Reported Impact of COVID-19 Workload and Stressors on School Nurses' Provision of Care During the 2021-2022 School Year: A Secondary Analysis of U.S. School Nurse Survey Data.

Many school nurses experienced increased work burden and stress during the COVID-19 pandemic. This analysis examined data from a Centers for Disease Control and Prevention cross-sectional, nationwide survey of school nurses in March 2022 to examine associations between school nurses' ability to conduct their core responsibilities and selected nurse and school factors among school nurses during the 2021-2022 school year and COVID-19 pandemic. Perceived adequate staffing and financial compensation reduced the odds of reported difficulties across all core school nursing tasks. Nurses without a registered nurse license and with higher caseloads were more likely to report difficulty in implementing specific tasks. The impact of these factors varied, with inadequate financial compensation having the largest association with school nurses' difficulty implementing all the core responsibilities. The study results improve our understanding of school nurses' challenges in implementing core school nursing responsibilities during the COVID-19 pandemic in the 2021-2022 school year.

Severe CNS involvement in a subset of long-term treated children with infantile-onset Pompe disease.

INTRODUCTION: The standard of care for patients with infantile-onset Pompe disease (IOPD) is enzyme replacement therapy (ERT), which does not cross the blood brain barrier. While neuromuscular manifestations of IOPD are well-described, central nervous system (CNS) manifestations of this disorder are far less characterized. Here we describe severe CNS-related neurological manifestations including seizures and encephalopathy in six individuals with IOPD. METHOD: We identified six children with IOPD who developed CNS manifestations such as seizures and/or encephalopathy. We studied their brain magnetic resonance imaging scans (MRIs) and graded the severity of white matter hyperintensities (WMHI) using the Fazekas scale scoring system as previously published. Longitudinal cognitive measures were available from 4/6 children. RESULTS: All six IOPD patients (4 males/2 females) had been treated with ERT for 12-15 years. Seizures and/or encephalopathy were noted at a median age at onset of 11.9 years (range 9-15 years). All were noted to have extensive WMHI in the brain MRIs and very high Fazekas scores which preceded the onset of neurological symptoms. Longitudinal IQ scores from four of these children suggested developmental plateauing. DISCUSSION: Among a subset of IOPD patients on long-term ERT, CNS manifestations including hyperreflexia, encephalopathy and seizures may become prominent, and there is likely an association between these symptoms and significant WMHI on MRI. Further study is needed to identify risk factors for CNS deterioration among children with IOPD and develop interventions to prevent neurological decline.

Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti-seizure medication.

Treatment-resistant epilepsy is among the most serious complications of cardiofaciocutaneous syndrome (CFCS), a rare disorder caused by germline variants in the RAS-MAPK signaling pathway. This study analyzed the clinical characteristics of epilepsy and response to anti-seizure medications (ASMs) in a multinational CFCS cohort. A caregiver survey provided data regarding seizure history, use of ASMs and other treatment approaches, adverse effects, caregiver perception of treatment response, and neurological disease burden impact among individuals with CFCS. Results from 138 survey responses were quantitatively analyzed in conjunction with molecular genetic results and neurological records. The disease burden impact of CFCS was higher among individuals with epilepsy (n = 74/138), especially those with more severe seizure presentation. Oxcarbazepine, a sodium-channel blocker, had the best seizure control profile with relatively infrequent adverse effects. The most commonly prescribed ASM, levetiracetam, demonstrated comparatively poor seizure control. ASM efficacy was generally similar for individuals with BRAF and MAP2K1 gene variants. The high proportion of patients with CFCS who experienced poor seizure control despite use of multiple ASMs highlights a substantial unmet treatment need. Prospective study of ASM efficacy and clinical trials of therapies to attenuate RAS-MAPK signaling may improve avenues for clinical management.

Where Patients Live Matter in Emergency Department Visits in Home Health Care: Rural/Urban Status and Neighborhood Socioeconomic Status.

An increasing body of evidence highlights the importance of an individual's place of residence on their health and functional outcomes. This study is based on Outcome and Assessment Information Set data to assess the differences in emergency department visits among Medicare home health care patients by patients' residence location (rural/urban status and neighborhood socioeconomic status). Compared to urban patients, a disproportionately higher proportion of rural patients lived in more or most disadvantaged neighborhoods (83.9% vs. 41.3%). Using linear probability regression models, patients in rural areas (coefficient = .02, p < .001) and disadvantaged neighborhoods (less disadvantaged: coefficient = .02, p < .001; more disadvantaged: coefficient = .034, p < .001; most disadvantaged: coefficient = .042, p < .001) were more likely to experience emergency department visits. Policymakers should consider utilizing area-based target interventions to mitigate gaps in home health care. Also, given that the majority of rural patients reside in disadvantaged neighborhoods, neighborhood characteristics should be considered in addressing rural-urban disparities and improving home health care.

The Trends in Health Care Utilization and Costs Associated With Primary Liver Cancer: An Analysis of United States Hospitals Between 2016 and 2019.

BACKGROUND: Primary liver cancer (PLC) has placed an increasing economic and resource burden on the health care system of the United States. We attempted to quantify its epidemiology and associated costs using a national inpatient database. METHODS: Hospital discharge and insurance claims data from the National Inpatient Sample were used to conduct this analysis. Patients diagnosed with PLC (hepatocellular carcinoma or cholangiocarcinoma) were included in the study population, which was then stratified using patient demographics, comorbidities, degree of cancer spread, liver disease complications, and other descriptors. Trends were analyzed via regression curves for each of these strata from the years 2016 to 2019, with special attention to patterns in hospitalization incidence, inpatient mortality rate, total costs, and average per-capita costs. The resulting curves were evaluated using goodness-of-fit statistics and P-values. RESULTS: Aggregate hospitalization incidence, inpatient mortality rates, and total costs were found to significantly increase throughout the study period (P=0.002, 0.002, and 0.02, respectively). Relative to their demographic counterparts, males, White Americans, and those older than 65 years of age contributed the largest proportions of total costs. These population segments also experienced significant increases in total expenditure (P=0.04, 0.03, and 0.02, respectively). Admissions deemed to have multiple comorbidities were associated with progressively higher total costs throughout the study period (P=0.01). Of the categorized underlying liver diseases, only admissions diagnosed with alcoholic liver disease or nonalcoholic fatty liver disease saw significantly increasing total costs (P=0.006 and 0.01), although hepatitis C was found to be the largest contributor to total expenses. CONCLUSIONS: From 2016 to 2019, total costs, admission incidence, and inpatient mortality rates associated with PLC hospitalization increased. Strata-specific findings may be reflective of demographic shifts in the PLC patient populations, as well as changes in underlying chronic liver disease etiologies.

Disparities in Successful Discharge to the Community Following Use of Medicare Home Health by Level of Neighborhood Socioeconomic Disadvantage.

Considering the importance of social and structural support and resources in recovering health, where people reside could lead to differences in health outcome in Medicare home health care. We used the 2019 Outcome and Assessment Information Set and Area Deprivation Index to examine the association between neighborhood context and successful discharge to community among older Medicare home health care users. Based on the multivariable logistic regression (OR: 0.84; 95% CI, 0.83-0.85) and conditional logistic regression models stratified by home health agency (OR: 0.95; 95% CI, 0.94-0.95), patients living in the most disadvantaged neighborhoods were less likely to experience successful discharge to community than others. Furthermore, the predicted probability of successful discharge to community decreased as the percentage of patients from the most disadvantaged neighborhoods within a home health agency increased. Policymakers should consider using area-level interventions and supports to reduce disparities in Medicare home health care.

The moderating role of neighborhood disadvantage on the link between functional limitations and self-rated health.

BACKGROUND: Self-rated health is an important health outcome and determinant of health. Improvements to our understanding on self-rated health could help design plans and strategies to improve self-rated health and achieve other preferred health outcomes. This study examined whether the link between functional limitations and self-rated health varies by neighborhood socioeconomic status. METHODS: This study used the Midlife in the United States study linked with the Social Deprivation Index developed by the Robert Graham Center. Our sample consist of noninstitutionalized middle to older adults in the United States (n = 6,085). Based on stepwise multiple regression models, we computed adjusted odds ratios to examine the relationships between neighborhood socioeconomic status, functional limitations, and self-rated health. RESULTS: Respondents in the socioeconomically disadvantaged neighborhoods were older, had higher percentage of females, non-White respondents, lower educational attainment, lower perceived neighborhood quality, and worse health status with greater number of functional limitations than those in socioeconomically advantaged neighborhoods. Results showed a significant interaction was found where neighborhood-level discrepancies in self-rated health was biggest among individuals with highest number of functional limitations (B = -0.28, 95% CI[0.53, -0.04], p = 0.025). Specifically, individuals with the highest number of functional limitations from the disadvantaged neighborhoods had higher self-rated health compared to those from advantaged neighborhoods. CONCLUSIONS: Our study findings highlight that neighborhood discrepancy in self-rated health is underestimated particularly among those with severe functional limitations. Moreover, when interpreting self-rated health status, values should not be taken face value, and should be considered together with the environmental conditions of where one resides.

The prognostic relationship between donor age and infectious risk in liver transplant patients with nonalcoholic steatohepatitis: Analysis of UNOS database.

BACKGROUND & AIMS: We investigate the effects of advancing donor age on the prognostic outcomes of patients with NASH who undergo liver transplant (LT), with a specialized attention toward infectious outcomes post-LT. METHODS: The UNOS-STAR registry was used to select 2005 to 2019 LT recipients with NASH, who were stratified by donor age into the following categories: recipients with younger donors (less than 50 years of age-reference), quinquagenarian donors, sexagenarian donors, septuagenarian donors, and octogenarian donors. Cox regression analyses were conducted for all-cause mortality, graft failure, infectious causes of death. RESULTS: From a total of 8888 recipients, the quinquagenarian, septuagenarian, and octogenarian donor cohorts showed greater risk of all-cause mortality (quinquagenarian: aHR 1.16 95%CI 1.03-1.30; septuagenarian: aHR 1.20 95%CI 1.00-1.44; octogenarian: aHR 2.01 95%CI 1.40-2.88). With advancing donor age, there was an increased risk of death from sepsis (quinquagenarian: aHR 1.71 95% CI 1.24-2.36; sexagenarian: aHR 1.73 95% CI 1.21-2.48; septuagenarian: aHR 1.76 95% CI 1.07-2.90; octogenarian: aHR 3.58 95% CI 1.42-9.06) and infectious causes (quinquagenarian: aHR 1.46 95% CI 1.12-1.90; sexagenarian: aHR 1.58 95% CI 1.18-2.11; septuagenarian: aHR 1.73 95% CI 1.15-2.61; octogenarian: aHR 3.70 95% CI 1.78-7.69). CONCLUSION: NASH patients who receive grafts from elderly donors exhibit higher risk of post-LT mortality, especially due to infection.

The trends in cost associated with liver transplantation in the US: Analysis of weighted hospital data.

This study aims to evaluate recent annualized trends in the cost-burden of inpatient hospitalizations associated with liver transplantation (LT) in the US as stratified by patient demographics and medical characteristics. From 2016 to 2019 National Inpatient Sample was used to select patients who underwent LT, from which the weighted charge estimates were derived and converted to admission costs using inflation-adjusted charge-to-cost ratios. The adjusted values were stratified using select patient variables and graphed across the respective years to derive goodness-of-fit for each trend (expressed with R2 and p -values). From 2016 to 2019, the estimated total number of LT-related hospitalizations in the US were 6685, 7075, 7260, and 7815 cases respectively. There was a general increase in the total cost of LT-related hospitalizations over the years: $945.75, $1010.23, $1052.46, and $1143.84 in millions of dollars (0.98, 0.01). Furthermore, positive trends in total cost were observed in the following strata: patients aged 35-49 (0.92, 0.04) and above 65 (0.91, 0.05), Whites (0.99, 0.01), those with congestive heart failure (0.98, 0.01), ≥2 comorbidities (0.97, 0.02), hepatic encephalopathy (0.93, 0.04), and those with private insurance (0.93, 0.04), as well as LT performed in the Northeast (0.94, 0.03), Midwest (0.92, 0.04), and South (0.91, 0.04). Total cost associated with hepatitis C declined significantly (0.94, 0.03). With respect to mean costs, positive trends were observed in the following strata: those with other or cryptogenic liver disease (0.93, 0.03), ≥2 comorbidities (0.96, 0.02), and LT performed in the Northeast region (0.93, 0.04). The number of liver transplants performed in the US, as well as the associated costs, are rising. Given the apparent rising costs in specific patient populations, economic and public health policies must focus on cost containment within these groups to ensure appropriate usage of resources.

Clinical implications of gender and race in patients admitted with autoimmune hepatitis: updated analysis of US hospitals.

Background: Autoimmune hepatitis (AIH) can result in end-stage liver disease that requires inpatient treatment of the hepatic complications. Given this phenomenon, it is important to analyse the impact of gender and race on the outcomes of patients who are admitted with AIH using a national hospital registry. Methods: The 2012-2017 National Inpatient Sample database was used to select patients with AIH, who were stratified using gender and race (Hispanics and blacks as cases and whites as reference). Propensity score matching was employed to match the controls with cases and compare mortality, length of stay and hepatic complications. Results: After matching, there were 4609 females and 4609 males, as well as 3688 blacks and 3173 Hispanics with equal numbers of whites, respectively. In multivariate analysis, females were less likely to develop complications, with lower rates of cirrhosis, ascites, variceal bleeding, hepatorenal syndrome, encephalopathy and acute liver failure (ALF); they also exhibited lower length of stay (adjusted OR, aOR 0.96 95% CI 0.94 to 0.97). When comparing races, blacks (compared with whites) had higher rates of ALF and hepatorenal syndrome related to ALF, but had lower rates of cirrhosis-related encephalopathy; in multivariate analysis, blacks had longer length of stay (aOR 1.071, 95% CI 1.050 to 1.092). Hispanics also exhibited higher rates of hepatic complications, including ascites, varices, variceal bleeding, spontaneous bacterial peritonitis and encephalopathy. Conclusion: Males and minorities are at a greater risk of developing hepatic complications and having increased hospital costs when admitted with AIH.

The nationwide trends in hospital admissions, deaths, and costs related to hepatitis C stratified by psychiatric disorders and substance use: an analysis of US hospitals between 2016 and 2019.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) is a prominent liver disease that often presents with mental illness. We stratify the HCV population and review its healthcare burden on the US hospital system. METHODS: The US National Inpatient Sample was used to select admissions related to HCV between 2016 and 2019. Weights were assigned to discharges, and trend analyses were performed. Strata were formed across demographics, comorbidities, psychiatric and substance use conditions, and other variables. Outcomes of interest included hospitalization incidences, mortality rates, total costs, and mean per-hospitalization costs. RESULTS: From 2016 to 2019, there were improvements in mortality and hospitalization incidence for HCV, as well as a decline in aggregate costs across the majority of strata. Exceptions that showed cost growth included admissions with multiple psychiatric, stimulant use, or poly-substance use disorders, and a history of homelessness. Admissions with no psychiatric comorbidities, admissions with no substance use comorbidities, and admissions with housing and without HIV comorbidity showed decreasing total costs. Along with per-capita mean costs, admissions with comorbid opioid use, bipolar, or anxiety disorder showed significant increases. No significant trends in per-capita costs were found in admissions without mental illness diagnoses. CONCLUSIONS: Most strata demonstrated decreases in hospitalization incidences and total costs surrounding HCV; however, HCV cases with mental illness diagnoses saw expenditure growth. Cost-saving mechanisms for these subgroups are warranted.

The differences in post-liver transplant outcomes of patients with autoimmune hepatitis who present with overlapping autoimmune liver diseases.

BACKGROUND: Patients with autoimmune hepatitis (AIH) may co-present with features of primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Using a national transplant registry, the outcomes of patients with these autoimmune liver conditions were compared. METHODS: The UNOS-STAR registry was used to select a study population of AIH, PSC, and PBC liver transplant (LT) patients. Living and multi-organ transplant cases were excluded. Using the UNOS-registered diagnoses, the study population was subdivided into those with nonoverlapping autoimmune liver diseases and those with overlapping forms (e.g., AIH-PBC). Outcomes were compared, using endpoints such as all-cause mortality, graft failure, and organ-system specific causes of death. RESULTS: The main analysis featured 2048 entries, with 1927 entries having nonoverlapping AIH, 52 entries having PSC overlap, and 69 entries having PBC overlap. Patients with PBC overlap were more likely to have graft failure (adjusted hazard ratio [aHR] 3.46 95% CI 1.70-7.05), mortality secondary to respiratory causes (aHR 3.57 95% CI 1.23-10.43), and mortality secondary to recurrent disease (aHR 9.53 95% CI 1.85-49.09). Case incidence rates reflected these findings, expressed in events per 1000 person-years. For patients with PBC overlap and nonoverlapping AIH cases, respectively. Graft failure: 28.87 events vs. 9.42 events, mortality secondary to respiratory causes: 12.83 deaths vs. 3.77 deaths, mortality secondary to recurrent disease: 6.42 deaths vs. 1.26 deaths. Those with AIH-PSC overlap experienced a higher risk of death from graft infection (aHR 10.43 95% CI 1.08-100.37; case-incidence rate: 3.89 vs. 0.31 mortalities per 1000 person-years). Supplementary analysis showed similar findings, in which overlapping autoimmune conditions were associated with higher adverse outcome rates. CONCLUSION: Patients with AIH-PBC overlap have higher risk of mortality due to recurrent liver disease and respiratory causes, and patients with AIH-PSC overlap have higher risk of mortality due to graft infection. While further prospective studies are needed to clarify the underlying mechanisms related to these findings, our study characterizes the prognostic implications of AIH overlap on post-LT mortality and graft failure risks.

Predicting Hospitalization among Medicaid Home- and Community-Based Services Users Using Machine Learning Methods.

We compare multiple machine learning algorithms and develop models to predict future hospitalization among Home- and Community-Based Services (HCBS) Users. Furthermore, we calculate feature importance, the score of input variables based on their importance to predict the outcome, to identify the most relevant variables to predict hospitalization. We use the 2012 national Medicaid Analytic eXtract data and Medicare Provider Analysis and Review data. Predicting any hospitalization, Random Forest appears to be the most robust approach, though XGBoost achieved similar predictive performance. While the importance of features varies by algorithm, chronic conditions, previous hospitalizations, as well as use of services for ambulance, personal care, and durable medical equipment were generally found to be important predictors of hospitalization. Utilizing prediction models to identify those who are prone to hospitalization could be useful in developing early interventions to improve outcomes among HCBS users.

Infantile epileptic spasms syndrome in children with cardiofaciocutanous syndrome: Clinical presentation and associations with genotype.

Gene variants that dysregulate signaling through the RAS-MAPK pathway cause cardiofaciocutaneous syndrome (CFCS), a rare multi-system disorder. Infantile epileptic spasms syndrome (IESS) and other forms of epilepsy are among the most serious complications. To investigate clinical presentation, treatment outcomes, and genotype-phenotype associations in CFCS patients with IESS, molecular genetics and clinical neurological history were reviewed across two large clinical research cohorts (n = 180). IESS presented in 18/180 (10%) cases, including 16 patients with BRAF variants and 2 with MAP2K1 variants. Among IESS patients with BRAF variants, 16/16 (100%) had sequence changes affecting the protein kinase domain (exons 11-16), although only 57% of total BRAF variants occurred in this domain. Clinical onset of spasms occurred at a median age of 5.4 months (range: 1-24 months). Among 13/18 patients whose IESS resolved with anti-seizure medications, 10 were treated with ACTH and/or vigabatrin. A substantial majority of CFCS patients with IESS subsequently developed other epilepsy types (16/18; 89%). In terms of neurodevelopmental outcomes, gross motor function and verbal communication were more limited in patients with a history of IESS compared to those without IESS. These findings can inform clinical neurological care guidelines for CFCS and development of relevant pre-clinical models for severe epilepsy phenotypes.

The clinical implications of pre-liver transplant diabetes on post-liver transplant outcomes in patients with NASH: analysis of the UNOS database.

BACKGROUND AND AIMS: The presence of perioperative diabetes may lead to increased mortality risks following liver transplant (LT) in patients with non-alcoholic steatohepatitis (NASH). This risk factor was evaluated using a UNOS-STAR national database. METHODS: The UNOS-STAR liver transplant registry 2005-2019 was used to select patients with NASH (including cryptogenic liver disease). The following populations were excluded: those younger than 18 years old and those with living donors/dual transplants. Selected patients were stratified into those with and without pre-LT diabetes and compared to the individual mortality endpoints using iterative Cox analyses. RESULTS: 6324 recipients with and 8251 without diabetes were selected. The median follow-up time was 3.07 years. Those with diabetes were older (58.50 vs. 54.50 years, p < 0.001), were more likely to be Hispanic or Asian, and had higher BMI than the non-diabetics (31.10 vs. 29.70 kg/m2 p < 0.001); however, there was no difference in gender (female 41.9 vs. 43.1% p = 0.170). Compared to non-diabetics, recipients with diabetes had a higher rate of all-cause mortality (61.68 vs. 47.80 per 1000 person-years). In multivariate iterations, pre-LT diabetes was associated with all-cause mortality (aHR 1.19 95% CI 1.11-1.27) as well as deaths due to cardiac (p = 0.014 aHR 1.24 95% CI 1.04-1.46) and renal causes (p = 0.039 aHR 1.38 95% CI 1.02-1.87). CONCLUSION: The presence of pre-LT diabetes is associated with all-cause mortality and deaths due to cardiac and renal causes following LT. The findings warrant an early preoperative screening procedure to ensure that patients with diabetes have their metabolic risk factors optimized prior to LT.

The Clinical Impact of Advanced Age on the Postoperative Outcomes of Patients Undergoing Gastrectomy for Gastric Cancer: Analysis Across US Hospitals Between 2011-2017.

PURPOSE: This study systematically evaluated the implications of advanced age on post-surgical outcomes following gastrectomy for gastric cancer using a national database. MATERIALS AND METHODS: The 2011-2017 National Inpatient Sample was used to isolate patients who underwent gastrectomy for gastric cancer. From this, the population was stratified into those belonging to the younger age cohort (18-59 years), sexagenarians, septuagenarians, and octogenarians. The younger cohort and each advanced age category were compared in terms of the following endpoints: mortality following surgery, length of hospital stay, charges, and surgical complications. RESULTS: This study included a total of 5,213 patients: 1,366 sexagenarians, 1,490 septuagenarians, 743 octogenarians, and 1,614 under 60 years of age. Between the younger cohort and sexagenarians, there was no difference in mortality (2.27 vs. 1.67%; P=0.30; odds ratio [OR], 1.36; 95% confidence interval [CI], 0.81-2.30), length of stay (11.0 vs. 11.1 days; P=0.86), or charges ($123,557 vs. $124,425; P=0.79). Compared to the younger cohort, septuagenarians had higher rates of in-hospital mortality (4.30% vs. 1.67%; P<0.01; OR, 2.64; 95% CI, 1.67-4.16), length of stay (12.1 vs. 11.1 days; P<0.01), and charges ($139,200 vs. $124,425; P<0.01). In the multivariate analysis, septuagenarians had higher mortality (P=0.01; adjusted odds ratio [aOR], 2.01; 95% CI, 1.18-3.43). Similarly, compared to the younger cohort, octogenarians had a higher rate of mortality (7.67% vs. 1.67%; P<0.001; OR, 4.88; 95% CI, 3.06-7.79), length of stay (12.3 vs. 11.1 days; P<0.01), and charges ($131,330 vs. $124,425; P<0.01). In the multivariate analysis, octogenarians had higher mortality (P<0.001; aOR, 4.03; 95% CI, 2.28-7.11). CONCLUSIONS: Advanced age (>70 years) is an independent risk factor for postoperative death in patients with gastric cancer undergoing gastrectomy.

Frequent Low-Dose Δ9-Tetrahydrocannabinol in Adolescence Disrupts Microglia Homeostasis and Disables Responses to Microbial Infection and Social Stress in Young Adulthood.

BACKGROUND: During adolescence, microglia are actively involved in neocortical maturation while concomitantly undergoing profound phenotypic changes. Because the teenage years are also a time of experimentation with cannabis, we evaluated whether adolescent exposure to the drug's psychotropic constituent, Δ9-tetrahydrocannabinol (THC), might persistently alter microglia function. METHODS: We administered THC (5 mg/kg, intraperitoneal) once daily to male and female mice from postnatal day (PND) 30 to PND44 and examined the transcriptome of purified microglia in adult animals (PND70 and PND120) under baseline conditions or following either of two interventions known to recruit microglia: lipopolysaccharide injection and repeated social defeat. We used high-dimensional mass cytometry by time-of-flight to map brain immune cell populations after lipopolysaccharide challenge. RESULTS: Adolescent THC exposure produced in mice of both sexes a state of microglial dyshomeostasis that persisted until young adulthood (PND70) but receded with further aging (PND120). Key features of this state included broad alterations in genes involved in microglia homeostasis and innate immunity along with marked impairments in the responses to lipopolysaccharide- and repeated social defeat-induced psychosocial stress. The endocannabinoid system was also dysfunctional. The effects of THC were prevented by coadministration of either a global CB1 receptor inverse agonist or a peripheral CB1 neutral antagonist and were not replicated when THC was administered in young adulthood (PND70-84). CONCLUSIONS: Daily low-intensity CB1 receptor activation by THC during adolescence may disable critical functions served by microglia until young adulthood with potentially wide-ranging consequences for brain and mental health.

Neurologic and neurodevelopmental complications in cardiofaciocutaneous syndrome are associated with genotype: A multinational cohort study.

PURPOSE: Dysregulation of RAS or its major effector pathway is the molecular mechanism of RASopathies, a group of multisystemic congenital disorders. Neurologic complications are especially challenging in the management of the rare RASopathy cardiofaciocutaneous (CFC) syndrome. This study evaluated clinical neurologic and neurodevelopmental features and their associations with CFC syndrome gene variants. METHODS: A multinational cohort of 138 individuals with CFC syndrome (BRAF = 90, MAP2K1 = 36, MAP2K2 = 10, KRAS = 2) was recruited. Neurologic presentation was captured via clinician review of medical records and caregiver-completed electronic surveys. Validated measures of seizure severity, adaptive function, and gross motor function were obtained. RESULTS: The overall frequency of intellectual disability and seizures was 82% and 55%, respectively. The frequency and severity of seizures was higher among individuals with BRAF or MAP2K1 variants than in those with MAP2K2 variants. A disproportionate incidence of severe, treatment-resistant seizures was observed in patients with variants in the catalytic protein kinase domain of BRAF and at the common p.Y130 site of MAP2K1. Neurodevelopmental outcomes were associated with genotype as well as seizure severity. CONCLUSION: Molecular genetic testing can aid in prediction of epilepsy and neurodevelopmental phenotypes in CFC syndrome. Study results identified potential CFC syndrome-associated variants in the development of relevant animal models for neurologic, neurocognitive, and motor function impairment.

Factors associated with federally qualified health center financial performance.

OBJECTIVES: To understand factors associated with federally qualified health center (FQHC) financial performance. STUDY DESIGN: We used multivariate linear regression to identify correlates of health center financial performance. We examined six measures of health center financial performance across four domains: margin (operating margin), liquidity (days cash on hand [DCOH], current ratio), solvency (debt-to-equity ratio), and others (net patient accounts receivable days, personnel-related expenses). We examined potential correlates of financial performance, including characteristics of the patient population, health center organization, and location/geography. DATA SOURCES: We use 2012-2017 Uniform Data System (UDS) files, financial audit data from Capital link, and publicly available data. DATA COLLECTION/EXTRACTION METHODS: We focused on health centers in the 50 US states and District of Columbia, which reported information to UDS for at least 1 year between 2012 and 2017 and had Capital link financial audit data. PRINCIPAL FINDINGS: FQHC financial performance generally improved over the study period, especially from 2015 to 2017. In multivariate regression models, a higher percentage of Medicaid patients was associated with better margins (operating margin: 0.06, p < 0.001), liquidity (DCOH: 0.67, p < 0.001; current ratio: 0.28, p = 0.001), and solvency (debt-to equity ratio: -0.08, p = 0.004). Moreover, a staffing mix comprised of more nonphysician providers was associated with better margin (operating margin: 0.21, p = 0.001) and liquidity (current ratio: 1.12, p < 0.001) measures. Patient-centered medical home (PCMH) recognition was also associated with better liquidity (DCOH: 19.01, p < 0.001; current ratio: 4.68, p = 0.014) and solvency (debt-to-equity ratio: -2.03, p < 0.001). CONCLUSIONS: The financial health of FQHCs improved with provisions of the Affordable Care Act, which included significant Medicaid expansion and direct funding support for health centers. FQHC financial health was also associated with key staffing and operating characteristics of health centers. Maintaining the financial health of FQHCs is critical to their ability to continuously provide affordable and high-quality care in medically underserved areas.