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The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.
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Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Polimorfismo de Nucleótido Simple/genética , Anciano , Persona de Mediana Edad , Accidente Cerebrovascular/genética , Predisposición Genética a la Enfermedad/genética , Aterosclerosis/genética , Cromosomas Humanos Par 3/genética , Factores de Riesgo , Genotipo , Arteriosclerosis Intracraneal/genéticaRESUMEN
BACKGROUND: The AntiEpileptic Drug Monitoring in PREgnancy (EMPiRE) model is the only available tool for predicting seizures in pregnant women with epilepsy (WWE) using anti-seizure medications (ASMs); however, its predictive performance requires validation. This study aimed to evaluate the predictive ability of this model in pregnant Chinese WWE and its potential usefulness in clinical practice. METHODS: Data of the EMPiRE model were derived from the EMPiRE study, a prospective multicenter cohort study that recruited women on ASM monotherapy (lamotrigine, carbamazepine, phenytoin or levetiracetam) or polytherapy (lamotrigine with either carbamazepine, phenytoin or levetiracetam). Based on the applicable population of the EMPiRE model, we evaluated 280 patients registered in the Wenzhou Epilepsy Follow-up Registry Database from January 1, 2010, to December 31, 2020. A total of 158 eligible patients were included in the validation cohort. We collected data on the baseline characteristics of patients, eight predictors of the EMPiRE model and outcome events. The outcome was the occurrence of tonic-clonic or non-tonic-clonic seizures at any time in pregnancy up to 6 weeks postpartum. We used the equation of the EMPiRE model to obtain the predicted probabilities of seizures. The predictive ability of the EMPiRE model was quantified by the C-statistic (scale 0-1, values > 0.5 show discrimination), GiViTI calibration test and decision curve analysis (DCA). RESULTS: Of 158 eligible patients, 96 patients (60.8%, 96/158) experienced one or more seizures at any time between pregnancy and 6 weeks postpartum. The EMPiRE model showed good discrimination with a C-statistic of 0.76 (95% confidence interval [CI] 0.70-0.84). The GiViTI calibration belt showed that the predicted probabilities, which ranged from 16 to 96% (95% CI), were lower than the actual probabilities. DCA indicated that the highest net proportional benefit was obtained for predicted probability thresholds of 15-18% and 54-96%. CONCLUSIONS: The EMPiRE model could discriminate well between WWE with and without seizures during pregnancy and 6 weeks postpartum, but the risk of seizures may be underestimated. The limitations of the model for specific medication regimens may limit its real-world application. If the model is further improved, it will be incredibly valuable.
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Anticonvulsivantes , Epilepsia , Embarazo , Femenino , Humanos , Anticonvulsivantes/uso terapéutico , Lamotrigina , Levetiracetam , Fenitoína , Estudios de Cohortes , Mujeres Embarazadas , Estudios Prospectivos , Epilepsia/tratamiento farmacológico , CarbamazepinaRESUMEN
Seizure control in women with epilepsy (WWE) during pregnancy is a vital concern. The aim of this study was to compare changes in seizure frequency and anti-seizure medication (ASM ) therapy in WWE in a real-world setting over three epochs (prepregnancy, pregnancy, and postpregnancy). We screened WWE who were pregnant between 1 January 2010 and 31 December 2020 from the epilepsy follow-up registry database of a tertiary hospital in China. We reviewed and collected follow-up data for the following time periods: 12 months before pregnancy (epoch 1), throughout pregnancy and the first 6 weeks postpartum (epoch 2), and from 6 weeks to 12 months postpartum (epoch 3). Seizures were classified into two categories: tonicâclonic/focal to bilateral tonicâclonic seizures and non-tonicâclonic seizures. The main indicator was the seizure-free rate over the three epochs. Using epoch 1 as a reference, we also compared the percentage of women with an increased seizure frequency, as well as changes in ASM treatment, in epochs 2 and 3. Ultimately, 271 eligible pregnancies in 249 women were included. The seizure-free rates in epoch 1, epoch 2, and epoch 3 were 38.4%, 34.7%, and 43.9%, respectively (P = 0.09). The top three ASMs used in the three epochs were lamotrigine, levetiracetam, and oxcarbazepine. Using epoch 1 as a reference, the percentages of women with increased frequencies of tonicâclonic/focal to bilateral tonicâclonic seizures in epoch 2 and epoch 3 were 17.0% and 14.8%, respectively, while the percentages of women with an increased frequency of non-tonicâclonic seizures in epoch 2 and epoch 3 were 31.0% and 21.8% (P = 0.02). The percentage of women whose ASM dosages were increased in epoch 2 was higher than that in epoch 3 (35.8% vs. 27.3%, P = 0.03). The seizure frequency during pregnancy may not differ significantly from that during prepregnancy and postpregnancy if WWE are treated according to the guidelines.
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Epilepsia , Complicaciones del Embarazo , Embarazo , Femenino , Humanos , Complicaciones del Embarazo/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Lamotrigina/uso terapéutico , Convulsiones/tratamiento farmacológicoRESUMEN
OBJECTIVES: To explore the association of plasma trimethylamine N-oxide (TMAO) concentration with large artery atherosclerotic (LAA) ischemic stroke and its role in predicting neurological outcome and major vascular event recurrence. MATERIALS AND METHODS: We performed a case-control study that included patients with first-ever LAA stroke as cases (n = 291) and asymptomatic patients as controls (n = 235). Clinical data and venous blood samples were collected within 72â hours after stroke. All subjects were followed for 3 months. TMAO level was detected by liquid chromatography mass spectrometry (LC-MS). Logistic and Cox proportional hazard regression were performed to evaluate plasma TMAO concentration as a predictor of LAA stroke and major vascular event recurrence, respectively. Kaplan-Meier survival analysis was performed to compare major vascular event recurrence between patients with high and low TMAO concentration. RESULTS: After adjusting for traditional stroke risk factors, the plasma TMAO level was significantly higher in the LAA stroke group than the control group (OR = 1.031, 95% CI 1.024-1.037, P < .001). At a cutoff level of 106.9â pg/ml, TMAO had a sensitivity of 63.23% and specificity of 80.00% in discriminating the LAA stroke subjects from the controls in Receiver operator characteristic (ROC) analysis. Kaplan-Meier survival analysis demonstrated TMAO plasma concentration was significantly relevant with recurrent vascular events (Log Rank, P = .006). Moreover, this association was still existed after adjusting for traditional risks (adjusted HR, 3.128; 95% CI, 1.018-9.610) in Cox regression model. But TMAO plasma levels were not relevant with functional disability after 3 months of the LAA stroke. CONCLUSION: Elevated plasma TMAO concentration was independently associated with LAA ischemic stroke. The risk of major vascular event recurrence increased by 2.128 times in the LAA stroke subjects with plasma TMAO level higher than 126.83â pg/mL. Plasma TMAO concentration might be a potential biomarker of major vascular event recurrence.
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Accidente Cerebrovascular Isquémico , Arterias , Estudios de Casos y Controles , Humanos , MetilaminasRESUMEN
Objective: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. Stroke-associated acute symptomatic seizures are an important risk factor: 20.8-34.3% of these patients will go on to develop PSE. Identifying these "high risk" individuals may result in earlier PSE diagnosis, treatment, and avoidance of seizure-related morbidity. This study was to identify predictors of PSE development in patients with stroke-associated acute symptomatic seizures. Participants and Methods: This was a retrospective cohort study of 167 patients with stroke-associated acute symptomatic seizures admitted to the Neurology Department of a tertiary Hospital of China, from 1 May 2006 to 30 January 2020. Both those with primary ischemic stroke and intracerebral hemorrhage were included in the study. Patient demographics, medical history, stroke-associated, and seizure-related variables were evaluated with univariable analysis and multivariable Cox regression analysis. PSE was defined as unprovoked seizures occurring > 7 days post-stroke. Data points were extracted from medical records and supplemented by tele-interview. Results: Of the 167 patients with stroke-associated acute symptomatic seizures, 49 (29.3%) developed PSE. NIHSS score > 14 [hazard ratio (HR) 2.98, 95% CI 1.57-5.67], longer interval from stroke to acute symptomatic seizures (days 4-7 post-stroke) (HR 2.51, 95% CI 1.37-4.59) and multiple acute symptomatic seizures (HR 5.08, 95% CI 2.58-9.99) were independently associated with PSE development. This association remained in the sub-analysis within the ischemic stroke cohort. In the sub-analysis of the hemorrhagic stroke cohort, multilobar involvement (HR 4.80, 95% CI 1.49-15.39) was also independently associated with development of PSE. Further, we developed a nomogram to predict individual risk of developing PSE following stroke-associated acute symptomatic seizures. The nomogram showed a C-index of 0.73. Conclusion: More severe neurofunctional deficits (NIHSS score > 14), longer interval from stroke to acute symptomatic seizures (days 4-7 post-stroke), and multiple acute symptomatic seizures were independently associated with development of PSE in patients with stroke-associated acute symptomatic seizures. This knowledge may increase clinical vigilance for development of PSE, facilitating rapid diagnosis and treatment initiation, and subsequently reduce seizure-related morbidity.
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Objective: Autoimmune encephalitis (AE) is a severe but treatable autoimmune disorder that is diagnosed by antibody (Ab) testing. However, it is unrealistic to obtain an early diagnosis in some areas since the Ab status cannot be immediately determined due to time and technology restrictions. In our study, we aimed to validate the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score among patients diagnosed with possible AE as a predictive model to screen AE patients with antibodies to cell-surface proteins expressed in neurons. Methods: A total of 180 inpatients were recruited, and antibodies were detected through serological and/or cerebrospinal fluid (CSF) evaluations. The APE2 score was used to validate the predictive models of AE with autoantibodies. Results: The mean APE2 score in the Ab-positive cases was 7.25, whereas the mean APE2 score in the Ab-negative cases was 3.18 (P < 0.001). The APE2 score had a receiver operating characteristic (ROC) area under the curve of 0.924 [P < 0.0001, 95% confidence interval (CI) = 0.875-0.973]. With a cutoff score of 5, the APE2 score had the best psychometric properties, with a sensitivity of 0.875 and a specificity of 0.791. Conclusion: The APE2 score is a predictive model for AE with autoantibodies to cell-surface proteins expressed in neurons and was validated and shown to have high sensitivity and specificity in our study. We suggest that such a model should be used in patients with a suspected diagnosis of AE, which could increase the detection rate of Abs, reduce testing costs, and help patients to benefit from treatment quickly.
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Blood-brain barrier (BBB) disruption has been recognized as an early hallmark of multiple sclerosis (MS) pathology. Our previous studies have shown that 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) protected against experimental autoimmune encephalomyelitis (EAE), a classic animal model of MS. However, the potential effects of 2-BFI on BBB permeability have not yet been evaluated in the context of EAE. Herein, we aimed to investigate the effect of 2-BFI on BBB permeability in both an animal model and an in vitro BBB model using TNF-α to imitate the inflammatory damage to the BBB in MS. In the animal model, 2-BFI reduced neurological deficits and BBB permeability in EAE mice compared with saline treatment. The Western blot results indicated that 2-BFI not only alleviated the loss of the tight junction protein occludin caused by EAE but also inhibited the activation of the NR1-ERK signaling pathway. In an in vitro BBB model, 2-BFI (100 µM) alleviated the TNF-α-induced increase in permeability and reduction in expression of occludin in monolayer bEnd.3 cells. Similar protective effects were also observed after treatment with the NMDAR antagonist MK801. The Western blot results showed that the TNF-α-induced BBB breakdown and increase in NMDAR subunit 1 (NR1) levels and ERK phosphorylation could be blocked by pretreatment with 2-BFI or MK801. However, no additional effect was observed on BBB permeability or the expression of occludin and p-ERK after pretreatment with both 2-BFI and MK801. Our study indicates that 2-BFI alleviates the disruption of BBB in the context of inflammatory injury similar to that of MS by targeting NMDAR1, as well as by likely activating the subsequent ERK signaling pathway. These results provide further evidence for 2-BFI as a potential drug for the treatment of MS.
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Benzofuranos/uso terapéutico , Barrera Hematoencefálica/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Imidazoles/uso terapéutico , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Barrera Hematoencefálica/patología , Línea Celular , Encefalomielitis Autoinmune Experimental/patología , Femenino , Ratones Endogámicos C57BL , Ocludina/metabolismo , Permeabilidad/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Background and Purpose: The association between stress hyperglycemia and clinical outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis (IVT) is uncertain. We sought to analyze the association between the stress hyperglycemia ratio (SHR) using different definitions and clinical outcomes in acute patients with ischemic stroke undergoing IVT. Methods: A total of 341 patients with ischemic stroke receiving IVT were prospectively enrolled in this study. The SHR was evaluated using different equations: SHR1, fasting glucose (mmol/L)/glycated hemoglobin (HbA1c) (%); SHR2, fasting glucose (mmol/L)/[(1.59 × HbA1c)-2.59]; SHR3, admission blood glucose (mmol/L)/[(1.59 × HbA1c)-2.59]. A poor functional outcome was defined as a modified Rankin scale score of 3-6 at 3 months. Multivariate logistic regression analysis was used to identify the relationship between different SHRs and clinical outcomes after IVT. Results: A total of 127 (37.2%) patients presented with poor functional outcomes at 3 months. The predictive value of SHR1 for poor functional outcomes was better than that of SHR2 and SHR3 in receiver operating characteristic analyses. On multivariate analysis, SHR1 [odds ratio (OR) 14.639, 95% CI, 4.075-52.589; P = 0.000] and SHR2 (OR, 19.700; 95% CI; 4.475-86.722; P = 0.000) were independently associated with an increased risk of poor functional outcome but not SHR3. Conclusions: Our study confirmed that the SHR, as measured by SHR1 and SHR2, is independently associated with worse clinical outcomes in patients with ischemic stroke after intravenous thrombolysis. Furthermore, SHR1 has a better predictive performance for outcomes than other SHR definitions.
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Objective: Explore Chinese patients' risk-benefit preferences and willingness-to-pay (WTP) for antiepileptic drugs (AEDs) treatment through the discrete choice experiment (DCE). Method: Six attributes including the efficacy of AEDs, adverse reactions (digestive system, neuropsychic systems, and the effects on the fetus), dosing frequency and drug costs (to estimate patient WTP) were included in the DCE questionnaire based on results collected from literature reviews, expert consultation, and patient survey. The alternative-specific conditional logit model was used to analyze patient preference and WTP for each attribute and its level and to assess the sociodemographic impact and clinical characteristics. Results: A total of 151 valid questionnaires were collected. The result shows that five out of the six attributes are significant, except the dosing frequency. Among the six attributes, the efficacy of AEDs (10.0; 95% CI 8.9-11.1) is mostly concerned by patients, followed by the effects of AEDs on the fetus (8.9; 95% CI 7.7-10.1), duration of side effects in the neuropsychic system (4.9; 95% CI 3.7-6.0) and adverse reactions of the digestive system (3.2; 95% CI 1.5-4.2). The patients surveyed are willing to spend ¥ 1,246 (95% CI, ¥ 632- ¥ 1,861) per month to ensure 100% seizure control, and ¥ 1,112 (95% CI, ¥ 586-¥ 1,658) to reduce the risk of the drug affecting the fetus to 3%. Besides, it was found that personal characteristics including the intention for conception and AEDs treatment regimens have statistical significance. Conclusion: Improving the drug's efficacy and reducing its side effects are predominant considerations for patients with epilepsy in China, especially for those who are concerned about the seizure control and the drug effect on the fetus. This finding is useful to physicians and can encourage shared decision-making between the patients and their doctors in the clinic.
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OBJECTIVE: The aims of this study were to evaluate and compare the performance of the Chinese version of the Suicide Ideation Scale-Current (SSI-C) and the Suicide Ideation Scale-Worst (SSI-W) as suicide ideation screening tools in patients with epilepsy (PWE). METHODS: A consecutive sample of Chinese adult PWE recruited from a tertiary hospital completed the SSI-C and SSI-W and the suicidality module of the Chinese version of the Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0. RESULTS: A total of 260 consecutive PWE were recruited. The area under the curve (AUC) for the SSI-C was 0.831, and the optimal cutoff score was >1 (sensitivity 73%, specificity 91%); for the SSI-W, the AUC was 0.958, and the optimal cutoff score was >2 (sensitivity 94.6%, specificity 87.4%). The AUC for the SSI-W was larger than that for the SSI-C, and the two-factor structure was considered significant. CONCLUSION: Our results showed that the SSI-C and SSI-W had good validity as suicidal ideation screening tools in PWE in southern China and can be recommended for clinical suicidal ideation screening. The SSI-W is a better suicidal ideation screening tool than the SSI-C according to the results of our study.
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Epilepsia , Ideación Suicida , Adulto , China/epidemiología , Epilepsia/diagnóstico , Humanos , Escalas de Valoración Psiquiátrica , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: The aim of this study was to evaluate and compare the performance of the Chinese version of the Neurological Disorder Depression Inventory for Epilepsy (CNDDI-E) with that of the depression subscale of the Hospital Anxiety and Depression Scale (C-HADS-D) as screening tools for depression in the same patients with epilepsy (PWE). METHODS: A total of 213 consecutive PWE were evaluated. Receiver operating characteristic (ROC) analysis was performed using the C-NDDI-E and C-HADS-D as predictors and the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI) as the gold standard. RESULTS: The area under the curve (AUC) for the C-NDDI-E was 0.870, and the optimal cutoff score was >11 (sensitivity 85.71%, specificity 79.78%); for the C-HADS-D, the AUC was 0.804, and the optimal cutoff score was >5 (sensitivity 85.71%, specificity 62.36%). The AUC for the C-NDDI-E was larger than the AUC for the C-HADS-D, but the comparison of the AUCs revealed no significant differences (Pâ¯=â¯0.1444). CONCLUSION: Our findings indicate that the C-NDDI-E and C-HADS-D have high validity and support the use of these screening tools for depression in PWE. Moreover, the C-NDDI-E is a better screening scale for diagnosing depression than the C-HADS-D according to the results of this study.
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Depresión/epidemiología , Depresión/psicología , Epilepsia/epidemiología , Epilepsia/psicología , Escalas de Valoración Psiquiátrica/normas , Adulto , Área Bajo la Curva , China/epidemiología , Depresión/diagnóstico , Epilepsia/diagnóstico , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550-0.907; P = 0.006). The analysis of SNP-SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.
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Péptidos y Proteínas de Señalización Intracelular/genética , Arteriosclerosis Intracraneal/genética , Polimorfismo de Nucleótido Simple , Accidente Cerebrovascular/genética , Anciano , Femenino , Humanos , Arteriosclerosis Intracraneal/complicaciones , Masculino , Accidente Cerebrovascular/etiologíaRESUMEN
OBJECTIVE: The models currently available for predicting the risk of seizure recurrence after antiepileptic drug (AED) withdrawal in adult epilepsy patients include the prediction model developed by Lamberink et al (Lamberink model, 2017) and the Medical Research Council prediction model (MRC model, 1993). However, there was no external validation for the two models. The purpose of this study was to perform an independent external validation and a comparison of the Lamberink model and the MRC model in adult patients. METHODS: The study population was recruited from the Wenzhou Epilepsy Follow-up Registry Database (WEFURD). All the predictors of the Lamberink and MRC models and the occurrence of seizure recurrence in the participants were collected based on the WEFURD. Participants' predicted probabilities of seizure recurrence were obtained by a Web-based tool and the prognostic index formula. The external validation of the Lamberink model and the MRC model were quantified by discrimination, calibration, and decision curve analysis (DCA). RESULTS: Of 212 patients, 126 (59.4%) had seizure recurrence after AED withdrawal. The Lamberink 2-year model, the Lamberink 5-year model, the MRC 1-year model, and the MRC 2-year model had areas under the curve of 0.71 (95% confidence interval [CI] = 0.64-0.78), 0.68 (95% CI = 0.60-0.76), 0.60 (95% CI = 0.50-0.69), and 0.58 (95% CI = 0.50-0.66), respectively. Additionally, the Lamberink 2-year model had a significantly better integrated discrimination improvement than the MRC 2-year model (P < .001). Regarding calibration, the Lamberink 2-year model (P = .121) and the MRC 1-year model (P = .264) were well calibrated, but the Lamberink 5-year model (P = .022) and the MRC 2-year model (P = .008) were not. In the DCA, the Lamberink 2-year model performed well at threshold probabilities of 30%-65%. SIGNIFICANCE: This external validation shows that the Lamberink 2-year model might be more accurate and has greater clinical benefit than others for guiding drug withdrawal in adult epilepsy clinics.
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Anticonvulsivantes , Reglas de Decisión Clínica , Convulsiones , Adulto , Femenino , Humanos , Masculino , Recurrencia , Factores de Riesgo , Adulto JovenRESUMEN
The interleukin 6 receptor (IL6R) gene has been shown to locate in the chromosome 1q21 associated with metabolic syndrome (MetS), a condition related to the augmented risk of ischaemic stroke (IS), cardiovascular diseases and all-cause mortality. The aim of this study was to assess the relationship between IL6R gene polymorphisms and IS in patients with MetS in the Chinese Han population. We designed a case-control study enrolling 447 patients with MetS plus IS and 438 patients with MetS alone. Tag single nucleotide polymorphisms (SNPs) of the IL6R gene were determined by a fine-mapping strategy and genotyped using SNPscan technology. A logistic regression model was used to analzse the associations between the genetic variations in IL6R and the risk of IS in MetS patients. The linkage disequilibrium (LD) analysis was performed and four gamete rules were used to define the block. The haplotypes was reconstructed by the SNPstats software. Two SNPs were significantly related to the risk of IS in MetS patients after adjusting for potential confounders as follows: regarding rs12083537, the GG genotype and the GA genotype decreased the risk of IS in the MetS patients compared with the IS risk in the patients with the AA genotype (multivariate-adjusted, P = 0.005); and regarding rs8192284, the CC genotype and the AC genotype decreased the risk of IS compared with the IS risk in the patients with the AA genotype (multivariate-adjusted, P = 0.004). Strong LD was existed in block 2 and the haplotype analysis showed that compared with the ACCG haplotype, the ATCT haplotype (adjusted OR 1.700; 95% CI 1.246-2.319; P = 0.001) increased the risk of IS in the MetS patients. The analysis of the SNP-SNP interactions showed that rs8192284 was the most influential contributor to the risk of IS in the MetS patients. Our results indicate that rs12083537 and rs8192284 in the IL6R gene might be related to the risk of IS in MetS patients.
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Accidente Cerebrovascular Isquémico/genética , Síndrome Metabólico/complicaciones , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-6/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Haplotipos/genética , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Approximately two-thirds of patients with newly diagnosed epilepsy become seizure-free after antiepileptic drug (AED) treatment. A crucial issue for these patients and their families, especially after a long period of seizure freedom, is when to stop their medications. OBJECTIVE: The aim of this study was to identify the optimal timing of AED withdrawal in adults with focal epilepsy who had been seizure-free for ≥ 2 years. METHODS: Adults with focal epilepsy who had been seizure-free for ≥ 2 years were recruited. Based on their decision to discontinue (withdrawal) or continue (non-withdrawal) AED treatment, patients were assigned to withdrawal or non-withdrawal subgroups according to the length of remission (2 to < 3 years, 3 to < 4 years, 4 to < 5 years and ≥ 5 years). The relapse risks of the withdrawal and corresponding non-withdrawal subgroups were compared, and the relative relapse risks were assessed in a Cox proportional hazard regression model. RESULTS: A total of 213 eligible patients began to withdraw from AED treatment; 70 had been seizure-free for 2 to < 3 years, 62 had been seizure-free for 3 to < 4 years, 37 had been seizure-free for 4 to < 5 years and 44 had been seizure-free for ≥ 5 years. The figures for the corresponding non-withdrawal subgroups were 463, 334, 251 and 182, respectively. There was a significantly higher risk of seizure relapse in patients withdrawing from AEDs after 2 to < 5 years of seizure freedom than in the corresponding non-withdrawal controls, and the relative relapse risk was 3.052 (95% confidence interval [CI] 2.126-4.381; p < 0.001) for the seizure-free period of 2 to < 3 years, 3.617 (95% CI 2.384-5.488; p < 0.001) for 3 to < 4 years and 2.644 (95% CI 1.456-4.799; p = 0.001) for 4 to < 5 years. However, for patients who were seizure-free for ≥ 5 years, AED withdrawal did not significantly increase the risk of seizure relapse compared with that of patients continuing treatment (hazard ratio [HR] 1.362, 95% CI 0.634-2.926, p = 0.428). Compared with a seizure-free period of 2 to < 3 years, the relative relapse risk after AED withdrawal was significantly reduced only after being seizure-free for ≥ 5 years (HR 0.441, 95% CI 0.233-0.834; p = 0.012). CONCLUSION: Overall, for adults with focal epilepsy, withdrawal from AEDs significantly increased the risk of seizure relapse after being seizure-free for 2 to < 5 years, but might not increase the risk if the seizure-free period was ≥ 5 years.
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Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to validate the Chinese version of the Scale for Suicide Ideation-Worst (SSI-W) for screening suicide ideation in Chinese adult patients with epilepsy (PWE). METHOD: A consecutive sample of Chinese adult PWE from a tertiary hospital completed the SSI-W and the suicidality module of the Chinese version of the Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0. RESULTS: A total of 269 PWE completed the scales. According to the MINI, 59 patients (21.9%) had suicidal ideation. The Cronbach's α coefficient for the SSI-W was 0.96. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the SSI-W was 0.957 (95% confidence interval [CI]â¯=â¯0.935-0.980). With a cutoff score of 2 points, the SSI-W demonstrated the best psychometric properties: a sensitivity of 95.8%, a specificity of 87.3%, a positive predictive value (PPV) of 56.7%, and a negative predictive value (NPV) of 99.0%. The scores for items 11 (Reason for attempt) and 18 (Final acts) were not significantly different (pâ¯>â¯0.05) in patients with suicidal ideation, while the scores for the other items were significantly different between these groups of patients. CONCLUSION: The Chinese version of the SSI-W proved to be a reliable and effective assessment tool for screening suicidal ideation in Chinese adult PWE.
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Epilepsia/psicología , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Psicometría/instrumentación , Ideación Suicida , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Pueblo Asiatico , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
OBJECTIVE: The major cause of premature mortality in people with epilepsy (PWE) is suicide. Actual data on the risk of suicidal tendency in adult PWE in China are scarce. In our study, associations between possible risk factors and suicidal tendency in adult PWE in China were investigated. METHODS: People with epilepsy (nâ¯=â¯251) were recruited, and their demographic and clinical characteristics were evaluated. Suicide risk was examined using the suicidality module (SM) of the Mini International Neuropsychiatric Interview (MINI) Plus Chinese Version 5.0.0. RESULTS: Suicidal tendency was present in 36 (14.3%) of the 251 PWE. On the basis of the results of univariate analyses, family relationship (Pâ¯<â¯0.001), age at epilepsy onset (Pâ¯=â¯0.037), seizure-free period (Pâ¯=â¯0.041), seizures/month (Pâ¯=â¯0.015), depressive disorders (Pâ¯<â¯0.001), and number of antiepileptic drugs (AEDs) (Pâ¯=â¯0.017) were associated with suicidal tendency. Multivariate analysis revealed that moderate or poor family relationships (odds ratio (OR): 6.468, 95% confidence interval (CI): 2.418-17.300) and depressive disorders (OR: 3.548, 95% CI: 1.575-7.995) were associated with high odds of suicidal tendency. CONCLUSION: Suicidal tendency is common among adult PWE. This study reveals that family relationships and depressive disorders are independent risk factors for suicidal tendency among adult PWE. Therefore, while maintaining treatment of epilepsy, more attention should be directed to the social support and mental state of PWE to prevent suicide.
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Trastorno Depresivo/psicología , Epilepsia/psicología , Relaciones Familiares/psicología , Ideación Suicida , Intento de Suicidio/psicología , Adolescente , Adulto , Edad de Inicio , Anciano , Anticonvulsivantes/uso terapéutico , China/epidemiología , Trastorno Depresivo/epidemiología , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Suicidio/psicología , Suicidio/estadística & datos numéricos , Intento de Suicidio/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to evaluate the clinical reliability and validity of the Chinese version of the Patient Health Questionnaire 9 (C-PHQ-9) in patients with epilepsy. METHODS: A total of 213 consecutive adult patients with epilepsy were evaluated. Receiver operating characteristic (ROC) analysis was performed using C-PHQ-9 and Chinese version of Patient Health Questionnaire 2 (C-PHQ-2) as predictors and the Mini International Neuropsychiatric Interview Plus Version 5.0.0 as the gold standard. RESULTS: The C-PHQ-9 was easily understood and quickly finished by the patients. According to the gold standard, the prevalence of current major depressive disorder in this population was 16.4%. Cronbach's α coefficient for the C-PHQ-9 was 0.860. The ROC analysis showed an area under the curve (AUC) of 0.888 (95% confidence interval [CI]â¯=â¯0.838-0.927). At a cutoff score of >6, the C-PHQ-9 had a sensitivity of 82.86%, a specificity of 84.27%, a positive predictive value of 50.9%, and a negative predictive value of 96.2%. The C-PHQ-2 at a cutoff score of >1 resulted in the greatest balance of sensitivity and specificity (77.14% and 75.28%, respectively). CONCLUSION: Our findings support a high reliability and validity for the C-PHQ-9 as a screening tool for the detection of current major depression in Chinese patients with epilepsy.
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Trastorno Depresivo Mayor/diagnóstico , Epilepsia/psicología , Cuestionario de Salud del Paciente/normas , Psicometría/normas , Adolescente , Adulto , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Antiepileptic drugs (AEDs) have adverse psychotropic effects (APEs). To explore the risk factors for AED-induced APEs, we compared Chinese outpatients with epilepsy with and without AED-induced APEs. We reviewed the medical data of outpatients with epilepsy enrolled in the Epilepsy Long-term Follow Up Registry Study (ELFURS) between January 1, 2003 and December 31, 2015. Data on demographics, comorbidities, variables related to epilepsy, AED use, and APEs were collected. APEs were determined by experienced epileptologists based on the definition of "adverse drug reaction (ADR)" proposed by the World Health Organization (WHO) in 1972, and the causality relationship between APEs and suspected medications was assessed based on the WHO-UMC scale. APEs included effects on memory, sleep, behavior, mood, psychotic symptoms, and others in this study. We divided the study population into patients with and without AED-induced APEs and then compared the differences between the two groups using univariate and multivariate methods. A total of 3074 eligible patients were included in this study (1001 patients with AED-induced APEs and 2073 patients without AED-induced APEs). Of all APEs, the effects on memory and sleep were most pronounced. The results show that the female sex (odds ratio [OR] 1.242, 95% confidence interval [CI] 1.055-1.463), psychotic disorder comorbidities (OR 1.815, 95% CI 1.159-2.841), polytherapy with AEDs (OR 1.400, 95% CI 1.061-1.847), and the duration of epilepsy (OR 1.010, 95% CI 1.000-1.020) are significant nondrug risk factors for AED-induced APEs. Recognizing risk factors for APEs may help determine optimal treatment strategies for epilepsy.
Asunto(s)
Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Trastornos Psicóticos/etiología , Adulto , Anticonvulsivantes/uso terapéutico , Femenino , Humanos , Masculino , Pacientes Ambulatorios/estadística & datos numéricos , Trastornos Psicóticos/epidemiologíaRESUMEN
BACKGROUND: This active, open observational study aimed to investigate adverse drug reactions (ADRs) associated with six commonly used antiepileptic drugs (AEDs) in southern Chinese outpatients with epilepsy from 2003 to 2015. METHODS: The Wenzhou Epilepsy Follow-Up Registry Database (WEFURD) was established by a single epilepsy center in China in January 2003 to record AED efficacy and the associated ADRs by registered outpatients diagnosed with epilepsy. We reviewed the data of outpatients who had only taken one or more of six commonly used AEDs, namely, carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), oxcarbazepine (OXC), topiramate (TPM) and levetiracetam (LEV), and were registered in the WEFURD between 2003 and 2015. We evaluated the ADRs caused by the single or combined use of the above six specific AEDs based on the WHO-UMC scale. The data of the ADRs were categorized by age, sex, number of AEDs related to ADRs, medications, seriousness of ADRs, causality levels of the WHO-UMC scale and system organ class (SOC). The unit of analysis was one ADR. RESULTS: A total of 3069 epilepsy outpatients (1807 outpatients with 5049 eligible ADRs and 1262 outpatients without ADRs) were included. The overall ADR rate was 58.88% (1807/3069). An average of 2.79 ADRs (5049/1807) occurred per patient with an ADR; 53.8% of the 5049 ADRs were recorded in females, and 50.4% were caused by monotherapy. Of the ADRs, 10.6% (537/5049) were severe adverse reactions (SARs), including 34 serious adverse effects (SAEs). The SAR rates caused by one, two and three or more AEDs were 9.9, 10.0 and 19.6%, respectively (p < 0.001). Eighteen SOC categories were identified, and the top three were psychiatric disorders (1633/5049, 32.3%), neurological disorders (1222/5049, 24.2%) and gastrointestinal disorders (564/5049, 11.2%). Of the 537 SARs, skin and appendage disorders accounted for 24.4% (131/537). Among the 34 SAEs, serious allergies, fetal malformations, renal calculus and pancreatitis accounted for the majority. CONCLUSIONS: Our findings suggest that clinicians should pay attention to psychiatric ADRs and be alert for SARs, especially when three or more AEDs are used together. Moreover, active surveillance might provide another method of pharmacovigilance in China.