Use of a Bayesian approach in the design and evaluation of NCE2s.

Taiwan's regulatory agency defines New Chemical Entity 2 (NCE2) as a compound drug that has been approved and marketed for ten years in a top-ten pharmaceutically-advanced country but which is new in Taiwan. To apply for registration of NCE2 in Taiwan, a clinical trial may be conducted in Taiwan to evaluate the efficacy and safety. Since the NCE2 has been approved in at least one of the top-ten pharmaceutically-advanced countries, we can borrow the information from all of the observed data from other countries to synthesize the data from both Taiwan and other countries to assess the NCE2 efficacy.

Comparison of the effects of serotonin-norepinephrine reuptake inhibitors versus selective serotonin reuptake inhibitors on cerebrovascular events.

Background: Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with an increased risk of intracranial hemorrhage. However, little is known about cerebrovascular risk in users of serotonin-norepinephrine reuptake inhibitors (SNRIs). Our aim was to determine the differential risk of cerebrovascular events between SSRIs and SNRIs.

Comparing individual angiotensin-converting enzyme inhibitors with losartan in the risk of hospitalization for pneumonia and related mortality: a nationwide cohort study.

Background: Angiotensin-converting enzyme (ACE) inhibitors might decrease the risk of pneumonia, but head-to-head comparisons with angiotensin receptor blockers (ARBs) were seldom made. The objective of this study was to evaluate incidence of pneumonia and mortality for different ACE inhibitors as compared to losartan, an ARB that has similar indications.

Methods: Adult patients aged more than 20 years who initiated ACE inhibitors and losartan between 1 January 2004 and 31 December 2009 were identified from Taiwan's National Health Insurance Database.

Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease.

Background: To contain cost, Taiwan's previous National Health Insurance Reimbursement Policy requested that physicians discontinue their patients' statin therapy once the serum cholesterol had reached appropriate levels. This allowed us to evaluate the association between statin continuation and the occurrence of atrial fibrillation/flutter and whether it was modified by chronic kidney disease (CKD) status.

Methods: Patients who initiated statin therapy between January 1, 2001 and December 31, 2009 were identified from a random sample of one million subjects in the Taiwan National Health Insurance Research Database.

Effects of selective serotonin reuptake inhibitors versus tricyclic antidepressants on cerebrovascular events: a nationwide population-based cohort study.

Depression is a common disorder worldwide and is strongly associated with stroke. Use of antidepressants could potentially decrease the risk of stroke in patients with depression. However, the role of selective serotonin reuptake inhibitors (SSRIs), the most frequently prescribed antidepressant in this era, in the risk of stroke showed inconsistent results.

Discontinuation of statin therapy associates with Parkinson disease: a population-based study.

Objective: To evaluate the effect of discontinuing statin therapy on incidence of Parkinson disease (PD) in statin users.

Methods: Participants who were free of PD and initiated statin therapy were recruited between 2001 and 2008. We examined the association between discontinuing use of statins with different lipophilicity and the incidence of PD using the Cox regression model with time-varying statin use.

Statins of high versus low cholesterol-lowering efficacy and the development of severe renal failure.

Background: The objective of this nationwide retrospective cohort study was to examine the renal outcomes of HMG-CoA reductase inhibitor (statin) initiators.

Methods: The patients who started to take statins with high cholesterol-lowering efficacy (atorvastatin and rosuvastatin) and low efficacy (lovastatin, simvastatin, pravastatin, and fluvastatin) between 1 January 2001 and 31 December 2008 were identified from the Taiwan National Health Insurance claims database. The outcome of interest was severe renal failure, defined as the composite endpoint of hemodialysis, peritoneal dialysis, and kidney transplantation.

Antidepressant use and the risk of upper gastrointestinal bleeding in psychiatric patients: a nationwide cohort study in Taiwan.

The magnitude of risk between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding (UGIB) is still unknown in patients with psychiatric diseases. The aim of this study was to quantify the risk of UGIB induced by use of antidepressants with different affinities for serotonin transporters in psychiatric patients using Taiwan's nationwide health insurance claims database. We conducted a propensity score- matched retrospective cohort study and identified 304,606 psychiatric patients who initiated antidepressant treatment during the 2005-2006 period.

Value of preapproval safety data in predicting postapproval hepatic safety and assessing the legitimacy of class warning.

Objective: The objective of this study was to systematically evaluate whether preapproval safety data for nonhepatotoxic drugs and hepatotoxic drugs can be compared to improve preapproval prediction of postapproval hepatic safety and to assess the legitimacy of applying class warnings.

Methods: Drugs within a therapeutic class that included at least one drug that had been withdrawn from the market because of liver toxicity or had a warning of potential liver toxicity issued by major regulatory agencies, and at least one drug free from such regulatory action, were identified and divided into two groups: drugs with and drugs without regulatory action. Preapproval clinical data [including the elevation rates of alanine aminotransferse (ALT) and withdrawal due to liver toxicity, the number of patients with combined elevation of ALT and bilirubin, and liver failure] and nonclinical data (including chemical structures, metabolic pathways, and other significant findings in animal studies) were compared between the two groups.

Non-steroidal anti-inflammatory drugs use and risk of upper gastrointestinal adverse events in cirrhotic patients.

Background/aims: The upper gastrointestinal (GI) toxicity associated with non-steroidal anti-inflammatory drugs (NSAID) use among cirrhotic patients remains unclear. The objective of this study was to evaluate the risk of upper GI adverse events associated with celecoxib and oral and parenteral non-selective NSAIDs in cirrhotic patients.

Methods: All the patients aged ≥ 20 years with a diagnosis of cirrhosis hospitalized for variceal bleeding and non-variceal upper GI adverse events (oesophageal, gastric, duodenal ulcer, bleeding; gastritis and duodenitis) in 2006 were identified using ICD-9-CM diagnosis codes from inpatient claims from the Taiwan National Health Insurance Database.

Association of galactose single-point test levels and phenytoin metabolic polymorphisms with gingival hyperplasia in patients receiving long-term phenytoin therapy.

Study Objective: To evaluate whether the occurrence or severity of gingival hyperplasia is associated with liver function test results or phenytoin metabolism.

Design: Prospective analysis.

Setting: University-affiliated medical center in Taipei, Taiwan.

Association of polymorphisms in NR1I2 and ABCB1 genes with epilepsy treatment responses.

Objectives: The aim of this study was to investigate whether the polymorphisms in the NR1I2 and ABCB1 genes were associated with epilepsy treatment responses.

Methods & Results: NR1I2and ABCB1 polymorphisms were genotyped in 114 drug-resistant epileptic patients, 213 seizure-free patients and 287 normal controls. Highly specific real-time PCR was applied to detect the variants by using TaqMan allelic specific probe.

Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis.

Aim: To test the hypothesis that the variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis.

Methods: A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1,091, and 1,456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency.

Screening CYP3A single nucleotide polymorphisms in a Han Chinese population with a genotyping chip.

Human cytochrome P450 (CYP)3A is a major P450 enzyme found in the liver and gastrointestinal tract. It plays an important role in the metabolism of a wide variety of drugs, some endogenous steroids and harmful environmental contaminants. It has been shown that CYP3A alleles encoding enzymes with little or no activity are largely created by single nucleotide polymorphisms (SNPs) in the sequences of these genes.

Genetic factors related to unconjugated hyperbilirubinemia amongst adults.

Some variations in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene are involved in the development of unconjugated hyperbilirubinemia. We hypothesize that other genetic factors may also be associated with this disease. A total of 227 adults with normal routine haematology and liver function (apart from bilirubin testing for which they revealed bilirubin > or = 25.

Polymorphisms of uridine-diphosphoglucuronosyltransferase 1A7 gene in Taiwan Chinese.

Aim: Single nucleotide polymorphisms (SNPs) of uridine-diphosphoglucuro-nosyltransferase 1A7 (UGT1A7) gene are associated with the development of orolaryngeal cancer, hepatocellular carcinoma, and colorectal cancer. We performed this research to establish the techniques for determining UGT1A7 gene and basic data of this gene for Taiwan Chinese.

Methods: We collected blood samples from 112 healthy adults and 505 subjects carrying different genotypes of UGT1A1, and determined the promoter area and the entire sequence of UGT1A7 exon 1 by polymerase chain reaction.

Quality of life in Taiwanese adults with chronic rhino-sinusitis.

Background And Purpose: Chronic rhino-sinusitis (CRS) is a disease in prevalence. This study evaluates the impact of this disorder to Taiwanese patients' general and sinus-related health status among Taiwanese patients with CRS.

Methods: A total of 201 consecutive CRS patients (male:female: 107:94, mean age: 40.

Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes.

Background: For clinical treatment, a smaller dosage of propranolol is often used among Chinese people. Propranolol is metabolized by polymorphic CYP2D6. We postulate that the lower propranolol dosage in Chinese is due to a slower CYP2D6 metabolism.

Coinheritance of variant UDP-glucuronosyl transferase 1A1 gene and glucose-6-phosphate dehydrogenase deficiency in adults with hyperbilirubinemia.

A total of 115 male adults with unconjugated hyperbilirubinemia were divided into six subgroups according to their glucose-6-phosphate dehydrogenase (G6PD) status (normal and deficient) and UDP-glucuronosyl transferase 1 (UGT1) A1 genotypes (heterozygous variation, compound heterozygous variation and homozygous variation). The mean (SD) value of serum bilirubin in the subjects with G6PD deficiency and homozygous variation in UGT1A1 gene was 51.3 (17.