Patterns of antiseizure medication utilization in the Human Epilepsy Project.

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.

NR5A1 mutations are not associated with male infertility in Indian men.

NR5A1 or steroidogenic factor 1 (SF1) is an autosomal gene, which encodes a protein that is a member of nuclear receptor family. NR5A1 regulates the transcription of numerous genes that are expressed in hypothalamic-pituitary-gonadal axis and adrenal cortex which in turn, coordinate the gonadal development, steroidogenesis and sex differentiation. Several mutations in NR5A1 have been reported to cause gonadal dysgenesis with adrenal insufficiency in individuals with 46,XY karyotype. However, studies in the past few years have shown that NR5A1 mutations can also contribute to primary ovarian insufficiency and impaired spermatogenesis. As there is no genetic study on NR5A1 in Indian infertile men, we have sequenced the entire coding region (exons 2-7) of NR5A1 in 502 infertile men of which, 414 were non-obstructive azoospermic and 88 severe oligozoospermic, along with 427 ethnically matched fertile controls. Interestingly, none of the mutations reported to be associated with male infertility were found in our study, except one polymorphism, rs1110061. However, it was not significantly different between infertile and fertile groups (p = .76). In addition, we have identified six intronic variants; but none of them was significantly associated with male infertility.

A review on versatile applications of biomaterial/polycationic chitosan: An insight into the structure-property relationship.

Chitosan is a versatile and generous biopolymer obtained by alkaline deacetylation of naturally occurring chitin, the second most abundant biopolymer after cellulose. The excellent physicochemical properties of polycationic chitosan are attributed to the presence of varied functional groups such as amino, hydroxyl, and acetamido groups enabling researchers to tailor the structure and properties of chitosan by different methods such as crosslinking, grafting, copolymerization, composites, and molecular imprinting techniques. The prepared derivatives have diverse applications in the food industry, water treatment, cosmetics, pharmaceuticals, agriculture, textiles, and biomedical applications. In this review, numerous applications of chitosan and its derivatives in various fields have been discussed in detail with an insight into their structure-property relationship. This review article concludes and explains the chitosan's biocompatibility and efficiency that has been done so far with future usage and applications as well. Moreover, the possible mechanism of chitosan's activity towards several emerging fields such as energy storage, biodegradable packaging, photocatalysis, biorefinery, and environmental bioremediation are also discussed. Overall, this comprehensive review discusses the science and complete information behind chitosan's wonder function to improve our understanding which is much needful as well as will pave the way towards a sustainable future.

Mood and Anxiety Disorders and Suicidality in Patients With Newly Diagnosed Focal Epilepsy: An Analysis of a Complex Comorbidity.

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

Interrater Reliability of Expert Electroencephalographers Identifying Seizures and Rhythmic and Periodic Patterns in EEGs.

BACKGROUND AND OBJECTIVES: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC. METHODS: This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as "seizure (SZ)," "lateralized periodic discharges (LPDs)," "generalized periodic discharges (GPDs)," "lateralized rhythmic delta activity (LRDA)," "generalized rhythmic delta activity (GRDA)," or "other." EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement [PA] between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability. RESULTS: Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median [range] of variance explained ([Formula: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Formula: see text]: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds. DISCUSSION: Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus.

Development of Expert-Level Classification of Seizures and Rhythmic and Periodic Patterns During EEG Interpretation.

BACKGROUND AND OBJECTIVES: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as "ictal-interictal-injury continuum" (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns. METHODS: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet, to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes. RESULTS: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and "other" classes, SPaRCNet exceeds the following percentages of 20 experts-ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively. DISCUSSION: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists.

Bridging Intention and Action for Employee Well-Being Using the Intentional Action (InAct) Process: Workshop-Lecture Series.

BACKGROUND: Employee wellness programs can help manage stress and alleviate burnout. OBJECTIVE: To pilot and disseminate the Intentional Action(InAct) concept for employee wellbeing. METHODS: Five independent interactive workshop-lectures with an automated audience response system. Descriptive analysis of participant response data. RESULTS: Participants (n = 275): rated spirituality, physical environment and nutrition the most highly in contributing to their present well-being. Ninety-eight percent (n = 269) of participants identified a focus area to work on. The well-being area most selected was Exercise, (35% n = 95), however, other non-traditional areas, including Personal and Professional Development (18% n = 48), Relationships and Communication (17% n = 47), were selected, along with mind-body connection and mindful awareness (6% n = 15 and n = 16). CONCLUSION: The pilot engaged employees to reflect and set goals for their future well-being. Healthcare institutions implementing programs should consider a broad range of whole person strategies addressing employee well-being, which go beyond the traditional focus on exercise and nutrition.

Medical Cannabis State and Federal Regulations: Implications for United States Health Care Entities.

Thirty-six states and four territories in the United States have legalized cannabis for medical and/or recreational use. Marijuana, however, continues to be classified as a schedule I substance under the Federal Controlled Substance Act and remains illegal under US federal law. The incongruity between state and federal legislation creates various challenges for stakeholders: patients, medical trainees, providers, and health care institutions. This communication provides an overview of the major policies impacting Cannabis sativa use within the United States, various state and federal regulations, and highlights potential implications for health care institutions moving forward. Existing literature, regulations, and policies on medical marijuana (MMJ) use in health care settings were searched, reviewed, analyzed, and distilled. As a consequence of legislative inconsistencies, there is insufficient clarity and resultant challenges regarding MMJ usage, prescription, possession, education, and research-related policies for health care stakeholders across the United States. Coupled with limited scientific evidence on the clinical efficacy of MMJ, the needs of the patient and the quality of health care delivery may be affected as hospitals balance the competing risks of being legislatively compliant while protecting the rights of patients and health care employees. There is a recognized need to better define acceptable MMJ policies and regulations in health care settings that are evidence-based, legally compliant, and adequately address the needs of both patients and providers. Given the complexity of the legal and policy landscape, there are potential opportunities for improvement, including in medical education and training, research, and usage oversight of MMJ for stakeholders in the United States.

Sounds of seizures.

PURPOSE: A phase I feasibility study to determine the accuracy of identifying seizures based on audio recordings. METHODS: We systematically generated 166 audio clips of 30 s duration from 83 patients admitted to an epilepsy monitoring unit between 1/2015 and 12/2016, with one clip during a seizure period and one clip during a non-seizure control period for each patient. Five epileptologists performed a blinded review of the audio clips and rated whether a seizure occurred or not, and indicated the confidence level (low or high) of their rating. The accuracy of individual and consensus ratings were calculated. RESULTS: The overall performance of the consensus rating between the five epileptologists showed a positive predictive value (PPV) of 0.91 and a negative predictive value (NPV) of 0.66. The performance improved when confidence was high (PPV of 0.96, NPV of 0.70). The agreement between the epileptologists was moderate with a kappa of 0.584. Hyperkinetic (PPV 0.92, NPV 0.86) and tonic-clonic (PPV and NPV 1.00) seizures were most accurately identified. Seizures with automatisms only and non-motor seizures could not be accurately identified. Specific seizure-related sounds associated with accurate identification included disordered breathing (PPV and NPV 1.00), rhythmic sounds (PPV 0.93, NPV 0.80), and ictal vocalizations (PPV 1.00, NPV 0.97). CONCLUSION: This phase I feasibility study shows that epileptologists are able to accurately identify certain seizure types from audio recordings when the seizures produce sounds. This provides guidance for the development of audio-based seizure detection devices and demonstrate which seizure types could potentially be detected.

Early myoclonus following anoxic brain injury.

BACKGROUND: It is unknown whether postanoxic cortical and subcortical myoclonus are distinct entities with different prognoses. METHODS: In this retrospective cohort study of 604 adult survivors of cardiac arrest over 8.5 years, we identified 111 (18%) patients with myoclonus. Basic demographics and clinical characteristics of myoclonus were collected. EEG reports, and, when available, raw video EEG, were reviewed, and all findings adjudicated by 3 authors blinded to outcomes. Myoclonus was classified as cortical if there was a preceding, time-locked electrographic correlate and otherwise as subcortical. Outcome at discharge was determined using Cerebral Performance Category. RESULTS: Patients with myoclonus had longer arrests with less favorable characteristics compared to patients without myoclonus. Cortical myoclonus occurred twice as often as subcortical myoclonus (59% vs 23%, respectively). Clinical characteristics during hospitalization did not distinguish the two. Rates of electrographic seizures were higher in patients with cortical myoclonus (43%, vs 8% with subcortical). Survival to discharge was worse for patients with myoclonus compared to those without (26% vs 39%, respectively), but did not differ between subcortical and cortical myoclonus (24% and 26%, respectively). Patients with cortical myoclonus were more likely to be discharged in a comatose state than those with subcortical myoclonus (82% vs 33%, respectively). Among survivors, good functional outcome at discharge was equally possible between those with cortical and subcortical myoclonus (12% and 16%, respectively). CONCLUSIONS: Cortical and subcortical myoclonus are seen in every sixth patient with cardiac arrest and cannot be distinguished using clinical criteria. Either condition may have good functional outcomes.

A major miss in prognostication after cardiac arrest: Burst suppression and brain healing.

We report a case with therapeutic hypothermia after cardiac arrest where meaningful recovery far exceeded anticipated negative endpoints following cardiac arrest with loss of brainstem reflexes and subsequent status epilepticus. This man survived and recovered after an out-of-hospital cardiac arrest followed by a 6-week coma with absent motor responses and 5 weeks of burst suppression. Standard criteria suggested no chance of recovery. His recovery may relate to the effect of burst-suppression on EEG to rescue neurons near neuronal cell death. Further research to understand the mechanisms of therapeutic hypothermia and late restoration of neuronal functional capacity may improve prediction and aid end-of-life decisions after cardiac arrest.

Macular and retinal nerve fiber layer analysis of normal and glaucomatous eyes in children using optical coherence tomography.

PURPOSE: To evaluate macular and nerve fiber layer (NFL) thickness in normal and glaucomatous eyes of children 3 to 17 years old using optical coherence tomography (OCT-3). DESIGN: Observational cross-sectional study. METHODS: One hundred fifty-six eyes of 79 patients were enrolled in this institutional study. Fifty-two eyes (33.3%) met criteria for glaucoma and 104 (66.7%) were normal. There were 44 female (55.6%) and 35 male (44.3%) subjects whose ages ranged from 3 to 17 years old (mean 9.5 years, standard deviation 3.5 years, median 9 years). The OCT-3 (Carl Zeiss Meditec, Dublin, California) was used to obtain a fast macular thickness map as well as a fast retinal NFL map of each eye. Data from specific locations around the macula, as well as total macular volume, was analyzed. Similarly, the retinal NFL scan reports average NFL thickness from specific locations around the optic nerve. Data from the superior temporal and inferior temporal sections was analyzed. RESULTS: There was a statistically significant difference in macular thickness and NFL thickness when normal eyes were compared against those with glaucoma, in all quadrants studied (all P values

The influence of thread geometry on biomechanical load transfer to bone: A finite element analysis comparing two implant thread designs.

BACKGROUND: The success of dental implants depends on the manner in which stresses are transferred to the surrounding bone. An important consideration is to design an implant with a geometry that will minimize the peak bone stresses caused by standard loading. The aim of this study was to assess the influence of implant thread geometry on biomechanical load transfer and to compare the difference between two different thread designs. MATERIALS AND METHODS: A three-dimensional finite element model of D2 bone representing mandibular premolar region was constructed. Two implants of differing thread geometries, 13-mm length, and 4-mm diameter along with superstructures were simulated. One design featured fourfold microthread of 0.4-mm pitch, 0.25-mm depth in the crestal one-third; 0.8-mm pitch, 0.5-mm depth in the apical two-third. The other design had a single-pitch microthread of 0.8-mm pitch, 0.25-mm depth in the crestal one-third; 0.8-mm pitch, 0.5-mm depth in the apical two-third. A static axial load of 100-N was applied to the occlusal surface of the prosthesis. ANSYS CLASSIC 9.0 (PA,USA)software was used for stress analysis as von Mises stresses. RESULTS: A comparison of von Mises stresses between two thread designs revealed that fourfold microthread allows better stress distribution within the implant body by 43.85%, abutment by 15.68%, its superstructure by 39.70% and 36.30% within cancellous bone as compared to single-pitch microthread. The effective stress transfer to the cortical bone is lowered by 60.47% with single-pitch microthread. CONCLUSION: Single-pitch microthread dissipates lesser stresses to cortical bone while the implant body, abutment, and superstructure absorb more stress. This will have a positive influence on the bone-implant contact and contribute to preservation of crestal bone. Implant with single pitch microthread will thus be preferable to be used in areas where the amount of cortical bone available is less.