well as develop machine learning models trained on codified health record data (features) and clinician chart review (gold standard) and test model detection performance. METHODS: A gold standard classification of suicide-related emergencies was determined through clinician manual review of clinical notes from 600 emergency department visits between 2015 and 2019 by children aged 10 to 17 years. Visits classified with nonfatal suicide attempt or intentional self-harm using the Centers for Disease Control and Prevention surveillance case definition list of ICD-10-CM codes and suicide-related chief complaint were compared with the gold standard classification. Machine learning classifiers (least absolute shrinkage and selection operator-penalized logistic regression and random forest) were then trained and tested using codified health record data (eg, child sociodemographics, medications, disposition, and laboratory testing) and the gold standard classification. The accuracy, sensitivity, and specificity of each detection approach and relative importance of features were examined. RESULTS: SITB accounted for 47.3% (284/600) of the visits. Suicide-related diagnostic codes missed nearly one-third (82/284, 28.9%) and suicide-related chief complaints missed more than half (153/284, 53.9%) of the children presenting to emergency departments with SITB. Sensitivity was significantly lower for male children than for female children (0.69, 95% CI 0.61-0.77 vs 0.84, 95% CI 0.78-0.90, respectively) and for preteens compared with adolescents (0.66, 95% CI 0.54-0.78 vs 0.86, 95% CI 0.80-0.92, respectively). Specificity was significantly lower for detecting preparatory acts (0.68, 95% CI 0.64-0.72) and attempts (0.67, 95% CI 0.63-0.71) than for detecting ideation (0.79, 95% CI 0.75-0.82). Machine learning-based models significantly improved the sensitivity of detection compared with suicide-related codes and chief complaint alone. Models considering all 84 features performed similarly to models considering only mental health-related ICD-10-CM codes and chief complaints (34 features) and models considering non-ICD-10-CM code indicators and mental health-related chief complaints (53 features). CONCLUSIONS: The capacity to detect children with SITB may be strengthened by applying a machine learning-based approach to codified health record data. To improve integration between clinical research informatics and child mental health care, future research is needed to evaluate the potential benefits of implementing detection approaches at the point of care and identifying precise targets for suicide prevention interventions in children.

Structural Factors in Health Care Associated With the Mental Health Needs of Black Women in California During the Perinatal Period.

OBJECTIVE: To identify structural factors associated with the receipt of mental health care treatment among Black women in California during pregnancy and after childbirth. DESIGN: Secondary analysis of data from the population-based Listening to Mothers in California survey. PARTICIPANTS: The sample included 194 non-Latina Black women in the postpartum period. METHODS: We used descriptive statistics, including differences between means and logistic regression, to conduct a series of bivariate analyses. RESULTS: Most respondents (84.4%, n = 163) reported symptoms of perinatal mood and anxiety disorders prenatally, and half (50% n = 97) reported symptoms of perinatal mood and anxiety disorders in the postpartum period. Only 12.3% to 14.6% of those who reported symptoms received mental health care treatment. Furthermore, 21.2% (n = 38) of respondents were not screened for postpartum depression. Respondents with private insurance coverage were more likely to report receipt of mental health care after childbirth (OR = 4.6; 95% confidence interval [1.5, 13.5]) compared to respondents with public insurance coverage. CONCLUSION: Our results suggest a high prevalence of unmet mental health needs among non-Latina Black women who lived in California during the perinatal period. Practitioners in clinical settings may be more likely to make referrals to mental health care for women with private insurance coverage in the postpartum period.