Epilepsy Surgery for Pharmacoresistant Temporal Lobe Epilepsy: A Decision Analysis

Context Patients with pharmacoresistant epilepsy have increased mortality compared with the general population, but patients with pharmacoresistant temporal lobe epilepsy who meet criteria for surgery and who become seizure-free after anterior temporal lobe resection have reduced excess mortality vs those with persistent seizures. Objective To quantify the potential survival benefit of anterior temporal lobe resection for patients with pharmacoresistant temporal lobe epilepsy vs continued medical management. Design Monte Carlo simulation model that incorporates possible surgical complications and seizure status, with 10 000 runs. The model was populated with health-related quality-of-life data obtained directly from patients and data from the medical literature. Insufficient data were available to assess gamma-knife radiosurgery or vagal nerve stimulation. Main Outcome Measures Life expectancy and quality-adjusted life expectancy. Results Compared with medical management, anterior temporal lobe resection for a 35-year-old patient with an epileptogenic zone identified in the anterior temporal lobe would increase survival by 5.0 years (95% CI, 2.1-9.2) with surgery preferred in 100% of the simulations. Anterior temporal lobe resection would increase quality-adjusted life expectancy by 7.5 quality-adjusted life-years (95%, CI, −0.8 to 17.4) with surgery preferred in 96.5% of the simulations, primarily due to increased years spent without disabling seizures, thereby reducing seizure-related excess mortality and improving quality of life. The results were robust to sensitivity analyses. Conclusion The decision analysis model suggests that on average anterior temporal lobe resection should provide substantial gains in life expectancy and quality-adjusted life expectancy for surgically eligible patients with pharmacoresistant temporal lobe epilepsy compared with medical management

Seizures in Alzheimer Disease. Who, When, and How Common?

Background: Transient symptoms in Alzheimer disease (AD) are frequent and include seizures, syncope, and episodes of inattention or confusion. The incidence of seizures in AD and predictors of which patients with AD might be more predisposed to them is based primarily on retrospective studies and is not well established. Objective: To determine the incidence and predictors of new-onset unprovoked seizures. Design: Prospective cohort study. Setting: Three academic centers. Patients: Four hundred fifty-three patients with probable AD observed prospectively from mild disease stages since 1992. Main Outcome Measure: Informant interviews every 6 months included questions about whether the patient had a seizure (convulsion, fainting, or “funny” spell) and whether diagnosis or treatment for epilepsy or seizure was made. Two epileptologists independently retrospectively reviewed all available medical records for 52 patients with positive responses to either of these questions, and using a specific checklist form, events were diagnosed as to whether they were unprovoked seizures (intrarater concordance, κ = 0.67). Diagnosis of unprovoked seizures constituted the event in survival analyses. Potential predictors included sex, age, race/ethnicity, educational achievement, duration of illness, baseline cognition and function, depression, medical comorbidities, and time-dependent use of cholinesterase inhibitors and neuroleptic agents, apolipoprotein E genotype, and previous electroencephalographic findings. Results: Over the course of 3518 visit-assessments (per patient: mean, 7.8; maximum, 27), 7 patients (1.5%) developed seizures. Younger age was associated with higher risk (hazard ratio, 1.23; 95% confidence interval, 1.08-1.41; P = .003 for each additional year of age) of seizure incidence. No other predictor was significant. The overall incidence of seizures was low (418 per 100 000 person-years of observation) although significantly higher than expected for idiopathic unprovoked seizures in similar age ranges of the general population (hazard ratio, 8.06; 95% confidence interval, 3.23-16.61). Conclusions: Unprovoked seizures are uncommon in AD, but they do occur more frequently than in the general population. Younger age is a risk factor for seizures in AD

Pharmacogenetics Meets Metabolomics: Discovery of Tryptophan as a New Endogenous OCT2 Substrate Related to Metformin Disposition

Genetic polymorphisms of the organic cation transporter 2 (OCT2), encoded by SLC22A2, have been investigated in association with metformin disposition. A functional decrease in transport function has been shown to be associated with the OCT2 variants. Using metabolomics, our study aims at a comprehensive monitoring of primary metabolite changes in order to understand biochemical alteration associated with OCT2 polymorphisms and discovery of potential endogenous metabolites related to the genetic variation of OCT2. Using GC-TOF MS based metabolite profiling, clear clustering of samples was observed in Partial Least Square Discriminant Analysis, showing that metabolic profiles were linked to the genetic variants of OCT2. Tryptophan and uridine presented the most significant alteration in SLC22A2-808TT homozygous and the SLC22A2-808G>T heterozygous variants relative to the reference. Particularly tryptophan showed gene-dose effects of transporter activity according to OCT2 genotypes and the greatest linear association with the pharmacokinetic parameters (Clrenal, Clsec, Cl/F/kg, and Vd/F/kg) of metformin. An inhibition assay demonstrated the inhibitory effect of tryptophan on the uptake of 1-methyl-4-phenyl pyrinidium in a concentration dependent manner and subsequent uptake experiment revealed differential tryptophan-uptake rate in the oocytes expressing OCT2 reference and variant (808G>T). Our results collectively indicate tryptophan can serve as one of the endogenous substrate for the OCT2 as well as a biomarker candidate indicating the variability of the transport activity of OCT2

The Effects of Differential Instruction on Korean Middle School Students English Collocation Acquisition

This study examined whether explicit or implicit teaching is more efficient in improving Korean middle school students English verb−noun collocation knowledge. Forty Korean EFL middle school students participated in the study and they were assigned to either the explicit instruction or implicit instruction group. The participants English verb−noun collocation knowledge was measured through pre-, immediate post-, and delayed post-tests over the 5-week experimental period, and a survey of participants opinions on the instruction they received was carried out. The results showed that the students who received the explicit collocation instruction displayed better learning outcomes, suggesting the immediate influence of the explicit instruction, and more importantly the sustained initial advantage. That is, the explicit group students did retain the target items significantly better than the implicit group students. The responses from the two groups also indicated the positive effects of the explicit collocation instruction. The explicit group students were mostly satisfied with the instruction and showed increased confidence in acquiring English collocations while the implicit students did not. This study provides L2 teachers with valuable information on how to teach L2 collocation more effectively

Helpfulness of online consumer reviews: readers' objectives and review cues

With the growth of e-commerce, online consumer reviews have increasingly become important sources of information that help consumers in their purchase decisions. However, the influx of online consumer reviews has caused information overload, making it difficult for consumers to choose reliable reviews. For an online retail market to succeed, it is important to lead product reviewers to write more helpful reviews, and for consumers to get helpful reviews more easily by figuring out the factors determining the helpfulness of online reviews. For this research, 75,226 online consumer reviews were collected from Amazon.com using a Web data crawler. Additional information on review content was also gathered by carrying out a sentiment analysis for mining review text. Our results show that both peripheral cues, including review rating and reviewer's credibility, and central cues, such as the content of reviews, influence the helpfulness of reviews. Based on dual process theories, we find that consumers focus on different information sources of reviews, depending on their purposes for reading reviews: online reviews can be used for information search or for evaluating alternatives. Our findings provide new perspectives to online market owners on how to manage online reviews on their Web sites

Implementing Smart Factory:A Fuzzy-set Analysis to Uncover Successful Paths

Despite the pervasiveness of the Fourth Industrial Revolution, few studies have examined the adoption of smart factories. Scholars have long examined firms' willingness to adopt smart factories. Thus, this study heeds this call by investigating the factors driving the adoption of smart factories. It employs a fuzzy-set configuration approach to capture the complex interactions underlying these drivers in the context of South Korean marine equipment firms. Based on data from a sample of 180 respondents, the findings revealed four complex paths with factors including government support, the entrepreneurial spirit of top management, efficiency expectation, and financial preparedness shaping the high and low implementation of smart factories. Theoretically, the findings are an exception to extant technology acceptance models. Practically, the attention of practitioners in South Korea and other similar contexts was drawn

Brain Computer Interface-Based Action Observation Game Enhances Mu Suppression in Patients with Stroke

Action observation (AO), based on the mirror neuron theory, is a promising strategy to promote motor cortical activation in neurorehabilitation. Brain computer interface (BCI) can detect a user’s intention and provide them with brain state-dependent feedback to assist with patient rehabilitation. We investigated the effects of a combined BCI-AO game on power of mu band attenuation in stroke patients. Nineteen patients with subacute stroke were recruited. A BCI-AO game provided real-time feedback to participants regarding their attention to a flickering action video using steady-state visual-evoked potentials. All participants watched a video of repetitive grasping actions under two conditions: (1) BCI-AO game and (2) conventional AO, in random order. In the BCI-AO game, feedback on participants’ observation scores and observation time was provided. In conventional AO, a non-flickering video and no feedback were provided. The magnitude of mu suppression in the central motor, temporal, parietal, and occipital areas was significantly higher in the BCI-AO game than in the conventional AO. The magnitude of mu suppression was significantly higher in the BCI-AO game than in the conventional AO both in the affected and unaffected hemispheres. These results support the facilitatory effects of the BCI-AO game on mu suppression over conventional AO

Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use

Purpose: To determine rates of cross-sensitivity of intolerable psychiatric and behavioral side effects (IPBSEs) among commonly used antiepileptic drugs (AEDs) in adult patients with epilepsy. Methods: IPBSE was defined as a psychiatric or behavioral side effect attributed to AED use that led to a decrease in dose or cessation of an AED. Cross-sensitivity was calculated and was defined as the likelihood of developing IPBSE to a specific AED given IPBSE to another AED. Our sample consisted of 2312 adult patients that were prescribed 2 or more AEDs. Non-AED confounders and were controlled for in all analyses. Results: Among the 2312 patients, 20.2% of patients who had taken at least 2 AEDs had IPBSE(s) attributed to at least one AED; 3.5% had IPBSE to two or more AEDs. History of treated depression and psychosis were found to be significant predictors (p < 0.001) of developing IPBSE and were controlled for in all AED-specific analyses. Cross-sensitivity was seen between LEV and ZNS (p < 0.001). There was a significant increase in odds of experiencing IPBSE to LEV (41.5%; OR = 2.7; p < 0.001) or ZNS (22.1%; OR = 3.5; p < 0.001) given a patient had IPBSE to another AED compared to having no IPBSE to other AEDs (20.5% and 7.5%, respectively). Conclusion: History of depression and psychosis increased risk of developing IPBSE to AEDs. The probability of experiencing IPBSE increased for a patient taking LEV or ZNS if the patient experienced IPBSE to another AED. Our results may be clinically useful for predicting IPBSE associated with certain AEDs

Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy

Psychiatric and behavioral side effects (PBSEs) are common, undesirable effects associated with antiepileptic drug (AED) use. The objective of the study was to compare the PBSE profiles of older and newer AEDs in a large specialty practice-based sample of patients diagnosed with epilepsy. As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 4085 adult patients (age: 18 years) newly started on an AED regimen. Psychiatric and behavioral side effects were determined by patient or physician report in the medical record, which included depressive mood, psychosis, anxiety, suicidal thoughts, irritability, aggression, and tantrum. Significant non-AED predictors of PBSE rate were first determined from 83 variables using logistic regression. Predictors were then controlled for in the comparison analysis of the rate of PBSEs and intolerable PBSEs (PBSEs that led to dosage reduction or discontinuation) between 18 AEDs. Psychiatric and behavioral side effects occurred in 17.2% of patients and led to intolerability in 13.8% of patients. History of psychiatric condition(s), secondary generalized seizures, absence seizures, and intractable epilepsy were associated with increased incidence of PBSE. Levetiracetam (LEV) had the greatest PBSE rate (22.1%). This was statistically significant when compared with the aggregate of the other AEDs (P<0.001, OR=6.87). Levetiracetam was also significantly (P<0.001) associated with higher intolerability rate (17.7%), dose decreased rate (9.4%), and complete cessation rate (8.3%), when compared with the aggregate of the other AEDs. Zonisamide (ZNS) was also significantly associated with a higher rate of PBSE (9.7%) and IPBSE (7.9%, all P<0.001). On the other hand, carbamazepine (CBZ), clobazam (CLB), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OXC), phenytoin (PHT), and valproate (VPA) were significantly associated with a decreased PBSE rates (P<0.001). Carbamazepine, GBP, LTG, PHT, and VPA were also associated with lower IPBSE rates when compared individually with the aggregate of other AEDs. All other AEDs were found to have intermediate rates that were not either increased or decreased compared with other AEDs. When each AED was compared to LTG, only CBZ had a significantly lower PBSE rate. The main limitations of this study were that the study design was retrospective and not blinded, and the AEDs were not randomly assigned to patients. Psychiatric and behavioral side effects occur more frequently in patients taking LEV and ZNS than any other AED and led to higher rates of intolerability. Lower PBSE rates were seen in patients taking CBZ, CLB, GBP, LTG, OXC, PHT, and VPA. Our findings may help facilitate the AED selection process. •Rates of psychiatric and behavioral side effect (PBSE) are compared between AEDs.•History of psychiatric condition and seizures failing to improve with ≥2 AEDs are associated with PBSEs.•History of absence and secondarily generalized seizures are associated with PBSEs.•Levetiracetam and zonisamide are associated with higher PBSEs.•Lower PBSE rates are seen in carbamazepine compared with that in lamotrigine