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Epilepsy care generates multiple sources of high-dimensional data, including clinical, imaging, electroencephalographic, genomic, and neuropsychological information, that are collected routinely to establish the diagnosis and guide management. Thanks to high-performance computing, sophisticated graphics processing units, and advanced analytics, we are now on the cusp of being able to use these data to significantly improve individualized care for people with epilepsy. Despite this, many clinicians, health care providers, and people with epilepsy are apprehensive about implementing Big Data and accompanying technologies such as artificial intelligence (AI). Practical, ethical, privacy, and climate issues represent real and enduring concerns that have yet to be completely resolved. Similarly, Big Data and AI-related biases have the potential to exacerbate local and global disparities. These are highly germane concerns to the field of epilepsy, given its high burden in developing nations and areas of socioeconomic deprivation. This educational paper from the International League Against Epilepsy's (ILAE) Big Data Commission aims to help clinicians caring for people with epilepsy become familiar with how Big Data is collected and processed, how they are applied to studies using AI, and outline the immense potential positive impact Big Data can have on diagnosis and management., (© 2024 The Author(s). Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: Myocardial Infarct Size (IS) determined soon after ST-segment elevation myocardial infarction (STEMI) has prognostic significance, and can be assessed by cardiac biomarker levels, electrocardiographic (ECG) parameters, and imaging modalities (including echocardiography and cardiac magnetic resonance imaging [CMRI])., Objectives and Methods: We evaluated methods of IS assessment, 12-lead ECG Selvester QRS scores and high-sensitivity Troponin T (hsTnT) levels measured ≥48hr (plateau phase of hsTnT elevation), compared to paired CMRIs and echocardiograms, in a prospective cohort of patients with STEMI undergoing percutaneous coronary intervention (PCI) during the index hospitalisation. Associations were determined between IS, as assessed by these methods, and 24-month major adverse cardiac events (MACE), a hierarchical composite of: death, stroke and hospitalization for heart failure., Results: Of 233 patients undergoing early CMRI after STEMI, 211 patients (86% male; 54% anterior MI) had first STEMIs, median age 56 years [interquartile range 50-64], of whom 165 (78%) underwent primary PCI and 46 (22%) pharmaco-invasive PCI. Ejection fraction improved from 48% [42-54] acutely to 52% [44-60] at 2 months (p< 0.05). Plateau phase hsTnT levels, QRS scoring and CMRI-determined IS post-STEMI correlated for anterior MIs (all comparisons r>0.4, p<0.01); highest tertiles of these 3 parameters predicted 24 month MACE (log-rank <0.01). Multi-variable binary logistic regression analysis showed 72h hsTnT levels predicted 24-month MACE (p<0.01)., Conclusion: Post-PCI treatment of STEMI, hsTnT levels measured ≥48h and Selvester QRS scoring correlated with CMRI-determined IS. These parameters predicted MACE at 24 months and should be routinely assessed for post-STEMI risk stratification., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sharma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Posterior shoulder instability (PSI) is an increasingly recognized cause of shoulder dysfunction particularly in young active patients and certain athlete populations. When evaluating the efficacy of treatment for PSI, specific outcome measures for this population are essential. The aim of the current research was to describe the development and evaluation of a patient reported outcome measure specific for PSI., Methods: A retrospective cohort study design of patients with PSI was used to develop and evaluate the "Posterior Shoulder Instability Questionnaire (PSI-Q)". Items for PSI-Q were generated through an expert focus group and existing questionnaires. Preliminary data analysis identified redundancy of items and resulted in the PSI-Q being refined. The final PSI-Q was evaluated on 128 patients with PSI with a structural lesion requiring surgical intervention. Participants were excluded in the absence of a posterior glenohumeral joint lesion. Internal consistency (Cronbach α and corrected item-total correlation), content validity, criterion validity, responsiveness, and test-retest reliability (intraclass correlation coefficient) were examined. Content validity, criterion validity and responsiveness were compared with the Melbourne Instability Shoulder Scale (MISS) and the Western Ontario Shoulder Instability Index (WOSI). The minimum detectable change score (MDC) was calculated., Results: The Cronbach α for the total scale preintervention and postintervention was high (α = 0.97). All five domains (pain, instability/weakness/stiffness, function, occupation and sport, and quality of life and satisfaction) demonstrated acceptable internal consistency for each subsection and the overall score of the scale (α > 0.70). The corrected-item total correlation for each domain was within an acceptable range. The responsiveness of the PSI-Q questionnaire was excellent (effect size, 2.06; standard response mean, 1.34) and was higher than the MISS and WOSI. There were no relevant floor effects and 1 ceiling effect. Reliability was excellent (intraclass correlation coefficient(1,1) = 0.93) and the calculated MDC was 10.9 points., Discussion: This study designed and validated a questionnaire specific for measuring symptoms and function in people with structural PSI requiring surgery. The PSI-Q demonstrates good measurement properties and provides an MDC that is useful for researchers and clinicians. In structural PSI, the PSI-Q has a higher responsiveness and more accurately reflects a patient's overall perceived shoulder status compared to current patient reported outcomes for shoulder instability. The psychometric properties of the PSI-Q are still to be determined in a nonsurgical population., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

The management of cardiogenic shock is an ongoing challenge. Despite all efforts and tremendous use of resources, mortality remains high. Whilst reversing the underlying cause, restoring/maintaining organ perfusion and function are cornerstones of management. The presence of comorbidities and preexisting organ dysfunction increases management complexity, aiming to integrate the needs of vital organs in each individual patient. This review provides a comprehensive overview of contemporary literature regarding the definition and classification of cardiogenic shock, its pathophysiology, diagnosis, laboratory evaluation, and monitoring. Further, we distill the latest evidence in pharmacologic therapy and the use of mechanical circulatory support including recently published randomized-controlled trials as well as future directions of research, integrating this within an international group of authors to provide a global perspective. Finally, we explore the need for individualization, especially in the face of neutral randomized trials which may be related to a dilution of a potential benefit of an intervention (i.e., average effect) in this heterogeneous clinical syndrome, including the use of novel biomarkers, artificial intelligence, and machine learning approaches to identify specific endotypes of cardiogenic shock (i.e., subclasses with distinct underlying biological/molecular mechanisms) to support a more personalized medicine beyond the syndromic approach of cardiogenic shock., (© 2024. The Author(s).)

Data standards are available for spinal cord injury (SCI). The International SCI Data Sets were created in 2002 and there are currently 27 freely available. In 2014 the National Institute of Neurological Disorders and Stroke developed clinical common data elements to promote clinical data sharing in SCI. The objective of this paper is to provide an overview of SCI data standards, describe learnings from the traumatic brain injury (TBI) field using data to enhance research and care, and discuss future opportunities in SCI. Given the complexity of SCI, frameworks such as a systems medicine approach and Big Data perspective have been advanced. Implementation of these frameworks require multi-modal data and a shift towards open science and principles such as requiring data to be FAIR (Findable, Accessible, Interoperable and Reusable). Advanced analytics such as artificial intelligence require data to be interoperable so data can be exchanged among different technology systems and software applications. The TBI field has multiple ongoing initiatives to promote sharing and data reuse for both pre-clinical and clinical studies, which is an opportunity for the SCI field given these injuries can often occur concomitantly. The adoption of interoperable standards, data sharing, open science, and the use of advanced analytics in SCI is needed to facilitate translation in research and care. It is critical that people with lived experience are engaged to ensure data are relevant and enhances quality of life., Competing Interests: Declaration of competing interest AAP is a consultant for ONWARD Medical and a shareholder of ResearchAlly, SpineAlly, and ONWARD Medical. VKN and SH are employees of the Praxis Spinal Cord Institute. None of the other authors have anything to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

During peripheral nervous system development, Schwann cells undergo Rac1-dependent cytoskeletal reorganization as they insert cytoplasmic extensions into axon bundles to radially sort, ensheath, and myelinate individual axons. However, our understanding of the direct effectors targeted by Rac1 is limited. Here, we demonstrate that striatin-3 and MOB4 are novel Rac1 interactors. We show that, similar to Rac1-null Schwann cells, Schwann cell specific ablation of striatin-3 causes defects in lamellipodia formation. In addition, conditional Schwann cell knockout of multiple striatin proteins presents a severe delay in radial sorting. Finally, we demonstrate here that deletion of Rac1 or striatin-1/3 in Schwann cells causes defects in Hippo pathway regulation, phosphorylation of the Hippo pathway effectors YAP and TAZ, and expression of genes co-regulated by YAP and TAZ, such as extracellular matrix receptors. In summary, our results indicate that striatin-3 is a novel Rac1 interactor, show that striatin proteins are required for peripheral nervous system development, and reveal a role for Rac1 in regulation of the Hippo pathway in Schwann cells.

Background: Chest wall perforator flaps are emerging in oncoplastic breast conservation, mostly as an alternative to mastectomy. However, standardization and consensus on patient selection, techniques, and outcomes have not yet been reached. The aim of this international multicentre collaborative study was to explore practice patterns and outcomes in high-volume centres from different countries., Methods: Patients with both pre-invasive and invasive breast cancer treated at the Uppsala University Hospital in Uppsala, Sweden, the Royal Marsden Hospital in London, UK, and the Westmead Breast Cancer Institute in Sydney, Australia, were included in this study. The rationale for offering chest wall perforator flaps and surgical outcomes were prospectively documented., Results: In total, 603 patients were analysed median age of 54 (interquartile range (i.q.r.) 48-63) years, median BMI of 25.0 (i.q.r. 22.5-28.1) kg/m2, median tumour extent of 30 (IQR 19-45) mm, median breast volume of 280 (i.q.r. 216-430) ml, and median calculated resection ratio of 16% (i.q.r. 9%-28%). In 67.7%, the treating surgeon had offered chest wall perforator flaps to avoid mastectomy. The procedure was performed as day surgery in 69.5% of patients, with an overall complication rate of 8.6% and the majority of complications being classified as Clavien-Dindo grade I (5.3% of patients). The re-excision rate was 15.9%, with only 1.5% of patients converting to a mastectomy. There were no flap losses. At a median follow-up of 22 (range 12 to 98) months, rates of local recurrence, distant recurrence, and breast cancer-related mortality were 1.9%, 4.9%, and 1.7% respectively., Conclusion: Chest wall perforator flaps are a useful option to allow more women to avoid mastectomy. In experienced hands, the procedure is safe and should be offered to suitable patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Objectives: To investigate whether there are empirically-detectable subgroups of concussion severity and recovery across three consecutive concussions, as well as to define risk factor and clinical assessment differences across subgroups., Methods: The present study was a retrospective chart review of 202 adolescents 13.17 ± 1.99 years old who presented to a concussion specialty clinic within 30 days of injury for multiple injuries between 2019 and 2020. Participants included patients from a specialty clinic for two (n = 202) or three (n = 68) total concussions. Latent class analysis (LCA) was used to identify subgroups based upon concussion symptom severity and recovery time. Risk factors (sex, age at first injury, and histories of anxiety, depression, migraine, motion sickness, ocular dysfunction, and attention-deficit/hyperactivity disorder [ADHD] or learning disability [LD]) were compared across subgroups., Results: A two-class solution yielded one group of 163 participants characterized by lower symptoms and shorter recovery times (80.7%, "normal") and 39 participants (19.3%, "miserable minority") characterized by higher symptoms and longer recovery times. Only female sex (OR = 4.91, p = 0.005) was a significant predictor of class membership. The miserable group presented for treatment nearly 4 days later (9.41 days) compared to the normal group (5.74 days) for the first injury, and almost 2 days later for the second injury (7.33 vs 5.26 days)., Conclusions: Approximately 1 in 5 patients who presented to a concussion specialty clinic for a repeat concussion were classified in the miserable minority subgroup. This subgroup was characterized by markedly higher initial symptom burdens and over double the recovery time., Level of Evidence: Retrospective cohort study, Level III evidence., Competing Interests: Conflicts of interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Systematic screening can help identify antiseizure medication (ASM)-associated adverse events (AEs) that may preclude patients from reaching effective doses or completing adequate trial periods. The Adverse Event Profile (AEP) is a self-completed instrument to identify the frequency of common AEs associated with ASM use. This study aimed to compare the AE profile of commonly used ASMs in adults with newly diagnosed focal epilepsy., Methods: The Human Epilepsy Project is a prospective, international, observational study investigating markers of treatment response in newly diagnosed focal epilepsy. Participants were enrolled within 4 months of treatment initiation. Adult participants on levetiracetam, lamotrigine, carbamazepine, or oxcarbazepine monotherapy who completed the AEP and Mini International Neuropsychiatric Interview at enrollment were included. Multivariable generalized linear and penalized logistic regression models assessed differences in total and itemized marginal AEP scores and dichotomized responses ("never/rarely" vs "sometimes/always")., Results: A total of 225 adults initiated on levetiracetam (n = 132, 59%), lamotrigine (n = 55, 24%), carbamazepine (n = 19, 8.4%), or oxcarbazepine (n = 19, 8.4%) were included. There were no significant differences in AEP total scores between ASMs. Patients with depression (adjusted marginal score ratio [aMSR] 1.23, 95% CI 1.09-1.39, p = 0.001) and anxiety (aMSR 1.15, 95% CI 1.04-1.26, p = 0.007) had worse AEP total scores than those without. After adjusting for depression and anxiety, levetiracetam users were >3 times more likely to report feelings of aggression (adjusted odds ratio [aOR] 3.38, 95% CI 1.07-10.7, p = 0.038) and almost half as likely to experience unsteadiness (aOR 0.45, 95% CI 0.21-0.99, p = 0.047) than lamotrigine users. Carbamazepine and oxcarbazepine had the highest rates of discontinuation (42.1%, each), followed by levetiracetam (34.8%) and lamotrigine (16.4%). Levetiracetam users had the highest proportion of discontinuations because of AEs alone (18%), and lamotrigine had the lowest (5%)., Discussion: Systematic screening for AEs in adults with newly diagnosed focal epilepsy on ASM monotherapy showed that those with comorbid psychiatric conditions report greater AEs overall, irrespective of ASM. Levetiracetam was associated with >3-fold risk of psychiatric AEs and half the risk of experiencing unsteadiness than lamotrigine. Levetiracetam had the highest proportion of discontinuations because of AEs alone, while lamotrigine had the lowest.

Objective: The Human Epilepsy Project (HEP) is a large multinational cohort study of people with newly diagnosed and treated focal epilepsy. HEP utilized the Cogstate Brief Battery (CBB) as a self-directed online assessment to examine cognitive outcomes in study participants. The CBB has previously been validated in healthy individuals and people with various brain disorders, but its use in adults participating in HEP has not been assessed. In this study, we describe how the CBB was used in the HEP cohort and assess factors associated with test completion among study participants., Methods: Enrollment data for HEP included 408 participants with comprehensive enrollment records, of whom 249 completed CBB assessments. HEP enrolled cognitively normal-range participants between the ages of 12 and 60 from June 29, 2012, to November 7, 2017, with newly diagnosed focal epilepsy and within 4 months of initial treatment. Baseline participant characteristics were analyzed, including demographics, pre-treatment seizure histories, MRI abnormalities, and the presence of any learning difficulties while in school, including formal learning disability diagnoses, repeated grades, and remediation. HEP participant characteristics for those who completed CBB testing were compared to those who did not using multiple logistic regression., Results: The analysis of HEP participants who completed CBB testing showed that, after controlling for other factors, male participants were more likely to engage in testing (OR 2.14, 95 % CI 1.29 to 3.5, p < 0.01), Black subjects were less likely (OR 0.45, 95 % CI 0.22 to 0.9, p = 0.02), primary English speakers were more likely (OR 3.1, 95 % CI 1.21 to 7.96, p = 0.02), and those with a history of learning challenges were less likely (OR 0.69, 95 % CI 0.49 to 0.97, p = 0.03). There were no significant associations between completing CBB testing and age, employment (employed or student vs not), education (higher education vs not), diagnostic delay, pre-diagnostic seizure burden, or initial seizure semiology (motor vs non-motor)., Significance: The findings from this study highlight factors associated with the application of remote and unsupervised assessments of cognition in a prospective cohort of adults with focal epilepsy. These factors can be considered when interpreting performance on the CBB in HEP, as well as assisting the design of future studies that use similar approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge the data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components, monophosphoryl lipid A (MPL) and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus-lining macrophages, monocytes, and DCs. AS01 induced DC maturation and a strong proinflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests that the onset of the immune response to AS01 required a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike the response to R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.

Background and Objectives: Participants with treatment-resistant epilepsy who are randomized to add-on placebo and remain in a trial for the typical 3 to 5-month maintenance period may be at increased risk of adverse outcomes. A novel trial design has been suggested, time to prerandomization monthly seizure count (T-PSC), which would limit participants' time on ineffective therapy. We reanalyzed 11 completed trials to determine whether the primary efficacy conclusions at T-PSC matched each of the original, longer trials., Methods: A total of 11 double-blind, placebo-controlled trials of levetiracetam, brivaracetam, lacosamide, topiramate, and lamotrigine for either focal-onset or generalized-onset epilepsy were selected. We evaluated the group-level and individual-level efficacy of treatments including the median percent reduction (MPR) in seizure frequency and 50% responder rate (50RR) at T-PSC, time to second seizure, and time to first seizure compared with the full-length trial., Results: The primary efficacy conclusions of 10 of the 11 trials would have been the same with a T-PSC design compared with the traditional design (the exception of lamotrigine had a very high initial placebo response). As a proportion of the full-length effect size, 90% of the MPR and 85% of the 50RR were seen at T-PSC (95% CI 73%-113% and 65%-110%, respectively). Using the T-PSC design, the time on blinded treatment was at least 312 participant-years shorter (40% of total duration) and 142,000 seizures occurred during this time (60% of total seizures). By contrast, the time to first or second seizure designs reproduced group-level effect size, but the primary efficacy conclusions of each trial and individual-level efficacy correspondence were fair to poor., Discussion: These results support the use of this trial design for new epilepsy medication trials because this reanalysis of 11 randomized controlled trials demonstrated that observation until T-PSC was sufficient to demonstrate efficacy while potentially improving participant safety by reducing the time of exposure to placebo and inadequate treatment. Despite analysis of 11 trials including 3,619 participants, we did not observe a significant reduction in the group-level effect size, which is directly related to statistical power. The next step is to evaluate whether T-PSC is sufficient to evaluate safety as measured by adverse events.

Background: Cardiogenic shock (CS) is common and survival outcomes have not substantially improved. Australia's geography presents unique challenges in the management of CS. The challenges and research priorities for clinicians pertaining to CS identification and management have yet to be described., Method: We used an exploratory sequential mixed methods design. Semi-structured interviews were conducted with 10 clinicians (medical and nursing) to identify themes for quantitative evaluation. A total of 143 clinicians undertook quantitative evaluation through online survey. The interviews and surveys addressed current understanding of CS, status of cardiogenic systems and future research priorities., Results: There were 143 respondents: 16 (11%) emergency, cardiology 22 (16%), 37 (26%) intensive care, 54 (38%) nursing. In total, 107 (75%) believe CS is under-recognised. Thirteen (13; 9%) of respondents indicated their hospital had existing CS teams, all from metropolitan hospitals, and 40% thought additional access to mechanical circulatory support devices was required. Five (5; 11%) non-tertiary hospital respondents had not experienced a delay in transfer of a patient in CS. All respondents felt additional research, particularly into the management of CS, was required., Conclusions: Clinicians report that CS is under-recognised and further research into CS management is required. Access to specialised CS services is still an issue and CS protocolised pathways may be of value., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The COVID-19 pandemic resulted in modifications to resident selection. The success of these new recruitment strategies as well as the impact on trainee attrition and competency is unknown. We previously evaluated how selection of general surgery applicants changed early in the pandemic. Here we supplement that work by reporting further modifications to the recruitment process and the perceived impact on resident attrition and competency., Methods: An anonymous cross-sectional survey sent via the Association of Program Directors in Surgery listserv in June 2022 to programs directors (PDs) at Accreditation Council for Graduate Medical Education accredited general surgery programs. Surveys contained demographic questions, 5-point Likert scale questions evaluating factors related to recruitment and match process, and postgraduate year 1 performance., Results: 60 PDs responded to the survey. PDs continue to value the same post-COVID factors related to determining a resident's commitment to surgery but began to shift back to nonvirtual based strategies to recruit applicants in this new interview cycle. PD commentary frequently noted desire to return to in-person interviewing. 5.4% of postgraduate year 1s comprising this first class of residents who underwent virtual-only interviews and rotations did not reach Accreditation Council for Graduate Medical Education level 1 milestones, similar to prior years. The attrition rate amongst this class increased from 1.3% to 2.7%., Conclusions: The attrition rate for postgraduate year 1 categorical general surgery residents has increased since the onset of the pandemic. The recruitment strategies adopted early in the pandemic have not maintained their initial perceived impact., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Individuals with epilepsy have increased risk of suicidal ideation (SI) and behaviors when compared with the general population. This relationship has remained largely unexplored in adolescents. We investigated the prevalence of suicidality in adolescents with newly diagnosed focal epilepsy within 4 months of treatment initiation and over the following 36 months., Methods: This was a post hoc analysis of the enrollment and follow-up data from the Human Epilepsy Project, an international, multi-institutional study that enrolled participants between 2012 and 2017. Participants enrolled were 11-17 years of age within 4 months of treatment initiation for focal epilepsy. We used data from the Columbia Suicide Severity Rating Scale (C-SSRS), administered at enrollment and over the 36-month follow-up period, along with data from medical records., Results: A total of 66 adolescent participants were enrolled and completed the C-SSRS. At enrollment, 14 (21%) had any lifetime SI and 5 (8%) had any lifetime suicidal behaviors (SBs). Over the following 36 months, 6 adolescents reported new onset SI and 5 adolescents reported new onset SB. Thus, the lifetime prevalence of SI within this population increased from 21% to 30% (14-20 adolescents), and the lifetime prevalence of SB increased from 8% to 15% (5-10)., Discussion: The prevalence of suicidality in adolescents with newly diagnosed focal epilepsy reported in our study is consistent with previous findings of significant suicidality observed in epilepsy. We identify adolescents as an at-risk population at the time of epilepsy diagnosis and in the following years.

Objective: A previous investigation of people with newly diagnosed focal epilepsy participating in the Human Epilepsy Project 1 (HEP1) revealed an association between learning difficulties and structural brain differences, suggesting an underlying relationship prior to seizure onset. To investigate physicians' practices of documentation learning difficulties during clinical encounters, we conducted a review of initial epileptologist encounter notes from HEP1 participants who self-reported early life learning difficulties separately as part of study enrollment., Methods: HEP1 enrolled 67 North American participants between June 2012 and November 2017 who self-reported one or more difficulties with learning (i.e., having repeated grade, receiving learning support/remediation, and/or formal diagnosis of a learning disability) prior to epilepsy diagnosis as part of the study enrollment. The epileptologist's initial encounter note was then reviewed in detail for each of these participants. Documentation of learning issues and specific diagnoses of learning disabilities was compared to participant characteristics. Regression analysis was used to test for any independent associations between participant characteristics and physician documentation of learning difficulties., Results: There were significant independent relationships between age, sex, and physician documentation of learning difficulties. On average, participants ages 22 and younger were 12.12 times more likely to have their learning difficulties documented compared to those 23 years and older (95 % CI: 2.226 to 66.02, p = 0.004). Additionally, male participants had 7.2 times greater odds of having their learning difficulty documented compared to female participants (95 % CI: 1.538 to 33.717, p = 0.012). There were no significant independent associations between race, language, employment, or geographical region., Significance: These findings highlight disparities in physician documentation for people with newly diagnosed focal epilepsy and a history of learning difficulties. In the HEP1 cohort, physicians were more likely to document learning difficulties in males and in younger individuals. Systematic practice standards are important for reducing healthcare disparities across populations, improving clinical care to individuals, as well as enabling more accurate retrospective study of clinical phenomenon., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) contributes greatly to morbidity, mortality, and health care costs worldwide. Hospital readmission rates are tracked closely and determine federal reimbursement dollars. No current modality or technology allows for accurate measurement of relevant HF parameters in ambulatory, rural, or underserved settings. This limits the use of telehealth to diagnose or monitor HF in ambulatory patients., Objective: This study describes a novel HF diagnostic technology using audio recordings from a standard mobile phone., Methods: This prospective study of acoustic microphone recordings enrolled convenience samples of patients from 2 different clinical sites in 2 separate areas of the United States. Recordings were obtained at the aortic (second intercostal) site with the patient sitting upright. The team used recordings to create predictive algorithms using physics-based (not neural networks) models. The analysis matched mobile phone acoustic data to ejection fraction (EF) and stroke volume (SV) as evaluated by echocardiograms. Using the physics-based approach to determine features eliminates the need for neural networks and overfitting strategies entirely, potentially offering advantages in data efficiency, model stability, regulatory visibility, and physical insightfulness., Results: Recordings were obtained from 113 participants. No recordings were excluded due to background noise or for any other reason. Participants had diverse racial backgrounds and body surface areas. Reliable echocardiogram data were available for EF from 113 patients and for SV from 65 patients. The mean age of the EF cohort was 66.3 (SD 13.3) years, with female patients comprising 38.3% (43/113) of the group. Using an EF cutoff of ≤40% versus >40%, the model (using 4 features) had an area under the receiver operating curve (AUROC) of 0.955, sensitivity of 0.952, specificity of 0.958, and accuracy of 0.956. The mean age of the SV cohort was 65.5 (SD 12.7) years, with female patients comprising 34% (38/65) of the group. Using a clinically relevant SV cutoff of <50 mL versus >50 mL, the model (using 3 features) had an AUROC of 0.922, sensitivity of 1.000, specificity of 0.844, and accuracy of 0.923. Acoustics frequencies associated with SV were observed to be higher than those associated with EF and, therefore, were less likely to pass through the tissue without distortion., Conclusions: This work describes the use of mobile phone auscultation recordings obtained with unaltered cellular microphones. The analysis reproduced the estimates of EF and SV with impressive accuracy. This technology will be further developed into a mobile app that could bring screening and monitoring of HF to several clinical settings, such as home or telehealth, rural, remote, and underserved areas across the globe. This would bring high-quality diagnostic methods to patients with HF using equipment they already own and in situations where no other diagnostic and monitoring options exist., (©Martin Huecker, Craig Schutzman, Joshua French, Karim El-Kersh, Shahab Ghafghazi, Ravi Desai, Daniel Frick, Jarred Jeremy Thomas. Originally published in JMIR Cardio (https://cardio.jmir.org), 26.06.2024.)

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver disease. At the cellular level, liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) which transdifferentiate into a myofibroblast-like phenotype that is contractile, proliferative and profibrogenic. HSC transdifferentiation induces genome-wide changes in gene expression that enable the cell to adopt its profibrogenic functions. We have previously identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation; however, the cellular targets of its deubiquitinating activity are poorly defined. Here, we describe a role for UCHL1 in regulating the levels and activity of hypoxia-inducible factor 1 (HIF1), an oxygen-sensitive transcription factor, during HSC activation and liver fibrosis. HIF1 is elevated during HSC activation and promotes the expression of profibrotic mediator HIF target genes. Increased HIF1α expression correlated with induction of UCHL1 mRNA and protein with HSC activation. Genetic deletion or chemical inhibition of UCHL1 impaired HIF activity through reduction of HIF1α levels. Furthermore, our mechanistic studies have shown that UCHL1 elevates HIF activity through specific cleavage of degradative ubiquitin chains, elevates levels of pro-fibrotic gene expression and increases proliferation rates. As we also show that UCHL1 inhibition blunts fibrogenesis in a pre-clinical 3D human liver slice model of fibrosis, these results demonstrate how small molecule inhibitors of DUBs can exert therapeutic effects through modulation of HIF transcription factors in liver disease. Furthermore, inhibition of HIF activity using UCHL1 inhibitors may represent a therapeutic opportunity with other HIF-related pathologies., (© 2024 The Author(s).)

A Swiss mountain dog, ~3 y old, was brought to a veterinary clinic because of a progressive enlargement of the abdomen. Upon clinical examination, a large mass was detected. After surgical extraction, the mass was confirmed to be a large ovarian teratoma. The weight of the tumor was > 16% of the dog's overall body weight. The dog recovered fully after surgery. The observations from this case suggest that, although teratomas are rare, prompt and accurate diagnosis is necessary to prevent further growth of these masses and to ensure positive outcomes., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Epilepsy diagnosis is often delayed or inaccurate, exposing people to ongoing seizures and their substantial consequences until effective treatment is initiated. Important factors contributing to this problem include delayed recognition of seizure symptoms by patients and eyewitnesses; cultural, geographical, and financial barriers to seeking health care; and missed or delayed diagnosis by health-care providers. Epilepsy diagnosis involves several steps. The first step is recognition of epileptic seizures; next is classification of epilepsy type and whether an epilepsy syndrome is present; finally, the underlying epilepsy-associated comorbidities and potential causes must be identified, which differ across the lifespan. Clinical history, elicited from patients and eyewitnesses, is a fundamental component of the diagnostic pathway. Recent technological advances, including smartphone videography and genetic testing, are increasingly used in routine practice. Innovations in technology, such as artificial intelligence, could provide new possibilities for directly and indirectly detecting epilepsy and might make valuable contributions to diagnostic algorithms in the future., Competing Interests: Declaration of interests JP has received research support from the Department of Neurology at the University of Colorado School of Medicine, the Colorado Clinical and Translational Sciences Institute, National Institutes of Health and National Institute of Neurological Disorders and Stroke, and the American Epilepsy Society. JP serves as chair of the professional advisory board for the Epilepsy Foundation of Colorado and Wyoming (unpaid), serves as the Epilepsy Section Editor for Current Neurology and Neuroscience Reports, and has received compensation for serving on the scientific advisory board for SK Life Science. ECF declares research support from Brain Foundation (Australia), LivaNova (USA), Lundbeck (Australia), Monash Partners STAR Clinician Fellowship, Sylvia and Charles Viertel Charitable Foundation, and The Royal Australian College of Physicians Fellows Research Establishment Fellowship. SMZ serves as the Neurodevelopmental Theme Lead for the Epilepsy Research Institute UK (unpaid). SMZ's institution has received grants related to epilepsy diagnostics from Epilepsy Research UK, Scottish Government Digital Health & Care, and Amazon Web Services. vCreate has contributed donations to SMZ's institution charity. JMW serves as the Associate Editor for Epilepsia (honorarium) and Developmental Medicine and Child Neurology, chief editor of the Pediatric Neurology sub-section of Frontiers in Neurology (honorarium), and serves on the National South African Advisory board for Novartis and Sanofi. JF receives salary support from the Epilepsy Foundation and for consulting work or attending Scientific Advisory Boards on behalf of the Epilepsy Study Consortium for Aeonian/Aeovian, Alterity Therapeutics, Anavex, Arkin Holdings, Angelini Pharma S.p.A, Arvelle Therapeutics, Athenen Therapeutics/Carnot Pharma, Autifony Therapeutics, Baergic Bio, Biogen, Biohaven Pharmaceuticals, BioMarin Pharmaceutical, BioXcel Therapeutics, Bloom Science, BridgeBio Pharma, Camp4 Therapeutics Corporation, Cerebral Therapeutics, Cerevel, Clinical Education Alliance, Coda Biotherapeutics, Corlieve Therapeutics, Crossject, Eisai, Eliem Therapeutics, Encoded Therapeutics, Engage Therapeutics, Engrail, Epalex, Epihunter, Epiminder, Epitel, Equilibre BioPharmaceuticals, Greenwich Biosciences, Grin Therapeutics, GW Pharma, Janssen Pharmaceutica, Jazz Pharmaceuticals, Knopp Biosciences, Lipocine, LivaNova, Longboard Pharmaceuticals, Lundbeck, Marinus, Mend Neuroscience, Merck, NeuCyte, Neumirna Therapeutics, Neurocrine, Neuroelectrics USA Corporation, Neuronetics, Neuropace, NxGen Medicine, Ono Pharmaceutical, Otsuka Pharmaceutical Development, Ovid Therapeutics, Paladin Labs, Passage Bio, Pfizer, Praxis, PureTech LTY, Rafa Laboratories, SK Life Sciences, Sofinnova, Stoke, Supernus, Synergia Medical, Takeda, UCB, Ventus Therapeutics, Xenon, Xeris, Zogenix, and Zynerba. JF has also received research support from the Epilepsy Study Consortium (funded by Andrews Foundation, Eisai, Engage, Lundbeck, Pfizer, SK Life Science, Sunovion, UCB, Vogelstein Foundation), Epilepsy Study Consortium/Epilepsy Foundation (funded by UCB), GW/FACES, and NINDS. JF is on the editorial board of The Lancet Neurology and Neurology Today. JF is Chief Medical/Innovation Officer for the Epilepsy Foundation. JF has received travel reimbursement related to research, advisory meetings, or presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Angelini Pharma S.p.A., Clinical Education Alliance, NeuCyte, Neurocrine, Praxis, and Xenon., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objectives: Many adolescents with undiagnosed focal epilepsy seek evaluation in emergency departments (EDs). Accurate history-taking is essential to prompt diagnosis and treatment. In this study, we investigated ED recognition of motor vs nonmotor seizures and its effect on management and treatment of focal epilepsy in adolescents., Methods: This was a retrospective analysis of enrollment data from the Human Epilepsy Project (HEP), an international multi-institutional study that collected data from 34 sites between 2012 and 2017. Participants were 12 years or older, neurotypical, and within 4 months of treatment initiation for focal epilepsy. We used HEP enrollment medical records to review participants' initial diagnosis and management., Results: A total of 83 adolescents were enrolled between 12 and 18 years. Fifty-eight (70%) presented to an ED before diagnosis of epilepsy. Although most ED presentations were for motor seizures (n = 52; 90%), many patients had a history of nonmotor seizures (20/52 or 38%). Adolescents with initial nonmotor seizures were less likely to present to EDs (26/44 or 59% vs 32/39 or 82%, p = 0.02), and nonmotor seizures were less likely to be correctly identified (2/6 or 33% vs 42/52 or 81%, p = 0.008). A history of initial nonmotor seizures was not recognized in any adolescent who presented for a first-lifetime motor seizure. As a result, initiation of treatment and admission from the ED was not more likely for these adolescents who met the definition of epilepsy compared with those with no seizure history. This lack of nonmotor seizure history recognition in the ED was greater than that observed in the adult group (0% vs 23%, p = 0.03) and occurred in both pediatric and nonpediatric ED settings., Discussion: Our study supports growing evidence that nonmotor seizures are often undiagnosed, with many individuals coming to attention only after conversion to motor seizures. We found this treatment gap is exacerbated in the adolescent population. Our study highlights a critical need for physicians to inquire about the symptoms of nonmotor seizures, even when the presenting seizure is motor. Future interventions should focus on improving nonmotor seizure recognition for this population in EDs.

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05-.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective . Brain-computer interfaces (BCIs) are neuroprosthetic devices that allow for direct interaction between brains and machines. These types of neurotechnologies have recently experienced a strong drive in research and development, given, in part, that they promise to restore motor and communication abilities in individuals experiencing severe paralysis. While a rich literature analyzes the ethical, legal, and sociocultural implications (ELSCI) of these novel neurotechnologies, engineers, clinicians and BCI practitioners often do not have enough exposure to these topics. Approach . Here, we present the IEEE Neuroethics Framework, an international, multiyear, iterative initiative aimed at developing a robust, accessible set of considerations for diverse stakeholders. Main results . Using the framework, we provide practical examples of ELSCI considerations for BCI neurotechnologies. We focus on invasive technologies, and in particular, devices that are implanted intra-cortically for medical research applications. Significance . We demonstrate the utility of our framework in exposing a wide range of implications across different intra-cortical BCI technology modalities and conclude with recommendations on how to utilize this knowledge in the development and application of ethical guidelines for BCI neurotechnologies., (Creative Commons Attribution license.)

Background: Health state utility values provide the quality component of quality-adjusted life years and are essential for health economic analyses, such as the National Institute for Health and Care Excellence Technology Appraisal. The aims of this systematic review were to: catalogue utility values for health states experienced by patients with hand conditions; provide pooled utility estimates for common hand conditions; and determine how utilities have been estimated., Methods: A PRISMA-compliant systematic review and meta-analysis was conducted (registered in PROSPERO, the international prospective register of systematic reviews (CRD42021226098)). Five databases were searched from inception until April 2023 (Embase, MEDLINE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials (CENTRAL)). All studies that reported primary utility values for hand health states in adult patients were eligible for inclusion. Pooled utility estimates were determined across conditions and intervention status using random-effects meta-analysis., Results: A total of 10 254 articles were identified; 57 studies met the full inclusion criteria and reported 363 distinct health state utility values. Health state utility values were estimated using a range of methods; the most common measure was the EQ-5D. Pooled utility estimates for carpal tunnel syndrome and hand osteoarthritis before surgical intervention were 0.69 (95% c.i. 0.66 to 0.73) and 0.63 (95% c.i. 0.60 to 0.67) respectively., Conclusion: Pooled utility estimates for patients with untreated carpal tunnel syndrome and hand osteoarthritis are 11% and 18% lower than age-matched population norms respectively. Hand conditions have a significant detrimental impact on health-related quality of life and this study provides catalogued utility values for use in future economic analyses to support the delivery of value-based hand surgery., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Importance: Establishing a formal definition for neurological device abandonment has the potential to reduce or to prevent the occurrence of this abandonment., Objective: To perform a systematic review of the literature and develop an expert consensus definition for neurological device abandonment., Evidence Review: After a Royal Society Summit on Neural Interfaces (September 13-14, 2023), a systematic English language review using PubMed was undertaken to investigate extant definitions of neurological device abandonment. Articles were reviewed for relevance to neurological device abandonment in the setting of deep brain, vagal nerve, and spinal cord stimulation. This review was followed by the convening of an expert consensus group of physicians, scientists, ethicists, and stakeholders. The group summarized findings, added subject matter experience, and applied relevant ethics concepts to propose a current operational definition of neurological device abandonment. Data collection, study, and consensus development were done between September 13, 2023, and February 1, 2024., Findings: The PubMed search revealed 734 total articles, and after review, 7 articles were found to address neurological device abandonment. The expert consensus group addressed findings as germane to neurological device abandonment and added personal experience and additional relevant peer-reviewed articles, addressed stakeholders' respective responsibilities, and operationally defined abandonment in the context of implantable neurotechnological devices. The group further addressed whether clinical trial failure or shelving of devices would constitute or be associated with abandonment as defined. Referential to these domains and dimensions, the group proposed a standardized definition for abandonment of active implantable neurotechnological devices., Conclusions and Relevance: This study's consensus statement suggests that the definition for neurological device abandonment should entail failure to provide fundamental aspects of patient consent; fulfill reasonable responsibility for medical, technical, or financial support prior to the end of the device's labeled lifetime; and address any or all immediate needs that may result in safety concerns or device ineffectiveness and that the definition of abandonment associated with the failure of a research trial should be contingent on specific circumstances.

Background & Aim: Robotic-assisted percutaneous coronary intervention (R-PCI) has been increasingly performed overseas. Initial observations have demonstrated its clinical efficacy and safety with additional potential benefits of more accurate lesion assessment and stent deployment, with reduced radiation exposure to operators and patients. However, data from randomised controlled trials or clinical experience from Australia are lacking., Methods: This was a single-centre experience of all patients undergoing R-PCI as part of the run-in phase for an upcoming randomised clinical trial (ACTRN12623000480684). All R-PCI procedures were performed using the CorPath GRX robot (Corindus Vascular Robotics, Waltham, Massachusetts, USA). Key inclusion criteria included patients with obstructive coronary disease requiring percutaneous coronary intervention. Major exclusion criteria included ST-elevation myocardial infarction, cardiogenic shock or lesions deemed unsuitable for R-PCI by the operator. Clinical success was defined as residual stenosis <30% without in-hospital major adverse cardiovascular events (MACE). Technical success was defined as the completion of the R-PCI procedure without unplanned manual conversion. Procedural characteristics were compared between early (cases 1-3) and later (cases 4-21) cases., Results: Twenty-one (21) patients with a total of 24 lesions were analysed. The mean age of patients was 66.5 years, and 66% of cases were male. Radial access was used in 18 cases (86%). Most lesions were American Heart Association/American College of Cardiology class B2/C (66%). Clinical success was achieved in 100% with manual conversion required in four cases (19%). No procedural complications or in-hospital MACE occurred. Compared to the early cases, later cases had a statistically significantly shorter fluoroscopy time (44.0mins vs 25.2mins, p<0.007), dose area product (967.3 dGy.cm 2 vs 361.0dGy.cm 2 , p=0.01) and air kerma (2484.3mGy vs 797.4mGy, p=0.009) with no difference in contrast usage (136.7mL vs 131.4mL, p=0.88)., Conclusions: We present the first clinical experience of R-PCI in Australia using the Corindus CorPath GRX robot. We achieved clinical success in all patients and technical success in the majority of cases with no procedural complications or in-hospital MACE. With increasing operator and staff experience, cases required shorter fluoroscopy time and less radiation exposure but similar contrast usage., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate the diagnostic accuracy of common interview questions used to distinguish a diagnosis of epilepsy from seizure mimics including non-epileptic seizures (NES), migraine, and syncope., Methods: 200 outpatients were recruited with an established diagnosis of focal epilepsy (n = 50), NES (n = 50), migraine (n = 50), and syncope (n = 50). Patients completed an eight-item, yes-or-no online questionnaire about symptoms related to their events. Sensitivity and specificity were calculated. Using a weighted scoring for the questions alone with baseline characteristics, the overall questionnaire was tested for diagnostic accuracy., Results: Of individual questions, the most sensitive one asked if events are sudden in onset (98 % sensitive for epilepsy (95 % CI: 89 %, 100 %)). The least sensitive question asked if events are stereotyped (46 % sensitive for epilepsy (95 % CI: 32 %, 60 %)). Overall, three of the eight questions showed an association with epilepsy as opposed to mimics. These included questions about "sudden onset" (OR 10.76, 95 % CI: (1.66, 449.21) p = 0.0047), "duration < 5 min" (OR 3.34, 95 % CI: (1.62, 6.89), p = 0.0008), and "duration not > 30 min" (OR 4.44, 95 % CI: (1.94, 11.05), p = <0.0001). When individual seizure mimics were compared to epilepsy, differences in responses were most notable between the epilepsy and migraine patients. Syncope and NES were most similar in responses to epilepsy. The overall weighted questionnaire incorporating patient age and sex produced an area under the ROC curve of 0.80 (95 % CI: 0.74, 0.87))., Conclusion: In this study, we examined the ability of common interview questions used by physicians to distinguish between epilepsy and prevalent epilepsy mimics, specifically NES, migraines, and syncope. Using a weighted scoring system for questions, and including age and sex, produced a sensitive and specific predictive model for the diagnosis of epilepsy. In contrast to many prior studies which evaluated either a large number of questions or used methods with difficult practical application, our study is unique in that we tested a small number of easy-to-understand "yes" or "no" questions that can be implemented in most clinical settings by non-specialists., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Several investigational agents are under evaluation in systemic lupus erythematosus (SLE) clinical trials but quantitative frameworks to enable comparison of their efficacy to reference benchmark treatments are lacking. To benchmark SLE treatment effects and identify clinically important covariates, we developed a model-based meta-analysis (MBMA) within a latent variable model framework for efficacy end points and SLE composite end point scores (BILAG-based Composite Lupus Assessment and Systemic Lupus Erythematosus Responder Index) using aggregate-level data on approved and investigational therapeutics. SLE trials were searched using PubMed and www.clinicaltrials.gov for treatment name, SLE and clinical trial as search criteria that resulted in four data structures: (1) study and investigational agent, (2) dose and regimen, (3) baseline descriptors, and (4) outcomes. The final dataset consisted of 25 studies and 81 treatment arms evaluating 16 different agents. A previously developed (K Goteti et al. 2022) SLE latent variable model of data from placebo arms (placebo + standard of care treatments) was used to describe aggregate SLE end points over time for the various SLE placebo and treatment arms in a Bayesian MBMA framework. Continuous dose-effect relationships using a maximum effect model were included for anifrolumab, belimumab, CC-220 (iberdomide), epratuzumab, lulizumab pegol, and sifalimumab, whereas the remaining treatments were modeled as discrete dose effects. The final MBMA model was then used to benchmark these compounds with respect to the maximal efficacy on the latent variable compared to the placebo. This MBMA illustrates the application of latent variable models in understanding the trajectories of composite end points in chronic diseases and should enable model-informed development of new investigational agents in SLE., (© 2023 EMD Serono Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Bayesian estimation is a powerful but underutilized tool for answering drug development questions. In this tutorial, the principles of Bayesian model development, assessment, and prior selection will be outlined. An example pharmacokinetic (PK) model will be used to demonstrate the implementation of Bayesian modeling using the nonlinear mixed-effects modeling software NONMEM., (© 2023 Metrum Research Group, Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The International League Against Epilepsy (ILAE) introduced a classification for seizure types in 2017 and updated the classification for epilepsy syndromes in 2022. These classifications aim to improve communication among healthcare professionals and help patients better describe their condition. So far, regulatory agencies have used different terminology. This paper stresses the crucial need for consistently adopting ILAE terminology in both regulatory processes and clinical practice. It highlights how language plays a significant role in healthcare communication and how standardized terminology can enhance patient comprehension. The ongoing review of guidelines by regulatory bodies offers a timely opportunity. Aligning regulatory terminologies holds the potential to facilitate discussions on future drug development and harmonize practices across diverse regions, ultimately fostering improved care and research outcomes in epilepsy treatment., (© 2023 International League Against Epilepsy.)

On January 15, 2022, an ongoing eruption at the Hunga-Tonga Hunga-Ha'apai volcano generated a large explosion which resulted in a globally observed tsunami and atmospheric pressure wave. This paper presents time series observations of the event from Australia including 503 mean sea level pressure (MSLP) sensors and 103 tide gauges. Data is provided in its original format, which varies between data providers, and a post-processed format with consistent file structure and time zone. High-pass filtered variants of the data are also provided to facilitate study of the pressure wave and tsunami. For a minority of tide gauges the raw sea level data cannot be provided, due to licence restrictions, but high-pass filtered data is always provided. The data provides an important historical record of the volcanic pressure wave and tsunami in Australia. It will be useful for research on atmospheric and ocean waves associated with large volcanic eruptions., (© 2024. Crown.)

We present the case of a woman in her 60s with Child-Pugh C cirrhosis who developed pericardial tamponade during an admission for a haemothorax secondary to a mechanical fall. The patient developed haemodynamic compromise with a rapid decline in renal function. During an open subxiphoid drain tube insertion, a pre-existing peritoneopericardial communication was noted, with ascites in the peritoneal cavity on view. The serum ascites albumin gradient was 14 g/L. Maximal medical therapy was commenced including diuresis and albumin, with adjunctive terlipressin infusion which restored her baseline renal function and resolved the effusion. We believe this is the first case report of using open drainage, maximal medical therapy and terlipressin to successfully treat hepatic hydropericardium and its subsequent renal compromise., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study was undertaken to ascertain the natural history and patterns of antiseizure medication (ASM) use in newly diagnosed focal epilepsy patients who were initially started on monotherapy., Methods: The data were derived from the Human Epilepsy Project. Differences between the durations of the most commonly first prescribed ASM monotherapies were assessed using a Cox proportional hazards model. Subjects were classified into three groups: monotherapy, sequential monotherapy, and polytherapy., Results: A total of 443 patients were included in the analysis, with a median age of 32 years (interquartile range [IQR] = 20-44) and median follow-up time of 3.2 years (IQR = 2.4-4.2); 161 (36.3%) patients remained on monotherapy with their initially prescribed ASM at the time of their last follow-up. The mean (SEM) and median (IQR) duration that patients stayed on monotherapy with their initial ASM was 2.1 (2.0-2.2) and 1.9 (.3-3.5) years, respectively. The most commonly prescribed initial ASM was levetiracetam (254, 57.3%), followed by lamotrigine (77, 17.4%), oxcarbazepine (38, 8.6%), and carbamazepine (24, 5.4%). Among those who did not remain on the initial monotherapy, 167 (59.2%) transitioned to another ASM as monotherapy (sequential monotherapy) and 115 (40.8%) ended up on polytherapy. Patients remained significantly longer on lamotrigine (mean = 2.8 years, median = 3.1 years) compared to levetiracetam (mean = 2.0 years, median = 1.5 years) as a first prescribed medication (hazard ratio = 1.5, 95% confidence interval = 1.0-2.2). As the study progressed, the proportion of patients on lamotrigine, carbamazepine, and oxcarbazepine as well as other sodium channel agents increased from a little more than one third (154, 34.8%) of patients to more than two thirds (303, 68.4%) of patients., Significance: Slightly more than one third of focal epilepsy patients remain on monotherapy with their first prescribed ASM. Approximately three in five patients transition to monotherapy with another ASM, whereas approximately two in five end up on polytherapy. Patients remain on lamotrigine for a longer duration compared to levetiracetam when it is prescribed as the initial monotherapy., (© 2023 International League Against Epilepsy.)

Background Aligning resident and training program attributes is critical. Many programs screen and select residents using assessment tools not grounded in available evidence. This can introduce bias and inappropriate trainee recruitment. Prior reviews of this literature did not include the important lens of diversity, equity, and inclusion (DEI). Objective This study's objective is to summarize the evidence linking elements in the Electronic Residency Application Service (ERAS) application with selection and training outcomes, including DEI factors. Methods A systematic review was conducted on March 30, 2022, concordant with PRISMA guidelines, to identify the data supporting the use of elements contained in ERAS and interviews for residency training programs in the United States. Studies were coded into the topics of research, awards, United States Medical Licensing Examination (USMLE) scores, personal statement, letters of recommendation, medical school transcripts, work and volunteer experiences, medical school demographics, DEI, and presence of additional degrees, as well as the interview. Results The 2599 identified unique studies were reviewed by 2 authors with conflicts adjudicated by a third. Ultimately, 231 meeting inclusion criteria were included (kappa=0.53). Conclusions Based on the studies reviewed, low-quality research supports use of the interview, Medical Student Performance Evaluation, personal statement, research productivity, prior experience, and letters of recommendation in resident selection, while USMLE scores, grades, national ranking, attainment of additional degrees, and receipt of awards should have a limited role in this process.

Conversion to a prepectoral implant pocket is considered the definitive treatment for breast animation after implant-based breast reconstruction. Although subtle movement of implants placed in the prepectoral plane may be noted on clinical examination by experienced surgeons, current data demonstrate complete resolution of animation deformity with prepectoral implant placement. We present the case of a middle-aged women who underwent breast implant pocket conversion from dual-plane to prepectoral plane for treatment of animation deformity. Although her postoperative recovery was unremarkable with initial resolution of animation, recurrent implant animation was evident on 3-month follow-up. Recurrent breast animation after conversion from dual-plane to prepectoral implant pocket is highly unusual and unreported in the current literature. Although revision surgery may identify potential causes, larger-scale research on contributing factors will be valuable in developing strategies to prevent recurrent animation after conversion to a prepectoral implant pocket., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: Visual assessment of magnetic resonance imaging (MRI) from the Human Epilepsy Project 1 (HEP1) found 18% of participants had atrophic brain changes relative to age without known etiology. Here, we identify the underlying factors related to brain volume differences in people with focal epilepsy enrolled in HEP1., Methods: Enrollment data for participants with complete records and brain MRIs were analyzed, including 391 participants aged 12-60 years. HEP1 excluded developmental or cognitive delay with intelligence quotient <70, and participants reported any formal learning disability diagnoses, repeated grades, and remediation. Prediagnostic seizures were quantified by semiology, frequency, and duration. T1-weighted brain MRIs were analyzed using Sequence Adaptive Multimodal Segmentation (FreeSurfer v7.2), from which a brain tissue volume to intracranial volume ratio was derived and compared to clinically relevant participant characteristics., Results: Brain tissue volume changes observable on visual analyses were quantified, and a brain tissue volume to intracranial volume ratio was derived to compare with clinically relevant variables. Learning difficulties were associated with decreased brain tissue volume to intracranial volume, with a ratio reduction of .005 for each learning difficulty reported (95% confidence interval [CI] = -.007 to -.002, p = .0003). Each 10-year increase in age at MRI was associated with a ratio reduction of .006 (95% CI = -.007 to -.005, p < .0001). For male participants, the ratio was .011 less than for female participants (95% CI = -.014 to -.007, p < .0001). There were no effects from seizures, employment, education, seizure semiology, or temporal lobe electroencephalographic abnormalities., Significance: This study shows lower brain tissue volume to intracranial volume in people with newly treated focal epilepsy and learning difficulties, suggesting developmental factors are an important marker of brain pathology related to neuroanatomical changes in focal epilepsy. Like the general population, there were also independent associations between brain volume, age, and sex in the study population., (© 2023 International League Against Epilepsy.)

Despite advances in therapy, the incidence of cardiogenic shock continues to increase, with significant mortality that has improved minimally over time. Treatment options for cardiogenic shock are complex and time-, resource-, and case volume-dependent, and involve multiple medical specialties. To provide early, more equitable, and standardised access to cardiogenic shock expertise with advanced therapies, cardiogenic shock teams with a protocolised treatment approach have been proposed. These processes have been applied across hospitals into integrated cardiogenic shock networks. This narrative review evaluates the role of cardiogenic shock teams, protocolised and regionalised shock networks, and the main individual components of protocolised shock management approaches., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

A conversion from subpectoral breast reconstruction to pre-pectoral breast reconstruction can help with animation resolution and improved patient satisfaction. We describe the conversion technique involving removal of the existing implant, creating a neo-pre-pectoral pocket and restoring the pectoral muscle to its natural position., (© 2023 Royal Australasian College of Surgeons.)

Background: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings., Methods: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected. The main outcome was inter-centre reliability, which was quantified using overall agreement, as well as the chance-corrected Krippendorff's alpha statistic. Based on the latter, the level of agreement was classified as: 'slight' (0.00-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80), or 'near-perfect' (>0.80)., Results: Twenty-one patients were reviewed at 12 retroperitoneal sarcoma multidisciplinary team meetings, giving a total of 252 assessments for analysis. Consistency between centres was only 'slight' to 'fair', with rates of overall agreement and Krippendorff's alpha statistics of 85.4 per cent (211 of 247) and 0.37 (95 per cent c.i. 0.11 to 0.57) for resectability; 80.4 per cent (201 of 250) and 0.39 (95 per cent c.i. 0.33 to 0.45) for treatment allocation; and 53.0 per cent (131 of 247) and 0.20 (95 per cent c.i. 0.17 to 0.23) for the organs proposed to be resected. Depending on the centre that they had attended, 12 of 21 patients could either have been deemed resectable or unresectable, and 10 of 21 could have received either potentially curative or palliative treatment., Conclusions: Inter-centre agreement between retroperitoneal sarcoma multidisciplinary team meetings was low. Multidisciplinary team meetings may not provide the same standard of care for patients with retroperitoneal sarcoma across Great Britain., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Invasive plants threaten biodiversity worldwide and effective management must control the target invader while conserving biodiversity. Herbicide is often used to control invasive plants, but potential negative impacts on biodiversity have led to spot spraying being recommended over boom spraying to minimize the exposure of nontarget species to chemicals. We examined the influence of herbicide application methods on off-target plant communities in threatened temperate grasslands of southeastern Australia, where spraying with the broadleaf herbicide fluroxypr is commonly used to control St. John's wort, Hypericum perforatum L. It is well established that fluroxypr effectively controls H. perforatum but few studies have examined its impact on native forbs. A spray drift experiment using water-sensitive cards indicated that ground surface coverage was higher for spot spraying (91%-99%) than for boom spraying (5%-31%). We established a replicated, 3-year, before-after-control-impact experiment across 48 1-m 2 quadrats to determine how three herbicide application methods (spot spray, fine boom and coarse boom) affected nontarget native forbs, the group most likely to be affected by broadleaf herbicides. This experiment was conducted in grasslands where H. perforatum was almost absent, so responses would reflect the direct impacts of the chemical, rather than structural changes resulting from removal of the target invader. Spot spraying decreased the probability of occurrence of native leguminous forbs, while increasing the occurrence of exotic leguminous forbs and the richness of all exotic species and exotic annual forbs. Spot spraying reduced the occurrence of the native Desmodium varians and the abundance of the native Chrysocephalum apiculatum. During this 3-year study, native species appeared to be impacted either directly by fluroxypr or indirectly by increased competition with exotic species. Where herbicide application is deemed crucial in these grasslands, we recommend boom spraying when H. perforatum density is moderate to high. Spot spraying should only be used when the density of H. perforatum is very low. Given the regional variation in H. perforatum density, the spatial scale of invasion, soil depth, and conservation values, we present a decision tree to assist managers in evaluating the costs and benefits of chemical control, indicating situations where alternative or modified methods could be used., (© 2023 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Background: A survey of laboratories in North American and Europe that routinely conduct fetal skeletal examinations was performed with the purpose of (1) understanding current terminology used for classifying skeletal findings in developmental toxicity (DT) studies and (2) understanding the criteria used to identify relatively common findings that sufficiently deviate from normal. The goal was to promote terminology harmonization and improve interlaboratory consistency in the criteria used to identify developmental anomalies., Methods: The survey, designed based on terminology for developmental anomalies recommended by an international collaboration (Makris et al., Congenital Anomalies, 2009;49(3):123-246), was conducted by a subgroup (authors of this publication) of the Royal Society of Biology's International Register of Fetal Morphologists (IRFM)., Results: Individual and summarized anonymized responses are provided here. The authors, who are expert fetal morphologists with experience performing fetal examinations, reviewed the responses and generated recommendations on preferred terminology and criteria for determining when morphological variations deviate from normal and warrant recording of the findings for skeletal observations in Sprague Dawley (SD) fetal rats. The objective of these recommendations is to complement Makris et al. (Congenital Anomalies, 2009;49(3):123-246)., Conclusion: The broad application will improve interlaboratory harmonization of recording fetal skeleton findings in developmental toxicity studies intended for regulatory submissions, including SEND (Standard for Exchange of Nonclinical Data)., (© 2023 Wiley Periodicals LLC.)

Introduction: To facilitate continuation of school feeding during COVID-19 school lockdowns, U.S. Congress authorized waivers to allow for school meals to be picked up by parents/guardians in non-school settings. We summarized school meals distribution and characterized reach in socially vulnerable neighborhoods in New Orleans, a city prone to environmental disasters, with a city-wide charter school system, and historically high levels of child poverty and food insecurity., Methods: School meals operations data were obtained from New Orleans, Louisiana (NOLA) Public Schools for 3/16/2020-5/31/2020. For each pick-up location, we estimated: average meals available (weekly), average meals served (weekly), number of weeks of operation, and rate of meal pick-up ([meals served/meals available]*100). These characteristics were mapped in QGIS v3.28.3, along with neighborhoods' Social Vulnerability Index (SVI). Pearson correlation and ANOVA were run to assess differences between operations characteristics and neighborhood SVI., Results: From 38 meal sites, 884,929 meals were available for pick-up; 74% of pick-up sites were in moderately/highly socially vulnerable areas. Correlations between average meals available and served, weeks of operation, rate of meal pick-up, and SVI were weak and not statistically significant. SVI was associated with average rate of meal pick-up but not other operations characteristics., Discussion: Despite the disaggregated nature of the charter school system, NOLA Public Schools successfully pivoted to providing children with pick-up meals due to COVID-19 lockdowns, with 74% of sites located in socially vulnerable neighborhoods. Future studies should describe the types of meals provided to students during COVID-19, in terms of diet quality and nutrient adequacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chaparro, French, Creveling, Ennin, Numa and Knapp.)