Anodal transcranial direct-current stimulation and non-verbal intelligence in autism spectrum disorder: A randomized controlled trial.

AIM: To understand the impact of anodal transcranial direct-current stimulation (tDCS) on non-verbal intelligence in high-functioning young adults with autism spectrum disorder (ASD). METHOD: Thirty individuals with ASD were randomly divided into three groups receiving 2 mA, 20 minutes daily anodal tDCS for 10 sessions. Group A received 10 sham tDCS sessions, group B five real followed by five sham sessions, and group C received 10 real tDCS sessions. The total score of non-verbal intelligence was measured using the Test of Nonverbal Intelligence, Fourth Edition. The left dorsolateral prefrontal cortex (LDLPFC) was targeted using the International 10-20 electroencephalography system, and concurrent cognitive training was avoided. RESULTS: Group C demonstrated a mean difference of 4.10 (95% confidence interval 1.41-6.79; p = 0.005) in Test of Nonverbal Intelligence scores compared with group A, with an effect size of 0.47. No significant differences were observed between groups A and B (p = 0.296), or between groups B and C (p = 0.140). INTERPRETATION: Ten sessions of anodal tDCS to the LDLPFC led to improved non-verbal intelligence among individuals with ASD. These results emphasize the potential of tDCS as a discrete method for boosting cognitive abilities in the high-functioning population with ASD. Future studies with larger groups of participants and extended observation periods are necessary to validate these findings.

Genetic variants associated with severe cutaneous adverse drug reactions induced by carbamazepine.

AIMS: Carbamazepine (CBZ) is one of the most common causative drugs of severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reactions with eosinophilia and systemic symptoms. Although genetic polymorphisms of the human leucocyte antigens (HLA) are well recognized key elements for the susceptibility to CBZ-induced SCARs, some evidence suggest that polymorphisms of microsomal epoxide hydrolase 1 (EPHX1) may also contribute to the risk of these SCARs. This study investigated the association between the HLA and EPHX1 polymorphisms on CBZ-induced SCARs in large sample sizes and well-defined SCARs patients. METHODS: Ninety-one CBZ-induced SCARs Thai patients and 144 CBZ-tolerant patients were enrolled in the study. The genotypes of HLA-A, HLA-B and EPHX1 were determined. RESULTS: Only 2 HLA alleles including HLA-B*15:02 and HLA-A*24:07 were statistically significant association with CBZ-induced SJS/TEN. The highest risk was observed in patients with HLA-B*15:02 allele (OR = 44.33, 95% confidence interval = 20.24-97.09, corrected P-value = 6.80 × 10-29 ). Moreover, HLA-B75 serotypes were significantly associated with CBZ-induced SJS/TEN groups with an odds ratio of 81.00 (95% confidence interval = 32.39-202.56, corrected P-value = 3.84 × 10-34 ). There is no association between EPHX1 c.337 T > C polymorphism and all phenotypes of CBZ-induced SCARs. CONCLUSION: The HLA-B*15:02 allele is the strongest genetic marker for the prediction of SJS/TEN induced by CBZ in Thai population. Screening for other alleles in the HLA-B75 serotype increases sensitivity for prediction of a life-threatening SCARs caused by CBZ.

Propensity Score Analysis of the Association between Chronic Obstructive Lung Disease and Stroke Outcome: Thailand's National Database.

INTRODUCTION: The impact of coexisting chronic obstructive lung disease (COPD) in patients with stroke remains unclear. This study aims to investigate the effect of COPD on survival and hospital outcomes among stroke patients. METHODS: The outcomes of patients with stroke between fiscal years 2005 and 2017 from Thailand's Universal Coverage Scheme database were compared between COPD and non-COPD patients using propensity score matching and flexible parametric survival model. RESULTS: A total of 805,561 patients were admitted with stroke during the study period, 12,650 (1.92%) of whom had been diagnosed with COPD. Participants with COPD were significantly older, were more likely to be male, and had higher prevalences of pre-existing atrial fibrillation, ischemic heart disease, and heart failure and a higher incidence of ischemic stroke (p < 0.001). The propensity score-matched groups were well balanced in terms of all observed covariates. Participants with COPD had higher incidences of pneumonia (odds ratio [OR] 1.98, 95% confidence interval [CI]: 1.83-2.15), urinary tract infection (OR 1.27, 95% CI: 1.14-1.42), sepsis (OR 1.50, 95% CI: 1.32-1.70), cardiac arrest (OR 1.50, 95% CI: 1.19-1.88), respiratory failure (OR 1.82, 95% CI: 1.69-1.96), acute kidney injury (OR 1.29, 95% CI: 1.14-1.46), and in-hospital death (OR 1.21, 95% CI: 1.13-1.30) than those without. The impact of COPD on mortality was highest at day 93 (hazard ratio [HR] 1.73, 95% CI: 1.60-1.87) and nonsignificant at day 965 of follow-up (HR 1.08, 95% CI: 1.00-1.16). CONCLUSIONS: COPD was associated with respiratory, cardiac, renal, and infectious complications and significantly impacted survival for up to 2.6 years.

The epidemiology of Guillain-Barré syndrome in Thailand over 13 years (2005-2017): A nationwide population-based retrospective cohort study.

There have been no published studies examining the epidemiology of Guillain-Barré syndrome (GBS) in large populations in Thailand. This study aimed to explore the incidence, patient characteristics, seasonality, treatments, and outcomes of GBS in Thailand. The National Health Security Office (NHSO) provided data on in-patient admission between fiscal year 2005 and 2017. We selected all patients with a primary diagnosis of GBS. We retrieved data regarding the total population from the Department of Provincial Administration. A total of 4521 patients with GBS were included. The median age was 42 years (IQR 22-56), and 61.5% were male. The incidence rate increased from 0.48 to 0.93 per 100 000 population over the 13 years. The incidence was increased with age and a male-to-female ratio of 1.6:1. There was seasonal variation in the rate of admission for GBS, with significantly more patients admitted in rainy vs summer (IRR 1.94, 95%CI 1.80-2.10, P < .001) and winter vs summer (IRR 1.48, 95%CI 1.36-1.60, P < .001). Treatment with IVIg increased from 4.4% to 29.6% (P < .001), whereas plasmapheresis decreased significantly from 4% to 1.32% (P = .017). The mortality rate was 3.5%. Elderly and young adults had a significantly higher mortality rate when compared to children and teenagers (P < .001 and P = .003). The incidence of GBS in Thailand was steady over 13 years and was greater in rainy and winter season. Treatment with IVIg increased while plasmapheresis decreased. Mortality was higher in elderly patients.

The Efficacy and Safety Profile of Generic Intravenous Levetiracetam in a Real-World Setting.

BACKGROUND: There are 3 main epileptic conditions in hospital settings that may require intravenous antiepileptic treatment: status epilepticus, acute repetitive convulsive seizures, and postoperative seizures. Generic intravenous levetiracetam (IV LEV) (Focale; Great Eastern Drug Co, Bangkok, Thailand), has been reported to have comparable efficacy to original IV LEV for treating status epilepticus and acute repetitive convulsive seizures in a randomized controlled trial. At present, there are limited data on the efficacy and tolerability of generic intravenous LEV in real-world situations. OBJECTIVE: This study aimed to evaluate the clinical outcomes of generic IV LEV in a real-world setting. METHODS: A retrospective study and analyses were conducted. All adult patients who used IV LEV at University Hospital, Khon Kaen University, Thailand from June 1, 2019, until February 15, 2020, were included. Data were analyzed and reported in terms of the efficacy and tolerability of generic IV LEV. RESULTS: Ninety-three patients received IV LEV by 3 indications: status epilepticus, acute repetitive convulsive seizures, and postoperative seizures. The proportions of these 3 indications were 41.94% (39 patients), 9.67% (9 patients), and 48.39% (45 patients), respectively. The average seizure control rate at 24 hours was 89.25%. The seizure control rate was significantly higher in the acute repetitive convulsive seizures and postoperative seizure groups than in the status epilepticus group when generic IV LEV was given as the first-line treatment (75.00%; 88.37% vs 50.00%; P 0.035). The average length of hospital stay was 18.24 (25.40) days. There was no significant discharge status among the 3 groups (P = 0.348). Moreover, the average mortality rate was 5.38%. Side effects were reported in 14 patients (15.05%). The 2 most common side effects were vomiting and bronchospasm (3 patients; 3.22%). There were 10 patients with uncontrolled seizures at 24 hours (10.75%). The only factor associated with uncontrolled seizures at 24 hours was a history of epilepsy. The uncontrolled seizure group had a higher proportion of epilepsy patients than the seizure-controlled group (70.00% vs 33.73%; P = 0.037). Poor discharge status (not improved/death) was 18.28% (17 patients). There was no significant factor between those with an improved or poor discharge status. CONCLUSIONS: Generic IV LEV was effective and relatively well tolerated in the 3 clinical settings (ie, status epilepticus, acute repetitive convulsive seizures, and postoperative seizures). Further clinical data are still required to confirm the results of this study.(Curr Ther Res Clin Exp. 2022; 83:XXX-XXX).

Safety of retigabine in adults with partial-onset seizures after long-term exposure: focus on unexpected ophthalmological and dermatological events.

BACKGROUND: Retigabine is an antiepileptic drug developed for the adjunctive treatment of adults with epilepsy and partial-onset seizures (POS). Following its approval in 2011, reports of ophthalmological/dermatological pigmentation/discoloration led to a restriction of the indication in 2013, and in 2017, retigabine was voluntarily withdrawn from the market because of its limited usage. Here, data are reported from four open-label extension studies focusing on long-term safety with particular emphasis on ophthalmological and dermatological events. METHODS: Studies 113413 (NCT01336621), 114873 (NCT01777139), 115097 (NCT00310388), and 115098 (NCT00310375) were multicenter, open-label extension studies of retigabine (300-1200 mg/day) for the adjunctive treatment of adults with POS. Safety assessments included monitoring treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). When new safety issues were identified, protocols were amended to include additional on-treatment safety evaluations, including ophthalmological and dermatological examinations. Patients who had abnormal retinal pigmentation, unexplained vision change, pigmentation of nonretinal ocular tissue, or abnormal discoloration of skin, lips, nails, and/or mucosa at the end of the treatment phase were asked to enter a safety follow-up continuation phase comprising 6-monthly ophthalmological/dermatological assessments. RESULTS: The safety population (patients receiving ≥1 dose of retigabine in the open-label phase) comprised 98, 30, 376, and 181 patients for studies 113413, 114873, 115097, and 115098, respectively. Mean (standard deviation) treatment exposure ranged from 529 (424) to 1129 (999) days. In total, 68%-96% and 4%-27% of patients across the studies experienced TEAEs and TE SAEs, respectively. There were seven on-treatment deaths and two after discontinuation. Overall, 14%-73% of patients had an on-treatment eye examination, of whom 8/53, 4/22, 17/54, and 14/36 had abnormal retinal pigmentation and 15/53, 7/22, 15/54, and 11/36 had nonretinal ocular pigmentation in studies 113413, 114873, 115097, and 115098, respectively. Four patients had confirmed acquired vitelliform maculopathy. In patients with unresolved events at discontinuation and ≥1 posttreatment follow-up, retinal pigmentation resolved completely in 1/3, 0/3, 0/10, and 1/7 patients and nonretinal ocular pigmentation in 1/4, 0/3, 8/10, and 4/6 patients, respectively. Overall, 12%-83% of patients had an on-treatment dermatological examination, of whom 11/58, 0/25, 23/46, and 23/37 had any-tissue discoloration, respectively. In patients with unresolved events at discontinuation and ≥1 posttreatment follow-up, discoloration of skin, lips, nails, and/or mucosa resolved completely in 2/3, 0/0, 7/13, and 1/11 patients, respectively. CONCLUSIONS: The safety profile of retigabine in adults with POS across four open-label studies was generally consistent with data from previous placebo-controlled studies. Discoloration of various tissues occurred in a proportion of patients treated with retigabine and resolved completely in a small number of these patients following treatment discontinuation. In addition, comprehensive eye examination identified a new adverse reaction of acquired vitelliform maculopathy in a limited number of patients.

Infective endocarditis is associated with worse outcomes in stroke: A Thailand National Database Study.

BACKGROUND: There is lack of data on the association between infective endocarditis (IE) and outcomes of mortality and complications in stroke. We aimed to compare characteristics and outcomes of stroke patients with and without IE. METHODS: We retrospectively examined the above association using data obtained from an insurance database which covers ~75% of the Thai population. All hospitalised strokes between 8 January 2003 and 31 December 2013 were included in the current study. Characteristics and outcomes were compared between stroke patients with or without IE, and then between two main stroke types. Multiple logistic regression models including propensity score-matched analyses were constructed to assess study outcomes controlling for age, sex, stroke type and comorbidities. RESULTS: A total of 590 115 stroke patients (mean (SD) age = 64.2 ± 13.7 years; ischaemic = 51.7%; haemorrhagic = 32.6%; undetermined = 15.7%) were included, of whom 2129 (0.36%) had stroke associated with IE. After adjustment, we found that IE was significantly associated with the following complications: arrhythmias (adjusted odds ratio (95% CI) 6.94 (6.29-7.66)), sepsis (1.24 (1.01-1.52)), pneumonia (1.34 (1.17-1.53)), respiratory failure (1.43 (1.24-1.66)) and in-hospital mortality (1.29 (1.13-1.47)) (P for all <.001). Patients with haemorrhagic stroke with IE had poorer outcomes for in-hospital mortality and respiratory failure compared with their counterparts with ischaemic stroke. Propensity score-matched analysis showed similar results. CONCLUSIONS: Our results suggest that stroke patients with IE differ from that of the general stroke population and these patients have worse outcomes. Future studies are needed to determine the best treatment strategies for stroke patients with IE.

Parkinson's disease and patient related outcomes in stroke: A matched cohort study.

OBJECTIVE: To evaluate post-stroke outcomes in patients with Parkinson's disease (PD). METHODS: A matched cohort study was performed. Stroke patients with PD and non-PD controls were extracted from the Thailand Universal Insurance Database. Logistic regressions were used to evaluate the association between PD and in-hospital outcomes (mortality and complications). The PD-associated long-term mortality was evaluated using Royston-Parmar models. RESULTS: A total of 1967 patients with PD were identified between 2003 and 2015 and matched to controls (1:4) by age, sex, admission year, and stroke type. PD patients had decreased odds of in-hospital death: OR (95% CI) 0.66 (0.52 - 0.84) and 0.61 (0.43 - 0.85) after ischaemic and haemorrhagic strokes, respectively. PD was associated with a length-of-stay greater than median (4 days) after both stroke types: 1.37 (1.21 - 1.56) and 1.45 (1.05 - 2.00), respectively. Ischaemic stroke patients with PD also had increased odds of developing pneumonia, sepsis and AKI: 1.52 (1.2 - 1.83), 1.54 (1.16 - 2.05), and 1.33 (1.02 - 1.73). In haemorrhagic stroke patients, PD was associated with pneumonia: 1.89 (1.31 - 2.72). Survival analyses showed that PD was protective against death in the short term (HR=0.66; 95% CI 0.53-0.83 ischaemic, and HR=0.50; 95% CI 0.37 - 0.68 haemorrhagic stroke), but leads to an increased mortality risk approximately 1 and 3 months after ischaemic and haemorrhagic stroke, respectively. CONCLUSION: PD is associated with a reduced mortality risk during the first 2-4 weeks post-admission but an increased risk thereafter, in addition to increased odds of in-hospital complications and prolonged hospitalisation.

Efficacy and safety of perampanel in generalized and focal to bilateral tonic-clonic seizures: A comparative study of Asian and non-Asian populations.

Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures and generalized tonic-clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non-Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12 years old) with focal + FBTC seizures received perampanel 2, 4, 8, or 12 mg or placebo; patients with GTC seizures received perampanel 8 mg or placebo (titration: 4-6 weeks; maintenance: 13 weeks). Efficacy endpoints included median percentage change in FBTC or GTC seizure frequency per 28 days and 50% responder rate relative to baseline. Median percentage change in FBTC seizure frequency was significantly greater for perampanel 8 and 12 mg than placebo in the Asian population (median difference from placebo: -30.32%, P = 0.0017; -30.06%, P = 0.0008, respectively) and perampanel 4, 8, and 12 mg in the non-Asian population (-35.07%, P = 0.0001; -37.78%, P < 0.0001; -34.53%, P < 0.0001, respectively). In both populations, median percentage change in GTC seizure frequency was significantly greater for perampanel 8 mg than placebo (median difference from placebo: Asian, -37.37%, P = 0.0139; non-Asian, -27.04%, P = 0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12 mg for FBTC seizures (Asian: 58.0%, P = 0.0017 and 58.6%, P = 0.0013, respectively; non-Asian: 59.3%, P < 0.0001 and 54.3%, P = 0.0050, respectively) and perampanel 8 mg for GTC seizures (Asian: 57.6%, P = 0.0209; non-Asian: 68.8%, P = 0.0329). Pooled FBTC/GTC seizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment-related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option for FBTC/GTC seizures in Asian populations.

One- to 10-year Status Epilepticus Mortality (SEM) score after 30 days of hospital discharge: development and validation using competing risks analysis.

BACKGROUND: Status epilepticus (SE) is an emergency neurological disorder that affects quality of life and is associated with high mortality risk. Three scores have been developed to predict the risk of in-hospital death, but these scores are poor discrimination of mortality after discharge. This study aimed to develop and validate a simple risk score for long-term mortality in SE patients. METHODS: This retrospective cohort study was conducted using SE patient data collected from Thailand's Universal Coverage Scheme database between the fiscal years of 2005 and 2015 and followed-up to 2016. Patients who died in hospital or within 30 days after discharge were excluded. Data were divided at random into either a derivation or validation set. A proportional hazards model for the sub-distribution of competing risks was fitted with backward stepwise method. The coefficients from the model were used to develop a point-based scoring system. The discrimination ability of the model was evaluated using a time-dependent receiver operating characteristic (ROC) curve. RESULTS: A total of 20,792 SE patients (with ages ranging from the first day of life to 99 years at first admission) were randomly separated into two groups: 13,910 in the development group and 6882 in the validation group. A sub-distribution hazard model was used to determine nine predictors to be included in the final model, which was, in turn, used to develop the scoring system: age (0-19 points), male (two points), brain tumor (12 points), stroke (three points), cancer (11 points), diabetes (three points), chronic kidney disease (five points), pneumonia (five points), and urinary tract infection (four points). The possible total score ranged from zero to 64 and the cumulative incidence function was used to determine the probability of mortality associated with each total score within the first 10 years after the first admission. The area under the ROC curve (AUC) of the first to last time point ranged from 0.760 to 0.738. CONCLUSION: A nine-factor risk score for predicting 10-year mortality in SE patients was developed. Further studies should focus on external validity and including a range seizure types and duration of seizure as the predictors.

Causes of death in patients with status epilepticus.

BACKGROUND: Status epilepticus (SE) is a neurological disorder that affects to the high mortality risk. Several studies reported predictors of mortality in SE; actual causes of death in hospital and out of hospital are limited. This study aimed to describe the case fatality and the causes of death in patients with SE. METHODS: This was a descriptive study using the data collected in the national data of the Universal Coverage Scheme in Thailand during the fiscal year 2005 to 2015. Patients who admitted to hospitals and diagnosed as SE were included. The vital status of patients with SE was linked with the Ministry of the Interior and was classified into three phases: in-hospital, short-term, and long-term. RESULTS: Among 24,802 patients with SE, 1861 (7.5%) died in hospital, 1910 (7.7%) died within 30 days after hospital discharge, and 4906 (19.8%) died after 30 days. In-hospital death, SE complications (45.9%), seizure (19.6%), and comorbidities (15.4%) were the three common causes of death. While the common causes in short-term and long-term mortality were SE complications (27.7% and 31.0%), comorbidities (28.1% and 26.7%), and other causes (22.4% and 21.9%). CONCLUSION: Status epilepticus complications and comorbidities were the common cause of death in patients with SE for all of three periods. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Pneumonia and Risk of Serious Adverse Outcomes in Hospitalized Strokes in Thailand.

BACKGROUND: The impact of stroke associated pneumonia (SAP) on stroke complications is not well understood; we aimed to study the association between SAP and adverse outcomes including in-hospital mortality, prolonged length of stay and the risk of developing common serious complications (sepsis, respiratory failure, and convulsions). METHODS: We retrospectively analyzed data from a cohort of 610,668 stroke patients drawn from the Universal Coverage Health Security Scheme (a national insurance database) in Thailand which covers ∼80% of the Thai population. Patients were hospitalized between October 2004 and January 2013. RESULTS: Pneumonia was present in 9.6 % (n = 58,586) of patients. Aspiration pneumonia was present in 6.2% (n = 38,060) and nonaspiration pneumonia in 3.4% (n = 20,526). After adjusting for age, sex, stroke type, and comorbidities, patients with SAP had significantly higher odds of in-hospital mortality (odds ratio [OR] 2.90: 2.83-2.96), long length of stay (OR 13.11: 12.83-13.40), sepsis (OR 8.49: 8.22-8.76), respiratory failure (OR 4.37: 4.27-4.48), and convulsions (OR 2.09: 2.00-2.17). On subanalysis, patients with nonaspiration pneumonia were found to have higher odds of adverse outcomes compared to aspiration pneumonia; the corresponding ORs (95% confidence interval) for above outcomes were 1.25 (1.21-1.30), 2.40 (2.32-2.49), 1.34 (1.28-1.40), 1.80 (1.73-1.88), and 1.19 (1.11-1.28), respectively. CONCLUSIONS: SAP is associated with higher odds of inpatient mortality, long length of stay, and risk of developing serious stroke complications. Nonaspiration pneumonia is associated with significantly higher likelihood of adverse outcomes compared to aspiration pneumonia in this patient population. Early identification and treatment of SAP is vital in reducing adverse outcomes in acute stroke.

Risk score predictive of mortality in status epilepticus according to a national database.

Status epilepticus (SE) is a serious neurologic condition with high morbidity and mortality rates. This study aimed to develop and validate a risk score that is predictive of mortality in patients with SE using clinical factors without electrocardiography. The inclusion criteria of this study were all patients diagnosed with SE and treated between 2005 and 2015. We retrospectively searched for eligible patients using the International Classification of Diseases, Tenth Revision (ICD-10) code for SE (G41) in the national Universal Health Coverage database. The outcome was death at discharge or within 30 days after discharge. Factors-associated death was analyzed using stepwise logistic regression analysis. Risk scores were developed based on the final logistic regression model. The final model was also validated. There were 10 924 patients used for model development and 10 808 used for model validation. The formula to determine the risk score for SE mortality was 5 × shock + 4 × age over 60 years old + 3.5 × heart diseases + 3 × acute renal failure + 3 × septicemia + 2.5 × central nervous system infection + 2.5 × age 41-60 years old + 2 × cancer + 2 × chronic renal failure + 1.5 × age 21-40 years old + 1 × pneumonia + 1 × respiratory failure + 1 × anemia. The risk scores of greater than 4 indicated risk for mortality with a sensitivity of 78.20% and specificity of 75.38%. The area under the receiver-operating characteristic (ROC) curve for death in the final model was 83.59%. The area under the ROC curve for the model validation group was 83.52%. SE patients who had a risk score of 4 or more were at high risk for death. Physicians should be aware of the high mortality rate in these particular patients.

Predictors of long-term mortality in status epilepticus.

BACKGROUND: There were several studies that have reported on the long-term mortality rate of status epilepticus (SE). However, these studies were conducted mainly in Western countries using small study populations. This study aimed to evaluate predictors for long-term mortality in SE using the Thai national healthcare database. METHODS: This study was conducted using the Thai national Universal Health Coverage (UC) database. The eligibility criteria for this study were that all patients were diagnosed with SE and had been admitted to any hospital between 2005 and 2015. Mortality was defined at discharge and at one, three, five, and 10 years. All eligible patients were categorized as either having survived or having died. The mortality rates were calculated at one, three, five, and 10 years. Factors associated with mortality were analyzed using backward multivariate Cox proportional hazard regression analysis. Kaplan-Meier was performed to estimate the survival rate. RESULTS: During the study period, there were 21,732 patients with SE admitted who met the study criteria. The total observation time was 85,821.28 person-years. Of the patients enrolled, 3642 (or 4.24 per 100 person-years [95% confidence interval (CI): 4.11-4.38]) died. Factors positively associated with mortality in patients with SE were central nervous system (CNS) infection, cancer, heart diseases, chronic renal failure, septicemia, pneumonia, respiratory failure, acute renal failure, and shock. Heart diseases had the highest adjusted hazard ratio at 2.69 (95% CI: 2.47-2.93). Two factors were negatively related with SE mortality: hypertension and urinary tract infection. CONCLUSION: Long-term mortality in patients with SE had both positive and negative predictors in the national database.

EQ-5D-based utilities and healthcare utilization in Thai adults with chronic epilepsy.

Quality of life and resource use are key parameters that justify economic values in treatments for epilepsy. Health profiles and service utilization were assessed in 224 adults with 15.7years of epilepsy in two super-tertiary care facilities in Thailand. The European Quality of Life, 5-Dimension (EQ-5D)-based utilities and subsequent outpatient (OP) visits and hospitalizations were determined with respect to seizure control outcomes that were assessed by neurologists. Mean utility and visual analogue scale (VAS) scores were respectively higher in 67 patients who are seizure-free (0.82 and 78.9) than in 157 patients who had uncontrolled or persistent seizures, which were divided into seizure reduction (0.79 and 75.5) and no improvement in seizure frequency (0.72 and 73.5). Controlling for patient characteristics, those who are seizure-free had significantly higher utility and VAS scores than those with no improvement by 0.10 (95% confidence interval (CI): 0.03-0.17) and 6.25 (95% CI: 0.09-12.41), respectively. Seizure-free patients were less likely to report pain or discomfort, as compared with patients with seizure reduction (odds ratio (OR): 0.41, 95% CI: 0.19-0.90) and patients with no improvement (OR: 0.32, 95% CI: 0.13-0.75). Over a six-month period, mean OP visits were significantly lower in seizure-free patients (2.27 times) than in those with seizure reduction (3.00 times) and those with no improvement (4.08 times). Mean hospitalizations over 12months among the three groups were 0.03, 0.24, and 0.14 times, respectively. For persistent seizures, 50% received only conventional antiepileptic drugs (AEDs). When epilepsy treatments are considered for their costs and effectiveness, utilities and healthcare use, conditional on seizure control status, can be applied for further analyses.

Comparative pharmacodynamic effects of two clopidogrel formulations under steady-state conditions in healthy Thai volunteers
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OBJECTIVE: Clopidogrel is a commonly used antiplatelet aggregation agent. Compared with the reference clopidogrel product, most commercially available generic clopidogrel products contain different crystalline forms of clopidogrel. This study was aimed to compare the pharmacodynamics of a commonly used generic clopidogrel product in Thailand with the reference clopidogrel product under steady state conditions. METHODS: A multiple-dose, randomized 2-way crossover study was conducted in 32 healthy male Thai volunteers. The subjects were assigned to receive 75 mg once daily of the test or the reference product for 7 days with a 2-week wash out period. Blood samples were collected on days 1, 5, 6, and 7 prior to drug administration and at 1, 2, 3, 4, 8, 12, and 24 hours after the last dose administered. The antiplatelet aggregation effects of clopidogrel were determined by using two different ex-vivo platelet aggregation tests including the whole blood impedance assay (WBA) and the VerifyNow® P2Y12 assay. Both pharmacodynamic parameters, the maximal antiplatelet effect (Emax) and the areas under the antiplatelet effect-time curve (AUEC0-24h), were calculated. RESULTS: Neither the mean values of Emax (90.70 ± 15.15 vs. 89.50 ± 10.71% inhibition) nor of AUEC0-24h (1,892.84 ± 657.22 vs. 1,853.58 ± 673.95% inhibition × h) under steady-state conditions obtained using the WBA method of these two clopidogrel products were significantly different. The results obtained using the VerifyNow® P2Y12 assay were consistent with those of the WBA assay. CONCLUSION: This study clearly demonstrated that ex-vivo antiplatelet aggregation effect under steady-state conditions of the test product was not significantly different from the reference product.
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Prediction of Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis in Acute Ischemic Stroke: The Symptomatic Intracranial Hemorrhage Score.

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) is common after intravenous thrombolysis in acute ischemic strokes (AISs). Available predictive scoring systems were derived mostly in the Western countries. METHODS: Retrospective data in 1 provincial and 4 regional hospitals in the northern part of Thailand were reviewed. Patients with AIS, to whom recombinant tissue plasminogen activator (rt-PA) had been prescribed, were classified into 3 groups: no intracranial hemorrhage (no ICH), asymptomatic intracranial hemorrhage (asICH) and sICH. Coefficients under the multilevel ordinal logistic model were transformed into item scores and sum scores. Measures of discrimination, calibration, and internal validation were analyzed. RESULTS: Among 1172 patients, there were 78.8% with no ICH (n = 923), 13.1% with asICH (n = 154), and 8.1% with sICH (n = 95). The final model was named "SICH score" and included 6 variables: valvular heart diseases, use of aspirin, systolic blood pressure prior to thrombolysis that is 140 mmHg or higher, National Institutes of Health Stroke Scale scores higher than 10 and 20, a platelet count lower than 250,000 cell/mm3, and use of intravenous antihypertensive drugs during thrombolysis, with an Area under Receiver Operating Characteristic of .75 (95% confidence interval, .71-.80). CONCLUSION: The SICH score could be an assisting tool to predict an individual risk of sICH after intravenous thrombolysis for AIS in Thai patients.

Rheumatic Mitral Valve Disease Is Associated With Worse Outcomes in Stroke: A Thailand National Database Study.

BACKGROUND AND PURPOSE: Rheumatic valvular heart disease is associated with the increased risk of cerebrovascular events, although there are limited data on the prognosis of patients with rheumatic mitral valve disease (RMVD) after stroke. METHODS: We examined the association between RMVD and both serious and common cardiovascular and noncardiovascular (respiratory and infective) complications in a cohort of hospitalized stroke patients based in Thailand. Factors associated with in-hospital mortality were also explored. Data were obtained from a National Insurance Database. All hospitalized strokes between October 1, 2004, and January 31, 2013, were included in the current study. Characteristics and outcomes were compared for RMVD and non-RMVD patients. Logistic regression, propensity score matching, and multivariate models were used to assess study outcomes. RESULTS: In total, 594 681 patients (mean [SD] age=64 [14.5] years) with a diagnosis of stroke (ischemic=306 154; hemorrhagic=195 392; undetermined=93 135) were included in this study, of whom 5461 had RMVD. Results from primary analyses showed that after ischemic stroke, and controlling for potential confounding covariates, RMVD was associated (P<0.001) with increased odds for cardiac arrest (odds ratio [95% confidence interval]=2.13 [1.68-2.70]), shock (2.13 [1.64-2.77]), arrhythmias (1.70 [1.21-2.39]), respiratory failure (2.09 [1.87-2.33]), pneumonia (2.00 [1.81-2.20]), and sepsis (1.39 [1.19-1.63]). In hemorrhagic stroke patients, RMVD was associated with increased odds (fully adjusted model) for respiratory failure (1.26 [1.01-1.57]), and in patients with undetermined stroke, RMVD was associated with increased odds (fully adjusted analyses) for shock (3.00 [1.46-6.14]), respiratory failure (2.70 [1.91-3.79]), and pneumonia (2.42 [1.88-3.11]). CONCLUSIONS: RMVD is associated with the development of cardiac arrest, shock, arrhythmias, respiratory failure, pneumonia, and sepsis after acute stroke.

Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population.

BACKGROUND: Phenytoin is one of the most common causative drugs of several types of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). Genetic polymorphisms of the human leukocyte antigens (HLA) and cytochromes P450 (CYP) have been proposed as key elements for the susceptibility to phenytoin-related SCAR in certain ethnicities. This study investigated the associations between the genetic polymorphisms of HLA class I and CYP2C9 and phenytoin-related SCAR in a Thai population. MATERIALS AND METHODS: Sixty phenytoin-related SCAR (i.e. 39 SJS/TEN and 21 DRESS) and 92 phenytoin-tolerant patients were enrolled in the study. The genotypes of HLA class I and CYP2C9 were determined. RESULTS: Six HLA alleles including HLA-A*33:03, HLA-B*38:02, HLA-B*51:01, HLA-B*56:02, HLA-B*58:01, and HLA-C*14:02 were significantly associated with phenytoin-related SJS/TEN, whereas only the HLA-B*51:01 was significantly associated with phenytoin-related DRESS. The odds ratios of phenytoin-related SJS/TEN in the patients who carried one of these alleles ranged from 4- to 10-fold. The frequencies of patients who carried the HLA-B*15:02 in the SJS/TEN (12.82%) or the DRESS (9.52%) groups were not significantly different from that of the controls (14.13%). The higher risk of phenytoin-related SJS/TEN was observed in the patients with CYP2C9*3 (odds ratio=4.30, 95% confidence interval=1.41-13.09, P<0.05). CONCLUSION: Neither SJS/TEN nor DRESS caused by phenytoin was significantly associated with the HLA-B*15:02. The CYP2C9*3 variant was significantly associated with phenytoin-related SJS/TEN, but not DRESS. Certain alleles of HLA, particularly HLA-B*56:02, were significantly associated with phenytoin-related SCAR in the study population.

Delirium in critical care: a study of incidence, prevalence, and associated factors in the tertiary care hospital of older Thai adults.

OBJECTIVES: Delirium is a common condition in older adults which can have devastating outcomes. The studies about delirium in intensive care units (ICU) are relatively rare compared to studies in the non-ICU setting. This study aimed to study the prevalence, incidence, and risk factors of delirium among older Thai adults in ICU. METHOD: Participants were older patients who were admitted to the ICU of Srinagarind Medical School, KhonKaen, Thailand from May 2013 to August 2014. Baseline characteristics were collected. Delirium was rated by trained clinical researchers using the Confusion Assessment Method for the ICU (CAM-ICU). Demographic data were analyzed using descriptive statistics. Regression analyses were used to analyze the outcomes. RESULTS: Delirium occurred in 44 of 99 patients (44.4%) with an incidence rate of 22.2% (22/99). The prevalence of delirium in mechanically ventilated patients was 62.5% (30/48). The majority of the patients had delirium within five days of ICU admission. Seven independent predisposing factors were identified using bivariate regressions: age, functional status, disease severity, having pneumonia, cognitive impairment, depression, or previous stroke. Numbers of additional drugs, bed changes, physical restraints, sleep deprivation, use of bladder catheters, and patients with mechanical ventilators were independent precipitating factors. For multivariate regressions, previous stroke, multiple bed changes, and physical restraints were the significant factors. CONCLUSION: The prevalence and incidence of delirium of older adults in the ICU setting in this study was high and comparable to prior studies. There are several significant risk factors associated with delirium which could be modified. These factors should be considered when designing effective preventive strategies of delirium.