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1.
Pediatrics ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38757175

ABSTRACT

BACKGROUND AND OBJECTIVES: Entrustable professional activities (EPAs) will be used for initial certification by the American Board of Pediatrics by 2028. Less than half of pediatric fellowships currently use EPAs for assessment, yet all will need to adopt them. Our objectives were to identify facilitators and barriers to the implementation of EPAs to assess pediatric fellows and to determine fellowship program directors' (FPD) perceptions of EPAs and Milestones. METHODS: We conducted a survey of FPDs from 15 pediatric subspecialties. EPA users were asked about their implementation of EPAs, barriers encountered, and perceptions of EPAs. Nonusers were queried about deterrents to using EPAs. Both groups were asked about potential facilitators of implementation and their perceptions of Milestones. RESULTS: The response rate was 65% (575/883). Of these, 344 (59.8%) were EPA users and 231 (40.2%) were nonusers. Both groups indicated work burden as a barrier to implementation. Nonusers reported more barriers than users (mean [SD]: 7 [3.8] vs 5.8 [3.4], P < .001). Both groups identified training materials and premade assessment forms as facilitators to implementation. Users felt that EPAs were easier to understand than Milestones (89%) and better reflected what it meant to be a practicing subspecialty physician (90%). In contrast, nonusers felt that Milestones were easy to understand (57%) and reflected what it meant to be a practicing subspecialist (58%). CONCLUSIONS: Implementing EPA-based assessment will require a substantial investment by FPDs, facilitated by guidance and easily accessible resources provided by multiple organizations. Perceived barriers to be addressed include FPD time constraints, a need for additional assessment tools, and outcomes data.

2.
Article in English | MEDLINE | ID: mdl-38558292

ABSTRACT

OBJECTIVE: Musculoskeletal ultrasound (MSUS) is widely used in adult rheumatology practice for diagnosis of arthritis and procedural guidance; however, it is not yet common practice in pediatric rheumatology. MSUS is advantageous to the pediatric population because it lacks radiation and eliminates need for sedation. This study aims to assess interest in, access to, and barriers to MSUS training in pediatric rheumatology fellowship programs in North America. METHODS: A survey was developed by pediatric rheumatology providers with experience in medical and/or MSUS education and distributed via REDCap anonymously in March 2022 (Supplementary Material). Eligible participants included current and recently graduated (<1 year) pediatric rheumatology fellows at a North American program. Descriptive statistics and bivariate analyses using design-based Pearson chi-squared tests were performed. RESULTS: Overall response rate was 78% (88/113), and 75% reported some form of MSUS training during fellowship. Only 36% indicated their program had a formal MSUS curriculum. Of those with MSUS training, 23% reported adult-only MSUS education. Eighty-four percent felt MSUS would be beneficial to their career. Major barriers to MSUS training included lack of MSUS-trained faculty, lack of time, and lack of hands-on MSUS sessions. Those who had access to MSUS training were significantly more interested in MSUS than those without (P = 0.0036). CONCLUSION: This study demonstrates that North American pediatric rheumatology fellows have a strong interest in learning MSUS, but they face significant challenges in accessing MSUS training (lack of MSUS-trained faculty, time, and access to hands-on training). MSUS should be incorporated into fellowship curriculum; however, implementation remains a challenge.

5.
J Med Educ Curric Dev ; 11: 23821205231225011, 2024.
Article in English | MEDLINE | ID: mdl-38268726

ABSTRACT

OBJECTIVE: To understand fellowship program directors' (FPDs) perspectives on facilitators and barriers to using entrustable professional activities (EPAs) in pediatric subspecialty training. METHODS: We performed a qualitative study of FPDs, balancing subspecialty, program size, geographic region and current uses of EPAs. A study coordinator conducted 1-on-1 interviews using a semistructured approach to explore EPA use or nonuse and factors supporting or preventing their use. Investigators independently coded transcribed interviews using an inductive approach and the constant comparative method. Group discussion informed code structure development and refinement. Iterative data collection and analysis continued until theoretical sufficiency was achieved, yielding a thematic analysis. RESULTS: Twenty-eight FPDs representing 11 pediatric subspecialties were interviewed, of whom 16 (57%) reported current EPA use. Five major themes emerged: (1) facilitators including the intuitive nature and simple wording of EPAs; (2) barriers such as workload burden and lack of a regulatory requirement; (2) variable knowledge and training surrounding EPAs, leading to differing levels of understanding; (3) limited current use of EPAs, even among self-reported users; and (4) complementary nature of EPAs and milestones. FPDs acknowledged the differing strengths of both EPAs and milestones but sought additional knowledge about the value added by EPAs for assessing trainees, including the impact on outcomes. CONCLUSIONS: Identified themes can inform effective and meaningful EPA implementation strategies: Supporting and educating FPDs, ongoing assessment of the value of EPAs in training, and practical integration with current workflow. Generating additional data and engaging stakeholders is critical for successful implementation for the pediatric subspecialties.

6.
Arthritis Care Res (Hoboken) ; 76(5): 600-607, 2024 May.
Article in English | MEDLINE | ID: mdl-38108087

ABSTRACT

Starting in 2015, pediatric rheumatology fellowship training programs were required by the Accreditation Council for Graduate Medical Education to assess fellows' academic performance within 21 subcompetencies falling under six competency domains. Each subcompetency had four or five milestone levels describing developmental progression of knowledge and skill acquisition. Milestones were standardized across all pediatric subspecialties. As part of the Milestones 2.0 revision project, the Accreditation Council for Graduate Medical Education convened a workgroup in 2022 to write pediatric rheumatology-specific milestones. Using adult rheumatology's Milestones 2.0 as a starting point, the workgroup revised the patient care and medical knowledge subcompetencies and milestones to reflect requirements and nuances of pediatric rheumatology care. Milestones within four remaining competency domains (professionalism, interpersonal and communication skills, practice-based learning and improvement, and systems-based practice) were standardized across all pediatric subspecialties, and therefore not revised. The workgroup created a supplemental guide with explanations of the intent of each subcompetency, 25 in total, and examples for each milestone level. The new milestones are an important step forward for competency-based medical education in pediatric rheumatology. However, challenges remain. Milestone level assignment is meant to be informed by results of multiple assessment methods. The lack of pediatric rheumatology-specific assessment tools typically result in clinical competency committees determining trainee milestone levels without such collated results as the foundation of their assessments. Although further advances in pediatric rheumatology fellowship competency-based medical education are needed, Milestones 2.0 importantly establishes the first pediatric-specific rheumatology Milestones to assess fellow performance during training and help measure readiness for independent practice.


Subject(s)
Clinical Competence , Education, Medical, Graduate , Fellowships and Scholarships , Pediatrics , Rheumatology , Rheumatology/education , Rheumatology/standards , Humans , Clinical Competence/standards , Education, Medical, Graduate/standards , Pediatrics/education , Pediatrics/standards
7.
BMC Med Educ ; 23(1): 720, 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37789289

ABSTRACT

BACKGROUND: Entrustable Professional Activities (EPA) and competencies represent components of a competency-based education framework. EPAs are assessed based on the level of supervision (LOS) necessary to perform the activity safely and effectively. The broad competencies, broken down into narrower subcompetencies, are assessed using milestones, observable behaviors of one's abilities along a developmental spectrum. Integration of the two methods, accomplished by mapping the most relevant subcompetencies to each EPA, may provide a cross check between the two forms of assessment and uncover those subcompetencies that have the greatest influence on the EPA assessment. OBJECTIVES: We hypothesized that 1) there would be a strong correlation between EPA LOS ratings with the milestone levels for the subcompetencies mapped to the EPA; 2) some subcompetencies would be more critical in determining entrustment decisions than others, and 3) the correlation would be weaker if the analysis included only milestones reported to the Accreditation Council for Graduate Medical Education (ACGME). METHODS: In fall 2014 and spring 2015, the Subspecialty Pediatrics Investigator Network asked Clinical Competency Committees to assign milestone levels to each trainee enrolled in a pediatric fellowship for all subcompetencies mapped to 6 Common Pediatric Subspecialty EPAs as well as provide a rating for each EPA based upon a 5-point LOS scale. RESULTS: One-thousand forty fellows were assessed in fall and 1048 in spring, representing about 27% of all fellows. For each EPA and in both periods, the average milestone level was highly correlated with LOS (rho range 0.59-0.74; p < 0.001). Correlations were similar when using a weighted versus unweighted milestone score or using only the ACGME reported milestones (p > 0.05). CONCLUSIONS: We found a strong relationship between milestone level and EPA LOS rating but no difference if the subcompetencies were weighted, or if only milestones reported to the ACGME were used. Our results suggest that representative behaviors needed to effectively perform the EPA, such as key subcompetencies and milestones, allow for future language adaptations while still supporting the current model of assessment. In addition, these data provide additional validity evidence for using these complementary tools in building a program of assessment.


Subject(s)
Education, Medical, Graduate , Internship and Residency , Humans , Child , Clinical Competence , Competency-Based Education/methods , Accreditation , Language
8.
Arthritis Care Res (Hoboken) ; 75(12): 2453-2462, 2023 12.
Article in English | MEDLINE | ID: mdl-37332054

ABSTRACT

OBJECTIVE: Juvenile systemic sclerosis (SSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed, but clearly defining appropriate outcomes is necessary if successful therapies are to be developed. Our objective here was to propose such outcomes. METHODS: This proposal is the result of 4 face-to-face consensus meetings with a 27-member multidisciplinary team of pediatric rheumatologists, adult rheumatologists, dermatologists, pediatric cardiologists, pulmonologists, gastroenterologists, a statistician, and patients. Throughout the process, we reviewed the existing adult data in this field, the more limited pediatric literature for juvenile SSc outcomes, and data from 2 juvenile SSc patient cohorts to assist in making informed, data-driven decisions. The use of items for each domain as an outcome measure in an open label 12-month clinical trial of juvenile SSc was voted and agreed upon using a nominal group technique. RESULTS: After voting, the domains agreed on were global disease activity, skin, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, and gastrointestinal involvement, and quality of life. Fourteen outcome measures had 100% agreement, 1 item had 91% agreement, and 1 item had 86% agreement. The domains of biomarkers and growth/development were moved to the research agenda. CONCLUSION: We reached consensus on multiple domains and items that should be assessed in an open label, 12-month clinical juvenile SSc trial as well as a research agenda for future development.


Subject(s)
Raynaud Disease , Scleroderma, Systemic , Adult , Child , Humans , Consensus , Quality of Life , Raynaud Disease/drug therapy , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/drug therapy , Scleroderma, Systemic/complications
9.
Pediatr Dermatol ; 40(5): 789-808, 2023.
Article in English | MEDLINE | ID: mdl-37316462

ABSTRACT

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.


Subject(s)
Dermatitis, Atopic , Psoriasis , Humans , Child , Methotrexate , Consensus , Psoriasis/drug therapy , Dermatitis, Atopic/drug therapy
10.
Med Teach ; 45(6): 650-657, 2023 06.
Article in English | MEDLINE | ID: mdl-36420760

ABSTRACT

OBJECTIVES: To examine the composition and processes of Clinical Competency Committees (CCCs) assigning entrustable professional activity (EPA) levels of supervision for pediatric subspecialty fellows and to examine fellowship program director (FPD) perspectives about using EPAs to determine fellows' graduation readiness. METHODS: A qualitative study was performed using one-on-one interviews with a purposeful sample of pediatric subspecialty FPDs to yield a thematic analysis. Semi-structured interview guides were used for participants who self-identified as EPA users or non-users. Inductive analysis and coding were performed on transcripts until theoretical sufficiency was attained. RESULTS: Twenty-eight FPDs were interviewed. There was significant variability in the composition and processes of CCCs across subspecialties. FPDs felt that CCCs intuitively understand what entrustment means, allowing for ease of application of level of supervision (LOS) scales and consensus. FPDs perceived that EPAs provided a global assessment of fellows and are one tool to determine graduation readiness. CONCLUSIONS: Although there was variability in the makeup and processes of CCCs across subspecialties, FPDs believe EPAs are intuitive and relatively easy to implement. Consensus can be reached easily using EPA-specific LOS scales focusing on entrustment. FPDs desire a better understanding of how EPAs should be used for graduation.


Subject(s)
Clinical Competence , Internship and Residency , Humans , Child , Competency-Based Education , Qualitative Research , Fellowships and Scholarships
11.
Front Psychiatry ; 13: 892849, 2022.
Article in English | MEDLINE | ID: mdl-35903635

ABSTRACT

The long-term impacts of Adverse Childhood Experiences (ACEs) are of increasing interest to researchers and practitioners, including the effectiveness of screening for ACEs to improve health and social outcomes. Despite a focus on implementing such practices, there has been little focus on ACEs experiences for women experiencing domestic violence and substance use, or consideration of practice responses around ACEs routine enquiry for domestic violence and related services. The Irish study discussed in this paper used an action research approach to implement ACEs routine enquiry within a domestic violence service for women accessing the service (n = 60), while also utilizing co-operative inquiry groups for practitioners both within the organization (n = 10) and with those working in associated fields of infant mental health, child protection, substance misuse and welfare and community support (n = 7). Of the 60 women who completed the ACEs routine enquiry in the study, over one-half (58 per cent) reported experiencing at least two ACEs in their childhood, including one-third of all respondents reporting experiencing four or more; service users reported significant levels of overlap between direct child maltreatment and adverse home environments. Reported parental substance misuse with the home environment was substantially higher than in general population studies. These findings offered early indications of both ACEs prevalence as well the types of ACEs that most define the experiences of the women presenting to a domestic violence service that supports women with substance misuse and other related issues. This paper discusses the ways in which the co-operative inquiry groups used this information and other processes to enhance practitioner, organizational, and inter-agency understanding and service responses. The practitioners felt that this form of ACEs routine enquiry, while not an end in itself, was a useful tool to engage women in conversations about trauma and intergenerational patterns and a basis for developing trauma-informed interventions. We conclude with discussion about: considerations of the risks of "individualizing" women's traumatic experiences; skills and supports for practitioners; and resource implications.

12.
Acad Pediatr ; 22(6): 881-886, 2022 08.
Article in English | MEDLINE | ID: mdl-34936942

ABSTRACT

OBJECTIVE: To determine the relationship between level of supervision (LOS) ratings for the Common Pediatric Subspecialty Entrustable Professional Activities (EPAs) with their associated subcompetency milestones across subspecialties and by fellowship training year. METHODS: Clinical Competency Committees (CCCs) in 14 pediatric subspecialties submitted LOS ratings for 6 Common Subspecialty EPAs and subcompetency milestone levels mapped to these EPAs. We examined associations between these subcompetency milestone levels and LOS ratings across subspecialty training year by fitting per-EPA linear mixed effects models, regressing LOS rating on milestone level and on training year. RESULTS: CCCs from 211 pediatric fellowship programs provided data for 369 first, 336 second, and 331 third year fellows. Mean subcompetency milestone levels increased similarly among subspecialties for most EPAs compared with the reference, Adolescent Medicine. Mean subcompetency milestones mapped to each EPA and mean EPA LOS ratings generally increased by training year across all subspecialties. CONCLUSIONS: Subcompetency milestones levels mapped to each Common Subspecialty EPA and the EPA LOS ratings increase similarly across subspecialties and by training year, providing validity evidence for using EPA LOS to assess pediatric subspecialty trainee performance. This study supports the development of tools to facilitated the CCC evaluation process across all pediatric subspecialties.


Subject(s)
Education, Medical, Graduate , Internship and Residency , Adolescent , Child , Clinical Competence , Competency-Based Education , Fellowships and Scholarships , Humans
13.
Acad Pediatr ; 21(8S): S140-S145, 2021.
Article in English | MEDLINE | ID: mdl-34740421

ABSTRACT

Despite our wealth, child poverty in the United States remains too high. The social safety net prevents and mitigates poverty for millions of children each year and evidence demonstrates long-term positive effects for recipients. But absent a commitment to universalism, our public investments in children produce uneven - and often inequitable - results. Our current system is heavily means-tested and work-conditioned. Though heavily targeted, it varies widely in adequacy and coverage by location and across population groups and it fails to serve all children in need. This article describes the evolution of the US social safety net for children over the last century. It traces the early 20th century origins of the contemporary system and the changes it saw through the mid-century's War on Poverty expansions and late 20th century's welfare reforms. Focusing specifically on federal cash and near-cash programs, it discusses key facets and principles of the current social safety net structure, its impact on children's health and economic well-being, remaining gaps, and promising advances for the future. Temporary improvements to the social safety net enacted as part of the pandemic response indicate important ways in which our public supports can reach more families, more consistently, moving forward. To reduce child poverty, one of the most promising approaches is to enact a national child allowance in the United States. Converting the existing Child Tax Credit into a universal child allowance, making it more generous, and delivering it to families on a regular basis throughout the year can accomplish this goal.


Subject(s)
Poverty , Social Welfare , Child , Child Health , Family , Humans , Motivation , United States
14.
Pediatrics ; 148(5)2021 11.
Article in English | MEDLINE | ID: mdl-34667096

ABSTRACT

BACKGROUND AND OBJECTIVES: Entrustable Professional Activities (EPAs) were developed to assess pediatric fellows. We previously showed that fellowship program directors (FPDs) may graduate fellows who still require supervision. How this compares with their expectations for entrustment of practicing subspecialists is unknown. METHODS: We surveyed US FPDs in 14 pediatric subspecialties through the Subspecialty Pediatrics Investigator Network between April and August 2017. For each of 7 common pediatric subspecialty EPAs, we compared the minimum level of supervision that FPDs required for graduation with the level they expected of subspecialists for safe and effective practice using the Friedman rank sum test and paired t test. We compared differences between subspecialties using linear regression. RESULTS: We collected data from 660 FPDs (response rate 82%). For all EPAs, FPDs did not require fellows to reach the level of entrustment for graduation that they expected of subspecialists to practice (P < .001). FPDs expected the least amount of supervision for the EPAs consultation and handovers. Mean differences between supervision levels for graduation and practice were smaller for clinical EPAs (consultation, handovers, lead a team) when compared with nonclinical EPAs (quality improvement, management, lead the profession and scholarship; P = .001) and were similar across nearly all subspecialties. CONCLUSIONS: Fellowship graduates may need continued development of clinical and nonclinical skills in their early practice period, underscoring a need for continued assessment and mentoring. Graduation readiness must be based on clear requirements, with alignment of FPD expectations and regulatory standards, to ensure quality care for patients.


Subject(s)
Clinical Competence , Pediatrics/education , Specialization , Trust , Administrative Personnel/statistics & numerical data , Humans , Linear Models , Patient Handoff , Referral and Consultation , Surveys and Questionnaires/statistics & numerical data , United States
15.
Pediatrics ; 148(2)2021 08.
Article in English | MEDLINE | ID: mdl-34321337

ABSTRACT

Primary Sjögren syndrome is an autoimmune disease characterized by inflammation of the salivary and lacrimal exocrine glands but can also present with systemic extraglandular manifestations, including pulmonary disease. Commonly described pulmonary manifestations of Sjögren syndrome include airway disease, interstitial lung disease, pulmonary arterial hypertension, and lymphoproliferative disorders. However, diffuse alveolar hemorrhage as a sequela of Sjögren syndrome has rarely been described in the adult literature and has never been described in a child. Here we report the case of an 11-year-old girl who presented with diffuse alveolar hemorrhage and was diagnosed with childhood-onset Sjögren syndrome who otherwise lacked typical clinical features, such as sicca symptoms, at the time of presentation. She was successfully treated with corticosteroids and rituximab, with sustained pulmonary remission 1 year post diagnosis. Our case highlights the heterogenous presentation of Sjögren syndrome in the pediatric population and the need for increased awareness among pediatric providers to recognize potential systemic manifestations of this disease to avoid delayed diagnosis.


Subject(s)
Hemorrhage/etiology , Lung Diseases/etiology , Sjogren's Syndrome/complications , Age of Onset , Child , Female , Humans , Sjogren's Syndrome/diagnosis
16.
Acad Med ; 96(7S): S22-S28, 2021 07 01.
Article in English | MEDLINE | ID: mdl-34183598

ABSTRACT

PURPOSE: Entrustable professional activities (EPAs) are one approach to competency-based medical education (CBME), and 7 EPAs have been developed that address content relevant for all pediatric subspecialties. However, it is not known what level of supervision fellowship program directors (FPDs) deem necessary for graduation. The Subspecialty Pediatrics Investigator Network (SPIN) investigated FPD perceptions of the minimum level of supervision required for a trainee to successfully graduate. METHOD: In 2017, SPIN surveyed all FPDs of accredited fellowships for 14 subspecialties. For each EPA, the minimum supervision level for graduation (ranging from observation only to unsupervised practice) was set such that no more than 20% of FPDs would accept a lower level. RESULTS: The survey response rate was 82% (660/802). The minimum supervision level for graduation varied across the 7 EPAs from 2 (direct) to 4 (indirect for complex cases), with significant differences between EPAs. The percentage of FPDs desiring a lower minimum supervision level ranged from 3% to 17%. Compared with the 4 nonclinical EPAs (quality improvement, management, lead within the profession, scholarship), the 3 clinical EPAs (consultation, handover, lead a team) had higher minimum supervision graduation levels (P < .001), with less likelihood that an FPD would graduate a learner below their minimum level (P < .001). CONCLUSIONS: Consensus among FPDs across all pediatric subspecialties demonstrates the potential need for ongoing supervision for graduates in all 7 common pediatric subspecialty EPAs after fellowship. As CBME programs are implemented, processes and infrastructure to support new graduates are important considerations for leaders.


Subject(s)
Competency-Based Education , Education, Medical, Graduate , Fellowships and Scholarships , Adolescent Medicine/education , Endocrinology/education , Gastroenterology/education , Hematology/education , Humans , Infectious Disease Medicine/education , Medical Oncology/education , Medicine , Neonatology/education , Pediatric Emergency Medicine/education , Pediatrics/education , Pulmonary Medicine/education , Surveys and Questionnaires
18.
Front Neurol ; 12: 615802, 2021.
Article in English | MEDLINE | ID: mdl-33679583

ABSTRACT

Background and Rationale: Bi-directional neuronal-glial communication is a critical mediator of normal brain function and is disrupted in the epileptic brain. The potential role of aberrant microglia and astrocyte function during epileptogenesis is important because the mediators involved provide tangible targets for intervention and prevention of epilepsy. Glial activation is intrinsically involved in the generation of childhood febrile seizures (FS), and prolonged FS (febrile status epilepticus, FSE) antecede a proportion of adult temporal lobe epilepsy (TLE). Because TLE is often refractory to treatment and accompanied by significant memory and emotional difficulties, we probed the role of disruptions of glial-neuronal networks in the epileptogenesis that follows experimental FSE (eFSE). Methods: We performed a multi-pronged examination of neuronal-glia communication and the resulting activation of molecular signaling cascades in these cell types following eFSE in immature mice and rats. Specifically, we examined pathways involving cytokines, microRNAs, high mobility group B-1 (HMGB1) and the prostaglandin E2 signaling. We aimed to block epileptogenesis using network-specific interventions as well as via a global anti-inflammatory approach using dexamethasone. Results: (A) eFSE elicited a strong inflammatory response with rapid and sustained upregulation of pro-inflammatory cytokines. (B) Within minutes of the end of the eFSE, HMGB1 translocated from neuronal nuclei to dendrites, en route to the extracellular space and glial Toll-like receptors. Administration of an HMGB1 blocker to eFSE rat pups did not decrease expression of downstream inflammatory cascades and led to unacceptable side effects. (C) Prolonged seizure-like activity caused overall microRNA-124 (miR-124) levels to plunge in hippocampus and release of this microRNA from neurons via extra-cellular vesicles. (D) Within hours of eFSE, structural astrocyte and microglia activation was associated not only with cytokine production, but also with activation of the PGE2 cascade. However, administration of TG6-10-1, a blocker of the PGE2 receptor EP2 had little effect on spike-series provoked by eFSE. (E) In contrast to the failure of selective interventions, a 3-day treatment of eFSE-experiencing rat pups with the broad anti-inflammatory drug dexamethasone attenuated eFSE-provoked pro-epileptogenic EEG changes. Conclusions: eFSE, a provoker of TLE-like epilepsy in rodents leads to multiple and rapid disruptions of interconnected glial-neuronal networks, with a likely important role in epileptogenesis. The intricate, cell-specific and homeostatic interplays among these networks constitute a serious challenge to effective selective interventions that aim to prevent epilepsy. In contrast, a broad suppression of glial-neuronal dysfunction holds promise for mitigating FSE-induced hyperexcitability and epileptogenesis in experimental models and in humans.

19.
Race Soc Probl ; 13(1): 34-48, 2021.
Article in English | MEDLINE | ID: mdl-33584866

ABSTRACT

More than one-third of US children live in families with three or more children. The contemporary impact of larger family size on children's family resources remains an under-explored point of inequity. Larger family size is not only more common among Black and Hispanic children, but Black and Hispanic children in larger families (Black children, especially so) face higher poverty risks relative to White children in larger families. This analysis uses children's number of siblings and children's race and ethnicity to chart the intersectional aspects of disparity in the risk and incidence of poverty and the anti-poverty effects of large federal cash supports, the Earned Income Tax Credit and Child Tax Credit. It draws upon 2014-2017 Current Population Survey data and the NBER TAXSIM calculator to apply 2018 tax law, inclusive of the Tax Cuts and Jobs Act of 2017. It reveals well-documented disparities in poverty rates and benefit access and receipt experienced by children of color are further exacerbated by policy structures that discriminate against an under-acknowledged aspect of children's family life: their family size. Racial bias in policy design that sees tax credit access mechanisms and earnings and benefit structures disproportionately exclude that Black and Hispanic children also disproportionately exclude Black and Hispanic children by their family size. Without reforms that tackle both inequities, policy action that closes the poverty gap between larger and smaller families will see the racial gap in child poverty remain.

20.
Epilepsia ; 62(3): 647-658, 2021 03.
Article in English | MEDLINE | ID: mdl-33475157

ABSTRACT

OBJECTIVE: Prolonged fever-induced seizures (febrile status epilepticus [FSE]) during early childhood increase the risk for later epilepsy, but the underlying mechanisms are incompletely understood. Experimental FSE (eFSE) in rats successfully models human FSE, recapitulating the resulting epileptogenesis in a subset of affected individuals. However, the powerful viral and genetic tools that may enhance mechanistic insights into epileptogenesis and associated comorbidities, are better-developed for mice. Therefore, we aimed to determine if eFSE could be generated in mice and if it provoked enduring changes in hippocampal-network excitability and the development of spontaneous seizures. METHODS: We employed C57BL/6J male mice, the strain used most commonly in transgenic manipulations, and examined if early life eFSE could be sustained and if it led to hyperexcitability of hippocampal networks and to epilepsy. Outcome measures included vulnerability to the subsequent administration of the limbic convulsant kainic acid (KA) and the development of spontaneous seizures. In the first mouse cohort, adult naive and eFSE-experiencing mice were exposed to KA. A second cohort of control and eFSE-experiencing young adult mice was implanted with bilateral hippocampal electrodes and recorded using continuous video-electroencephalography (EEG) for 2 to 3 months to examine for spontaneous seizures (epileptogenesis). RESULTS: Induction of eFSE was feasible and eFSE increased the susceptibility of adult C57BL/6J mice to KA, thereby reducing latency to seizure onset and increasing seizure severity. Of 24 chronically recorded eFSE mice, 4 (16.5%) developed hippocampal epilepsy with a latent period of ~3 months, significantly different from the expectation by chance (P = .04). The limbic epilepsy that followed eFSE was progressive. SIGNIFICANCE: eFSE promotes pro-epileptogenic network changes in a majority of C57BL/6J male mice and frank "temporal lobe-like" epilepsy in one sixth of the cohort. Mouse eFSE may thus provide a useful tool for investigating molecular, cellular, and circuit changes during the development of temporal lobe epilepsy and its comorbidities.


Subject(s)
Hippocampus/physiopathology , Seizures, Febrile/etiology , Status Epilepticus/etiology , Animals , Disease Models, Animal , Disease Susceptibility/physiopathology , Electrodes, Implanted , Electroencephalography , Excitatory Amino Acid Agonists/pharmacology , Female , Hot Temperature/adverse effects , Kainic Acid/pharmacology , Male , Mice , Mice, Inbred C57BL , Seizures, Febrile/physiopathology , Status Epilepticus/physiopathology , Translational Research, Biomedical
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