Current state of the epilepsy drug and device pipeline.

The field of epilepsy has undergone substantial advances as we develop novel drugs and devices. Yet considerable challenges remain in developing broadly effective, well-tolerated treatments, but also precision treatments for rare epilepsies and seizure-monitoring devices. We summarize major recent and ongoing innovations in diagnostic and therapeutic products presented at the seventeenth Epilepsy Therapies & Diagnostics Development (ETDD) conference, which occurred May 31 to June 2, 2023, in Aventura, Florida. Therapeutics under development are targeting genetics, ion channels and other neurotransmitters, and many other potentially first-in-class interventions such as stem cells, glycogen metabolism, cholesterol, the gut microbiome, and novel modalities for delivering electrical neuromodulation.

Preferences and experiences of parents/guardians of youth with epilepsy and intellectual disability on reproductive health counseling.

OBJECTIVE: To explore the experiences and preferences of parents/guardians of adolescents and young adults (AYA) of childbearing potential with co-occurring epilepsy and intellectual disability (ID) regarding counseling by neurologists on sexual and reproductive health (SRH) topics such as pregnancy, contraception, menstruation, and folic acid supplementation. METHODS: We conducted semi-structured interviews with parents/guardians of AYAs (12-28 years old) of childbearing potential with co-occurring epilepsy and ID, recruited from a tertiary-care children's hospital. We confirmed the diagnoses of epilepsy and ID with the patient's neurologist and parent/guardian. All degrees of ID (e.g. mild/moderate/severe) were eligible. We audio-recorded and transcribed interviews. Two coders performed qualitative thematic analysis. RESULTS: Twenty-five parents/guardians completed interviews. Themes included: (1) Parents/guardians believe their child to be immune from sexual abuse due to their supervision, yet desire counseling about abuse recognition and prevention, which they also report not occurring (2) A common opinion was that counseling on menstruation was more relevant to their child's life than counseling about pregnancy-related topics (3) Parents/guardians reported a lack of counseling on pregnancy-related topics such as folic acid supplementation and teratogenesis and generally also reported some degree of interest in hearing about these topics from neurologists (4) Parents/guardians also reported a lack of counseling on drug interactions between contraception and ASMs, and were highly interested in learning more about this topic (5) Parents/guardians want neurologists to initiate annual comprehensive SRH counseling at puberty about most topics, but report that they often initiate SRH discussions themselves. CONCLUSION: Parents/guardians of AYAs with epilepsy and ID prefer more frequent, neurologist-initiated, comprehensive conversations surrounding SRH particularly emphasizing menstruation and sexual abuse recognition/prevention. Findings may inform professional and patient education and health systems interventions including development of discussion guides and/or decision aides to improve SRH care for AYAs with epilepsy and ID.

Challenges and directions in epilepsy diagnostics and therapeutics: Proceedings of the 17th Epilepsy Therapies and Diagnostics Development conference.

Substantial efforts are underway toward optimizing the diagnosis, monitoring, and treatment of seizures and epilepsy. We describe preclinical programs in place for screening investigational therapeutic candidates in animal models, with particular attention to identifying and eliminating drugs that might paradoxically aggravate seizure burden. After preclinical development, we discuss challenges and solutions in the design and regulatory logistics of clinical trial execution, and efforts to develop disease biomarkers and interventions that may be not only seizure-suppressing, but also disease-modifying. As disease-modifying treatments are designed, there is clear recognition that, although seizures represent one critical therapeutic target, targeting nonseizure outcomes like cognitive development or functional outcomes requires changes to traditional designs. This reflects our increasing understanding that epilepsy is a disease with profound impact on quality of life for the patient and caregivers due to both seizures themselves and other nonseizure factors. This review examines selected key challenges and future directions in epilepsy diagnostics and therapeutics, from drug discovery to translational application.

Use of Natural Language Processing to Identify Sexual and Reproductive Health Information in Clinical Text.

OBJECTIVES: This study aimed to enable clinical researchers without expertise in natural language processing (NLP) to extract and analyze information about sexual and reproductive health (SRH), or other sensitive health topics, from large sets of clinical notes. METHODS: (1) We retrieved text from the electronic health record as individual notes. (2) We segmented notes into sentences using one of scispaCy's NLP toolkits. (3) We exported sentences to the labeling application Watchful and annotated subsets of these as relevant or irrelevant to various SRH categories by applying a combination of regular expressions and manual annotation. (4) The labeled sentences served as training data to create machine learning models for classifying text; specifically, we used spaCy's default text classification ensemble, comprising a bag-of-words model and a neural network with attention. (5) We applied each model to unlabeled sentences to identify additional references to SRH with novel relevant vocabulary. We used this information and repeated steps 3 to 5 iteratively until the models identified no new relevant sentences for each topic. Finally, we aggregated the labeled data for analysis. RESULTS: This methodology was applied to 3,663 Child Neurology notes for 971 female patients. Our search focused on six SRH categories. We validated the approach using two subject matter experts, who independently labeled a sample of 400 sentences. Cohen's kappa values were calculated for each category between the reviewers (menstruation: 1, sexual activity: 0.9499, contraception: 0.9887, folic acid: 1, teratogens: 0.8864, pregnancy: 0.9499). After removing the sentences on which reviewers did not agree, we compared the reviewers' labels to those produced via our methodology, again using Cohen's kappa (menstruation: 1, sexual activity: 1, contraception: 0.9885, folic acid: 1, teratogens: 0.9841, pregnancy: 0.9871). CONCLUSION: Our methodology is reproducible, enables analysis of large amounts of text, and has produced results that are highly comparable to subject matter expert manual review.

Lamotrigine and exogenous estrogen among females with epilepsy: A retrospective analysis of administrative claims data.

OBJECTIVE: Exogenous estrogen reduces lamotrigine serum concentrations. Little is known about whether providers adjust lamotrigine doses for addition of exogenous estrogen among people with epilepsy, despite expert recommendations. We determined the incidence of dose increases in lamotrigine following incident prescription of estrogen among females with epilepsy (FWE) in claims data. METHODS: We used Optum's de-identified Clinformatics® Data Mart Database to create a cohort of U.S. FWE prescribed lamotrigine at a stable dose, with a subsequent prescription for estrogen from 2011 to 2021. We calculated cumulative incidence functions of dose increases in lamotrigine following prescription of exogenous estrogen. We performed a Cox proportional hazards model for multiple candidate predictors of a lamotrigine dose increase. RESULTS: The cohort included 643 FWE, with median age of 31 (interquartile ratio [IQR] 20-42). The cumulative incidence of any lamotrigine increase was 28% (95% confidence interval [CI] 25%-32%). The median number of days after the first estrogen fill until the first lamotrigine adjustment was 118 (IQR 48-188). In unadjusted Cox models, older age, use of estrogen in hormone replacement therapy as opposed to contraception, and annual household income of $50,000-$99,999 (compared with <$50,000) were significant negative predictors of a dose adjustment in lamotrigine with hazard ratios (HRs) of 0.82 (95% CI 0.72-0.92), 0.63 (95% CI 0.42-0.95), and 0.62 (95% CI 0.40-0.95). In the adjusted Cox model, age and income remained significant predictors with HRs of 0.79 (95% CI 0.66-0.94) and 0.59 (95% CI 0.36-0.95). CONCLUSION: Dose increase of lamotrigine following addition of exogenous estrogen is rare among U.S. FWE, with potential disparities based on age and income level. More guidance may be needed for providers on this topic.

Co-production of online educational resources for adolescent and young adult females with epilepsy.

OBJECTIVE: To develop online patient education materials about epilepsy for adolescent and young adult females with epilepsy through co-production in partnership with patients, parents or caregivers, and multi-disciplinary healthcare providers who care for this population. METHODS: We recruited participants from Western/Central Pennsylvania, comprised of females with epilepsy ages 18-26 or parents of children with epilepsy ages 12-26. Healthcare providers who participated in the study were recruited nationally from disciplines of pediatric epilepsy, adult epilepsy, women's neurology, and adolescent medicine. We held three series of meetings to create the online materials from July to August 2021. RESULTS: Five adolescent and young adult females with epilepsy (ages 18-26, median age 22) and two parents of children with epilepsy were recruited and participated in meetings. The physician group was comprised of two adolescent medicine physicians, one adult neurologist with a specialization in women's neurology, one adult epileptologist, and one pediatric epileptologist. All participants were female. Several sets of meetings were held, which involved the creation of an empathy map to evaluate the needs and desires of our participants, topic list development, and specific content and formatting recommendations. After these meetings, content was created for the online materials and published on the Center for Young Women's Health (CYWH) website. CONCLUSION: Our team utilized co-production with a diverse group of partners to create educational materials that met the interests of adolescent and young adult females with epilepsy. This is a structured and reproducible methodology that could inform future educational intervention development in epilepsy.

Structured Engagement of Community Partners to Revise a Pregnancy Options Counseling Curriculum for Pediatric Residents.

OBJECTIVE: The engagement of community partners, including patients, is increasingly recognized as important in developing medical education curricula. Structured methodology for partner engagement in curriculum development is lacking in the existing literature. This article describes a structured approach to engaging community partners to provide input on revising a curriculum for pediatric residents about pregnancy options counseling with adolescents. METHODS: We used the five-step Method for Program Adaptation through Community Engagement: (1) development of a panel of community partners including patients and professionals, (2) and (3) partner evaluation of the existing curriculum and recommendations for revisions, (4) summarization of partner feedback, and (5) development of the revised curriculum. We surveyed partners about their perceived impact on the revision and satisfaction with the process. RESULTS: Seventeen partners participated. Five experienced adolescent pregnancy, while the remaining 12 included healthcare and social service professionals. All partners provided multiple recommendations, generating 124 discrete recommendations. Twenty recommendations were suggested by multiple individuals. The authors reviewed all recommendations by category during consensus meetings and determined which recommendations would be incorporated into the revised curriculum to meet stated learning objectives. We implemented 14 of these 20 recommendations, including adding a values clarification exercise, information about mental health crisis resources, and more detail about adoption. We also incorporated 15 individual recommendations pertaining to curriculum clarity. Recommendations from professionals and patients were similar. Fourteen out of 17 participants completed the survey at the close of the project. All respondents understood their roles, were satisfied with their degree of engagement, and felt that their expectations for participation were met or exceeded. CONCLUSIONS: This study describes a methodology for a formal process to engage community partners in curriculum development and revision processes. Such methodology can ensure that medical education curricula are optimally attuned to the needs of key community members and integrate the patient's voice.

A retrospective textual analysis of sexual and reproductive health counseling for adolescent and young adult people with epilepsy of gestational capacity.

Rationale The American Academy of Neurology (AAN) recommends annual sexual and reproductive health (SRH) counseling for all people with epilepsy of gestational capacity (PWEGC). Child neurologists report discussing SRH concerns infrequently with adolescents. Limited research exists regarding documentation of such counseling. METHODS: We retrospectively studied clinical notes using natural language processing to investigate child neurologists' documentation of SRH counseling for adolescent and young adult PWEGC. We segmented notes into sentences and evaluated for references to menstruation, sexual activity, contraception, folic acid, teratogens, and pregnancy. We developed training sets in a labeling application and used machine learning to identify additional counseling instances. We repeated this iteratively until we identified no new relevant sentences. We validated results using external reviewers; after removing sentences reviewers disagreed on (n = 13/400), we calculated Cohen's kappa values between the model and reviewers (>0.98 for all categories). We evaluated labeled texts for each patient per calendar year with descriptive statistics and logistic regression, adjusting for race/ethnicity, age, and teratogen use. RESULTS: Data comprised 971 PWEGC age 13-21 years with 2277 patient-years and 3663 outpatient child neurology notes. Nearly half of patient-years lacked SRH counseling documentation (49.1%). Among all patients, 38.0% never had SRH counseling documented. Documentation was present regarding menstruation in 26.7% of patient-years, folic acid in 25.0%, contraception in 21.9%, pregnancy in 3.5%, teratogens in 3.0%, and sexual activity in 1.8%. Documentation regarding menstruation and contraception was associated with prescription of antiseizure medications that have a higher risk of teratogenic effects (OR = 1.27, p = 0.020, 95% CI = [1.04,1.54]; OR = 1.27, p = 0.027, 95% CI = [1.03,1.58]). Documentation regarding contraception, folic acid, and sexual activity was increased among older patients (OR = 1.28, p < 0.001, 95% CI = [1.21,1.35]; OR = 1.26, p < 0.001, 95% CI = [1.19,1.32]; OR = 1.26, p = 0.004, 95% CI = [1.08,1.47]). Documentation regarding sexual activity was decreased among patients identifying as White/Non-Hispanic (OR = 0.39, p = 0.007, 95% CI = [0.20,0.78]). CONCLUSION: Child neurologists counsel PWEGC on SRH less frequently than recommended by the AAN based on documentation.

Preferences and Experiences Regarding Pregnancy Options Counseling in Adolescence and Young Adulthood: A Qualitative Study.

PURPOSE: Perspectives of adolescents and young adults (AYAs) experiencing pregnancy options counseling (POC) are absent from the literature. This study explores AYA experiences and preferences related to POC to inform best practice guidelines. METHODS: We conducted semistructured phone interviews in 2020-2021 among US-based individuals, 18-35 years old, who experienced a pregnancy less than 20 years of age. We performed qualitative descriptive analysis of positive and negative attributes of AYA's experiences with POC. RESULTS: Fifty participants reported 59 pregnancies (16 parenting, 19 abortions, 18 adoptions, three miscarriages) between the ages of 13 and 19 years. Positive attributes of POC experienced included: (1) provider communication that was compassionate, respectful, supportive, and attentive to nonverbal cues; (2) provider neutrality; (3) discussion of all pregnancy options; (4) asking about feelings, choice, life plans, and additional supports; (5) provision of informational materials; and (6) warm handoffs/follow-up facilitation. Negative attributes of POC experienced included: (1) judgmental, impersonal, or absent communication; (2) lack of counseling on all options and/or coercive/directive counseling; (3) insufficient time and supportive resources; and (4) confidentiality concerns. We identified no differences in these perspectives across pregnancy outcomes reported. Participants generally desired counseling about all options, with rare exceptions of ambivalence. DISCUSSION: Individuals who experienced an adolescent pregnancy described similar positive and negative attributes of POC regardless of preferred pregnancy outcome. Their perspectives highlight how crucial interpersonal communication skills are for effective POC for AYA. POC training across health care specialties should emphasize confidential, compassionate, and nonjudgmental care for AYA patients.

Provider Educational Needs and Preferences Regarding Transition from Pediatric to Adult Care in a Pediatric Health System.

INTRODUCTION: There is limited evidence on educational needs and preferences of pediatric health care professionals regarding transition from pediatric to adult health care. METHODS: We distributed an anonymous online survey to physicians and advanced practice providers at a large, free-standing children's hospital and associated primary care network to assess attitudes, practices, and educational preferences about transition. We analyzed data with descriptive statistics, chi-square, and logistic regression. RESULTS: A total of 178 providers responded (20% response rate) across 31 specialties (66% attending physicians, 19% fellows, and 15% advanced practice providers). Less than half (43%) were comfortable in their knowledge of transition, with fellows reporting significantly lower comfort than attendings ( P < .05). In total, 47% reported annually discussing transition with their patients (fellows: 17% vs. attendings: 50%, P < .05). Educational topics of greatest interest included legal (71%) and financial concerns (69%), whereas preferred educational formats included Grand Rounds/lectures (68%) and webinars (63%). Facilitators to transition included lists of local adult providers for transition (89%), parent/family educational resources (88%), and a medical summary template in the electronic health record (85%). DISCUSSION: Major gaps exist in attitudes and practices related to transition. Identified educational strategies may serve as targets to improve the transition process through educational interventions.

Health Care and Adoption Service Experiences of People Who Placed Children for Adoption During Adolescence: A Qualitative Study.

STUDY OBJECTIVE: To understand the perspectives of people who placed children for adoption during adolescence DESIGN: We conducted qualitative interviews with adults who placed children for adoption during adolescence. We recruited participants through social media and two adoption-related organizations. We audio-recorded and transcribed interviews. Using thematic analysis, 2 investigators coded the transcripts and identified themes. SETTING: Telephone interviews PARTICIPANTS: Adults ages 18-35 years old who placed children for adoption before they were 20 years old INTERVENTIONS: Semi-structured telephone interviews MAIN OUTCOME MEASURES: Qualitative data RESULTS: We conducted interviews with 18 individuals (median age of 32 years; range 21-35 years). The median age at pregnancy was 18 years (range 13-19 years). Seventeen participants identified as female and one as nonbinary. Themes included the following: (1) Negative experiences with counseling included limited empowerment to make choices about pregnancy or adoption options; (2) negative experiences with counseling included limited information about practical or financial support for pregnant adolescents; (3) negative experiences with the health care system included insensitivity or lack of awareness of the adoption plan at delivery; (4) positive experiences with counseling included comprehensive unbiased options counseling and adoption counseling emphasizing birth parent choice in openness and family placement; (5) positive experiences included longitudinal emotional support during pregnancy, particularly in ways that normalized adoption placement; and (6) participants desired therapy and/or psychological support following adoption placement. CONCLUSIONS: Individuals who chose adoption after adolescent pregnancy described positive and negative encounters with health care and adoption professionals that could serve as targets to improve the overall care experience for this population.

Preventive Approaches in Women's Neurology: Prepartum, Pregnancy, and Postpartum.

Women's neurology is the subspecialty within neurology concerned with the distinct healthcare needs of women. In this article, we review current literature and expert management strategies regarding disease-specific neurologic concerns of women, with an emphasis on issues related to contraception, pregnancy, and lactation. Health conditions that we discuss in this article include epilepsy, headache, stroke, multiple sclerosis, and Chiari I malformation. Current findings on neurologic disease in women suggest that many women with neurologic disease can safely manage their disease during pregnancy and have healthy children, though pregnancy planning is important in many conditions to mitigate risks and effective contraceptive management is important when pregnancy prevention is desired.

Preferences and experiences of women with epilepsy regarding sexual and reproductive healthcare provision.

RATIONALE: Women with epilepsy (WWE) have unique disease-specific considerations regarding their sexual and reproductive health (SRH), which impact decision-making around pregnancy and contraception. Understanding their perspectives, preferences, and experiences regarding SRH care contributes to optimizing patient-centered clinical practice. METHODS: We conducted individual semi-structured interviews with WWE aged 18-45 years, exploring their SRH care experiences and preferences. We audio-recorded and transcribed all interviews. Two coders used both inductive and deductive strategies to perform thematic analysis and identify key themes and representative quotes. RESULTS: Twenty WWE completed interviews (median age 23 years; range 18-43 years). Key themes included: 1) SRH counseling from neurologists often did not occur, was limited in scope, or contained misinformation, especially during adolescence and early adulthood. In particular, participants felt that they received poor counseling about contraception, fertility, folic acid, and teratogenic medications, which impacted their reproductive decision-making. 2) WWE report fragmented care between their neurologist and other SRH providers. 3) WWE prefer that their neurologists initiate routine comprehensive discussions about SRH. 4) Conversations about SRH should begin in adolescence and include private confidential discussions between neurologists and WWE. 5) Successful SRH conversations between neurologists and WWE involve detailed information, reassurance, and support for the patient's reproductive goals. CONCLUSION: WWE desire comprehensive, coordinated counseling and care regarding SRH and epilepsy, and often experience suboptimal SRH care. Better understanding of the SRH needs, preferences, and experiences of WWE will help inform interventions to optimize patient-centered SRH counseling and care by healthcare professionals, especially during adolescence.

A Survey of Healthcare Providers About Reproductive Healthcare for Adolescent Women With Epilepsy.

STUDY OBJECTIVE: To evaluate knowledge, attitudes, and practices about sexual and reproductive health (SRH) for adolescent and young adult (AYA) women with epilepsy among general pediatricians, adolescent medicine specialists, and pediatric gynecologists. DESIGN: Survey comprising previously validated and novel items that underwent content validity testing and was distributed through specialty listservs. Categorical variables analyzed with χ2 or Fisher exact tests, and continuous variables with Kruskal-Wallis tests. SETTING: Online. PARTICIPANTS: Physicians and Advanced practice providers. INTERVENTIONS: Online survey. MAIN OUTCOME MEASURE(S): Questions testing SRH knowledge, assessing confidence in SRH counseling practices and frequency of intended SRH counseling, and identifying barriers and facilitators to SRH provision for AYA women with epilepsy. RESULTS: Of 329 participants, 57% were general pediatricians, 27% were adolescent medicine specialists, and 16% were pediatric gynecologists. On 15 items assessing knowledge, general pediatricians scored significantly lower than respondents in the other specialties (P < .01). Among 11 items about confidence in SRH skills, general pediatricians were significantly less confident than respondents in the other specialties (P < .01). General pediatricians reported that they would perform annual counseling less often on 7 SRH counseling topics compared with respondents in the other specialties (P < .01). In all, 54% of the respondents reported that barriers to SRH provision include limited time during visits and lack of epilepsy knowledge. Respondents identified facilitators including guidelines/algorithms for managing SRH (83%), provider education (61%), and electronic health record alerts (60%). CONCLUSION: Responses suggest suboptimal knowledge, confidence, and care provision regarding SRH for AYA women with epilepsy, particularly among general pediatricians. Identified barriers and facilitators may serve as targets for interventions to improve SRH provision.

Pediatric Neurologists' Perspectives on Sexual and Reproductive Health Care for Adolescent and Young Adult Women With Epilepsy and Intellectual Disability.

OBJECTIVE: To explore perspectives of pediatric neurologists regarding sexual and reproductive health care for adolescent women with epilepsy (WWE) and intellectual disability. METHODS: We interviewed pediatric neurologists regarding sexual and reproductive health for WWE with intellectual disability. We audio-recorded and transcribed interviews and conducted qualitative analysis. RESULTS: 16 pediatric neurologists participated. Themes included the following: (1) Pediatric neurologists have differing perspectives about how intellectual disability affects WWE's sexual and reproductive health needs, (2) pediatric neurologists provide sexual and reproductive health counseling variable in content and frequency to this population, (3) pediatric neurologists tend to recommend longer-term methods of contraception for this population, and (4) pediatric neurologists are asked to be involved in decision-making around sterilization, yet express ethico-legal reservations. CONCLUSION: Our findings suggest pediatric neurologists provide variable, often suboptimal, sexual and reproductive health care for WWE and intellectual disability. Themes reveal ethical concerns among neurologists about sexual and reproductive health practices including sterilization. More tailored clinical guidelines and provider training on sexual and reproductive health for this population may be beneficial.

Sexual and reproductive health concerns of women with epilepsy beginning in adolescence and young adulthood.

BACKGROUND: Women with epilepsy (WWE) have potentially unique concerns regarding their sexual and reproductive health (SRH). Prior studies of WWE have focused narrowly on pregnancy and preconception experiences, and have not addressed concerns of nulliparous adolescent and young adult women not actively seeking pregnancy. METHODS: We conducted individual semi-structured interviews with WWE 18-45 years of age. We sampled to maximize diversity of age and parity, and intentionally included many adolescent and young adult nulliparous women not actively planning pregnancy. Interviews broadly addressed participants' SRH concerns and experiences. Interviews were audio-recorded and transcribed. Two coders performed qualitative analysis using thematic analysis with deductive and inductive approaches. RESULTS: Twenty WWE (median age 23 years, range 18-43 years) completed interviews. Twelve were nulliparous, six had children, one had a history of miscarriage only, and two were currently pregnant. WWE's narratives revealed significant concerns about family planning and reproductive health in the context of epilepsy, including: 1) seizures endangering pregnancies and children 2) teratogenic effects of antiseizure medication, 3) heritability of epilepsy, 4) antiseizure medication and epilepsy impacting fertility, and 5) interactions between antiseizure medication and contraception. CONCLUSION: WWE, including nulliparous adolescent and young adult women who are not actively planning pregnancy, have significant concerns about how their epilepsy interacts with SRH. SRH counseling for WWE should begin during adolescence and be incorporated into the transition process from pediatric to adult healthcare. Insights from WWE may aid in the creation of relevant patient-facing educational resources as well as provider-facing training and tools to meaningfully support the reproductive decision-making of WWE throughout their childbearing years.

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes.

PURPOSE: Obesity is a major public health problem. Understanding which genes contribute to obesity may better predict individual risk and allow development of new therapies. Because obesity of a mouse gene knockout (KO) line predicts an association of the orthologous human gene with obesity, we reviewed data from the Lexicon Genome5000TM high throughput phenotypic screen (HTS) of mouse gene KOs to identify KO lines with high body fat. MATERIALS AND METHODS: KO lines were generated using homologous recombination or gene trapping technologies. HTS body composition analyses were performed on adult wild-type and homozygous KO littermate mice from 3758 druggable mouse genes having a human ortholog. Body composition was measured by either DXA or QMR on chow-fed cohorts from all 3758 KO lines and was measured by QMR on independent high fat diet-fed cohorts from 2488 of these KO lines. Where possible, comparisons were made to HTS data from the International Mouse Phenotyping Consortium (IMPC). RESULTS: Body fat data are presented for 75 KO lines. Of 46 KO lines where independent external published and/or IMPC KO lines are reported as obese, 43 had increased body fat. For the remaining 29 novel high body fat KO lines, Ksr2 and G2e3 are supported by data from additional independent KO cohorts, 6 (Asnsd1, Srpk2, Dpp8, Cxxc4, Tenm3 and Kiss1) are supported by data from additional internal cohorts, and the remaining 21 including Tle4, Ak5, Ntm, Tusc3, Ankk1, Mfap3l, Prok2 and Prokr2 were studied with HTS cohorts only. CONCLUSION: These data support the finding of high body fat in 43 independent external published and/or IMPC KO lines. A novel obese phenotype was identified in 29 additional KO lines, with 27 still lacking the external confirmation now provided for Ksr2 and G2e3 KO mice. Undoubtedly, many mammalian obesity genes remain to be identified and characterized.

A survey of child neurologists about reproductive healthcare for adolescent women with epilepsy.

OBJECTIVE: To evaluate child neurologists' knowledge, attitudes, and practices regarding sexual and reproductive health (SRH) care for adolescent and young adult women with epilepsy (WWE). METHODS: Child neurologists (including attending physicians, residents, fellows, and advanced practitioners) completed an online survey distributed through subspecialty listservs. We analyzed results using descriptive statistics, chi-square, and logistic regression. RESULTS: Two hundred eight child neurologists completed the survey. Most believed that child neurologists should counsel young WWE on: teratogenesis (99%, n = 206/207), contraception-antiseizure medication interactions (96%, n = 194/202), pregnancy (95%, n = 198/206), contraception (89%, n = 184/206) and folic acid supplementation (70%, n = 144/205). Fewer respondents felt confident with such counseling (teratogenesis: 90%, n = 188/208, drug interactions: 65%, n = 133/208, pregnancy 75%, n = 156/208, contraception: 47-64%, n = 96-134/208, p < 0.05). Ninety-five percent (n = 172/181) reported ever discussing SRH with typically developing young WWE, compared to 78% (n = 141/181) for young WWE with mild intellectual disability (p < 0.01). One third (n = 56/170) who ever discussed SRH did not do so routinely. Respondents correctly answered 87% ±â€¯5% of knowledge questions about SRH for WWE, 80% ±â€¯4% of questions about teratogenic antiseizure medications, and 61% ±â€¯7% of questions about contraception-antiseizure drug interactions. The greatest barrier to SRH care was time constraints (80%, n = 149/186). The majority (64%, n = 119/186) identified solutions including longer appointment times and co-managing SRH care with other specialties. CONCLUSIONS: Findings reveal gaps in SRH care by child neurologists for adolescent and young adult WWE, especially those with mild intellectual disability. Provider-identified barriers and solutions may serve as targets to improve SRH care for this population.