[Show abstract][Hide abstract] ABSTRACT: Context:
Metformin is the first-line oral therapy for type 2 diabetes with proven benefits against cardiovascular risk. Recent evidence suggested that acarbose might be similar to metformin in glucose-lowering efficacy and cardiovascular risk reduction. Therefore, international guidelines have suggested the use of acarbose as alternative first-line antidiabetic therapy.
To compare the cardiovascular outcomes in the first-line users of acarbose vs metformin. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: A nationwide cohort study was conducted by analyzing the Taiwan National Health Insurance (NHI) Database. A total of 17,366 acarbose initiators and 230,023 metformin initiators were identified between January 1, 2009 and December 31, 2010. The primary outcome is hospitalization due to any cardiovascular events, including acute myocardial infarction, congestive heart failure, and ischemic stroke. The propensity score method was used to adjust for baseline differences between the two groups. Patients were followed from drug initiation to the earliest of outcome occurrence, death or disenrollment from NHI, or study termination.
In intention-to-treat analyses, acarbose was associated with a higher risk of any cardiovascular event (adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI], 1.01-1.09), heart failure (HR, 1.08; 95% CI, 1.00-1.16), and ischemic stroke (HR, 1.05, 95% CI, 1.00-1.10) than metformin. No significant difference in risk was found in subgroups of patients with or without underlying hypertension, ischemic heart disease, or cerebrovascular disease. Similar results were found in auxiliary as-treated analyses or analyses stratified by propensity score quintiles.
Our data do not support that acarbose has a cardio-protective effect similar to metformin as a first-line antidiabetic agent.
[Show abstract][Hide abstract] ABSTRACT: A strategy based on a regioselective 6-O-desulfation reaction and negative ion electrospray ionization tandem mass spectrometry (ESI-MS(n)) was developed for the structural delineation of isomeric chondroitin sulfate oligosaccharides. Product ions resulting from the glycosidic cleavage provided information about the number of sulfate groups in each sugar residue. After the regioselective 6-O-desulfation reaction, the number of sulfate groups on each residue was obtained using a tandem mass spectrometry analysis of the reaction product. The sulfation pattern could be obtained based on the product ions of analytes before and after the desulfation reaction. The strategy was demonstrated using a series of tetrasaccharides prepared from shark cartilage chondroitin sulfate D. Among the 12 identified tetrasaccharides, six structures had not been reported before.
[Show abstract][Hide abstract] ABSTRACT: 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. Antidepressants were classified as high- (HA group), intermediate- (IA group), or low-affinity (LA group) serotonin reuptake inhibitors. Patients in the LA group were matched 1:1 to those in the HA and IA groups according to their propensity scores. Subjects who were successfully matched were followed up from the date of antidepressant initiation to first hospitalization for UGIB, drug discontinuation, transition to or addition of antidepressants in another group, or the study's end (whichever occurred first). A total of 153,486 psychiatric patients were successfully matched, and 498 first UGIB events were identified. Compared with the LA group, patients in the HA group had a higher risk for UGIB (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.11-1.71). The HR (95% CI) of the IA group was 1.11 (95% CI, 0.88-1.41). The trend for elevated UGIB risk with increasing affinity of serotonin transporters was statistically significant (P < 0.01). Elderly patients and those with prior UGIB history were more susceptible to the harmful effects. Our findings suggest that the use of high-affinity serotonin reuptake inhibitors may increase the risk for UGIB in psychiatric patients.
[Show abstract][Hide abstract] ABSTRACT: A strategy based on negative ion electrospray ionization tandem mass spectrometry and closed-ring labeling with both 8-aminopyrene-1,3,6-trisulfonate (APTS) and p-aminobenzoic acid ethyl ester (ABEE) was developed for linkage and branch determination of high-mannose oligosaccharides. X-type cross-ring fragment ions obtained from APTS-labeled oligosaccharides by charge remote fragmentation provided information on linkages near the non-reducing terminus. In contrast, A-type cross-ring fragment ions observed from ABEE-labeled oligosaccharides yielded information on linkages near the reducing terminus. This complementary information provided by APTS- and ABEE-labeled oligosaccharides was utilized to delineate the structures of the high-mannose oligosaccharides. As a demonstration of this approach, the linkages and branches of high-mannose oligosaccharides Man(5)GlcNAc(2), Man(6)GlcNAc(2), Man(8)GlcNAc(2), and Man(9)GlcNAc(2) cleaved from the ribonuclease B were assigned from MS(2) spectra of ABEE- and APTS-labeled derivatives.
Journal of the American Society for Mass Spectrometry 06/2012; 23(8):1408-18. DOI:10.1007/s13361-012-0420-0 · 2.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies have documented the increased cardiovascular risk associated with the use of some nonsteroidal anti-inflammatory drugs (NSAIDs). Despite this, many old NSAIDs are still prescribed worldwide. Most of the studies to date have been focused on specific oral drugs or limited by the number of cases examined. We studied the risk of new acute myocardial infarction (AMI) hospitalization with current use of a variety of oral and parenteral NSAIDs in a nationwide population, and compared our results with existing evidence.
We conducted a case-crossover study using the Taiwan's National Health Insurance claim database, identifying patients with new AMI hospitalized in 2006. The 1-30 days and 91-120 days prior to the admission were defined as case and matched control period for each patient, respectively. Uses of NSAIDs during the respective periods were compared using conditional logistic regression and adjusted for use of co-medications.
8354 new AMI hospitalization patients fulfilled the study criteria. 14 oral and 3 parenteral NSAIDs were selected based on drug utilization profile among 13.7 million NSAID users. The adjusted odds ratio, aOR (95% confidence interval), for risk of AMI and use of oral and parenteral non-selective NSAIDs were 1.42 (1.29, 1.56) and 3.35 (2.50, 4.47), respectively, and significantly greater for parenteral than oral drugs (p for interaction<0.01). Ketorolac was associated with the highest AMI risk among both of oral and parenteral NSAIDs studied, the aORs were 2.02 (1.00, 4.09) and 4.27 (2.90, 6.29) respectively. Use of oral flurbiprofen, ibuprofen, sulindac, diclofenac, and parenteral ketoprofen were also significantly associated with increased AMI risk. The results of the present study were consistent with the majority of evidence from previous studies.
The collective evidence revealed the tendency of increased AMI risk with current use of some NSAIDs. A higher AMI risk associated with use of parenteral NSAIDs was observed in the present study. Ketorolac had the highest associated risk in both oral and parenteral NSAIDs studied. Though further investigation to confirm the association is warranted, prescribing physicians and the general public should be cautious about the potential risk of AMI when using NSAIDs.
[Show abstract][Hide abstract] ABSTRACT: Preclinical and observational studies raise the concern about the safety of insulin glargine in terms of cancer initiation and promotion. This study is designed to examine cancer incidence associated with use of insulin glargine vs. intermediate/long-acting human insulin (HI).
A retrospective cohort study using the Taiwan National Health Insurance claims database was conducted to identify adult patients with type 2 diabetes mellitus and without a history of cancer who initiated insulin glargine (n = 10,190) or intermediate/long-acting HI (n = 49,253) during 2004-2007. Exclusive users were followed from the date of insulin initiation to the earliest of cancer diagnosis, death, disenrollment, or December 31 2007. We estimated adjusted hazard ratios and 95% confidence intervals (CIs) with Cox proportional hazards models adjusting for baseline propensity score.
The incidence rate of all cancer per 1,000 person-years was 13.8 for insulin glargine initiators (179 cases) and 16.0 for intermediate/long-acting HI initiators (1,445 cases) during an average follow-up of 2 years. No significant difference in overall cancer risk between insulin glargine initiators and HI initiators was found. For men, however, the adjusted hazard ratio of insulin glargine use as compared with intermediate/long-acting HI was 2.15 (95% CI 1.01-4.59) for pancreatic cancer, and 2.42 (95% CI 1.50-8.40) for prostate cancer. The increased risk was not observed among women.
Insulin glargine use did not increase the risk of overall cancer incidence as compared with HI. The positive associations with pancreatic and prostate cancer need further evaluation and validation.
PLoS ONE 06/2011; 6(6):e21368. DOI:10.1371/journal.pone.0021368 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Limited studies assessed cerebrovascular safety of individual nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the risk of ischemic and hemorrhagic stroke associated with short-term use of selective and nonselective NSAIDs in a Chinese population with a high incidence of stroke.
A retrospective case-crossover study was conducted by analyzing the Taiwan National Health Insurance Database. We identified all ischemic and hemorrhagic stroke patients in 2006, aged >or=20 years, based on International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from inpatient claims and defined the index date as the date of hospitalization. For each patient, we defined case period as 1 to 30 days before the index date and control period as 91 to 120 days before the index date. A pharmacy prescription database was searched for NSAID use during the case and control periods. We calculated adjusted ORs and their 95% CIs with a conditional logistic regression model.
A total of 28 424 patients with ischemic stroke and 9456 patients with hemorrhagic stroke were included. For ischemic stroke, a modest increased risk was evident for all oral NSAIDs with adjusted ORs (95% CI) ranging from 1.20 (1.00 to 1.44) for celecoxib to 1.90 (1.39 to 2.60) for ketorolac. For hemorrhagic stroke, oral ketorolac was associated with a significantly higher risk with OR of 2.69 (1.56 to 4.66). Significantly increased risk was found for parenteral NSAIDs, in particular ketorolac, with an OR of 3.92 (3.25 to 4.72) for ischemic stroke and 5.98 (4.40 to 8.13) for hemorrhagic stroke.
Use of selective and nonselective NSAIDs was associated with an increased risk of both ischemic and hemorrhagic stroke, strikingly high for parenteral ketorolac.