Emergency Department Visits Among Children Aged 0-17 by Selected Characteristics: United States, 2019-2020.

With the disruptions to access and use of care caused by the COVID-19 pandemic, emergency department (ED) visit rates decreased from 2019 to 2020 among children and adolescents (1). The ED visit rate for children under age 1 year in 2020 was nearly one-half of the rate in 2019, and the rate for those aged 1-17 years decreased over the same period (2). This report uses data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) (3,4) to compare ED visits for children aged 0-17 from 2019 to 2020, by age group, sex, and race and ethnicity, and to assess changes in wait time at ED visits.

Emergency Department Visits Related to Mental Health Disorders Among Adults, by Race and Hispanic Ethnicity: United States, 2018-2020.

Objective-This report describes emergency department (ED) visits related to mental health disorders among adults and assesses differences in mental health-related ED visit characteristics by race and Hispanic ethnicity.

Experiences Related to the COVID-19 Pandemic Among U.S. Physicians in Office-based Settings, 2020-2021.

Objective-To assess final estimates of physician experiences related to COVID-19 and to compare preliminary estimates used in NCHS early-release dashboards with final estimates in this report.

Immune dysregulation caused by homozygous mutations in CBLB.

CBL-B is an E3 ubiquitin ligase that ubiquitinates proteins downstream of immune receptors to downregulate positive signaling cascades. Distinct homozygous mutations in CBLB were identified in 3 unrelated children with early-onset autoimmunity, one of whom also had chronic urticaria. Patient T cells exhibited hyperproliferation in response to anti-CD3 cross-linking. One of the mutations, p.R496X, abolished CBL-B expression, and a second mutation, p.C464W, resulted in preserved CBL-B expression. The third mutation, p.H285L in the SH2 domain of CBL-B, was expressed at half the normal level in the patient's cells. Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient's p.H285L mutation, had T and B cell hyperproliferation in response to antigen receptor cross-linking. CblbH257L mice had increased percentages of T regulatory cells (Tregs) that had normal in vitro suppressive function. However, T effector cells from the patient with the p.H285L mutation and CblbH257L mice were resistant to suppression by WT Tregs. Bone marrow-derived mast cells from CblbH257L mice were hyperactivated after FcεRI cross-linking, and CblbH257L mice demonstrated exaggerated IgE-mediated passive anaphylaxis. This study establishes CBL-B deficiency as a cause of immune dysregulation.

National Hospital Care Survey Demonstration Projects: Examination of Inpatient Hospitalization and Risk of Mortality Among Patients Diagnosed With Pneumonia.

Objective-This report demonstrates the ability of data from the National Hospital Care Survey (NHCS) linked to the National Death Index (NDI) to provide information on inpatient hospitalizations and in-hospital and post-acute mortality among patients hospitalized for a specific condition, in this case pneumonia.

Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα).

Inhibitor of nuclear factor kappa B kinase alpha (IKKα) is critical for p100/NF-κB2 phosphorylation and processing into p52 and activation of the noncanonical NF-κB pathway. A patient with recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine and liver was found to have a homozygous p.Y580C mutation in the helix-loop-helix domain of IKKα. The mutation preserves IKKα kinase activity but abolishes the interaction of IKKα with its activator NF-κB­inducing kinase and impairs lymphotoxin-ß­driven p100/NF-κB2 processing and VCAM1 expression. Homozygous IKKαY580C/Y580C mutant mice phenocopy the patient findings; lack marginal zone B cells, germinal centers, and antigen-specific T cell response to cutaneous immunization; have impaired Il17a expression; and are susceptible to cutaneous Staphylococcus aureus infection. In addition, these mice demonstrate a severe reduction in medullary thymic epithelial cells, impaired thymocyte negative selection, a restricted TCRVß repertoire, a selective expansion of potentially autoreactive T cell clones, a decreased frequency of regulatory T cells, and infiltration of liver, pancreas, and lung by activated T cells coinciding with organ damage. Hence, this study identifies IKKα deficiency as a previously undescribed cause of primary immunodeficiency with associated autoimmunity.

Mechanisms underlying genetic susceptibility to multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a pediatric complication of severe acute respiratory syndrome coronavirus 2 infection that is characterized by multiorgan inflammation and frequently by cardiovascular dysfunction. It occurs predominantly in otherwise healthy children. We previously reported haploinsufficiency of suppressor of cytokine signaling 1 (SOCS1), a negative regulator of type I and II interferons, as a genetic risk factor for MIS-C. OBJECTIVES: We aimed to identify additional genetic mechanisms underlying susceptibility to severe acute respiratory syndrome coronavirus 2-associated MIS-C. METHODS: In a single-center, prospective cohort study, whole exome sequencing was performed on patients with MIS-C. The impact of candidate variants was tested by using patients' PBMCs obtained at least 7 months after recovery. RESULTS: We enrolled 18 patients with MIS-C (median age = 8 years; interquartile range = 5-12.25 years), of whom 89% had no conditions other than obesity. In 2 boys with no significant infection history, we identified and validated hemizygous deleterious defects in XIAP, encoding X-linked inhibitor of apoptosis, and CYBB, encoding cytochrome b-245, beta subunit. Including the previously reported SOCS1 haploinsufficiency, a genetic diagnosis was identified in 3 of 18 patients (17%). In contrast to patients with mild COVID-19, patients with defects in SOCS1, XIAP, or CYBB exhibit an inflammatory immune cell transcriptome with enrichment of differentially expressed genes in pathways downstream of IL-18, oncostatin M, and nuclear factor κB, even after recovery. CONCLUSIONS: Although inflammatory disorders are rare in the general population, our cohort of patients with MIS-C was enriched for monogenic susceptibility to inflammation. Our results support the use of next-generation sequencing in previously healthy children who develop MIS-C.

Data-driven approaches to care delivery: Actionable informatics in the DoD's primary care behavioral health program.

INTRODUCTION: Transforming administrative health care data into meaningful metrics has been critical to the implementation of the Department of Defense's Primary Care Behavioral Health (PCBH) program. METHODS: Data from clinical encounters with PCBH providers are used to develop metrics of program performance collaboratively. Metrics focus on describing the PCBH program and patients, provider fidelity to the model, and provider performance. These metrics form two key deliverables: a monitoring dashboard for program managers and a training dashboard for expert trainers conducting site visits. RESULTS: Behavioral health consultants (BHCs) conducted nearly 200,000 encounters with more than 100,000 unique patients in fiscal year 2019 at more than 170 locations in 6 countries and 37 states. Administrative data derived from these encounters were used to create a variety of metrics that describe practice and performance at both the provider and program levels. These metrics are delivered through a variety of analytic products to stakeholders who use that information to make data-driven decisions about program direction and provider training. DISCUSSION: We discuss examples of program management decisions and expert trainer actions based on these dashboards, highlighting the benefits of continued collaboration between analysts and program managers. Specifically, excerpts from several dashboards illustrate how penetration and productivity metrics yield specific, tailored action plans to improve care delivery and provider performance. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Regulatory involvement of the PerR and SloR metalloregulators in the Streptococcus mutans oxidative stress response.

Streptococcus mutans is a commensal of the human oral microbiome that can promote dental caries under conditions of dysbiosis. This study investigates metalloregulators and their involvement in the S. mutans oxidative stress response. Oxidative stress in the human mouth can derive from temporal increases in reactive oxygen species (ROS) after meal consumption and from endogenous bacterial ROS-producers that colonize the dentition. We hypothesize that the S. mutans PerR (SMU.593) and SloR (SMU.186) metalloregulatory proteins contribute to the regulation of oxidative stress genes and their products. Expression assays with S. mutans UA159 wild type cultures exposed to H2O2 reveal that H2O2 upregulates perR, and that PerR represses sloR transcription upon binding directly to Fur and PerR consensus sequences within the sloR operator. In addition, the results of Western blot experiments implicate the Clp proteolytic system in SloR degradation under conditions of H2O2-stress. To reveal a potential role for SloR in the H2O2-resistant phenotype of S. mutans GMS802 (a perR-deficient strain), we generated a sloR/perR double knockout mutant, GMS1386, where we observed upregulation of the tpx and dpr antioxidant genes. These results are consistent with GMS802 H2O2 resistance and with a role for PerR as a transcriptional repressor. Cumulatively, these findings support a reciprocal relationship between PerR and SloR during the S. mutans oxidative stress response and begin to elucidate the fitness strategies that evolved to foster S. mutans persistence in the transient environments of the human oral cavity.IMPORTANCEIn 2020, untreated dental caries, especially in the permanent dentition, ranked among the most prevalent infectious diseases worldwide, disproportionately impacting individuals of low socioeconomic status. Untreated caries can lead to systemic health problems and has been associated with extended school and work absences, inappropriate use of emergency departments, and an inability for military forces to deploy. Together with public health policy, research aimed at alleviating S. mutans -induced tooth decay is important because it can improve oral health (and overall health), especially in underserved populations. This research, focused on S. mutans metalloregulatory proteins and their gene targets, is significant because it can promote virulence gene control in an important oral pathogen, and contribute to the development of an anti-caries therapeutic that can reduce tooth decay.

Combined immunodeficiency due to a mutation in the γ1 subunit of the coat protein I complex.

The coat protein I (COPI) complex mediates retrograde trafficking from the Golgi to the endoplasmic reticulum (ER). Five siblings with persistent bacterial and viral infections and defective humoral and cellular immunity had a homozygous p.K652E mutation in the γ1 subunit of COPI (γ1-COP). The mutation disrupts COPI binding to the KDEL receptor and impairs the retrieval of KDEL-bearing chaperones from the Golgi to the ER. Homozygous Copg1K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice. This study establishes the role of γ1-COP in the ER retrieval of KDEL-bearing chaperones and thereby the importance of ER homeostasis in adaptive immunity.

Rates of prescription orders for United States active duty service members diagnosed with alcohol use disorder.

Background: Alcohol-use disorders (AUD) pose a significant challenge for the United States (US) military. The US Department of Defense has strongly recommended several medications for use in the treatment of patients with diagnosed AUD. This study assessed the prescription of medications for active duty service members (ADSMs) diagnosed with AUD in the US Military Health System (MHS). Methods: Rates of prescription orders were retrospectively examined from 2010 to 2017 among ADSMs with an incident diagnosis of moderate-to-severe AUD. The rate of prescription orders was defined as the proportion of ADSMs with an ICD-9 or ICD-10 diagnosis code of alcohol dependence who received an order for acamprosate, disulfiram, naltrexone, and/or topiramate at a military treatment facility in the year following their incident diagnosis. Results: ADSMs receiving an order for at least one medication in the year following their incident AUD diagnosis increased from 8.8% in 2010 to 16.2% in 2017 (RR = 1.84, 95% CI, 1.76, 1.93). Oral naltrexone was ordered most frequently among this patient population, while injectable naltrexone, a medication option meant to ease and improve adherence, was ordered for a smaller proportion of patients. Conclusions: Most ADSMs who might benefit from prescriptions for AUD are not receiving them as part of their treatment despite strong clinical evidence and Department of Defense policy support for their use among this cohort.

Emergency Department Visits Among Adults With Mental Health Disorders: United States, 2017-2019.

Mental health disorders, which include mental illnesses and substance use disorders, are a group of conditions characterized by alterations in thinking, emotions, or behavior (1). In 2019, 61.2 million adults aged 18 and over in the United States had a mental health disorder in the past year (2). This report presents data on emergency department (ED) visits by adults with mental health disorders.

More than expected? Assessing departures from additivity in health care utilization after mild traumatic brain injury in military personnel with pre-existing mental health conditions.

OBJECTIVE: Prior research indicates that there is an additive association between traumatic brain injury and mental health diagnoses on health-care utilization. This assumed additivity has not been formally assessed. The objective of this study was to estimate additive and multiplicative interactions associated with mild traumatic brain injury (mTBI) and pre-existing health conditions. METHOD: Active-duty military patient records over a nine-year period were sampled within four exposure groups (N = 4500 per group) defined jointly by incident mTBI and pre-existing mental health diagnoses. Outpatient and inpatient health encounters were compared between the four exposure groups using generalized linear models for count and proportion outcomes. Additive interactions were estimated using the interaction contrast ratio. Multiplicative interactions were estimated as a product term in the generalized linear models. RESULTS: The joint association of mTBI and pre-existing mental health diagnoses with health-care utilization, overall, was less than multiplicative and greater than additive. Patients with both exposures experienced more health-care utilization than expected under the assumed additivity (independence) of the two exposures. PTSD and anxiety diagnoses were the MH diagnoses associated with the largest interaction contrast values specific to total outpatient encounters. CONCLUSIONS: Studies of the interaction of two diagnoses on subsequent health-care utilization should examine both additive and multiplicative interactions. The greater-than-additive findings in this study indicate that there may be synergy, for at least some patients, between mTBI injury and mental health that complicates the treatment course.

Manganese Uptake, Mediated by SloABC and MntH, Is Essential for the Fitness of Streptococcus mutans.

Early epidemiological studies implicated manganese (Mn) as a possible caries-promoting agent, while laboratory studies have indicated that manganese stimulates the expression of virulence-related factors in the dental pathogen Streptococcus mutans To better understand the importance of manganese homeostasis to S. mutans pathophysiology, we first used RNA sequencing to obtain the global transcriptional profile of S. mutans UA159 grown under Mn-restricted conditions. Among the most highly expressed genes were those of the entire sloABC operon, encoding a dual iron/manganese transporter, and an uncharacterized gene, here mntH, that codes for a protein bearing strong similarity to Nramp-type transporters. While inactivation of sloC, which encodes the lipoprotein receptor of the SloABC system, or of mntH alone had no major consequence for the overall fitness of S. mutans, simultaneous inactivation of sloC and mntH (ΔsloC ΔmntH) impaired growth and survival under Mn-restricted conditions, including in human saliva or in the presence of calprotectin. Further, disruption of Mn transport resulted in diminished stress tolerance and reduced biofilm formation in the presence of sucrose. These phenotypes were markedly improved when cells were provided with excess Mn. Metal quantifications revealed that the single mutant strains contained intracellular levels of Mn similar to those seen with the parent strain, whereas Mn was nearly undetectable in the ΔsloC ΔmntH strain. Collectively, these results reveal that SloABC and MntH work independently and cooperatively to promote cell growth under Mn-restricted conditions and that maintenance of Mn homeostasis is essential for the expression of major virulence attributes in S. mutansIMPORTANCE As transition biometals such as manganese (Mn) are essential for all forms of life, the ability to scavenge biometals in the metal-restricted host environment is an important trait of successful cariogenic pathobionts. Here, we showed that the caries pathogen Streptococcus mutans utilizes two Mn transport systems, namely, SloABC and MntH, to acquire Mn from the environment and that the ability to maintain the cellular levels of Mn is important for the manifestation of characteristics that associate S. mutans with dental caries. Our results indicate that the development of strategies to deprive S. mutans of Mn hold promise in the combat against this important bacterial pathogen.

Healthcare worker experiences with Option B+ for prevention of mother-to-child HIV transmission in eSwatini: findings from a two-year follow-up study.

BACKGROUND: Prevention of mother-to-child transmission (PMTCT) across sub-Saharan Africa has rapidly shifted towards Option B+, an approach in which all HIV+ pregnant and breastfeeding women initiate lifelong antiretroviral therapy (ART) independent of CD4+ count. Healthcare workers (HCW) are critical to the success of Option B+, yet little is known regarding HCW acceptability of Option B+, particularly over time. METHODS: Ten health facilities in the Manzini and Lubombo regions of eSwatini transitioned from Option A to Option B+ between 2013 and 2014 as part of the Safe Generations study examining PMTCT retention. Fifty HCWs (5 per facility) completed questionnaires assessing feasibility and acceptability: (1) prior to transitioning to Option B+, (2) two months post transition, and (3) approximately 2 years post Option B+ transition. This analysis describes HCW perceptions and experiences two years after transitioning to Option B+. RESULTS: Two years after transition, 80% of HCWs surveyed reported that Option B+ was easy for HCWs, noting that it was particularly easy to explain and coordinate. Immediate ART initiation also reduced delays by eliminating need for laboratory tests prior to ART initiation. Additionally, HCWs reported ease of patient follow-up (58%), documentation (56%), and counseling (58%) under Option B+. Findings also indicate that a majority of HCWs reported that their workloads increased under Option B+. Sixty-eight percent of HCWs at two years post-transition reported more work under Option B+, specifically noting increased involvement in adherence counseling, prescribing/monitoring medications, and appointment scheduling/tracking. Some HCWs attributed their higher workloads to increased client loads, now that all HIV-positive women were initiated on ART. New barriers to patient uptake, and issues related to retention, adherence, and follow-up were also noted as challenges face by HCW when implementing Option B+. CONCLUSIONS: Overall, HCWs found Option B+ to be acceptable and feasible while providing critical insights into the practical issues of universal ART. Further strengthening of the healthcare system may be necessary to alleviate worker burden and to ensure effective monitoring of client retention and adherence. HCW perceptions and experiences with Option B+ should be considered more broadly as countries implement Option B+ and consider universal treatment for all HIV+ individuals. TRIAL REGISTRATION: http://clinicaltrials.gov NCT01891799 , registered on July 3, 2013.

Predicting Arrest in a Sample of Youth Perinatally Exposed to HIV: The Intersection of HIV and Key Contextual Factors.

We examined the role of youth HIV status and other key factors on past-year arrest in perinatally HIV-exposed but uninfected (PHIV-) and perinatally HIV-infected (PHIV+) youth using data from a multi-site study of psychosocial behaviors in PHIV-exposed urban youth (N = 340; 61% PHIV+; 51% female; ages 9-16 at baseline). Youth and caregivers were administered 5 interviews, spanning approximately 7.5 years. Using longitudinal logistic mixed-effect models, we explored the association between past year arrest, internal [e.g., substance use disorder (SUD)] and external (e.g., neighborhood arrest rates) contextual factors, and social-regulation processes (e.g., in-school/work). Arrest rates increased from 2.6 to 19.7% across follow-ups; there were no differences in arrest over time by HIV status. In the final model, odds of arrest were greater for youth who were male, with SUD, ≥ 18 years old, with high levels of city stress, and neither in school nor employed. PHIV-exposed, urban youth have much higher rates of arrest than national samples. Lack of differences in arrest by HIV status suggests key contextual factors are more important in promoting arrest.

High risk of loss to follow-up among South African children on ART during transfer, a retrospective cohort analysis with community tracing.

INTRODUCTION: Decentralization of HIV care for children has been recommended to improve paediatric outcomes by making antiretroviral treatment (ART) more accessible. We documented outcomes of children transferred after initiating ART at a large tertiary hospital in the Eastern Cape of South Africa. METHODS: Electronic medical records for all children 0-15 years initiating ART at Dora Nginza Hospital (DNH) in Port Elizabeth, South Africa January 2004 to September 2015 were examined. Records for children transferred to primary and community clinics were searched at 16 health facilities to identify children with successful (at least one recorded visit) and unsuccessful transfer (no visits). We identified all children lost to follow-up (LTF) after ART initiation: those LTF at DNH (no visit >6 months), children with unsuccessful transfer, and children LTF after successful transfer (no visit >6 months). Community tracing was conducted to locate caregivers of children LTF and electronic laboratory data were searched to measure reengagement in care, including silent transfers. RESULTS: 1,582 children initiated ART at median age of 4 years [interquartile range (IQR): 1-8] and median CD4+ of 278 cells/mm3 [IQR: 119-526]. A total of 901 (57.0%) children were transferred, 644 (71.5%) to study facilities; 433 (67.2%) children had successful transfer and 211 (32.8%) had unsuccessful transfer. In total, 399 children were LTF: 105 (26.3%) from DNH, 211 (52.9%) through unsuccessful transfer and 83 (20.8%) following successful transfer. Community tracing was conducted for 120 (30.1%) of 399 children LTF and 66 (55.0%) caregivers were located and interviewed. Four children had died. Among 62 children still alive, 8 (12.9%) were reported to not be in care or taking ART and 18 (29.0%) were also not taking ART. Overall, 65 (16.3%) of 399 children LTF had a laboratory result within 18 months of their last visit indicating silent transfer and 112 (28.1%) had lab results from 2015 to 2016 indicating current care. CONCLUSION: We found that only two-thirds of children on ART transferred to primary and community health clinics had successful transfer. These findings suggest that transfer is a particularly vulnerable step in the paediatric HIV care cascade.

Examining the Intersection of Bullying and Physical Relationship Violence Among New York City High School Students.

Research is just beginning to explore the intersection of bullying and relationship violence. The relationship between these forms of youth aggression has yet to be examined in diverse urban centers, including New York City (NYC). This study seeks to identify intersections of joint victimization from bullying and electronic bullying (e-bullying) with physical relationship violence (pRV). This study examines data from the NYC Youth Risk Behavior Survey (YRBS), a representative sample of NYC public high school students, to assess the concurrent victimization from bullying at school and e-bullying with pRV, operationalized as physical violence by a dating partner in the past 12 months. Students who reported being bullied at school and e-bullied had increased odds (bullied: OR = 2.5, 95% CI [2.1, 2.9]; e-bullied: OR = 3.0, 95% CI [2.6, 3.5]) of also being victimized by pRV compared with those who did not report being bullied or e-bullied. In logistic regression models, being bullied at school and being e-bullied remained significant predictors of students' odds of reporting pRV (bullied: AOR = 2.6, 95% CI [2.2, 3.1]; e-bullied: AOR = 3.0, 95% CI [2.5, 3.6]) while controlling for race, gender, sexual orientation, and age. This research is the first to assess the intersection of victimization from bullying and e-bullying with pRV in a large, diverse, random sample of urban high school students. In this sample, students who report being bullied or e-bullied are more likely also to report pRV than students who have not been bullied or e-bullied. This research has potential implications for educators, adolescent health and social service providers, and policy makers to tailor programs and enact policies that jointly address bullying and pRV. Future studies are needed to longitudinally assess both victimization from and perpetration of bullying and pRV.