Sleep Bruxism in Thai Obstructive Sleep Apnea Patients.

OBJECTIVES: To investigate the prevalence of sleep bruxism (SB) in Thai obstructive sleep apnea (OSA) patients and to identify demographic characteristics and specific sleep parameters associated with SB. METHODS: A total of 119 medical records, each containing full-night type I polysomnography from Thai patients with OSA, were included. SB was detected using surface electromyography of the masseter muscle. SB was diagnosed when the SB index reached at least two episodes per hour of sleep. The differences in demographic characteristics and sleep parameters between SB and non-SB groups were analysed. Multivariate logistic regression analysis was performed to determine the associated factors for SB. RESULTS: Among Thai patients diagnosed with OSA, 50.4% concurrently experienced SB, predominantly of the tonic type. The study revealed a higher prevalence of SB in males compared to females. The SB group demonstrated significantly higher values in the apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), Arousal Index (AI), and Respiratory Arousal Index (RAI) compared to the non-SB group. Multivariate logistic regression analysis indicated that a lower body mass index (BMI), higher ESS, and increased severity of AHI were significantly associated with SB. CONCLUSIONS: The study revealed that half of Thai patients diagnosed with OSA also exhibited SB. Male, AHI, ESS, AI, and RAI appeared to be potential correlates for the presence of SB. Lower BMI, higher ESS, and elevated AHI can be factors associated with SB in Thai OSA patients. CLINICAL RELEVANCE: The prevalence of SB among Thai patients diagnosed with OSA and the factors associated with its occurrence were investigated.

Prevalence and Predictors of Postictal Confusion After Electroconvulsive Therapy.

OBJECTIVE: To investigate the prevalence and predictors of postictal confusion (PIC) in patients who received electroconvulsive therapy (ECT). METHODS: We conducted chart reviews for 79 patients who were receiving inpatient ECT. Subjects with PIC were identified. PIC was defined by confusion, disorientation, motor restlessness, purposeless movement, and nonresponse to verbal commands following ECT within an hour, intravenous benzodiazepine was necessary to manage disturbed behavior. Multivariable logistic regression analysis was used to examine the association of PIC with demographic and clinical variables. RESULTS: Prevalence of PIC was 36.7%. In 912 ECT sessions, the occurrence of PIC was 86 times. Patients with PIC (n = 29) had significant higher body mass index (BMI) (27 ± 6.6 kg/m2 vs 24.1 ± 5.2 kg/m2, t = -2.22, df = 77, p = 0.029) than patients without PIC (n = 50). PIC associated with BMI (Pearson correlation = 0.25, p = 0.029). BMI was significant predictor of PIC after adjusting for other covariates (odds ratio = 0.91, 95% CI= 0.83-0.99, p < 0.035). CONCLUSION: PIC was not uncommon in patients receiving ECT. BMI was an independent predictor of PIC. Psychiatrists should be aware of the risks of PIC in patients with high BMI receiving ECT.

Impact of Albumin and Omeprazole on Steady-State Population Pharmacokinetics of Voriconazole and Development of a Voriconazole Dosing Optimization Model in Thai Patients with Hematologic Diseases.

This study aimed to identify factors that significantly influence the pharmacokinetics of voriconazole in Thai adults with hematologic diseases, and to determine optimal voriconazole dosing regimens. Blood samples were collected at steady state in 65 patients (237 concentrations) who were taking voriconazole to prevent or treat invasive aspergillosis. The data were analyzed using a nonlinear mixed-effects modeling approach. Monte Carlo simulation was applied to optimize dosage regimens. Data were fitted with the one-compartment model with first-order absorption and elimination. The apparent oral clearance (CL/F) was 3.43 L/h, the apparent volume of distribution (V/F) was 47.6 L, and the absorption rate constant (Ka) was fixed at 1.1 h-1. Albumin and omeprazole ≥ 40 mg/day were found to significantly influence CL/F. The simulation produced the following recommended maintenance doses of voriconazole: 50, 100, and 200 mg every 12 h for albumin levels of 1.5-3, 3.01-4, and 4.01-4.5 g/dL, respectively, in patients who receive omeprazole ≤ 20 mg/day. Patients who receive omeprazole ≥ 40 mg/day and who have serum albumin level 1.5-3 and 3.01-4.5 g/dL should receive voriconazole 50 and 100 mg, every 12 h, respectively. Albumin level and omeprazole dosage should be carefully considered when determining the appropriate dosage of voriconazole in Thai patients.

Low Body Weight Increases the Risk of Ischemic Stroke and Major Bleeding in Atrial Fibrillation: The COOL-AF Registry.

We aimed to determine if low body weight (LBW) status (<50 kg) is independently associated with increased risk of ischemic stroke and bleeding in Thai patients with non-valvular atrial fibrillation (NVAF). (1) Background: It has been unclear whether LBW influence clinical outcome of patients with NVAF. (2) Methods: This prospective multicenter cohort study included patients enrolled in the COOL-AF Registry. The following data were collected: demographic data, medical history, risk factors and comorbid conditions, laboratory and investigation data, and medications. Follow-up data were collected every 6 months. Clinical events during follow-up were confirmed by the adjudication committee. (3) Results: A total of 3367 patients were enrolled. The mean age was 67.2 ± 11.2 years. LBW was present in 338 patients (11.3%). Anticoagulant and antiplatelet was prescribed in 75.3% and 26.2% of patients, respectively. Ischemic stroke, major bleeding, intracerebral hemorrhage (ICH), and death occurred during follow-up in 2.9%, 4.4%, 1.4%, and 7.7% of patients, respectively, during 25.7 months follow-up. LBW was an independent predictor of ischemic stroke, major bleeding, ICH, and death, with a hazard ratio of 2.40, 1.79, 2.37, and 2.65, respectively. (4) Conclusions: LBW was independently associated with increased risk of adverse outcomes in Thai patients with NVAF. This should be carefully considered when balancing the risks and benefits of stroke prevention among patients with different body weights.

Number of Electroconvulsive Therapy Sessions required for Thai Psychiatric Patients: a Retrospective Study.

OBJECTIVE: To study predictors of the number of electroconvulsive therapy (ECT) sessions required for symptom remission in psychiatric patients. PATIENTS AND METHODS: We conducted chart reviews for 95 patients whose condition remitted following inpatient ECT. We analyzed the clinical characteristics of the patients and compared the number of ECT sessions between adult (age 18-59 years) and elderly (age ≥ 60 years) patients. RESULTS: The overall mean ± SD of the number of ECT sessions was 11.8 ± 4.7 (range: 6-24). By diagnosis, it was 13.3 ± 5.5 for individuals with schizophrenia, 10.1 ± 2.7 for schizoaffective disorder, 14.4 ± 5.6 for bipolar depression, 9.4 ± 1.9 for bipolar mania, 10.9 ± 4.3 for major depressive disorder (MDD), and 11.8 ± 4.3 for those with other diagnoses. For MDD, the number of ECT sessions in elderly patients (13.4 ± 4.6) was statistically greater than that in adult patients (9 ± 2.9) (p = 0.008). CONCLUSION: The number of ECT sessions varied by age and diagnosis. The number of ECT sessions in elderly MDD patients was higher than that in adult MDD patients.

Efficacy and Safety of Switching from Low-Dose Statin to High-Intensity Statin for Primary Prevention in Type 2 Diabetes: A Randomized Controlled Trial.

INTRODUCTION: Statin intensification is required in patients who have high-risk for cardiovascular events. However, it is unclear if this is needed in whom plasma LDL-C target was achieved with low-dose statin for primary prevention. We investigated the efficacy and safety of switching from low-dose statin to high-intensity statin among type 2 diabetes (T2D) who had achieved plasma LDL-C <100 mg/dl with low-dose statin treatment. METHODS: T2D patients with no atherosclerotic cardiovascular disease who had plasma LDL-C level <100 mg/dl while taking simvastatin ≤20 mg/day were randomized to continue using the same dosage of simvastatin (low-dose statin group; LS) for 12 weeks, or to switch to atorvastatin 40 mg/day for 6 weeks, and then, if tolerated, to atorvastatin 80 mg/day for 6 weeks (high-intensity statin group; HS). Biochemical test and adverse events were evaluated at baseline, 6 weeks, and 12 weeks. RESULTS: One hundred and fifty patients (76 LS, 74 HS, mean age 58.9±8.9 years, 72% female) were included. The mean baseline plasma LDL-C level on statin was slightly higher in the HS group (71.9±13.6 vs. 68.1±14.2 mg/dl, p=0.09). The HS group had a significantly lower plasma LDL-C level at both 6 and 12 weeks (both p<0.001). Plasma LDL-C <40 mg/dl was found more frequently in the HS group (23.0% vs. 3.9%, p<0.001). Discontinuation of statin due to adverse effects was more frequent in the HS group (5.4% vs. 1.3%, p=0.38 for atorvastatin 40 mg/day, 12.2% vs. 1.3%, p=0.03 for atorvastatin 80 mg/day). No serious adverse events were observed in either group. CONCLUSION: Switching from low-dose statins to high-intensity statins resulted in a significant reduction in plasma LDL-C levels, and was fairly well tolerated during a 12-week study period.

High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer.

Background: KRAS, NRAS, and BRAF gene mutations are the most clinically relevant and frequently reported in colorectal cancer (CRC). Although data on these genes are frequently reported in several counties, data specific to these genes among Thai population are scarce. The aim of this study was to investigate and identify molecular alterations associated with colon cancer in Thai population, and to determine the impact of these genetic aberrations on clinical outcome. Methods: DNA from 108 archived formalin-fixed, paraffin-embedded (FFPE) tissue samples that histologically confirmed adenocarcinoma of stage II-III colon cancer between 2010 and 2012 at Siriraj Hospital (Bangkok, Thailand) were extracted. Gene mutational analysis was performed by next-generation sequencing (NGS) using an Oncomine Solid Tumor DNA kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Results: A total of 22 somatic gene mutations were detected. The mutation frequency observed in KRAS, NRAS, BRAF, PIK3CA, and FBXW7 mutations was 47.2%, 1.9%, 1.9%, 12%, and 14.8%, respectively. KRAS mutation codon 12, 13, 59, 61, 117, and 146 mutations were identified in 29.6%, 8.3%, 1.8%, 0.9%, 0.0%, and 8.3%, respectively. KRAS Exon 4 had better DFS compared with Exon 2 and 3. Conclusions: This study is the first to comprehensively report hotspot mutations using NGS in Thai colon cancer patients. The most commonly identified gene mutation frequencies among Thai patients (KRAS, NRAS, BRAF, TP53, and PIK3CA) were similar to the gene mutation frequencies reported in Western population, except for subgroup of KRAS codon 146 and FBXW7 mutations that had a slightly higher frequency.

Factors associated with low health-related quality of life among younger and older Thai patients with non-valvular atrial fibrillation.

PURPOSE: The aim of this study was to investigate the factors associated with low health-related quality of life (HRQoL) compared between younger and older Thai patients with non-valvular atrial fibrillation (NVAF). METHODS: This is a cross-sectional analysis of baseline data from a prospective NVAF registry from 24 hospitals located across Thailand. Patient demographic, clinical, lifestyle, and medication data were collected at baseline. EuroQOL/EQ-5D-3L was used to assess HRQoL. Health utility was calculated for the entire study population, and low HRQoL was defined as the lowest quartile. Multivariate logistic regression was used to identify factors that significantly predict low HRQoL among younger and older (≥ 65 years) patients with NVAF. RESULTS: Among the 3218 participants that were enrolled, 61.0% were aged older than 65 years. Mean HRQoL was lower in older than in younger patients (0.72 ± 0.26 vs. 0.84 ± 0.20; p < 0.001). Factors associated with low HRQoL among younger NVAF patients were the treatment-related factors bleeding history (p = 0.006) and taking warfarin (p = 0.001). Among older patients, the NVAF-related complications ischemic stroke or TIA, heart failure (HF), and dementia (all p < 0.001) were all significantly associated with low HRQoL. Dementia is the factor that most adversely influences low HRQoL among older NVAF. Interestingly, symptomatic NVAF was found to be a protective factor for low HRQoL (p < 0.001). CONCLUSIONS: Bleeding history and taking warfarin among younger patients, and ischemic stroke/TIA, HF, and dementia among older patients are significant predictors of low HRQoL. These factors should be taken into consideration when selecting treatment options for patients with NVAF.

Stimulus intensity determined by dose-titration versus age-based methods in electroconvulsive therapy in Thai patients.

OBJECTIVES: This study aimed to compare the accuracy of the stimulus intensity (SI) calculated by age-based methods with that using the dose-titration method. METHODS: The initial seizure threshold (IST) was determined using a standardized dose titration in hospitalized Thai patients treated with right unilateral (RUL, n=32) and bilateral (BL, n=57) electrode placement. The correlation between the IST and clinical variables was analyzed. The estimated SI based on the patient's age was compared with the SI determined by dose titration. RESULTS: Age was highly predictive of the IST for both groups (RUL, P=0.012; BL, P=0.045). Gender (P=0.006) and anticholinergic drug use (P=0.025) predicted the IST for the BL group. For the RUL group, the mean±SD (median) SI estimated using the half-age and age methods was 158±46 (169) mC and 315±92 (338) mC, respectively. The SI determined using the dose-titration method was higher compared with the half-age method and lower compared with the age method. For the RUL group, 31% of subjects using the half-age method and 22% of subjects using the age method would have received an SI within ±20% of that computed using dose titration. Additionally, 19% of subjects using the half-age method and 19% using the age method would have received unacceptably low (<50%) or high (>200%) intensities. For the BL group, 18% of subjects using the half-age method and 32% using the age method would have received an SI within ±20% of that computed using dose titration. Additionally, 39% with the half-age method and 18% with the age method would have received an unacceptably low or high SI, respectively. CONCLUSION: Age strongly predicts the IST, but it does not robustly predict the SI compared with dose titration because the SI calculated using age-based methods results in an unacceptably low or high SI that is associated with a marked risk of adverse effects or inadequate response. We recommend the dose-titration method to determine the SI.

Distribution of the Epstein-Barr virus in the normal stomach and gastric lesions in Thai population.

The Epstein-Barr virus (EBV) is one of the infectious agents found in stomach tissue. Recently, EBV-associated gastric carcinoma (EBVaGC) was classified as a new subtype of gastric carcinoma. To date, there is a lack of knowledge about the distribution and prevalence of EBV infection in both the normal stomach and various gastric lesions, including EBVaGC, in the Thai population. In this study, we detected EBV in the normal stomach (NS; n = 19), chronic gastritis (CG; n = 36), intestinal metaplasia (IM; n = 40), gastric dysplasia (GD; n = 15), and gastric adenocarcinoma (GC; n = 33) by polymerase chain reaction (PCR) amplification of the latent membrane protein (LMP1) gene of EBV. EBV-PCR amplification was positive in 42.1%, 36.1%, 22.5%, 13.3%, and 33.3% of NS, CG, IM, GD, and GC, respectively. For further clarification in EBVaGC, we performed EBV-encoded small RNA in situ hybridization (EBER-ISH) in PCR-positive cases of GD and GC. Four GC cases were EBER-ISH positive (12.1%), while both GD cases were EBER-ISH negative. In addition, we determined the distribution of the EBV strain (type A or B) based on EBNA3C sequence and EBV variants based on LMP1 variation (wild-type and 30-bp deletion variants; wt-LMP1 or del-LMP1). The results showed that type A and wt-LMP1 were the most prevalent in all lesions. In conclusion, EBV is common in both the NS and gastric lesions, and the frequency of EBVaGC was 12.1% in Thai patients.

Prevalence of Somatic KCNJ5 Mutations in Thai Patients With Aldosterone-Producing Adrenal Adenomas.

Somatic KCNJ5 mutations result in excess aldosterone production and are reported to be more common in Asia than elsewhere. To assess the prevalence of somatic KCNJ5 mutations in Thai patients with aldosterone-producing adrenal adenomas (APAs) in a single tertiary center, we analyzed the paraffin-embedded tissue of KCNJ5 mutations from 96 patients with sporadic APAs who underwent unilateral laparoscopic adrenalectomy at our center during 2007 to 2016. We also assessed the clinical characteristics, treatment outcomes, and biochemistry and histologic differences among patients with and without somatic KCNJ5 mutations. Of the 96 patients with APA, 67 (70%) had somatic mutations of the KCNJ5 gene: 39 patients with p.G151R, 26 patients with p.L168R, one patient with p.T158A, and one patient with p.W126R. All patients presented with hypertension. Hypokalemia was documented in 98% of patients. The hypertension cure rate at 1 year after surgery was 35%. Patients with somatic KCNJ5 mutations required more potassium supplementation and had adrenal histology compatible with zona fasciculata-like cells compared with patients without the mutations (all P < 0.05). There were no significant differences in preoperative plasma aldosterone concentration (PAC), plasma renin activity, aldosterone/renin ratio, potassium level, treatment of hypertension, tumor size, and hypertension cure rate among patients in the KCNJ5-mutant and nonmutant groups. In a multivariate analysis, a higher PAC was associated with the presence of somatic KCNJ5 mutations. In summary, the prevalence of somatic KCNJ5 mutations in patients with sporadic APAs in Thailand, an Asian country with residents of different ethnic backgrounds, is comparable to previous reports in Asia.

Not only the Sugar, Early infarct sign, hyperDense middle cerebral artery, Age, Neurologic deficit score but also atrial fibrillation is predictive for symptomatic intracranial hemorrhage after intravenous recombinant tissue plasminogen activator.

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) is the most unwanted adverse event in patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (i.v. rt-PA). Many tool scores are available to predict the probability of sICH. Among those scores, the Sugar, Early infarct sign, hyperDense middle cerebral artery, Age, Neurologic deficit (SEDAN) gives the highest area under the curve-receiver operating characteristic value. OBJECTIVE: We aimed to examine any factors other than the SEDAN score to predict the probability of sICH. METHODS: Patients with acute ischemic stroke treated with i.v. rt-PA within 4.5 h time window from January 2010 to July 2012 were evaluated. Compiling demographic data, risk factors, and comorbidity (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation (AF), ischemic heart disease, valvular heart disease, previous stroke, gout, smoking cigarette, drinking alcoholic beverage, family history of stroke, and family history of ischemic heart disease), computed tomography scan of patients prior to treatment with rt-PA, and assessing the National Institutes of Health Stroke Scale (NIHSS) score for the purpose of calculating SEDAN score were analyzed. RESULTS: Of 314 patients treated with i.v. rt-PA, there were 46 ICH cases (14.6%) with 14 sICH (4.4%) and 32 asymptomatic intracranial hemorrhage cases (10.2%). The rate of sICH occurrence was increased in accordance with the increase in the SEDAN score and AF. Age over 75 years, early infarction, hyperdense cerebral artery, baseline blood sugar more than 12 mmol/l, NIHSS as 10 or more, and AF were the risk factors to develop sICH after treated with rt-PA at 1.535, 2.501, 1.093, 1.276, 1.253, and 2.492 times, respectively. CONCLUSIONS: Rather than the SEDAN score, AF should be a predictor of sICH in patients with acute ischemic stroke after i.v. rt-PA treatment in Thai population.

Population pharmacokinetics and dose optimisation of ritonavir-boosted atazanavir in Thai HIV-infected patients.

There is evidence that Thai patients receiving standard doses of ritonavir (RTV)-boosted atazanavir (ATV/r) have high exposure to atazanavir (ATV) leading to a higher risk of toxicity. A lower dose of ATV/r may provide adequate exposure in this population. However, pharmacokinetic data on ATV/r in Thai patients required for dose adjustment are limited. This study aimed to develop a population pharmacokinetic model of ATV/r and to determine the influence of patient characteristics on ATV pharmacokinetics. Monte Carlo simulations were performed to estimate the proportion of patients achieving target ATV trough concentration (Ctrough) with the standard ATV/r dose of 300/100 mg and a low dose of 200/100 mg once daily (OD). A total of 127 Thai HIV-infected patients were included in this study. One random blood sample was collected to determine ATV and RTV concentrations at each clinic visit from 100 patients. Intensive data from 27 patients enrolled in previous studies were also included. Data were analysed using the non-linear mixed-effects modelling approach. A one-compartment model with first-order absorption and elimination and absorption lag time best described the data. The population mean clearance of ATV/r was 4.93 L/h in female patients and was 28.7% higher in male patients. Simulation results showed a higher proportion of patients achieving ATV Ctrough within the target range with ATV/r 200/100 mg compared with 300/100 mg. The 200/100 mg OD dose of ATV/r provides adequate ATV exposure in Thai HIV-infected patients. Therefore, a lower dose of ATV/r should be considered for Thai and Asian populations.

Clinical profiles and treatment outcomes of systemic corticosteroids for toxic epidermal necrolysis: A retrospective study.

Toxic epidermal necrolysis (TEN) is an uncommon severe cutaneous adverse reaction. Although controversies remain in the pathophysiology and management of this condition, improvements in survival and morbidity have been observed over the past decade. The aim of the present study was to demonstrate the clinical profiles of TEN in Thai patients and the treatment outcome with dexamethasone pulse therapy assessed by using the Severity of Illness Score for Toxic Epidermal Necrolysis (SCORTEN). Medical records of all patients with TEN were collected retrospectively from January 2002 to December 2012. Epidemiological features, etiologies, treatments and clinical outcomes were reviewed. Of 18 patients, the female to male ratio was 1:1 and the mean age was 49.7 years. Cephalosporins (27.8%), phenytoin (16.7%), carbamazepine, sulfonamide drugs and allopurinol (11.1% each) were implicated as leading causes of TEN. Hepatitis was the most frequent complication (77.8%). Pulsed high doses of dexamethasone 1-1.5 mg/kg per day for a short period were administrated in all cases. Two of the 18 patients receiving corticosteroids (SCORTEN 5 and 6) died. The mortality rate was 11% (2/18 patients), however, no patient receiving systemic corticosteroids died if the patients had less than 4 points on SCORTEN. The clinical features of Thai patients with TEN were similar to other reports. In conclusion, in addition to withdrawal of the suspected agent and intensive supportive care, the administration of short-term dexamethasone pulse therapy, particularly during the initial phase, may be beneficial in reducing the mortality rate.

Association of ABCB1 C3435T polymorphism with phenobarbital resistance in Thai patients with epilepsy.

WHAT IS KNOWN AND OBJECTIVE: One-third of patients with epilepsy are resistant to anti-epileptic drugs (AEDs). Drug-resistant epilepsy is believed to be multifactorial involving both genetic and non-genetic factors. Genetic variations in the ABCB1 gene encoding the drug efflux transporter, p-glycoprotein (p-gp), may influence the interindividual variability in AED response by limiting drugs from reaching their target. Phenobarbital (PB), one of the most cost-effective and widely used AEDs in developing countries, has been reported to be transported by p-gp. This study aimed to investigate the association of a genetic variant, ABCB1 3435C>T, and non-genetic factors with phenobarbital response in Thai patients with epilepsy. METHODS: One hundred and ten Thai patients with epilepsy who were treated with PB maintenance doses were enrolled in this study. Two phenotypic groups, PB-responsive epilepsy and PB-resistant epilepsy, were defined according to the International League Against Epilepsy (ILAE) criteria. Subjects were genotyped for ABCB1 3435C>T (rs1045642). Multiple logistic regression analysis was tested for the association of ABCB1 3435C>T polymorphism and non-genetic factors with PB response. RESULTS AND DISCUSSION: Sixty-two PB-responsive epilepsy subjects and 48 PB-resistant epilepsy subjects were identified. All genotype frequencies of the ABCB1 3435C>T SNP were consistent with the Hardy-Weinberg equilibrium (P > 0·05). The ABCB1 3435C>T polymorphism and type of epilepsy were associated with response to PB. Patients with PB-resistant epilepsy had a significantly higher frequency of ABCB1 3435CC genotype and had focal epilepsy more often than patients with PB-responsive epilepsy (adjusted OR = 3·962, 95% CI = 1·075-14·610, P-value = 0·039; adjusted OR = 5·936, 95% CI = 2·272-15·513, P-value < 0·001, respectively). The model explained 25·5% of the variability in response to PB (R(2)  = 0·255). WHAT IS NEW AND CONCLUSION: Thai patients of ABCB1 3435CC genotype and with focal epilepsy were more often PB resistant. Those two factors partly account for the variability in Thai epilepsy patients' response to phenobarbital.