BACKGROUND: Women and underrepresented in medicine and the health sciences (URiM) faculty face inequities in advancement. Career sponsorship may be a remedy. Few studies have described sponsorship in academic medicine and none across an institution. OBJECTIVE: To examine faculty awareness, experiences, and perceptions of sponsorship at a large academic health center. DESIGN: Anonymous online survey. PARTICIPANTS: Faculty with a ≥50% appointment. MAIN MEASURES: The survey contained 31 Likert, multiple-choice, yes/no, and open-ended questions about familiarity with the concept of sponsorship; experience of having or being a sponsor; receipt of specific sponsorship activities; sponsorship impact and satisfaction; mentorship and sponsorship co-occurrence; and perception of inequities. Open-ended questions were analyzed using content analysis. KEY RESULTS: Thirty-one percent of the surveyed faculty (903/2900) responded of whom 53% (477/903) were women and 10% (95/903) were URiM. Familiarity with sponsorship was higher among assistant (91%, 269/894) and associate (182/894; 64%) professors versus full professors (38%, 329/894); women (67%, 319/488) versus men (62%, 169/488); and URiM (77%, 66/517) versus non-URiM faculty (55%, 451/517). A majority had a personal sponsor (528/691; 76%) during their career and were satisfied with their sponsorship (64%, 532/828). However, when responses from faculty of different professorial ranks were stratified by gender and URiM identity, we observed possible cohort effects. Furthermore, 55% (398/718) of respondents perceived that women received less sponsorship than men and 46% (312/672) that URiM faculty received less than their peers. We identified seven qualitative themes: sponsorship importance, growing awareness and change, institutional biases and deficiencies, groups getting less sponsorship, people with sponsorship power, conflation with mentorship, and potential for negative impact. CONCLUSIONS: A majority of respondents at a large academic health center reported sponsorship familiarity, receipt, and satisfaction. Yet many perceived persistent institutional biases and the need for systematic change to improve sponsorship transparency, equity, and impact.

Most academic health sciences centers offer faculty leadership development programs (LDPs); however, the outcomes of LDPs are largely unknown. This article describes perspectives from our 12-year experience cultivating a formal faculty LDP within an academic health center and longitudinal outcomes of our LDP. Responding to faculty concerns from University of California San Francisco's (UCSF) 2001 Faculty Climate Survey, UCSF established the UCSF-Coro Faculty Leadership Collaborative (FLC) in 2005. The FLC focused on building leadership skills using a cohort-based, experiential, interactive and collaborative learning approach. From 2005 to 2012, FLC has conducted training for 136 graduates over 7 cohorts with 97.6% completion rate. FLC faculty participants included 64% women and 13% underrepresented minority (URM). The proportions of graduates attaining leadership positions within UCSF such as deans or department chairs among all, URM, and women URM graduates were 9.6%, 33.3% and 45.5%, respectively. A 2013 online survey assessed 2005-2012 graduates' perceived impacts from 8 months to 8 years after program completion and showed 91.7% of survey respondents felt the program both increased their understanding of UCSF as an organization and demonstrated the University's commitment to foster faculty development. Qualitative results indicated that graduates perceived benefits at individual, interpersonal, and organizational levels. Though we did not directly assess impact on faculty recruitment and retention, the findings to date support cohort-based experiential learning in faculty leadership training development.

Objective

This article aims to determine the prevalence of caregiving among faculty at a large academic health sciences institution, to examine the effect of gender and other demographic and professional covariates on caregiving status, and to explore caregiver-generated policy recommendations.

Method

A cross-sectional, mixed-methods survey was collected from June through August 2018. Participants were faculty within one of the institution's health professional schools (dentistry, medicine, nursing, or pharmacy) receiving at least 50% salary from the institution. In addition to demographic information, we collected academic series and rank, and assessed association between covariates on caregiving status using logistic regression. We analyzed open-ended responses using thematic analysis to identify themes in caregiver barriers and policy suggestions.

Results

Among 657 eligible respondents, 11.4% were informal caregivers. Women were more likely to be caregivers than men (aOR 2.53, 95% CI: 1.40, 4.78), as were older faculty. Caregivers identified unsupportive climate or unrealistic work expectations, concern about career advancement, insufficient information about policies, and concern about colleague burden as barriers to support. Suggestions for workplace support included improved leave policies, increased flexibility, caregiver resource support, improved clarity and dissemination of policy information, and financial support.

Conclusions

Women faculty are more likely to be informal caregivers, exacerbating disparities within academic medicine for promotion and retention among women faculty. Institutions might include caregiving status in annual burnout surveys to guide the development of structural support and policies for extension of family leave beyond childbearing (or catastrophic leave), flexibility in work hours, and subsidized eldercare services.

Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 1

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control the expression of their target genes via RNA interference. There is increasing evidence that expression of miRNAs is dysregulated in neuronal disorders, including epilepsy, a chronic neurological disorder characterized by spontaneous recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis in the subgranular zone as well as gliosis and neuronal cell loss in the cornu ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated regulation of target genes could be involved in hippocampal cell remodeling. A miRNA screen was performed in hippocampal focal and non-focal brain tissue samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of 215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9% (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene assays confirmed RNA interference for hsa-miR-34c-5p with 3'-UTR sequences of GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3'-UTR sequences of SOX11, MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3'-UTR sequences of the transcription factor SOX11 identified two different binding sites for hsa-miR-212-3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR-212-3p and miR-132-3p suggest that both miRNAs work synergistically to control Sox11 expression. Taken together, these results suggest that differential miRNA expression in neurons could contribute to an altered function of the transcription factor SOX11 and other genes in the setting of epilepsy, resulting not only in impaired neural differentiation, but also in imbalanced neuronal excitability and accelerated drug export.

Context

The optimal pharmacologic treatment for early convulsive status epilepticus is unclear.

Objective

To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm.

Data sources

Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists.

Study selection

Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes.

Data extraction

Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm.

Results

A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm.

Conclusions

Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline.

BACKGROUND AND OBJECTIVES: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

Background

Epilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype-genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy.

Results

EPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants.

Conclusions

EPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review.

Infantile spasms (IS) and Lennox-Gastaut syndrome (LGS) are epileptic encephalopathies characterized by early onset, intractable seizures, and poor developmental outcomes. De novo sequence mutations and copy number variants (CNVs) are causative in a subset of cases. We used exome sequence data in 349 trios with IS or LGS to identify putative de novo CNVs. We confirm 18 de novo CNVs in 17 patients (4.8%), 10 of which are likely pathogenic, giving a firm genetic diagnosis for 2.9% of patients. Confirmation of exome-predicted CNVs by array-based methods is still required due to false-positive rates of prediction algorithms. Our exome-based results are consistent with recent array-based studies in similar cohorts and highlight novel candidate genes for IS and LGS.

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1 in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 × 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de novo mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction.