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BACKGROUND AND OBJECTIVE: Rhabdomyolysis (RM) is a life-threatening adverse drug reaction in which statins are the one commonly related to RM. The study aimed to explore the association between statin used and RM or other muscular related adverse events. In addition, drug interaction with statins were also assessed. METHODS: All extracted prescriptions were grouped as lipophilic and hydrophilic statins. RM outcome was identified by electronically screening and later ascertaining by chart review. The study proposed 4 models, i.e., logistic regression (LR), Bayesian network (BN), random forests (RF), and extreme gradient boosting (XGBoost). Features were selected using multiple processes, i.e., bootstrapping, expert opinions, and univariate analysis. RESULTS: A total of 939 patients who used statins were identified consisting 15, 9, and 19 per 10,000 persons for overall outcome prevalence, using statin alone, and co-administrations, respectively. Common statins were simvastatin, atorvastatin, and rosuvastatin. The proposed models had high sensitivity, i.e., 0.85, 0.90, 0.95 and 0.95 for LR, BN, RF, and XGBoost, respectively. The area under the receiver operating characteristic was significantly higher in LR than BN, i.e., 0.80 (0.79, 0.81) and 0.73 (0.72, 0.74), but a little lower than the RF [0.817 (95% CI 0.811, 0.824)] and XGBoost [0.819 (95% CI 0.812, 0.825)]. The LR model indicated that a combination of high-dose lipophilic statin, clarithromycin, and antifungals was 16.22 (1.78, 148.23) times higher odds of RM than taking high-dose lipophilic statin alone. CONCLUSIONS: The study suggested that statin uses may have drug interactions with others including clarithromycin and antifungal drugs in inducing RM. A prospective evaluation of the model should be further assessed with well planned data monitoring. Applying LR in hospital system might be useful in warning drug interaction during prescribing.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Rabdomiólise , Teorema de Bayes , Claritromicina/efeitos adversos , Mineração de Dados , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Rabdomiólise/induzido quimicamente , Rabdomiólise/epidemiologiaRESUMO
BACKGROUND: Clinic blood pressure measurement (CBPM) is currently the most commonly used form of screening for hypertension, however it might have a problem detecting white coat hypertension (WCHT) and masked hypertension (MHT). Home blood pressure measurement (HBPM) may be an alternative, but its diagnostic performance is inconclusive relative to CBPM. Therefore, this systematic review aimed to estimate the performance of CBPM and HBPM compared with ambulatory blood pressure measurement(ABPM) and to pool prevalence of WCHT and MHT. METHODS: Medline, Scopus, Cochrane Central Register of Controlled Trials and WHO's International Clinical Trials Registry Platform databases were searched up to 23rd January 2020. Studies having diagnostic tests as CBPM or HBPM with reference standard as ABPM, reporting sensitivity and specificity of both tests and/or proportion of WCHT or MHT were eligible. Diagnostic performance of CBPM and HBPM were pooled using bivariate mixed-effect regression model. Random effect model was applied to pool prevalence of WCHT and MHT. RESULTS: Fifty-eight studies were eligible. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of CBPM, when using 24-h ABPM as the reference standard, were 74% (95% CI: 65-82%), 79% (95% CI: 69%, 87%), and 11.11 (95% CI: 6.82, 14.20), respectively. Pooled prevalence of WCHT and MHT were 0.24 (95% CI 0.19, 0.29) and 0.29 (95% CI 0.20, 0.38). Pooled sensitivity, specificity, and DOR of HBPM were 71% (95% CI 61%, 80%), 82% (95% CI 77%, 87%), and 11.60 (95% CI 8.98, 15.13), respectively. CONCLUSIONS: Diagnostic performances of HBPM were slightly higher than CBPM. However, the prevalence of MHT was high in negative CBPM and some persons with normal HBPM had elevated BP from 24-h ABPM. Therefore, ABPM is still necessary for confirming the diagnosis of HT.
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Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão/diagnóstico , Visita a Consultório Médico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Hipertensão Mascarada/diagnóstico , Hipertensão Mascarada/fisiopatologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Hipertensão do Jaleco Branco/diagnóstico , Hipertensão do Jaleco Branco/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Although an increase in the burden of Alzheimer's disease (AD) is evident worldwide, knowledge of costs and health-related quality of life (HRQOL) associated with AD in low- and middle-income countries is still lacking. OBJECTIVES: This study aimed to collect real-world cost and HRQOL data, and investigate their associations with multiple disease-severity indicators among AD patients in Thailand. METHODS: We recruited AD patients aged ≥60 years accompanied by their caregivers at a university-affiliated tertiary hospital. A one-time structured interview was conducted to collect disease-severity indicators, HRQOL, and caregiving information using standardized tools. The hospital's database was used to retrieve healthcare resource utilization occurred over 6 months preceding the interview date. Costs were annualized and stratified based on cognitive status. Generalized linear models were employed to evaluate determinants of costs and HRQOL. RESULTS: Among 148 community-dwelling patients, average annual total societal costs of AD care were $8014 (95% confidence interval [CI]: $7295-$8844) per patient. Total costs of patients with severe stage ($9860; 95% CI: $8785-$11 328) were almost twice as high as those of mild stage ($5524; 95% CI: $4649-$6593). The major cost driver was direct medical costs, particularly those incurred by AD prescriptions. Functional status was the strongest determinant for both total costs and patient's HRQOL (P value <.001). CONCLUSION: Our real-world findings suggest the distinct major cost driver that results from expensive AD treatment, emphasizing the demand of country-specific cost evidence. Increases in cognitive and functional status are significantly associated with decreases in total costs of AD care and improvement in patient's HRQOL.
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Doença de Alzheimer/fisiopatologia , Efeitos Psicossociais da Doença , Qualidade de Vida , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Gastos em Saúde , Nível de Saúde , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , TailândiaRESUMO
BACKGROUND: POEMS syndrome is a plasma cell disorder, which clinically manifests from paraneoplastic syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. The most common ocular manifestation is optic disc swelling, whereas other ocular manifestations; cystoid macular edema, serous macular detachment, venous sinus thrombosis, infiltrative orbitopathy, uveitis, neovascularization of the disc, peripapillary choroidal neovascularization and optic disc drusen, had also been reported. CASE PRESENTATION: A 52-year-old Thai man presented with 5-day sudden painless visual loss in the left eye. Ocular examination revealed visual acuity of 20/20 and no light perception in the right and left eye, respectively. Right fundoscopic examination was significant for hyperemic generalized optic disc swelling. Left fundoscopic examination revealed opaque and edematous entire retina giving the appearance of central retinal artery occlusion (CRAO) along with pallid "chalky white" optic disc swelling. Fluorescein angiography showed profound leakage of bilateral optic nerve heads and arteriolar filling defect in macular area along with leakage of small retinal arterioles in the left eye. Indocyanine green angiography demonstrated choroidal filling defect in the left eye only. Neuroimaging showed enhancement and luminal narrowing of left internal carotid artery, early subacute watershed infarctions in the left cerebral hemisphere and pachymeningeal enhancement. Cerebrospinal fluid analysis revealed high protein level with normal opening pressure. Intravenous methylprednisolone was initially started without any benefit. After extensive investigations, diagnosis of "POEMS syndrome" was made based on polyneuropathy, elevated lambda light chain level, elevated plasma vascular endothelial growth factor (VEGF), hepatomegaly, spinal sclerotic bone lesions, and thrombocytosis. Furthermore, sural nerve biopsy demonstrated neuropathy and positive VEGF staining. He was treated with eight cycles of bortezomib, cyclophosphamide and dexamethasone (BorCyDex). Polyneuropathy and thrombocytosis had remarkably improved after 2nd cycle, whereas, visual impairment had shown no recovery. Hepatomegaly was significantly reduced after the completion of BorCyDex. Our case eventually received autologous hematopoietic stem cell transplantation with high dose melphalan. CONCLUSIONS: To our knowledge, we illustrated the first patient given CRAO as the first presentation and ocular finding ever reported in POEMS syndrome. Both cerebral and ocular infarctions were presumably the result of VEGF-induced cranial vasculopathy as evidenced by neuroimaging.
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Síndrome POEMS/complicações , Síndrome POEMS/patologia , Oclusão da Artéria Retiniana/etiologia , Oclusão da Artéria Retiniana/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Non-ataxic symptoms of spinocerebellar ataxias (SCAs) vary widely and often overlap with various types of SCAs. Duration and severity of the disease and genetic background may play a role in such phenotypic diversity. We conducted the study in order to study clinical characteristics of common SCAs in Thailand and the factors that may influence their phenotypes. METHODS: 131 (49.43%) out of 265 Thai ataxia families with cerebellar degeneration had positive tests for SCA1, SCA2, Machado-Joseph disease (MJD) or SCA6. The study evaluated 83 available families including SCA1 (21 patients), SCA2 (15), MJD (39) and SCA6 (8). Comparisons of frequency of each non-ataxic sign among different SCA subtypes were analysed. Multivariate logistic regression analyses were undertaken to analyze parameters in association with disease severity and size of CAG repeat. RESULTS: Mean ages at onset were not different among patients with different SCAs (40.31 ± 11.33 years, mean ± SD). Surprisingly, SCA6 patients often had age at onset and phenotypes indistinguishable from SCA1, SCA2 and MJD. Frequencies of ophthalmoparesis, nystagmus, hyperreflexia and areflexia were significantly different among the common SCAs, whilst frequency of slow saccade was not. In contrast to Caucasian patients, parkinsonism, dystonia, dementia, and facial fasciculation were uncommon in Thai patients. Multivariate logistic regression analysis demonstrated that ophthalmoparesis (p < 0.001) and sensory impairment (p = 0.025) were associated with the severity of the disease. CONCLUSIONS: We described clinical characteristics of the 4 most common SCAs in Thailand accounting for almost 90% of familial spinocerebellar ataxias. There were some different observations compared to Caucasian patients including earlier age at onset of SCA6 and the paucity of extrapyramidal features, cognitive impairment and facial fasciculation. Severity of the disease, size of the pathological CAG repeat allele, genetic background and somatic heterogeneity of pathological alleles may influence clinical expressions of these common SCAs.
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Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Adolescente , Adulto , Idade de Início , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Ataxias Espinocerebelares/fisiopatologia , Tailândia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Rivastigmine is a cholinesterase inhibitor for treatment of mild to moderate Alzheimer's disease (AD) and dementia associated with Parkinson's disease. The new patch formulation was recently made available. We assessed the safety, tolerability, and cognitive outcome of rivastigmine patch in treatment of mild to moderate AD in clinical practice in Thailand. METHODS: A multicentre, hospital-based, prospective observational study was conducted in nine hospitals across Thailand. Patients with probable mild to moderate AD who received the rivastigmine patch were enrolled. Data were collected data at baseline, weeks 4-8 and after week16. RESULTS: A total of 116 AD patients were screened, and three were excluded. Of 113 patients, 62.8% were women with a mean age of 73.3 ± 9.2 years; 79.7% were newly diagnosed. One-third of all patients had been using antipsychotic or antidepressant medication. Common comorbidities were hypertension and dyslipidemia. The Thai Mental State Examination score significantly increased from 18.6 to 20.3 (weeks 4-8) and 20.4 (week 16+) (P < 0.001). Scores based on physicians' (Clinical Global Impression) and caregivers' (Patients' Caregiver Global Impression of Change) impressions of improvement suggested minimal improvement. Because of adverse events, seven patients's dosages were reduced 10 cm(2) to 5 cm(2) or from 5 cm(2) to nothing. Itching was the most common adverse symptom. CONCLUSIONS: During the first 16 weeks after initiation of rivastigmine patch therapy, patients with probable mild to moderate AD had statistically significant improvement in cognitive function, but clinically marginal benefit. Rivastigmine was safe and well tolerated.
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Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/administração & dosagem , Cognição/efeitos dos fármacos , Fenilcarbamatos/administração & dosagem , Idoso , Doença de Alzheimer/psicologia , Inibidores da Colinesterase/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fenilcarbamatos/efeitos adversos , Estudos Prospectivos , Rivastigmina , Índice de Gravidade de Doença , Tailândia , Adesivo Transdérmico , Resultado do TratamentoRESUMO
Background: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases affecting primarily proximal muscles. Major subtypes include dermatomyositis, polymyositis, inclusion body myositis, immune-mediated necrotizing myopathy and antisynthetase syndrome. Overexpression of sarcoplasmic myxovirus-resistance protein A (MxA) has been observed in muscle biopsy specimens of dermatomyositis but is rarely seen in other subtypes of IIM and other myopathies. Objective: We evaluate the expression of sarcoplasmic MxA and its diagnostic value in IIM and other myopathies. Methods: One hundred and thirty-eight muscle biopsy specimens with the diagnosis of IIM and other myopathies from 2011 to 2020 were reviewed and stained for MxA by immunohistochemistry. The difference of the expression of MxA between IIM and other myopathies was analyzed by Fisher's exact test, and the sensitivity and specificity of MxA immunohistochemistry in the diagnosis of IIM were assessed. Results: MxA protein was positive in 16/138 (11.6%) specimens. All 12 dermatomyositis specimens positive for MxA protein were positive in perifascicular area pattern. Only dermatomyositis specimens had a significantly higher percentage of positive sarcoplasmic MxA expression than specimens of other subtypes of IIM (p<0.001). Sarcoplasmic MxA expression for dermatomyositis diagnosis had a sensitivity of 46.15% (95% CI 26.59-66.63%) and a specificity of 94.44% (95% CI 81.34-99.32%) with the positive and negative likelihood ratio of 8.31 (95% CI 2.03-34.01) and 0.57 (95% CI 0.40-0.82), respectively. Conclusion: The MxA immunohistochemistry is highly specific for dermatomyositis and should be added to a routine inflammatory panel of muscle biopsy. MxA expression should be cautiously interpreted to avoid pitfalls.
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Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab), and off-label mAb drugs (e.g., rituximab and tocilizumab). The FDA-approved mAbs have high efficacy but more expensive compared to the off-labels, and thus are less accessible. This systematic review and network meta-analysis (NMA) was to assess the efficacy and safety of both classes of mAbs compared to the current standard treatments. Methods: Systematically searches were conducted in MEDLINE and SCOPUS from inception until July 2021. Randomized-controlled trials (RCTs) were eligible if they compared any pair of treatments (mAbs, immunosuppressive drugs, or placebo) in adult patients with NMOSD. Studies with AQP4-IgG positive or negative were used in the analysis. Probability of relapse and time to event were extracted from the Kaplan-Meier curves using Digitizer. These data were then converted into individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate the median time to relapse and relative treatment effects using hazard ratios (HR). Two-stage NMA was used to determine post-treatment annualized relapse rate (ARR), expanded disability status score (EDSS) change, and serious adverse events (SAE). Risk of bias was assessed using the revised cochrane risk of bias tool. Results: A total of 7 RCTs with 776 patients were eligible in the NMA. Five of the seven studies were rated low risk of bias. Both FDA-approved and off-label mAbs showed significantly lower risk of relapse than standard treatments, with HR (95% CI) of 0.13 (0.07, 0.24) and 0.16 (0.07, 0.37) respectively. In addition, the FDA-approved mAbs had 20% lower risk of relapse than the off-label mAbs, but this did not reach statistical significance. The ARRs were also lower in FDA-approved and off-label mAbs than the standard treatments with the mean-difference of-0.27 (-0.37,-0.16) and-0.31(-0.46,-0.16), respectively. Conclusion: The off-label mAbs may be used as the first-line treatment for improving clinical outcomes including disease relapse, ARR, and SAEs for NMOSD in countries where resources and accessibility of the FDA-approved mAbs are limited. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283424, identifier: CRD42021283424.
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The slow-channel congenital myasthenic syndrome is an autosomal dominant neuromuscular disorder caused by mutations in different subunits of the acetylcholine receptor. Fluoxetine, a common antidepressant and long-lived open-channel blocker of acetylcholine receptor, has been reported to be beneficial in the slow-channel congenital myasthenic syndrome. Here we report a prospective open label study of fluoxetine treatment in some affected members of a Thai family with slow-channel congenital myasthenic syndrome caused by a novel p.Gly153Ala (c.518G > C) mutation in CHRNA1 in the AChR α subunit. These patients showed significant clinical improvement following fluoxetine treatment but their respiratory function responded variably.
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Fluoxetina , Síndromes Miastênicas Congênitas , Fluoxetina/uso terapêutico , Humanos , Mutação , Síndromes Miastênicas Congênitas/tratamento farmacológico , Síndromes Miastênicas Congênitas/genética , Estudos Prospectivos , Receptores Colinérgicos/genética , TailândiaRESUMO
BACKGROUND: Previous meta-analyses of treatments for Bell's palsy are still inconclusive due to different comparators, insufficient data, and lack of power. We therefore conducted a network meta-analysis combining direct and indirect comparisons for assessing efficacy of steroids and antiviral treatment (AVT) at 3 and 6 months. METHODS: We searched Medline and EMBASE until September 2010 using PubMed and Elsviere search engines. A network meta-analysis was performed to assess disease recovery using a mixed effects hierarchical model. Goodness of fit of the model was assessed, and the pooled odds ratio (OR) and 95% confidence interval (CI) were estimated. RESULTS: Six studies (total n = 1805)were eligible and contributed to the network meta-analysis. The pooled ORs for resolution at 3 months were 1.24 (95% CI: 0.79 - 1.94) for Acyclovir plus Prednisolone and 1.02 (95% CI: 0.73 - 1.42) for Valacyclovir plus Prednisolone, versus Prednisolone alone. Either Acyclovir or Valacyclovir singly had significantly lower efficacy than Prednisolone alone, i.e., ORs were 0·44 (95% CI: 0·28 - 0·68) and 0·60 (95% CI: 0·42 - 0·87), respectively. Neither of the antiviral agents was significantly different compared with placebo, with a pooled OR of 1·25 (95% CI: 0·78 - 1·98) for Acyclovir and 0·91 (95% CI: 0·63 - 1·31) for Valacyclovir. Overall, Prednisolone-based treatment increased the chance of recovery 2-fold (95% CI: 1·55 - 2·42) compared to non-Prednisolone-based treatment. To gain 1 extra recovery, 6 and 26 patients need to be treated with Acyclovir and prednisolone compared to placebo and prednisolone alone, respectively. CONCLUSIONS: Our evidence suggests that the current practice of treating Bell's palsy with AVT plus corticosteroid may lead to slightly higher recovery rates compared to treating with prednisone alone but this does not quite reach statistical significance; prednisone remains the best evidence-based treatment.
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Aciclovir/uso terapêutico , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Paralisia de Bell/tratamento farmacológico , Glucocorticoides/uso terapêutico , Quimioterapia Combinada , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a leading health issue, causing economic burden in India. Pharmacotherapy is a major cost driver in diabetic care usually funded through out of pocket expenditure; however, there has been a very limited economic evaluation evidence to guide the choice of diabetes pharmacotherapy in India. Therefore, this study aims to evaluate the long-term cost-effectiveness of dapagliflozin (sodium glucose transporter 2 inhibitor) compared to commonly used sulfonylureas as second-line drugs in Indian patients with T2DM. METHODS: Cost-utility analysis was employed to estimate the costs and health outcomes using a Markov model with 1-year cycle length during a lifetime horizon based on an Indian payer's perspective. A treatment pathway with dapagliflozin as second-line therapy was compared to sulfonylureas after failure of initial metformin therapy. Clinical and cost data were collected from literature reviews and available secondary data sources. Both costs and outcomes were discounted at a 3% annual discount rate. The results were presented as the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to test parameter uncertainties. RESULTS: Compared to sulfonylurea, dapagliflozin was estimated to incur an additional cost of â¹182,632 (US$2,446) with an expected 3.49 life years (LY) or 1.72 quality adjusted life years (QALY) gained, resulting in an ICER of â¹52,270 (US$699) per LY gained, or â¹106,133 (US$1,421) per QALY gained. Uncertainty analyses showed that the ICER values were not sensitive to changes in most parameters. CONCLUSION: Dapagliflozin would be cost-effective compared to sulfonylureas as the second line added to metformin for T2DM patients based on an Indian payer's perspective.
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PURPOSE: To analyze radiological characteristics of the extraocular muscles (EOMs) in myasthenia gravis (MG) patients with ocular manifestations. PATIENTS AND METHODS: This retrospective case-control study included all MG cases with ocular manifestations, who attended a neuro-ophthalmology clinic at a university hospital, Bangkok, from April 2009 to June 2018. They experienced double vision and ophthalmoplegia. Control participants had normal eye movements. Orbital scans were thoroughly reviewed. We measured muscle thickness (MT) of the superior rectus, inferior rectus, medial rectus and lateral rectus muscles in both eyes using magnetic resonance imaging or computed tomography scan. The sum of the muscle thickness at all sites was calculated (MTsum). Comparisons of the mean MT of each muscle type and the mean MTsum between the MG and control groups were performed by using Student's t-test. MRI signal intensities of the EOMs were also recorded. RESULTS: Twenty MG cases and 20 controls were included in the study. The mean MTsum was 23.7 (standard deviation 4.8) mm in the MG group and 32.6 (3.5) mm in the controls. There were statistically significant differences between the two groups with respect to the mean MT and mean MTsum (p <0.001). In the MG group, there was a negative correlation between the MTsum and disease duration (p= 0.03). By using coronal T2-weighted orbital MRI with fat suppression (T2W/FS), the most frequent finding was isointensity with central hypointensity of the EOMs in the MG group. CONCLUSION: Atrophic EOMs were frequently found in the MG group, particularly in chronic cases. Isointensity with central hypointensity of EOMs on T2W/FS was also common in the MG group. These findings highlight the importance of muscle involvement in MG and may be helpful for clinical decision-making.
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OBJECTIVE: Patients treated with statins for dyslipidemia may still have a residual risk of atherosclerotic cardiovascular disease (ASCVD). To determine whether genetic variants in the cholesteryl ester transport protein (CETP), rs3764261 (C>A), rs708272 (G>A), and rs12149545 (G>A) affect ASCVD risk, we studied the association of these variants with dyslipidemia in statin-treated patients. PATIENTS AND METHODS: We included 299 adult Thai patients treated with a statin (95 men and 204 women). Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis. We used logistic regression models adjusted for potential confounders of age, body mass index, blood pressure, insulin resistance, and statin dosage to analyze the association between CETP variants and atherogenic lipoprotein patterns. RESULTS: CETP polymorphisms of rs3764261 and rs708272, but not rs12149545, were significantly associated with high-density lipoprotein cholesterol (HDL-C), apoA-I, triglycerides, very low-density lipoprotein (VLDL)-C, and large LDL (LDL1-C) levels as well as mean LDL particle size (all p < 0.020). However, no significant difference was observed in total cholesterol, LDL-C, or apoB levels by CETP variants. Regardless of sex, the combination of rs3764261 (CC genotype) and rs708272 (GG or GA genotypes) showed a stronger association with atherogenic dyslipidemia, including features of decreased HDL-C, elevated triglycerides, and LDL subclass pattern B (odds ratio [OR] = 2.99, 95% confidence interval [CI]: 1.78-5.02) compared with the single variant rs3764261 (OR = 2.11, 95% CI: 1.27-3.50) or rs708272 (OR = 2.12, 95% CI: 1.29-3.49). CONCLUSION: The polymorphisms of CETP rs3764261 (CC genotype) and rs708272 (GG and GA genotypes) may have a higher susceptibility to atherogenic dyslipidemia. Testing for CETP rs3764261 and rs708272 may serve as a surrogate marker for lipid management in statin-treated patients, which may help individualize treatment for reducing the residual risk of ASCVD.
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INTRODUCTION: Molecular imaging has been developed and validated in Thai patients, comprising a portion of patients in the dementia registry. This should provide a more accurate diagnosis of the etiology of dementia, which was the focus of this study. METHODS: This was a multicenter dementia study. The baseline characteristics, main presenting symptoms, and results of investigations and cognitive tests of the patients were electronically collected in the registry. Functional imaging and/or molecular imaging were performed in patients with an equivocal diagnosis of the causes of dementia, especially in atypical dementia or young onset dementia (YOD). RESULTS: There were 454 patients in the study. The mean age of the patients was 78 years, with 60% female. Functional imaging and/or molecular imaging were performed in 57 patients (57/454 patients, 13%). The most common cause of dementia was Alzheimer's disease (AD; 50%), followed by vascular dementia (VAD; 24%), dementia with Lewy bodies (6%), Parkinson's disease dementia (6%), frontotemporal dementia (FTD; 2.6%), progressive supranuclear palsy (2%), multiple system atrophy (0.8%), and corticobasal syndrome (0.4%). YOD accounted for 17% (77/454 patients), with a mean age of 58 years. The causes of YOD were early onset amnestic AD (44%), VAD (16%), behavioral variant FTD (8%), posterior cortical atrophy (6.5%), and logopenic variant primary progressive aphasia (5.2%). CONCLUSION: AD was the most common cause of dementia in Thai patients and the distribution of other types of dementia and main presenting symptoms were similar to previous reports in Western patients; however, the proportion of YOD was higher.
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AIM: To investigate the variations and the frequencies of the SLCO1B1 gene in the Thai population. METHODS: Collected samples were categorized into five regions of Thailand. DNA samples were genotyped for two variants, c.388A>G and c.521T>C of the SLCO1B1, using TaqMan® real-time PCR. RESULTS: The minor allele frequencies (MAFs) of two single nucleotide polymorphisms (SNPs) were not significantly different among the five regions. The most frequent haplotype was SLCO1B1*1b (frequency: 0.654), followed by *1a (frequency: 0.217), *15 (frequency: 0.128), and *5 (frequency: 0.001). We observed a similar frequency of OATP1B1 transporter phenotypes compared to other populations. 75.85% of the Thai subjects showed normal OATP1B1 activity, 22.5% showed intermediate OATP1B1 activity, and 1.58% showed low OATP1B1 activity. CONCLUSION: This study reported the frequencies of the SLCO1B1 variants and the subsequent OATP1B1 activity in a large cohort of Thais that can provide important information for the guidance of personalized drug therapy.
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Burning and stabbing pain in the feet and lower limbs can have a significant impact on the activities of daily living, including walking, climbing stairs and sleeping. Peripheral neuropathy in particular is often misdiagnosed or underdiagnosed because of a lack of awareness amongst both patients and physicians. Furthermore, crude screening tools, such as the 10-g monofilament, only detect advanced neuropathy and a normal test will lead to false reassurance of those with small fiber mediated painful neuropathy. The underestimation of peripheral neuropathy is highly prevalent in the South-East Asia region due to a lack of consensus guidance on routine screening and diagnostic pathways. Although neuropathy as a result of diabetes is the most common cause in the region, other causes due to infections (human immunodeficiency virus, hepatitis B or C virus), chronic inflammatory demyelinating polyneuropathy, drug-induced neuropathy (cancer chemotherapy, antiretrovirals and antituberculous drugs) and vitamin deficiencies (vitamin B1 , B6 , B12 , D) should be actively excluded.
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Neuropatias Diabéticas/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Sudeste Asiático/epidemiologia , Neuropatias Diabéticas/patologia , Humanos , Doenças do Sistema Nervoso Periférico/patologia , PrognósticoRESUMO
BACKGROUND: Several studies on clinical practice for Duchenne muscular dystrophy (DMD) have been conducted in Western countries. However, there have been only a few similar studies in Asia and Oceania. Here, we investigate the steroid therapy-related clinical practice for DMD among the local experts. In 2015, we conducted a DMD expert survey in Asia and Oceania to acquire information regarding patients with DMD and to assess current clinical practice with the cooperation of Asian and Oceanian Myology Centre, a neuromuscular disease research network. RESULTS: We obtained survey responses from 87 out of 148 clinicians (62%) from 13 countries and regions. In China, 1385 DMD patients were followed-up by 5 respondent neurologists, and 84% were between 0 and 9 years of age (15% were 10-19 years, 1% > 19 years). While in Japan, 1032 patients were followed-up by 20 clinicians, and the age distribution was similar between the 3 groups (27% were 0-9 years, 35% were 10-19 years, 38% were >19 years). Most respondent clinicians (91%) were aware of DMD standard of care recommendations. Daily prednisolone/prednisone administration was used most frequently at initiation (N = 45, 64%). Inconsistent opinion on steroid therapy after loss of ambulation and medication for bone protection was observed. CONCLUSIONS: Rare disease research infrastructures have been underdeveloped in many of Asian and Oceanian countries. In this situation, our results show the snapshots of current medical situation and clinical practice in DMD. For further epidemiological studies, expansion of DMD registries is necessary.
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Distrofia Muscular de Duchenne/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Esteroides/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , China , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Japão , Masculino , Oceania , Sociedades Médicas/estatística & dados numéricos , Adulto JovemRESUMO
Aims: Due to the lack of studies evaluating compliance or persistence with Alzheimer's Disease (AD) treatment outside High-Income Countries (HICs), this study aimed to assess compliance, persistence, and factors associated with non-compliance and non-persistence by utilizing existing "real-world" information from multiregional hospital databases in Thailand.Materials and methods: Study subjects were retrospectively identified from databases of five hospitals located in different regions across Thailand. AD patients aged ≥60 years who were newly-prescribed with donepezil, galantamine, rivastigmine, or memantine between 2013 and 2017 were eligible for analysis. The Medication Possession Ratio (MPR) was used as a proxy for compliance, while the Kaplan-Meier survival analysis was employed to estimate persistence. Logistic and Cox regressions were used to assess determinants of non-compliance and non-persistence, adjusted for age and gender.Results: Among 698 eligible patients, mean (SD) MPR was 0.83 (0.25), with 70.3% of the patients compliant to the treatment (having MPR ≥ 0.80). Half of the patients discontinued their treatment (having a treatment gap >30 days) within 177 days with a 1-year persistence probability of 21.1%. The patients treated in the university-affiliated hospital were more likely to be both non-compliant (OR = 1.71; 95% CI = 1.21-2.42) and non-persistent (HR = 1.33; 95% CI = 1.12-1.58). In addition, non-compliance was higher for those prescribed with single AD treatment (OR = 2.52; 95% CI = 1.35-4.69), while non-persistence was higher for those unable to reimburse for AD treatment (HR = 1.34; 95% CI = 1.11-1.62).Limitations: By using retrospective databases, a difficulty in validating whether the medications are actually taken after being refilled may over-estimate the levels of compliance and persistence. Meanwhile, possible random coding errors may under-estimate the strength of association findings.Conclusions: This study reveals the situation of compliance and persistence on AD treatment for the first time outside HICs. The determinants of non-compliance and non-persistence underline key areas for improvement.
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Doença de Alzheimer/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , TailândiaRESUMO
OBJECTIVE: To investigate the clinical characteristics, laboratory features, and treatment outcomes of Thai patients compared between those with necrotizing autoimmune myopathy (NAM) and those with other idiopathic inflammatory myopathies (IIMs) or non-NAM. METHODS: This multicenter case-control study included patients aged ≥ 18 years who were diagnosed with IIMs by muscle pathology, and who had relevant clinical and laboratory data, including muscle enzymes, from at least 3 follow-up visits during a 1-year period. Baseline clinical and laboratory data were recorded. Serum myositis-specific autoantibodies (MSAs) were obtained on the date of recruitment. RESULTS: Of the 70 included patients, 67% had NAM, and 33% had non-NAM. The mean age of patients was 50.5 ± 15.9 years, 67% were female, and the median duration of symptoms was 2 months (IQR, 1-4). History of cancer was significantly higher in non-NAM (21.7% vs. 2.1%, p = 0.01). Gottron's papules were significantly more prevalent in non-NAM (21.7% vs. 4.3%, p = 0.04). Non-NAM had a higher prevalence of anti-Mi-2a (17.4% vs. 2.1%, p = 0.04) and Mi-2b (17.4% vs. 0.0%, p = 0.01); however, the presence of other MSAs, including anti-HMGCR and anti-SRP, was similar between groups. Improvement in motor power and treatment intensification with glucocorticoid and/or immunosuppressive agents 3 times throughout the follow-up period was similar between groups (NAM 46.8% vs. non-NAM 34.8%, p = 0.34). CONCLUSION: NAM is indistinguishable from non-NAM by clinical manifestations, serology, or laboratory findings, except that pathognomonic skin sign of Gottron's papules and anti-Mi2 are suggestive of dermatomyositis. The integration of clinical, serological, and pathological data is essential for making a diagnosis of NAM.Key Points⢠NAM is indistinguishable from non-NAM by clinical manifestations, serology, or laboratory findings.⢠The integration of clinical, serological, and pathological data is essential for making a diagnosis of NAM.
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Miosite/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Eletromiografia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/tratamento farmacológico , Miosite/patologia , Pele/patologiaRESUMO
BACKGROUND: The analysis of fresh frozen muscle specimens is standard following routine muscle biopsy, but this service is not widely available in countries with limited medical facilities, such as Thailand. Nevertheless, immunohistochemistry (IHC) analysis is essential for the diagnosis of patients with a strong clinical suspicion of muscular dystrophy, in the absence of mutations detected by molecular genetics. As the successful labelling of sarcolemmal membrane-associated proteins in formalin-fixed and paraffin-embedded (FFPE) muscle sections using IHC staining has rarely been described, this study aimed to develop a reproducible IHC method for such an analysis. METHODS: Thirteen cases were studied from the files of the Department of Pathology, Mahidol University. Diagnoses included three Duchenne muscular dystrophy (DMD), one Becker muscular dystrophy (BMD), one dysferlinopathy, and several not-specified muscular dystrophies. IHC was performed on FFPE sections at different thicknesses (3 µm, 5 µm, and 8 µm) using the heat-mediated antigen retrieval method with citrate/EDTA buffer, followed by an overnight incubation with primary antibodies at room temperature. Antibodies against spectrin, dystrophin (rod domain, C-terminus, and N-terminus), dysferlin, sarcoglycans (α, ß, and γ), and ß-dystroglycan were used. Frozen sections were tested in parallel for comparative analysis. RESULTS: Antibodies labelling spectrin, dystrophin (rod domain and C-terminus), dysferlin, sarcoglycans (α, ß, and γ), and ß-dystroglycan clearly exhibited sarcolemmal staining in FFPE sections. However, staining of FFPE sections using the antibody directed against the N-terminus of dystrophin was unsuccessful. The absence of labeling for dystrophins and dysferlin in FFPE sections was documented in all three DMD patients and the dysferlinopathy patient. The BMD diagnosis could not be made using IHC in FFPE sections alone because of a lack of staining for the dystrophin N-terminus, indicating a limitation of this method. CONCLUSIONS: We developed a reliable and reproducible IHC technique using FFPE muscle. This could become a valuable tool for the diagnosis of some muscular dystrophies, dystrophinopathies, sarcoglycanopathies (LGMD2D, LGMD2E, and LGMD2C), and dysferlinopathy, especially in situations where the analysis of fresh frozen muscle samples is not routinely available.