Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.

Impact of positive airway pressure therapy on intraocular pressure in obstructive sleep apnea: A systematic review.

BACKGROUND: Positive airway pressure (PAP) therapy has been reported to have variable effect on intraocular pressure (IOP) in patients with obstructive sleep apnea (OSA) . The objective of this review is to present a qualitative assessment of available literature on impact of PAP on IOP in patients of OSA.Method: Online databases were searched for relevant articles up to September 2023. It included randomized control trial (RCT), prospective observational study, case control study, cross-sectional study, published abstract having relevant information. The comparator group consisted of OSA patients not receiving the PAP therapy or the pre-PAP IOP. Studies reporting change in IOP immediately after PAP use, at 1 month and at 1 year of PAP use were included. For quality assessment Cochrane Risk of Bias tool version 2 and NIH study quality assessment tool for Before-After (Pre-Post) Studies with No Control Group was used.Result: In this systematic review of ten clinical studies with 191 patients of OSA, use of continuous positive airway pressure (CPAP) therapy led to an immediate increase in IOP but it was not significantly different from non-CPAP users. One month and 1 year of CPAP use led to a significant increase in IOP from the baseline value. CONCLUSION: The available albeit limited evidence suggests that CPAP use, particularly at higher pressures, is linked to an elevation in IOP. However, high quality evidence from well-designed RCTs is needed to confirm or refute this findings.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient-centered outcomes in daily practice.

Culture change and lessons learned from ten years in the VA centers of excellence in primary care education.

BACKGROUND: Team-based care is critical to achieving health care value while maximizing patient outcomes. Few descriptions exist of graduate-level team training interventions and practice models. Experience from the multisite, decade-long Veterans Affairs (VA) Centers of Excellence in Primary Care Education provides lessons for developing internal medicine training experiences in interprofessional clinical learning environments. METHODS: A review of multisite demonstration project transforming traditional silo-model training to interprofessional team-based primary care. Using iterative quality improvement approaches, sites evaluated curricula with learner, faculty and staff feedback. Learner- and patient-level outcomes and organizational culture change were examined using mixed methods, within and across sites. Participants included more than 1600 internal medicine, nurse practitioner, nursing, pharmacy, psychology, social work and physical therapy trainees. This took place in seven academic university-affiliated VA primary care clinics with patient centered medical home design RESULTS: Each site developed innovative design and curricula using common competencies of shared decision making, sustained relationships, performance improvement and interprofessional collaboration. Educational strategies included integrated didactics, workplace collaboration and reflection. Sites shared implementation best practices and outcomes. Cross-site evaluations of the impacts of these educational strategies indicated improvements in trainee clinical knowledge, team-based approaches to care and interest in primary care careers. Improved patient outcomes were seen in the quality of chronic disease management, reduction in polypharmacy, and reduced emergency department and hospitalizations. Evaluations of the culture of training environments demonstrated incorporation and persistence of interprofessional learning and collaboration. CONCLUSIONS: Aligning education and practice goals with cross-site collaboration created a robust interprofessional learning environment. Improved trainee/staff satisfaction and better patient care metrics supports use of this model to transform ambulatory care training. TRIAL REGISTRATION: This evaluation was categorized as an operation improvement activity by the Office of Academic Affairs based on Veterans Health Administration Handbook 1058.05, in which information generated is used for business operations and quality improvement (Title 38 Code of Federal Regulations Part 16 (38 CFR 16.102(l)). The overall project was subject to administrative oversight rather Human Subjects Institutional Review Board, as such informed consent was waived as part of the project implementation and evaluation.

Construction and validation of an algorithm to separate focal and generalised epilepsy using clinical variables: A comparison of machine learning approaches.

PURPOSE: Epilepsy type, whether focal or generalised, is important in deciding anti-seizure medication (ASM). In resource-limited settings, investigations are usually not available, so a clinical separation is required. We used a naïve Bayes approach to devise an algorithm to do this, and compared its accuracy with algorithms devised by five other machine learning methods. METHODS: We used data on 28 clinical variables from 503 patients attending an epilepsy clinic in India with defined epilepsy type, as determined by an epileptologist with access to clinical, imaging, and EEG data. We adopted a machine learning approach to select the most relevant variables based on mutual information, to train the model on part of the data, and then to evaluate it on the remaining data (testing set). We used a naïve Bayes approach and compared the results in the testing set with those obtained by several other machine learning algorithms by measuring sensitivity, specificity, accuracy, area under the curve, and Cohen's kappa. RESULTS: The six machine learning methods produced broadly similar results. The best naïve Bayes algorithm contained eleven variables, and its accuracy was 92.2% in determining epilepsy type (sensitivity 92.0%, specificity 92.7%). An algorithm incorporating the best eight of these variables was only slightly less accurate - 91.0% (sensitivity 89.6%, and specificity 95.1%) - and easier for clinicians to use. CONCLUSION: A clinical algorithm with eight variables is effective and accurate at separating focal from generalised epilepsy. It should be useful in resource-limited settings, by epilepsy-inexperienced doctors, to help determine epilepsy type and therefore optimal ASMs for individual patients, without the need for EEG or neuroimaging.

Therapeutic Potential of Cornus Genus: Navigating Phytochemistry, Pharmacology, Clinical Studies, and Advanced Delivery Approaches.

The genus Cornus (Cornaceae) plants are widely distributed in Europe, southwest Asia, North America, and the mountains of Central America, South America, and East Africa. Cornus plants exhibit antimicrobial, antioxidative, antiproliferative, cytotoxic, antidiabetic, anti-inflammatory, neuroprotective and immunomodulatory activities. These plants are exploited to possess various phytoconstituents such as triterpenoids, iridoids, anthocyanins, tannins and flavonoids. Pharmacological research and clinical investigations on various Cornus species have advanced significantly in recent years. Over the past few decades, a significant amount of focus has also been made into developing new delivery systems for Cornus mas and Cornus officinalis. This review focuses on the morphological traits, ethnopharmacology, phytochemistry, pharmacological activities and clinical studies on extracts and active constituents from plants of Cornus genus. The review also highlights recent novel delivery systems for Cornus mas and Cornus officinalis extracts to promote sustained and targeted delivery in diverse disorders. The overwhelming body of research supports the idea that plants from the genus Cornus have therapeutic potential and can be investigated in the future for treatingseveral ailments.

Stimuli-responsive magnetic silica-poly-lactic-co-glycolic acid hybrid nanoparticles for targeted cancer chemo-immunotherapy.

Chemotherapy and immunotherapy are two important modalities in cancer management. However, due to multiple reasons, a monotherapy is only partially effective. Hence, if used concurrently in targeted and stimuli-responsive manner, it could have been superior therapeutically. To facilitate co-delivery of chemotherapeutic and immunotherapeutic agent to the target cancer cells, engineered nanoparticles, i.e., a pH-responsive polymer PLGA-coated magnetic silica nanoparticles (Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs) encapsulating paclitaxel (PTX) and siRNA against programmed cell death ligand-1 (PD-L1) are synthesized and characterized. Developed nanoparticles demonstrated pH-sensitive sustained drug release up to 10 days. In vitro 4T1 cell line studies showed efficient cellular uptake, PD-L1 gene downregulation, and apoptosis. Further, in vivo efficacy studies carried out in the mice model demonstrated a significant reduction of tumor growth following treatment with dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs as compared with monotherapy with Fe3O4-SiO2-PLGA-PDA-PTX NPs. The high therapeutic efficacy observed with dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs was mainly due to the cytotoxic effect of PTX combined with targeted silencing of the gene of interest, i.e., PD-L1, which in turn improve CD8+ T cell-mediated cancer cell death as evident with increased proliferation of CD8+ T cells in co-culture experiments. Thereby, dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs may have a promising anti-cancer treatment potential against breast cancer; however, the beneficial effects of dual loading of PTX + PD-L1 siRNA may be corroborated against other cancer models such as lung and colorectal cancer models as well as in clinical trials.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

A bis-quinoline ruthenium(II) arene complex with submicromolar cytotoxicity in castration-resistant prostate cancer cells.

A new Ru(II) arene chlorido organometallic complex [(η6-p-cymene)(L)RuCl]PF6 (named as pCYRuL) using 2-bis(quinolin-2-ylmethylene) hydrazine (L) was developed that exhibits potent anticancer activity against castration-resistant prostate cancer (CRPC) (IC50 = 0.71 µM), and it is 45 times more effective than the standard drug cisplatin (IC50 = 31.3 µM) in a castration-resistant human prostatic adenocarcinoma cell line (PC-3) but non-toxic in normal human kidney cells (HK2) as well as normal breast cells (MCF10A) and found that pCYRuL exerted anticancer activity via apoptosis induction and cell cycle arrest in the G2/M phase of PC-3 cells.

The triggering pathway, the metabolic amplifying pathway, and cellular transduction in regulation of glucose-dependent biphasic insulin secretion.

Introduction: Insulin secretion is a highly regulated process critical for maintaining glucose homeostasis. This abstract explores the intricate interplay between three essential pathways: The Triggering Pathway, The Metabolic Amplifying Pathway, and Cellular Transduction, in orchestrating glucose-dependent biphasic insulin secretion.Mechanism: During the triggering pathway, glucose metabolism in pancreatic beta-cells leads to ATP production, closing ATP-sensitive potassium channels and initiating insulin exocytosis. The metabolic amplifying pathway enhances insulin secretion via key metabolites like NADH and glutamate, enhancing calcium influx and insulin granule exocytosis. Additionally, the cellular transduction pathway involves G-protein coupled receptors and cyclic AMP, modulating insulin secretion.Result and Conclusion: These interconnected pathways ensure a dynamic insulin response to fluctuating glucose levels, with the initial rapid phase and the subsequent sustained phase. Understanding these pathways' complexities provides crucial insights into insulin dysregulation in diabetes and highlights potential therapeutic targets to restore glucose-dependent insulin secretion.

Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke: a randomized controlled pilot trial (NACTLYS).

There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of N-acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an acute ischemic stroke within 4.5 h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (p = 0.99), intracranial hemorrhage (p = 0.21), symptomatic intracerebral hemorrhage (p = 0.47), or extracranial bleeding (p = 0.21). Median NIHSS at 24 h was significantly lower in the intervention group (p = 0.03). Functional outcomes and three-month mortality were similar between groups (p = 0.85 and p = 0.99 respectively). The co-administration of N-acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3 months. While no substantial differences were noted, a slightly improved early neurological outcome was observed in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of N-acetylcysteine as a thrombolytic agent in acute ischemic stroke.Trial Registration Clinical Trials Registry India-CTRI/2019/05/019305.

Exploring Models of Exposure to Primary Care Careers in Training: a Narrative Review.

Multiple models of clinical exposure to primary care exist within undergraduate medical education (UME) and graduate medical education (GME). In this narrative review, we explore the evidence behind these different models of exposure, their alignment with positive promoters of primary care careers, and the pros and cons of each. Without positive exposure to primary care during training, sustaining the future primary care work force becomes increasingly challenging. Here, we explore multiple models of clinical exposure in UME, including longitudinal integrated clerkships, primary care tracks, and primary care clerkships. Within GME, we will review the impact of primary care tracks, Area Health Education Centers, block scheduling models, and continuity clinic scheduling models. The goal of this narrative review is to allow educators to think broadly and intentionally about the array of models to develop positive primary care experiences and perceptions in training, ultimately sustaining the primary care workforce.

Development of Health Professions Education Competencies for a National Fellowship Program: A Group Consensus Process.

ABSTRACT: Health professions educators need knowledge, skills, and attitudes to provide high-quality education within dynamic clinical learning environments. Although postgraduate training opportunities in health professions education (HPE) have increased significantly, no shared competencies exist across the field. This article describes the systematic development of postgraduate HPE competencies for the Health Professions Education, Evaluation, and Research (HPEER) Advanced Fellowship, a 2-year, interprofessional, post-master's degree and postdoctoral HPE training program funded through the Department of Veterans Affairs' Office of Academic Affiliations. Using a modified RAND/University of California at Los Angeles Appropriateness Method, the authors developed competencies from March 2021 to August 2021 that were informed by current practices and standards in HPE. Literature reviews were conducted of published literature from November 2020 to February 2021 and gray literature from February to March 2021, identifying 78 and 274 HPE training competencies, respectively. These competencies were combined with 71 competencies submitted by program faculty from 6 HPEER fellowship sites, resulting in 423 initial competencies. Competencies were organized into 6 primary domains and condensed by deleting redundant items and combining overlapping concepts. Eight subject matter experts completed 3 Delphi surveys and met during 2 nominal group technique meetings. The final 25 competencies spanned 6 domains: teaching methods and learning theories; educational assessment and program evaluation; educational research methods; diversity, equity, and inclusion; interprofessional practice and team science; and leadership and management. In addition to informing the national HPEER curriculum, program evaluation, and learner assessment, these advanced competencies describe the knowledge, skills, and attitudes health professions educators need to provide high-quality education with an emphasis on the global and societal impact of HPE. These competencies represent a step toward leveraging HPE expertise to establish competencies to drive HPE program changes. Other programs should report their competencies and competency development processes to spur further dialog and progress.

Comparison of nutritional quality of fourteen wild Linum species based on fatty acid composition, lipid health indices, and chemometric approaches unravelling their nutraceutical potential.

Fatty acid profiles of 14 Linum species was determined by GC-MS analysis to study the nutritional quality of Linum species based on fatty acid composition, lipid health indices, and chemometric approaches. L. lewisii and L. marginale found to have the highest content of ALA i.e., 65.38 % and 62.79 %, respectively, L. tenuifolium recorded the highest linoleic acid content (69.69 %), while, L. catharticum recorded highest oleic acid (27.03 %). Health indices viz. polyunsaturated fatty acids/saturated fatty acids ratio, n-6/n-3 fatty acids ratio, atherogenicity, thrombogenicity, oxidability, oxidative stability, hypocholesterolemic/hypercholesterolemic fatty acids, and peroxidisability calculated based on the fatty acid composition revealed that all the linseed species except L. aristatum, L. tenuifolium and L. hudsoniodes have healthy fatty acid composition. L. lewisii clearly emerges as a promising species followed by L. bienne with great values across multiple indices, making them as a potential candidate for dietary or nutritional interests. The lipid profile of Linum species could be well distinguished by two principal components by Principal Component Analysis (PCA).

Development and Implementation of a Medical School Course Integrating Basic, Clinical, and Health Systems Sciences.

OBJECTIVE: In recent years, significant steps have been made in integrating basic science and clinical medicine. There remains a gap in adding the third pillar of education: health systems science (HSS). Core clerkships represent an ideal learning venue to integrate all three. Students can experience the value of integrating basic science as they learn clinical medicine in environments where HSS is occurring all around them. METHODS: We outline the creation of Sciences and Art of Medicine Integrated (SAMI), a course that runs parallel with the clerkship year and integrates basic science and HSS with clinical medicine. A complete description of the planning and implementation of SAMI is provided. We include the participants and educational setting, the goals and objectives, and the structure of each session. To encourage the integration of basic science, HSS, and clinical medicine, students utilize a series of tools, described in detail. Examples of each tool are provided utilizing a case of a patient presenting with obstructive sleep apnea. RESULTS: We successfully implemented this course with positive reception from students. CONCLUSION: This course represents a step not only toward the integration of HSS with basic science and clinical medicine but also an advancement in training future clinicians to provide high-value care. Future curricular development must consider the validation of a measure of clinical reasoning that assesses a student's ability to think in a cognitively integrated fashion about basic science, HSS, and clinical medicine demonstrated by enhanced justification of clinical reasoning and a more holistic approach to planning patient care.

Comprehensive Outcome Assessment and Quality of Life Following Epilepsy Surgery.

BACKGROUND: Seizure freedom without deficits is the primary goal for epilepsy surgery. However, patients with medically refractory epilepsy commonly suffer from many co-morbidities related to mood, cognition, and sleep as well as social problems and resultant stigma. While epilepsy surgery literature does describe quality of life (QOL) and neuropsychological outcomes, there is a paucity of information on various common non-seizure outcomes, especially pertaining to mood, sleep, cognition, and social aspects. The objective of this study was to evaluate the role of various non-seizure parameters on post-epilepsy surgery QOL. METHODS: Consecutive adult patients operated for refractory epilepsy at least 1 year prior to initiation of this study were included and classified as seizure-free (group 1) or non-seizure-free (group 2). QOL was assessed using the QOLIE-31 instrument; patients with a T score less than 40 were categorized as "poor QOL." Non-seizure parameters assessed were cognition, mood disturbances, social improvement, social stigma, and sleep disturbances. Categorization into "good" and "poor" outcome subgroups on each item was carried out by dichotomization of scores. RESULTS: Thirty-seven patients (16 F) [mean age 23.5 ± 5.6 years] were evaluated; 26 were seizure-free (group 1). In this group, impaired memory, lower language scores, depression, not having been employed, not receiving education prior to surgery, and experiencing social stigma were factors significantly associated with poor QOL. In group 2, all patients had poor QOL scores. CONCLUSION: Non-seizure factors related to common epilepsy co-morbidities and social issues are highly prevalent among seizure-free patients reporting poor QOL after epilepsy surgery.

Comparative Efficacy of Chemical Peeling Agents in the Treatment of Melasma.

BACKGROUND: Melasma is a complex skin disorder characterized by brown or dark patches, primarily affecting facial areas. Despite numerous treatment options, the effective management of melasma remains challenging. This study aims to fill a gap in the literature by rigorously comparing the effectiveness of three prevalent chemical peeling agents, 15% trichloroacetic acid (TCA), 15% phenol, and 2% glycolic acid, in treating melasma. MATERIALS AND METHODS: A randomized controlled trial was conducted involving patients who were clinically diagnosed with melasma. Participants were divided into three groups, each receiving one of the chemical peeling treatments. The primary measure of efficacy was the Melasma Area and Severity Index (MASI) score, recorded before and after the treatment series. Side effects were also documented and analyzed. RESULTS: Preliminary findings suggest a significant reduction in MASI scores in the group treated with 15% TCA peel. The average MASI score reduction was 8.5 points for the TCA group, 6.0 points for the phenol group, and 5.2 points for the glycolic acid group. Side effects such as redness and mild irritation were noted but were least prevalent in the TCA group. CONCLUSION: Our study indicates that 15% TCA peel is not only effective but also comparatively safer in treating melasma. It shows a more rapid and significant improvement in reducing melasma symptoms than 15% phenol and 2% glycolic acid peels. However, further research is warranted to validate these findings over a larger population.