Chia-Hsuin Chang

Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis.

Evidence suggests that a high concentration of C-reactive protein (CRP) is a cardiovascular risk factor and an important correlate of cognitive disorders and depression. Recently, population-based studies examining the association between CRP and stroke, cognitive impairment, or depression have been done but have not yet been systematically reviewed. Here we present a systematic review of the associations between CRP and stroke, cognitive impairment, and depression. Hospital or clinic-based studies were excluded because the inferences might not be easily applicable to the general population. 19 eligible studies of CRP were selected: seven for stroke, six for cognitive disorders, and six for depression. Raised CRP concentrations were associated with history of stroke and increased risk of incident stroke. Meta-analysis of studies with long follow-up (>8 years) showed that the risk for stroke in healthy individuals with the highest quartile of CRP concentrations increased nearly 70% compared to those with the lowest quartile. High concentrations of CRP were predictive of cognitive decline and dementia. The relations of CRP to depression were all cross-sectional and were not consistent. We conclude that high concentrations of CRP are associated with increased risk of stroke and cognitive impairment. The association between CRP and depression should be studied prospectively.

Association of thiazolidinediones with liver cancer and colorectal cancer in type 2 diabetes mellitus

The objective of this nationwide case‐control study was to evaluate the risk of specific malignancy in diabetic patients who received thiazolidinediones (TZDs). A total of 606,583 type 2 diabetic patients, age 30 years and above, without a history of cancer were identified from the Taiwan National Health Insurance claims database during the period between January 1 2000 and December 31 2000. As of December 31 2007, patients with incident cancer of liver, colorectal, lung, and urinary bladder were included as cases and up to four age‐ and sex‐matched controls were selected by risk‐set sampling. Logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) between TZDs and cancer incidence. A total of 10,741 liver cancer cases, 7,200 colorectal cancer cases, and 70,559 diabetic controls were included. A significantly lower risk of liver cancer incidence was found for any use of rosiglitazone (OR: 0.73, 95% CI: 0.65‐0.81) or pioglitazone (OR: 0.83, 95% CI: 0.72‐0.95), respectively. The protective effects were stronger for higher cumulative dosage and longer duration. For colorectal cancer, rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk (OR: 0.86; 95% CI: 0.76‐0.96). TZDs were not associated with lung and bladder cancer incidence, although a potential increased risk for bladder cancer with pioglitazone use ≥3 years could not be excluded (OR: 1.56; 95% CI: 0.51‐4.74). Conclusion: The use of pioglitazone and rosiglitazone is associated with a decreased liver cancer incidence in diabetic patients. The effects on occurrence of specific cancer types may be different for pioglitazone and rosiglitazone. (HEPATOLOGY 2012;)

Incidence and prevalence rates of diabetes mellitus in Taiwan: Analysis of the 2000–2009 Nationwide Health Insurance database

BACKGROUND/PURPOSE Formerly, Taiwans diabetic population has been estimated by surveys conducted at irregular intervals and using different sampling methods. To obtain nationwide data on the incidence and prevalence of diabetes mellitus (DM) in Taiwan, we performed an analysis of the 2000-2009 claim data from the National Health Insurance (NHI) database. METHODS One-third of the claims in the NHI database from 2000 to 2009 were randomly sampled. DM was defined by three or more outpatient visits with diagnostic codes (ICD-9-CM: 250 or A code: A181) within 1 year or by one inpatient discharge diagnosis of DM. Confirmation of type 1 diabetes mellitus was based on the issue of a catastrophic illness certificate with the same diagnostic codes. Age and/or gender distribution for DM were determined. RESULTS In accordance with the global trend for DM, with a near constant standardized incidence rate, there was a more than 70% increase in the total diabetic population, or a 35% increase in the standardized prevalence rate, in Taiwan from 2000 to 2009. The incidence of diabetes was higher in men, especially in the 20-59-year-old age group, and the total number of men with diabetes exceeded the number of women with diabetes in 2005. However, the prevalence and incidence rates in women over the age of 60 years were higher than those in men. Type 1 DM was present in less than 1% of the diabetic population in Taiwan. CONCLUSION The incidence of diabetes, including type 1, remained stable over this 10-year period in Taiwan. However, the incidence rate in men aged 20-59 years was higher than that in age-matched women. With our nationwide database, subgroup analysis of DM incidence can be performed to refine our health policies for the prevention, screening, and treatment of diabetes mellitus.

The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis

Objective:To examine the efficacy and safety of proton pump inhibitors in comparison with histamine-2 receptor antagonists for stress-related upper gastrointestinal bleeding prophylaxis among critical care patients. Data Sources:PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Study Selection:Randomized, controlled trials that directly compare proton pump inhibitors with histamine-2 receptor antagonists in prevention of stress-related upper gastrointestinal bleeding in intensive care unit patients published before May 30, 2008. Data Extraction:Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. The primary outcome was the incidence of stress-related upper gastrointestinal bleeding, and the secondary outcome measures were the incidence of pneumonia and intensive care unit mortality. Data Synthesis:The random effect model was used to estimate the pooled risk difference between two treatment arms irrespective of drug, dosage, and route of administration. Results:We identified seven randomized, controlled trials with a total of 936 patients for planned comparison. The overall pooled risk difference (95% confidence interval; p value; I2 statistics) of stress-related upper gastrointestinal bleeding comparing proton pump inhibitors vs. histamine-2 receptor antagonists was −0.04 (95% confidence interval, −0.09-0.01; p = .08; I2 = 66%). In the sensitivity analysis, removing the Levy study significantly reduced the heterogeneity (from I2 = 66% to I2 = 26%) and shifted the overall risk difference closer to the null (pooled risk difference, −0.02; 95% confidence interval, −0.05-0.01; p = .19). There was no difference between proton pump inhibitors and histamine-2 receptor antagonists therapy in the risk of pneumonia and intensive care unit mortality, with pooled risk differences of 0.00 (95% confidence interval, −0.04-0.05; p = .86; I2 = 0%) and 0.02 (95% confidence interval, −0.04-0.08; p = .50; I2 = 0%), respectively. Conclusions:This meta-analysis did not find strong evidence that proton pump inhibitors were different from histamine-2 receptor antagonists in terms of stress-related upper gastrointestinal bleeding prophylaxis, pneumonia, and mortality among patients admitted to intensive care units. Because of limited trial data, future well-designed and powerful randomized, clinical trials are warranted.

Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials

Background The active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death for inhaled medications in patients with COPD. Methods Through systematic database searching, we identified randomised controlled trials of tiotropium Soft Mist Inhaler, tiotropium HandiHaler, long-acting β2 agonists (LABAs), inhaled corticosteroids (ICS), and LABA-ICS combination with at least a 6-month treatment duration. Direct comparison and mixed treatment comparison (MTC) meta-analyses were conducted to estimate the pooled ORs of death for each comparison. Results 42 trials with 52 516 subjects were included. The MTC meta-analysis with the fixed effect model indicated tiotropium Soft Mist Inhaler was associated with an universally increased risk of overall death compared with placebo (OR 1.51; 95% CI 1.06 to 2.19), tiotropium HandiHaler (OR 1.65; 95% CI 1.13 to 2.43), LABA (OR 1.63; 95% CI 1.10 to 2.44) and LABA-ICS (OR 1.90; 95% CI 1.28 to 2.86). The risk was more evident for cardiovascular death, in patients with severe COPD, and at a higher daily dose. LABA-ICS was associated with the lowest risk of death among all treatments. No excess risk was noted for tiotropium HandiHaler or LABA. The results were similar for MTC and direct comparison meta-analyses, with less precision in the random effects model. Conclusion Our study provided a comparative safety spectrum for each category of inhaled medications. Tiotropium Soft Mist Inhaler had a higher risk of mortality and should be used with caution.

Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999–2004: a national health insurance data set study

Diabet. Med. 27, 636–643 (2010)

Systematic Review and Meta-Analysis of the Tolerability and Hepatotoxicity of Antifungals in Empirical and Definitive Therapy for Invasive Fungal Infection

ABSTRACT To evaluate the tolerability and liver safety profiles of the systemic antifungal agents commonly used for the treatment of invasive fungal infection, we conducted a systematic review and meta-analysis of randomized controlled trials published before 31 August 2009. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. We used the beta-binomial model to account for variation across studies and the maximum likelihood method to estimate the pooled risks. We identified 39 studies with more than 8,000 enrolled patients for planned comparisons. The incidence rates of treatment discontinuation due to adverse reactions and liver injury associated with antifungal therapy ranged widely. The pooled risks of treatment discontinuation due to adverse reactions were above 10% for amphotericin B formulations and itraconazole, whereas they were 2.5% to 3.8% for fluconazole, caspofungin, and micafungin. We found that 1.5% of the patients stopped itraconazole treatment due to hepatotoxicity. Furthermore, 19.7% of voriconazole users and 17.4% of itraconazole users had elevated serum liver enzyme levels, although they did not require treatment discontinuation, whereas 2.0% or 9.3% of fluconazole and echinocandin users had elevated serum liver enzyme levels but did not require treatment discontinuation. The results were similar when we stratified the data by empirical or definitive antifungal therapy. Possible explanations for antifungal agent-related hepatotoxicity were confounded by antifungal prescription to patients with a high risk of liver injury, the increased chance of detection of hepatotoxicity due to prolonged treatment, or the pharmacological entity.

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. Results: Among the 43,810 statin initiators, the incidence rate for PD was 1.68 and 3.52 per 1,000,000 person-days for lipophilic and hydrophilic statins, respectively. Continuation of lipophilic statins was associated with a decreased risk of PD (hazard ratio [HR] 0.42 [95% confidence interval 0.27–0.64]) as compared with statin discontinuation, which was not modified by comorbidities or medications. There was no association between hydrophilic statins and occurrence of PD. Among lipophilic statins, a significant association was observed for simvastatin (HR 0.23 [0.07–0.73]) and atorvastatin (HR 0.33 [0.17–0.65]), especially in female users (HR 0.11 [0.02–0.80] for simvastatin; HR 0.24 [0.09–0.64] for atorvastatin). As for atorvastatin users, the beneficial effect was seen in the elderly subgroup (HR 0.42 [0.21–0.87]). However, long-term use of statins, either lipophilic or hydrophilic, was not significantly associated with PD in a dose/duration-response relation. Conclusions: Continuation of lipophilic statin therapy was associated with a decreased incidence of PD as compared to discontinuation in statin users, especially in subgroups of women and elderly. Long-term follow-up study is needed to clarify the potential beneficial role of lipophilic statins in PD.

Oral Insulin Secretagogues, Insulin, and Cancer Risk in Type 2 Diabetes Mellitus

BACKGROUND Hyperinsulinemia might be the mechanism leading to an increased cancer risk in patients with type 2 diabetes. The objective was to evaluate the association between oral insulin secretagogues, insulins, and cancer incidence. METHODS A total of 108,920 patients with newly diagnosed type 2 diabetes were identified from the Taiwan National Health Insurance claims database during the period from 1 January 2000 to 31 December 2000. As of 31 December 2007, patients with incident cancer were included as cases, and up to four age- and sex-matched controls were selected by risk-set sampling. Logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) between antidiabetic medication and cancer incidence. RESULTS A total of 8,194 incident cancer cases and 32,776 diabetic controls were included. A significantly increased risk for overall cancer incidence was found for any use of insulin (OR, 1.97; 95% CI, 1.85-2.09) and glinides (OR, 1.16; 95% CI, 1.06-1.28). Significantly increased risks were found for first- and second-generation sulfonylureas (OR, 1.08; 95% CI, 1.01-1.15), but not for third-generation drug, glimepiride (OR, 1.00; 95% CI, 0.93-1.08). Use of insulin and glinides was associated with higher risks for liver, colorectal, lung, stomach, and pancreas cancer, whereas sulfonylurea was mainly associated with an increased risk of liver cancer. CONCLUSIONS The results showed that sulfonylureas and glinides increased the risk for overall cancer, but to a lesser extent than insulin. Therapies that are associated with cancer risks certainly require further investigation.

Distribution according to histologic type and outcome by gender and age group in Taiwanese patients with lung carcinoma

The results from previous studies suggested that the clinical characteristics and outcomes of patients with lung carcinoma vary between gender and age groups. The objective of the current study was to assess the trend in the evolution of the histologic types in Taiwan and to compare the outcomes of patients with lung carcinoma between different gender and age groups.