Accounting for unobserved population dynamics and aging error in close-kin mark-recapture assessments.

Obtaining robust estimates of population abundance is a central challenge hindering the conservation and management of many threatened and exploited species. Close-kin mark-recapture (CKMR) is a genetics-based approach that has strong potential to improve the monitoring of data-limited species by enabling estimates of abundance, survival, and other parameters for populations that are challenging to assess. However, CKMR models have received limited sensitivity testing under realistic population dynamics and sampling scenarios, impeding the application of the method in population monitoring programs and stock assessments. Here, we use individual-based simulation to examine how unmodeled population dynamics and aging uncertainty affect the accuracy and precision of CKMR parameter estimates under different sampling strategies. We then present adapted models that correct the biases that arise from model misspecification. Our results demonstrate that a simple base-case CKMR model produces robust estimates of population abundance with stable populations that breed annually; however, if a population trend or non-annual breeding dynamics are present, or if year-specific estimates of abundance are desired, a more complex CKMR model must be constructed. In addition, we show that CKMR can generate reliable abundance estimates for adults from a variety of sampling strategies, including juvenile-focused sampling where adults are never directly observed (and aging error is minimal). Finally, we apply a CKMR model that has been adapted for population growth and intermittent breeding to two decades of genetic data from juvenile lemon sharks (Negaprion brevirostris) in Bimini, Bahamas, to demonstrate how application of CKMR to samples drawn solely from juveniles can contribute to monitoring efforts for highly mobile populations. Overall, this study expands our understanding of the biological factors and sampling decisions that cause bias in CKMR models, identifies key areas for future inquiry, and provides recommendations that can aid biologists in planning and implementing an effective CKMR study, particularly for long-lived data-limited species.

National audit of pathways in epileptic seizure referrals (NAPIER): A national, multicentre audit of first seizure clinics throughout the UK and Ireland.

BACKGROUND: Current guidelines set clinical standards for the management of suspected first seizures and epilepsy. We aimed to assess if these standards are being met across first seizure clinics nationally, to describe variations in care and identify opportunities for service delivery improvement. METHODS: Multicentre audit assessing the care of adults (≥16 years) referred to first seizure clinics from 31st December 2019 going backwards (30 consecutive patients per centre). Patients with pre-existing diagnosis of epilepsy were excluded. Anonymised referral, clinic, and follow-up data are reported with descriptive statistics. RESULTS: Data provided for 727 patients from 25 hospitals in the UK and Ireland (median age 41 years [IQR 26-59], 52% males). Median time to review was 48 days (IQR 26-86), with 13.8% (IQR 3.3%-24.0%) of patients assessed within 2 weeks. Seizure recurrence was seen in 12.7% (IQR 6.6%-17.4%) of patients awaiting first appointment. Documentation for witness accounts and driving advice was evident in 85.0% (IQR 74.0%-100%) and 79.7% (IQR 71.2%-96.4%) of first seizure/epilepsy patients, respectively. At first appointment, discussion of sudden unexpected death in epilepsy was documented in 30.1% (IQR 0%-42.5%) of patients diagnosed with epilepsy. In epilepsy patients, median time to MRI neuroimaging was 37 days [IQR 22-56] and EEG was 30 days [IQR 19-47]. 30.4% ([IQR 0%-59.5%]) of epilepsy patients were referred to epilepsy nurse specialists. CONCLUSIONS: There is variability nationally in the documented care of patients referred to first seizure clinics. Many patients are facing delays to assessment with epilepsy specialists with likely subsequent impact on further management.

Preventing Teratogenicity in Women with Epilepsy.

Over the last 50 years there has been a significant increase in our understanding of the issues faced by women with epilepsy, in both planning and undertaking pregnancy. The risks of teratogenicity associated with antiseizure medications have emerged slowly. The major pregnancy registers have substantially contributed to our knowledge about teratogenic risk associated with the commonly used antiseizure medications. However, there are substantial gaps in our knowledge about the potential risks associated with many third-generation drugs. The remit of the pregnancy registers and the wider research focus has moved beyond anatomical major congenital malformations. Increasingly neurodevelopmental and behavioral abnormalities have been investigated after in utero exposure to antiseizure medications. Public health approaches can help reduce the risk of teratogenicity. However, neurologists still have a vital role in reducing the risk of teratogenicity at an individual level for women attending their clinic. They also have responsibility to ensure that women with epilepsy are aware of the rationale for the different available options.

A retrospective study of the correlation between duration of monitoring in the epilepsy monitoring unit and diagnostic yield.

OBJECTIVE: Long-term video-electroencephalographic (LTVEM) monitoring is a valuable tool in the evaluation of paroxysmal clinical events. However, vEEG itself is costly. Hence, we aimed to establish if longer duration of monitoring (DOM) is associated with higher diagnostic yield. METHOD: A retrospective review of patients admitted into the epilepsy monitoring unit (EMU) for the diagnostic evaluation of paroxysmal events was performed. Patients' demographic, clinical characteristics, and vEEG data were analyzed. In the cohort of patients with DOM > 7 days, the reasons for prolonged DOM were identified and the differences in clinical characteristics and vEEG data between conclusive and inconclusive studies were analyzed. RESULT: A total of 501 patients were included. Four hundred and thirty-six (87 %) patients had conclusive studies. Of these patients, 67.9 % patients with conclusive studies received diagnosis within the first 7 days of monitoring with the highest on day 7. The likelihood of conclusive studies decreased beyond 7 days. A total of 175 had DOM > 7 days, of which 140 (80 %) had conclusive studies. In the cohort with DOM > 7 days, patients with previous abnormal routine EEG, previous vEEG monitoring, first event recorded before day 5 of admission and ≥1 events recorded during vEEG monitoring were more likely to have conclusive studies. The most common reason for prolonging DOM beyond 7 days was to adequately record multiple semiologically distinctive events (76 %). CONCLUSION: Our study supports that longer DOM is associated with an increase in diagnostic yield. More than one-third of our cohort were monitored beyond 7 days with majority (80 %) being conclusive. Our findings may guide clinicians in planning the DOM and predicting the likelihood of conclusive vEEG studies in patients with prolonged DOM based on the clinical characteristics and vEEG data.

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer.

Importance: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration. Objective: To examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making. Design, Setting, and Participants: Patients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022. Exposure: New and/or previous diagnosis of breast cancer. Main Outcomes and Measures: Disease management recommendations that were changed as a result of genetic testing results are reported. Results: Clinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]). Conclusions and Relevance: In this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

The emerging story of Sodium Valproate in British newspapers- A qualitative analysis of newspaper reporting.

BACKGROUND: Sodium valproate is a significant human teratogen. Newspapers are a potential source of useful public health information, but the extent to which concerns around valproate were presented to the public via newspapers has not been evaluated. AIM: To explore how sodium valproate has been portrayed by UK newspapers over the last several decades. METHOD: Thematic analysis of all newspaper articles up to July 2020 with key terms 'Valproate' and 'Epilim'. Articles were retrieved with LexisNexis. Temporal variation in thematic content was analysed. RESULTS: 275 articles were identified for analysis. Teratogenicity was the key theme in 86% of newspaper articles, failure of duty of care of medical professionals to communicate the risks of valproate in 68%, improving its regulation with public health interventions in 51% and litigation against Sanofi who produce valproate in 31%. Reporting was minimal pre-2000 and peaked in the recent 5 years. CONCLUSION: Issues surrounding valproate have been covered by UK newspapers, with a predominant focus on its teratogenic effects.

Perceptions about mental healthcare for people with epilepsy in Africa.

BACKGROUND: Mental illness is commonly comorbid with epilepsy. In sub-Saharan Africa there exists limited access to neurological and psychiatric services predisposing to a "treatment gap" in epilepsy and mental healthcare. AIMS: To understand healthcare providers' knowledge, attitudes, and management practices toward epilepsy and comorbid mental illness in sub-Saharan Africa. METHODS: A cross-sectional online survey following the STROBE guidance was conducted among healthcare providers in sub-Saharan Africa. Eleven questions looking to ascertain clinician demographics, knowledge of epilepsy, and comorbid mental illness as well as management practices were developed. FINDINGS: Of 203 responses most (92%) respondents recognized a bi-directional relationship between mental health and epilepsy. However, mental illness screening in people newly diagnosed with epilepsy was infrequently performed (14%). Only 1 in 7 (16%) respondents had high confidence in their clinical competence at managing psychiatric comorbidities. Most would value further training (74%) and improvements to be made in current management practices within their local healthcare settings (94%). CONCLUSIONS: This pilot study highlights the need to improve the awareness of management of mental disorders in populations with epilepsy within sub-Saharan Africa in health providers there.

Survey of the perceived treatment gap in status epilepticus care across Sub-Saharan countries from the perspective of healthcare providers.

BACKGROUND: Status epilepticus (SE) is a serious condition disproportionately affecting Sub-Saharan African (SSA) countries. Little is known about healthcare provider experiences. This study investigated the healthcare provider perspective of SE care. METHODS: A pilot questionnaire was developed for healthcare professionals in SSA countries. It was distributed online at a conference concerning epilepsy care and local coordinators distributed the questionnaire in their networks. It was available online between 16th Jan and 1st Feb 2021. The unvalidated questionnaire questioned practitioner demographics, experience, confidence in SE care, common etiologies encountered, anticipated prognosis in their setting, available treatments, and barriers to care. We assessed practitioner perceptions not their knowledge base around SE care. Thematic analysis was used for open-ended questions. RESULTS: Fifty nine responses were received from 11 countries. Respondents (44% nurses, 46% doctors) reported poor level of adequate SE training (mean self-reported confidence in training 2.9/10 (0/10 very inadequate and 10/10 very adequate training). Delays in arriving at hospital were common with 15 (32%) taking three or more hours and 28 (62%) proposing transport issues and distance were the main reasons for delay. Urban location was significantly associated with clinician confidence. Less than 20% used prehospital benzodiazepine treatment. 46 (78%) stated benzodiazepines were first-line hospital drug management, and 52 (88%) indicated alternative second-line hospital treatments were available. CONCLUSION: A substantial perceived treatment gap in the management of SE in SSA is identified by staff working in SSA. Key issues are around staff training, patient education, medication access, and compliance.

Readability of online sources of information regarding epilepsy surgery and its impact on decision-making processes.

INTRODUCTION: People with epilepsy can have cognitive deficits, including difficulty with reading tasks. This can potentially impact on how written information is understood. Websites increasingly provide information about different medical interventions including epilepsy surgery. Our aim was to assess the readability of a sample of one hundred patient-oriented educational English language websites related to epilepsy surgery. METHODS: A Google search was carried out using the terms epilepsy and surgery, and a sample of forty-nine websites from both the UK and the US were chosen. These websites were uploaded to a freely available online readability scoring tool (readabilityformulas.com) and seven measures of readability generated were examined. Other data including use of figures/diagrams, patient narratives, and mention of the risks/benefits of surgery were noted. RESULTS: The majority of the websites analyzed in this study were found to be 'difficult' to read for the average reading level of the population (n = 1-impossible, 10-very difficult, 23-difficult, 14 fairly difficult). Only 1 website was considered suitable for average reading level. The use of infographics was variable - some webpages used them extensively to reiterate the textual information and other websites did not. DISCUSSION AND CONCLUSION: The available online patient information literature is likely to be too difficult for the average reader to understand. It is important that websites are accessible, reliable, and aid understanding related to epilepsy surgery, taking potential cognitive deficits into consideration.

Priority concerns for people with intellectual and developmental disabilities during the COVID-19 pandemic.

BACKGROUND: The approach taken to support individuals during the coronavirus disease 2019 (COVID-19) pandemic needs to take into account the requirements of people with intellectual disabilities and/or autism, who represent a major vulnerable group, with higher rates of co-occurring health conditions and a greater risk of dying prematurely. To date, little evidence on COVID-related concerns have been produced and no report has provided structured feedback from the point of view of people with intellectual disabilities and/or autism or of their family/carers. AIMS: To provide systemised evidence-based information of the priority concerns for people with intellectual disabilities and/or autism regarding the COVID-19 pandemic. METHOD: Senior representatives of major UK-based professional and service-user representative organisations with a stake in the care of people with intellectual disabilities and/or autism were contacted to provide a list of concerns across three domains: 'mental health and challenging behaviour', 'physical health and epilepsy' and 'social circumstances and support'. The feedback was developed into statements on frequently reported priorities. These statements were then rated independently by expert clinicians. A video-conference meeting to reconcile outliers and to generate a consensus statement list was held. RESULTS: Thirty-two organisations were contacted, of which 26 (81%) replied. From the respondent's data, 30 draft consensus statements were generated. Following expert clinician review, there was initially strong consensus for seven statements (23%), increasing to 27 statements (90%) following video conferencing. CONCLUSIONS: These recommendations highlight the expectations of people with intellectual disabilities and/or autism in the current pandemic. This could support policymakers and professionals' deliver and evidence person-centred care.

"The Brain Society": The First Two Years of an Undergraduate Neuroscience Society in Northern Ireland.

The Queen's University Belfast Brain Society was set up in September 2018 to promote interest in the human brain. There were three main goals: firstly to provide opportunities for medical students to learn from neurologists and neurosurgeons outside their formal curriculum; secondly the Brain Society aimed to organise events that included students from other disciplines and to members of the general public who were interested in learning about aspects of neuroscience; thirdly to tackle neurophobia. In the last two years, there have been 14 events, ranging from formal lectures, to practical sessions and to patient-focused information evenings. We have sold over 1,600 tickets. This article covers how the Brain Society was set up, to inform students in other universities about the Belfast experience.

What can Google Trends and Wikipedia-Pageview analysis tell us about the landscape of epilepsy surgery over time?

BACKGROUND: Epilepsy surgery is an effective treatment for drug-resistant epilepsy. Some centers have noticed changes in referral patterns. AIM: The aim of this study was to determine if online infodemiological data related to epilepsy surgery reflect reported changes in referrals to surgical centers. METHODS: Google Trends and Pageview analysis of temporal trends of searches conducted in Google and Wikipedia for epilepsy surgery, using key search terms such as "epilepsy surgery" and terms related to pathology, operation type, and investigative practice. RESULTS: Over the 15-year time period studied by Google trend analysis, when the initial three-year epoch and final three-year epoch are compared, a 56.1% decline in search volume for "epilepsy surgery" was observed. Vagus nerve stimulation and laser ablation are increasingly searched items. Pageview analysis shows that temporal lobe epilepsy remains the most commonly searched subtype of epilepsy and hippocampal sclerosis was searched for more than focal cortical dysplasia. CONCLUSION: This study suggests a lower search interest over time in epilepsy surgery, and various associated terms, with increased interest in vagus nerve stimulation and laser ablation procedures over time. There is no clear indication from these data regarding the apparent shift from mesial temporal cases to an increase in extratemporal case workload.

Structured testing during seizures: A practical guide for assessing and interpreting ictal and postictal signs during video EEG long term monitoring.

BACKGROUND: Ictal and postictal testing carried out in long-term epilepsy monitoring units is often sub-optimal. Recently, a European consensus protocol for testing patients during and after seizures was developed by a joint taskforce of the International League Against Epilepsy - Commission on European Affairs and the European Epilepsy Monitoring Unit Association. AIM: Using this recently developed standardised assessment battery as a framework, the goal of this narrative review is to outline the proposed testing procedure in detail and explain the rationale for each individual component, focusing on the underlying neurobiology. This is intended to serve as an educational resource for staff working in epilepsy monitoring units. METHODS: A literature review of PubMed was performed; using the search terms "seizure", "ictal", "postictal", "testing", "examination", and "interview". Relevant literature was reviewed and relevant references were chosen. The work is presented as a narrative review. RESULTS: The proposed standardised assessment battery provides a comprehensive and user-friendly format for ictal-postictal testing, and examines consciousness, language, motor, sensory, and visual function. CONCLUSION: The standardised approach proposed has the potential to make full use of data recorded during video EEG increasing the diagnostic yield with regards to lateralisation and localisation, aiding both presurgical and diagnostic studies.

Investigative practice into sudden death in epilepsy: A global survey.

OBJECTIVES: Sudden death is a recognized consequence of epilepsy. Little is known about the practice of confirming the cause of sudden death from most nations. We sought to determine how often autopsy is undertaken, clinician confidence in cause of death and identify the factors which may influence autopsy utilization. MATERIALS & METHODS: An online questionnaire survey was sent to all International League Against Epilepsy (ILAE) chapters chairpersons, asking them to complete the survey based on their perceptions in their country. Questions included: confidence in cause of death in people with epilepsy, frequency of autopsy uptake, and perceived barriers to an accurate diagnosis and ongoing research work. Data were analyzed by chi-squared, Kruskal-Wallis and Spearman rank analysis. RESULTS: Responses were obtained from 77 of 114 individual chapter leaders (68%). Legal, coronial, family attitudes, including cultural and religious factors, to autopsy were considered the major barriers to obtaining an accurate diagnosis. Only 13% had a high level of confidence in the accuracy of the cause of death. There was greater confidence in the diagnosis of the causes of sudden death in epilepsy in the countries with higher autopsy rates. Sixty-six percent of responders were not aware of published or unpublished research or audits on sudden death in epilepsy in their country in the last decade. CONCLUSIONS: Significant disparities exist in the investigation of sudden death in epilepsy across countries and identified factors in this study provide an opportunity to formulate a global public health strategy to help overcome this gap.

Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

PURPOSE: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. METHODS: An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. RESULTS: More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher's exact test P = .4241). CONCLUSION: Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.

Online behavior of people visiting a scientific website on epilepsy.

We investigated the online behavior of Internet users consulting the website of the Italian Chapter of the International League Against Epilepsy (Lega Italiana Contro l'Epilessia [LICE]). We obtained the visualization statistics of the LICE website using AWStats (https://awstats.sourceforge.io/) and Google Trends (https://trends.google.com/trends/), and compared the statistics of years 2010, 2014, and 2017. The following variables were analyzed: number of unique visitors and visits, visit duration, the day of week and rush hours, most downloaded documents, most viewed pages, keyphrases and keywords used for online searches, origins of searches, and geographic trends of Google searches related to the LICE. The total numbers of unique visitors, visits and page views remained quite stable over time. Most visits (70 to 76.7%) lasted less than 30 s. The most frequent keyphrases and keywords used for online searches were related to clinical guidelines and driving license. Among the most frequently downloaded documents were general guides on epilepsy. The pages with the list of epilepsy centers endorsed by the LICE and those with the list of LICE guidelines were among those most frequently viewed, together with educational videos. Most users directly accessed the website without being referred from external links. No information on geographic origin of Google searches was available. The visualization statistics suggested two distinct populations of visitors. The first one is likely represented by physicians who seek specialist information on diagnosis and management of epilepsy, including guidelines. The second population is represented by lay people who seek accessible and easily comprehensible information to better understand epilepsy and know which centers are best for its management.