Churn-Shiouh Gau

Interfacial properties of Pluronics and the interactions between Pluronics and cholesterol/DPPC mixed monolayers.

Pluronics are triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) with wide range of hydrophilic-lipophilic balance. In order to investigate the relationship between the chemical structures of Pluronics and the interfacial properties at the air-water interface by monolayer techniques, Pluronics L61, P65, F68, P84, P123, L35, and P105 were selected. Since cholesterol influenced substantially the molecular packing stage and the characteristics of cell membranes, the interactions between Pluronics and model cell membranes in the absence and presence of cholesterol were compared. The results of pi-A isotherms and surface elasticities of Pluronic monolayers indicated that the first and second transition like stage were mainly affected by the numbers of EO and PO monomers, respectively. Pluronics with higher hydrophobicities demonstrated larger surface activities and penetration abilities to dipalmitoylphosphatidylcholine (DPPC) monolayers, which might be due to hydrophobic interactions and van der Waals forces. In the presence of cholesterol, hydrogen bonding effects was supposed to exist between the 3beta-hydroxy group of cholesterol and ether oxygen of PEO chains, which led Pluronic F68, with the longest PEO chain herein, to exhibit significantly higher penetration ability. Our findings proposed a theoretical basis for selection of optimized drug carriers and the starting point for further investigations.

Injury-Proneness of Youth with Attention-Deficit Hyperactivity Disorder: A National Clinical Data Analysis in Taiwan.

Limited literature documents injury-proneness of attention-deficit hyperactivity disorder in western population. However, only a few studies prospectively investigated the prediction of ADHD to injuries without considering other psychiatric and physical conditions and there is lack of such data in Asian population. To prospectively examine the prediction of ADHD to the risk of injury in a national sample of Taiwan, we conducted this study with samples including 1965 6-18-year-old youths with newly diagnosis of ADHD from 1999 to 2003, and 7860 sex-, age- and index day-matched non-ADHD controls from Taiwans National Health Insurance Research Database (1997-2008). Relevant psychiatric and physical disorders, demographics, and medications were also included in the Cox proportional hazard models with injury as the outcome. Our results showed that ADHD cases had a roughly 2-fold and 5-fold higher risk of each injury, and overall injury than controls after considering all confounding factors, respectively. In addition to ADHD, use of anxiolytics, antidepressants, and antipsychotics, and comorbid physical illnesses also predicted the injury prospectively. Our findings strongly support that ADHD predicted injury risks and imply that physicians should take the risk of injury into consideration while prescribing medications other than stimulants to patients with ADHD, especially anxiolytics.

A Prospective Study of Hepatitis during Antituberculous Treatment in Taiwanese Patients and a Review of the Literature

BACKGROUND/PURPOSE The present study prospectively investigated the incidence of and factors associated with hepatitis during antituberculous treatment in patients with tuberculosis and various underlying diseases. The results were compared with those of previously published studies. METHODS Patients treated with antituberculous agents were enrolled from July 1, 2000 to July 31, 2001, in the divisions of chest and infectious diseases at National Taiwan University Hospital and followed until November 30, 2001. Hepatitis was defined as an aminotransferase level>5 times the upper limit of normal (ULN), or >3 times ULN in the presence of symptoms of hepatitis, or total bilirubin level>3 mg/dL. Studies reporting the incidence of hepatitis during antituberculous treatment were reviewed for comparison. RESULTS Among 261 patients, median age was 58 years (range, 17-90 years), 17.7% had abnormal baseline liver function tests and 18.4% had concurrent hepatotoxic drug use. Fifteen patients (5.7%) had hepatitis B virus infection, 17 (6.5%) had hepatitis C virus infection, 14 (5.4%) had liver cirrhosis, and 15 (5.7%) had human immunodeficiency virus infection. Hepatitis occurred in 42 patients (16.1%), with 60% of the events in the first 2 months of treatment. Such an incidence was comparable to that in other Asian countries (5.3-18.2%) and slightly higher than that in Western countries (2.4-19%). In multivariate analysis, abnormal liver function tests at baseline and liver cirrhosis were independent factors for development of hepatitis. CONCLUSION Elevation of liver function tests was not uncommon during antituberculous treatment, especially in the first 2 months. Patients with abnormal liver function tests at baseline or liver cirrhosis should be closely monitored.

A pharmacoeconomic analysis of atypical antipsychotics and haloperidol in first-episode schizophrenic patients in taiwan.

The study prospectively examined the economic outcomes and comedications among first-episode schizophrenic patients treated with monotherapy of second-generation antipsychotic agents (SGAs) continuously as compared with each other and with haloperidol. The sample included 3047 out of Taiwans national sample of 29,341 first-episode schizophrenic patients, who were selected, based on International Classification of Disease, Ninth Revision code 295, from the National Health Insurance original claims data from 1999 to 2004. They were treated with only 1 of the following antipsychotic agents: haloperidol (n = 526), clozapine (n = 224), risperidone (n = 827), olanzapine (n = 824), zotepine (n = 286), or quetiapine (n = 360), without changing antipsychotics during the observation for at least 1 year (mean, 1.80 years; SD, 0.93 years) for each subject. Economic outcomes included clinic visits, prescription days, frequencies and duration of hospitalizations, and total and separate treatment costs (outpatient department- and hospital-related costs). Comedications included use of anticholinergic, anxiolytic, hypnotic/sedative, and antidepressant agents. Patients treated with SGAs had lower number and shorter durations of hospitalizations than did haloperidol-treated patients, except for the clozapine group. Olanzapine was associated with the lowest hospitalization rates per year (mean, 1.63 vs 2.83). In terms of cost, haloperidol was more expensive in total hospitalization expenses (mean, US

Association between mood stabilizers and hypothyroidism in patients with bipolar disorders: a nested, matched case‐control study

3215 per year) and total treatment cost (mean,

The association between carbamazepine and valproate and adverse cutaneous drug reactions in patients with bipolar disorder: a nested matched case-control study.

3769 per year) than olanzapine, zotepine, or quetiapine. In general, there was no difference among the haloperidol and SGA groups in terms of rates of comedications. The reduced number of hospitalizations and then lower total hospitalization costs seem to be more than the offset of high medication acquisition costs of SGAs.

Use of antipsychotics and risk of cerebrovascular events in schizophrenic patients: a nested case-control study.

OBJECTIVES This study investigated whether lithium, carbamazepine, and valproate increased the risk for hypothyroidism using Taiwans National Health Insurance Dataset. METHODS The sample included 557 bipolar disorder patients with incident hypothyroidism first diagnosed between 1998 and 2004, and 2,228 sex-, age-, and index date-matched bipolar disorder patients without hypothyroidism from 1996-2004. We compared the use of lithium, carbamazepine, and valproate before the onset of hypothyroidism between the two groups using a conditional logistical regression model. RESULTS Compared with patients who had never used any of the three mood stabilizers, patients were more likely to have hypothyroidism if they only used carbamazepine [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.07-2.65]; or comedication of lithium and valproate (OR = 2.40; 95% CI: 1.70-3.40), lithium and carbamazepine (OR = 1.52; 95% CI: 1.10-2.08), and three mood stabilizers (OR = 2.34; 95% CI: 1.68-3.25). There was a dose-response relationship between the number of mood stabilizers and risk for hypothyroidism (OR = 1.34, 95% CI: 1.21-1.49) and a significant interaction between lithium and valproate on the risk for hypothyroidism (p = 0.020). CONCLUSIONS Our findings indicate that lithium, carbamazepine, and valproate may increase the risk for hypothyroidism, particularly if combined, and suggest regular monitoring of thyroid function and monotherapy of mood stabilizers for treating patients with bipolar disorders.

Waist-to-hip ratio correlates with homocysteine levels in male patients with coronary artery disease

Objective: This study investigated the association between 2 mood stabilizers (carbamazepine and valproate) and other medications (including other anticonvulsants) and the risks of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) among patients with bipolar disorder. Methods: Using the data of patients with bipolar disorder between March 1997 and December 2004 from the Psychiatric Inpatient Medical Claims databank, we identified 72 patients with bipolar disorder who had an inpatient or outpatient diagnosis of EM, SJS, or TEN by the International Classification of Diseases, Ninth Revision, Classical Modification code 695.1 and 288 controls with the absence of EM, SJS, or TEN diagnosis who were matched for sex, age, and index day. The use of carbamazepine, valproate, and other medications during the 60 days before the index date of diagnosis of EM, SJS, or TEN were compared. Results: Results showed that carbamazepine (odds ratio, 3.7; 95% confidence interval, 2.0-6.8) and valproate use (odds ratio, 2.2; 95% confidence interval, 1.2-4.2) significantly predicted EM, SJS, or TEN. Other significant predictors for EM, SJS, or TEN included other anticonvulsants (phenytoin, phenobarbital, and lamotrigine), cephalosporin, some nonsteroid anti-inflammatory drugs (acetic acid derivatives and fenamates [mefenamic acid]), salicylates, and acetaminophen. The most predictive exposures were carbamazepine, valproate, other anticonvulsants, and acetaminophen. We also found that the combination of carbamazepine and acetaminophen further increased the risk for the occurrence of EM, SJS, or TEN. There was no interaction effect from age and sex. Conclusions: Our study suggests that carbamazepine and valproate as well increase the risk for EM, SJS, or TEN. We should be especially cautious about the combined use of carbamazepine and acetaminophen.

Sex Differences in the Treatment and Outcome of Patients with Acute Coronary Syndrome After Percutaneous Coronary Intervention: A Population-Based Study

ObjectiveThis nested case-control study assessed the association between antipsychotic use and cerebrovascular adverse events among schizophrenic patients. MethodsUsing Taiwan’s National Health Insurance Research Database, we identified 9715 newly diagnosed schizophrenic patients during 2001 to 2009. Within the schizophrenic cohort, 386 cases of cerebrovascular events and 772 matched control subjects (1:2 ratio) were further identified. Conditional logistic regression models were used to examine the association between the use of antipsychotics (timing, duration, and type) and risk of cerebrovascular events. ResultsCurrent users of antipsychotics were associated with a 2-fold risk of stroke (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.11–1.39; P = 0.02) as compared with nonusers. Among current users, patients who used antipsychotics less than 15 days (adjusted OR, 9.41; 95% CI, 3.08–28.71; P < 0.01) and 16 to 30 days (adjusted OR, 6.90; 95% CI, 1.09–43.69; P = 0.04) were associated with an extremely high risk of stroke. The risk of stroke was greater for patients who used first-generation antipsychotics alone or combination of first- and second-generation antipsychotics, with adjusted ORs of 2.75 (95% CI, 1.34–5.64; P < 0.01) and 2.37 (95% CI, 1.20–4.68; P = 0.01), respectively, but not in patients who used second-generation antipsychotic alone. ConclusionsThis population-based study extends previous evidence by documenting the increased cerebrovascular events associated with antipsychotic use in a schizophrenic cohort. A temporal association of such risk was reported in our study. Further studies are needed to assess the risk-benefit profile of first- and second-generation antipsychotics in this patient population.

The evolution and challenges for the international harmonization of the regulation of pharmaceutical excipients in Taiwan

Abstract Background: Obesity and homocysteine are important risk factors for cardiovascular disease. The relation between pattern of obesity and homocysteine is unclear. The objective of this study was to investigate the relation between pattern of obesity and plasma total homocysteine (tHcy) level in male patients with coronary artery disease (CAD). Methods: A total of 63 male patients (mean age 66.2 years) with angiographically documented CAD were enrolled. Overnight fasting blood samples were measured for plasma tHcy, serum folic acid and serum vitamin B12 levels. Anthropometric measurements included waist-to-hip ratio (WHR) and body mass index (BMI). Results: The mean WHR was 0.90±0.05, mean BMI 24.6±3.3 kg/m2 and the mean plasma tHcy level 11.6±3.2 μmol/L. In univariate analysis, plasma tHcy level correlated significantly with serum vitamin B12 level, serum folic acid level, WHR, estimated creatinine clearance, aspirin use and fibrate use. There was no significant association between plasma tHcy level and BMI. In multivariate analysis, only WHR (β-value 22.263, p<0.001), serum level of vitamin B12 (β-value –0.004, p=0.003), estimated creatinine clearance (β-value –4.154, p=0.003) and use of fibrates (β-value 2.307, p=0.031) were independent predictors of plasma tHcy level. Conclusions: WHR, but not BMI, is a strong independent predictor of plasma tHcy level in male patients with CAD. Clin Chem Lab Med 2008;46:125–30.