[show abstract][hide abstract] ABSTRACT: Apelin regulates insulin sensitivity and secretion in animals. However, whether plasma apelin predicts incident diabetes in humans remains unknown.
We studied a cohort including 447 subjects (148 men, 299 women) without diabetes and followed for an average of 3y. Diabetes was diagnosed by an oral glucose tolerance test, plasma hemoglobin A1c, and if the subject was taking medications for diabetes. Plasma apelin-12 at baseline was measured with a commercial kit.
Plasma apelin concentrations were higher in women than in men at baseline (p=0.007). During follow-up, 43 subjects developed type 2 diabetes. Higher plasma apelin concentrations were associated with a higher risk of diabetes in men (p=0.049) but not in women. Plasma apelin predicted incident type 2 diabetes in men (hazard ratio, 2.13, 95% CI 1.29-3.51, p<0.05), but not in women, adjusted for age, family history of diabetes, hemoglobin A1c, body mass index, hypertension, and HOMA2-IR. Apelin could improve the prediction ability beyond traditional risk factors in men, and the sensitivity and specificity of plasma apelin at 0.9ng/ml for this prediction were 63.2% and 58.9%, respectively. In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 100-125mg/dl, or OGTT-2h-PG 140-199mg/dl), the risk for developing diabetes was higher in those with higher plasma apelin concentration than in those with lower plasma apelin concentrations (10.6%/year vs. 5.1%/year, p<0.001).
Plasma apelin is a novel biomarker for predicting type 2 diabetes in men.
Clinica chimica acta; international journal of clinical chemistry 04/2014; · 2.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Concerns about an increased cardiovascular risk with the angiotensin receptor blocker, olmesartan, prompted the current study to examine associations between olmesartan and other angiotensin receptor blockers with overall and cause-specific mortalities. We collected patients who started to use losartan, valsartan, irbesartan, candesartan, telmisartan, and olmesartan between January 1, 2004, and December 31, 2009, from Taiwan's National Health Insurance claims database. Prescribed drug types, dosage, and other clinical information were collected. Overall mortality and cause-specific mortality were ascertained through linkages with Taiwan's National Death Registry. Two follow-up analyses, labeled intention-to-treat and as-treated, were conducted. A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) using losartan as the reference group. A total of 690 463 subjects were included, with a mean follow-up ranging from a low of 2.8 years for olmesartan to a high of 4.1 years for irbesartan. Subjects who began with valsartan had a modest but significantly increased risk of overall mortality (HR, 1.04; 95% CI, 1.02-1.06) compared with losartan. Irbesartan (HR, 0.96; 95% CI, 0.94-0.99), candesartan (HR, 0.95; 95% CI, 0.92-0.99), telmisartan (HR, 0.93; 95% CI, 0.90-0.96), and olmesartan (HR, 0.93; 95% CI, 0.88-0.97) were associated with a slightly lower overall mortality risk than losartan. The analysis indicates that the differences in mortality risk among individual angiotensin receptor blockers were only marginal and thus less likely to be clinically important. Although uncontrolled confounding might still exist, olmesartan does not seem to increase cardiovascular risk compared with losartan.
[show abstract][hide abstract] ABSTRACT: The process of weaning may impose cardiopulmonary stress on ventilated patients. Heart rate variability (HRV), a noninvasive tool to characterize autonomic function and cardiorespiratory interaction, may be a promising modality to assess patient capability during the weaning process. We aimed to evaluate the association between HRV change and weaning outcomes in critically ill patients.
This study included 101 consecutive patients recovering from acute respiratory failure. Frequency domain analysis, including very low frequency, low frequency, high frequency and total power, of HRV was assessed during a 1-hour spontaneous breathing trial (SBT) through a T-piece and following extubation after successful SBT.
Out of 101 patients, 24 (24%) had SBT failure and HRV analysis in these patients showed a significant decrease in total power (P = 0.003); 77 patients passed SBT and were extubated, but 13 (17%) of them required reintubation within 72 hours. In successfully extubated patients, very low frequency and total power from SBT to post-extubation significantly increased (P = 0.003 and P = 0.004, respectively). Instead, patients with extubation failure were unable to increase HRV after extubation.
HRV responses differ between patients with different weaning outcomes. Measuring HRV change during the weaning process may help clinicians predict weaning results and in the end, improve patient care and outcome.
Critical care (London, England) 01/2014; 18(1):R21. · 4.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: -This study examined the effect of radiofrequency catheter ablation (RFA) on reducing morbidity and mortality among patients with atrial fibrillation (AF).
-A retrospective cohort of AF patients without prior stroke or heart failure (HF) who underwent RFA between 2003 and 2009 was identified using Taiwan's National Health Insurance claims database. Outpatients with AF who met the same enrollment criteria but did not receive RFA were matched (up to 1:20) by hospitals and dates to serve as controls. Outcomes of interest were death, stroke, or hospitalization for HF. A proportional hazard Cox regression model adjusted by propensity scores (based on age, sex, hypertension, diabetes, co-morbidities, medications, and medical resource utilization) was applied to estimate the hazard ratio and 95% confidence interval. A total of 846 AF patients who received RFA and 11,324 matched AF controls were included, with a mean follow-up of 3.74 and 3.96 years, respectively. RFA was associated with a lower hazard for stroke (HR: 0.57, 95% CI: 0.35-0.94, p = 0.026). The reduction in the hazard for death and HF did not reach statistical significance (HR: 0.88, 95% CI: 0.62-1.23, p = 0.451 and HR: 0.78, 95% CI: 0.55-1.12, p = 0.185, respectively). Additional analysis using death as a competing risk showed similar results for stroke and HF.
-RFA did not reduce mortality or hospitalization for HF during the immediate 3.5-year follow-up. Although a beneficial effect on stroke prevention associated with RFA was suggested, residual confounding due to unmeasured factors remains a concern.
Circulation Arrhythmia and Electrophysiology 01/2014; · 5.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
Acute thoracic empyema is a common clinical problem worldwide, resulting in substantial morbidity and mortality. The objective of this study was to report its clinical characteristics and to evaluate whether thoracoscopic surgery is associated with a lower rate of in-hospital mortality compared with nonoperative drainage.
Between 2001 and 2010, we retrospectively reviewed the clinical characteristics, bacteriological studies, and treatment outcomes of 602 patients with acute thoracic empyema. Thoracoscopic surgery was performed in 417 (69.2%) patients, while the remaining patients underwent nonoperative drainage. After treatment, 77 patients (12.8%) died in the hospital. A propensity score-based process, matched on potential risk factors for in-hospital mortality, was performed to select patients with equalized potential prognostic factors in the thoracoscopy and nonoperative groups. The log-rank test was used to compare the survival time with discharge between the two matched groups.
Multivariate analysis showed that age, malignancy, chronic lung disease, chronic renal insufficiency, liver cirrhosis, polymicrobial infection, and positive bacterial culture were risk factors for in-hospital mortality. The propensity score-matched analysis showed that the in-hospital mortality difference was significant (p = 0.014) and the Kaplan–Meier survival analysis revealed a higher survival rate to discharge (p < 0.001 by log-rank test), both favoring thoracoscopy over nonoperative drainage.
Acute thoracic empyema carries a high mortality rate, especially in elderly patients with coexisting medical conditions and polymicrobial and positive bacterial cultures. Our study results also showed that thoracoscopy is feasible and might provide better chances for survival in borderline operable patients than nonoperative drainage.
Journal of the Formosan Medical Association 01/2014; · 1.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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. The outcome was atrial fibrillation/flutter. A proportional hazard regression model with time-varying statin use was applied to estimate the hazard ratios (HR) and 95% confidence intervals (CIs) for atrial fibrillation/flutter according to current statin use versus treatment discontinuation, adjusted for baseline disease risk scores and time-varying covariates.
A total of 6767 CKD and 63,678 non-CKD patients initiating statin therapy were included and followed for an average of 4.0 years. A total of 1118 participants experienced new-onset atrial fibrillation/flutter. The incidence of atrial fibrillation/flutter was approximately 2 fold higher in the CKD patients. Continuation of statin therapy was associated with a 22% (adjusted hazard ratio 0.78; 95% CI: 0.65–0.93) and 57% (adjusted HR 0.43; 95% CI: 0.27–0.68) decrease in atrial fibrillation/flutter hazard as compared with discontinuation in non-CKD and CKD patients, respectively.
Continuation of statin therapy was associated with a decreased risk of atrial fibrillation/flutter among CKD and non-CKD patients. However, further randomized studies are still needed to assess the association.
[show abstract][hide abstract] ABSTRACT: Data are limited on the efficacy and safety of pegylated interferon plus ribavirin for patients with hepatitis C virus genotype 1 (HCV-1) receiving hemodialysis.
To compare the efficacy and safety of combination therapy with pegylated interferon plus low-dose ribavirin and pegylated interferon monotherapy for treatment-naive patients with HCV-1 receiving hemodialysis.
Open-label, randomized, controlled trial. (ClinicalTrials.gov: NCT00491244) SETTING: 8 centers in Taiwan.
205 treatment-naive patients with HCV-1 receiving hemodialysis.
48 weeks of pegylated interferon-α2a, 135 µg weekly, plus ribavirin, 200 mg daily (n = 103), or pegylated interferon-α2a, 135 µg weekly (n = 102).
Sustained virologic response rate and adverse event-related withdrawal rate.
Compared with monotherapy, combination therapy had a greater sustained virologic response rate (64% vs. 33%; relative risk, 1.92 [95% CI, 1.41 to 2.62]; P < 0.001). More patients receiving combination therapy had hemoglobin levels less than 8.5 g/dL than those receiving monotherapy (72% vs. 6%; risk difference, 66% [CI, 56% to 76%]; P < 0.001). Patients receiving combination therapy required a higher dosage (mean, 13 946 IU per week [SD, 6449] vs. 5833 IU per week [SD, 1169]; P = 0.006) and longer duration (mean, 29 weeks [SD, 9] vs. 18 weeks [SD, 7]; P = 0.004) of epoetin-β than patients receiving monotherapy. The adverse event-related withdrawal rates were 7% in the combination therapy group and 4% in the monotherapy group (risk difference, 3% [CI, -3% to 9%]).
Open-label trial; results may not be generalizable to patients on peritoneal dialysis.
In treatment-naive patients with HCV-1 receiving hemodialysis, combination therapy with pegylated interferon plus low-dose ribavirin achieved a greater sustained virologic response rate than pegylated interferon monotherapy.
National Center of Excellence for Clinical Trial and Research.
Annals of internal medicine 12/2013; 159(11):729-38. · 13.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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. We aimed to assess the association between the use of different types of antidepressants, SSRIs and tricyclic antidepressants (TCAs), and the risk of cerebrovascular events in patients with depression or anxiety. A nationwide population-based cohort study was retrospectively conducted in patients with depression or anxiety who started to take SSRIs and TCAs identified from the Taiwan National Health Insurance claims database (2001-2009). We examined the association between the 2 types of antidepressants and incidence of stroke using a proportional hazard model adjusted for stroke risk factors. Among the 24,662 SSRI and 14,736 TCA initiators, the crude incidence rate for stroke was 10.03 and 13.77 per 100 person-years, respectively. Selective serotonin reuptake inhibitor use was not associated with risk of stroke as compared with TCAs in the time-fixed analysis. After adjusting for baseline propensity scores in the time-varying analysis, SSRI use significantly reduced risk of stroke as compared with TCAs with the adjusted hazard ratio of 0.67 (95% confidence interval, 0.47-0.96). The effect persisted even after considering the antidepressant dosage (hazard ratio, 0.65 [0.42 to 0.99]). In summary, use of SSRIs was associated with a reduced risk for stroke, as compared with TCAs, in this specific disease population.
Journal of clinical psychopharmacology 10/2013; · 5.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: It remains unclear whether exposure to low-level mercury (Hg) is associated with impaired renal function, and whether omega-3 fatty acid (FA) intake could affect the association of interest. The current study examined the association of blood Hg and omega-3 FAs with renal function using data from 1046 subjects aged 40 or above from the 2003-2004 National Health and Nutrition Examination Survey. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and occurrence of albuminuria. Logistic regression analyses were applied to assess the association of interest with confounding variable adjustment. The analyses indicated that blood Hg was associated with reduced eGFR (<60mL/min/1.73m(2)) in a dose-response fashion (p<0.05). The association was particularly apparent with adjustment for blood omega-3 FA levels. The adjusted odds ratio for having reduced eGFR was 2.94 (95% confidence interval=1.04-8.33) in the highest tertile of blood Hg as compared with the lowest tertile. There was no significant association between Hg exposure and albuminuria. In summary, this study demonstrates that Hg exposure is associated with increased odds of having lower GFR in the US population aged 40 or above. A statistical association with albuminuria was not apparent. We also observed that omega-3 FA intake may play a preventive role in Hg-induced nephrotoxicity. Additional studies are warranted to determine the sources, exposure routes, and forms of Hg most responsible for observed associations.
International journal of hygiene and environmental health 10/2013; · 2.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: The relationship between statin use and lung cancer remains unclear. Patients with diabetes mellitus, who are at higher risks for both cancer and atherosclerosis, are usually indicated for statin use. The objective was to explore the relationship between statins, lung squamous cell carcinoma (SCC), and lung adenocarcinoma incidence in diabetic patients.
A cohort of 596,812 type 2 diabetic patients was identified from the Taiwan National Health Insurance claims database in the year 2000, and followed until the earliest of lung cancer diagnosis, death, or December 31, 2007. A Cox regression model with time-varying statin use was applied to estimate the hazard ratio (HR) of lung cancer incidence comparing use and nonuse of statins. A sensitivity analysis was applied to examine the association after adjustment for smoking effect.
In the original diabetic cohort, 60,969 statin users and 535,843 statin nonusers were identified. In a median follow-up time of 7.9 years, a total of 1182 incident SCC cases and 2345 adenocarcinoma cases developed. Initial analysis showed a decreased risk of SCC if statins were ever used (HR, 0.69; 95% confidence interval, 0.60-0.81). However, the relative risk would be 0.92 for males and 0.90 for females for statins after adjusting for smoking effect. There was no association between statin use and adenocarcinoma (HR, 0.97; 95% confidence interval, 0.88-1.07), with similar findings after controlling for smoking effect.
There is no statistically significant association between statin use with lung cancer incidence in diabetic patients after adjustment for the confounding effect attributed to cigarette smoking.
Journal of the Formosan Medical Association 09/2013; · 1.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: Taiwan's Bureau of National Health Insurance launched the National Antiviral Treatment Program (NATP) in 2003 to reimburse patients for antiviral drugs and interferons for chronic hepatitis B and C. The objective was to examine the impact of the NATP on the incidence and mortality due to hepatocellular carcinoma (HCC).
The cumulative numbers of NATP participants were retrieved from the National Health Insurance claims database. The national incidence and mortality rates of HCC were obtained from the Taiwan Cancer Registry in each quarter from 1979 to 2009. An interrupted time-series analysis was applied to test the temporal trend change before and after NATP.
From 1979 to 1995, the HCC incidence increased in men and women of all age groups. From 2003 to 2009, 31,155 men and 10,769 women received anti-hepatitis B virus therapy, whereas 13,939 men and 10,721 women received anti-hepatitis C virus therapy. The incidence of HCC reached a plateau and then started to decline in men aged 30-39 (slope change P=0.003), 50-59 (P=0.051), and 60-69 years (P<0.001). A similar trend was noted in women aged 50-59 (P=0.035), 60-69 (P=0.006), and 70-79 years (P=0.052). The HCC mortality rate had been decreasing since 1996 and a further decline was observed after 2004 in men aged 60-69 years and women aged 60-79 years.
There is a strong temporal relationship between NATP and the stabilization of the HCC incidence and related mortality. The cost-effectiveness of the NATP needs further evaluation.
[show abstract][hide abstract] ABSTRACT: To evaluate the effect of discontinuing statin therapy on incidence of Parkinson disease (PD) in statin users.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to examine the relationship between renin-angiotensin system genotypes and the pharmacogenetics of angiotensin-converting enzyme (ACE) inhibitors in Chinese patients with coronary artery disease (CAD).
Patients with angiographic CAD were recruited from 1995 to 2003. The baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphisms, six polymorphisms of the angiotensinogen (AGT) gene, and A-1166C polymorphisms of the angiotensin-II type I receptor gene (AGT1R)] were established. Patients were divided into two groups (ACE inhibitor or no ACE inhibitor) and followed for up to 12 years. Kaplan-Meier curves and Cox regression models were used to determine the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models.
Of the 784 patients, 432 were treated with ACE inhibitors and 352 were not. ACE inhibitors were associated with a lower MACE rate at 4000 days. In addition, the ACE I/D gene D and AGT1R gene C alleles were associated with a higher MACE rate on the basis of a multivariate regression analysis. This effect was attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE inhibitors* ACE gene, hazard ratio: 0.8, 95% confidence interval: 0.62-0.94, P=0.03).
ACE inhibitors were associated with a significant decrease in MACE in Chinese patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.
Pharmacogenetics and Genomics 04/2013; 23(4):181-9. · 3.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study aimed to explore the association between obstructive sleep apnea (OSA) severity and pharyngeal parameters using sub-mental ultrasonography (US), and investigate the accuracy of US for identifying severe OSA patients.
One hundred and five consecutive referrals for suspected OSA were enrolled. The diameters of the retro-glossal (RG) and retro-palatal (RP) regions were measured via sub-mental US upon expiration during tidal breathing, forced inspiration, and Müller maneuver (MM). Independent factors associated with severe OSA identified from two-thirds of randomly-selected patients (model-development group) were used to construct a model for predicting severe OSA. The accuracy of the model was validated in the remaining one-third of patients (validation group).
Fifty severe OSA patients, 30 with mild-moderate OSA, and 25 without OSA were enrolled. Compared to non-OSA and mild-moderate OSA patients, those with severe OSA had narrower RP diameter in all three maneuvers. Using the prediction model constructed with changes of RP diameters at MM and neck circumference, the independent predictors of severe OSA in the model-development group had 100% sensitivity and 65% specificity.
Sub-mental US can accurately discriminate the severity of OSA and be used to identify patients with severe OSA.
PLoS ONE 01/2013; 8(5):e62848. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objectives. Graft failure after heart transplantation led to poor outcomes. We tried to analyze the outcomes of extracorporeal membrane oxygenation (ECMO) rescue in graft survival after transplantation. Methods. A retrospective review of 385 consecutive heart transplants revealed 46 patients of graft failure requiring ECMO rescue (48 episodes). The pretransplant and ECMO-related variables were evaluated. Results. The median age was 37.7 ± 18.8 years, and the median support time was 155 ± 145 hours. Success rate was 47.9% (23/48). Pretransplant ECMO use was 25% (12/48) and they had 58.3% mortality. The success rate in "early" graft failures was 51.4% (18/35) and 50% for "late" graft failure. The ischemic time with graft failure (178 ± 70 min) was significantly longer than that without graft failure. Preoperative status and the longer ischemic time may be the major factors for failure. Long-term 5-year survival demonstrated significant survival difference between graft failure and nongraft failure. No survival difference was shown between "early" and "late" graft failure. Conclusions. Graft failure still carried high mortality if advanced circulatory support was required. Early graft failure and late graft failure had similar outcomes. Further investigation of the risk factors shows that ECMO does play a role of rescue in catastrophic conditions.
The Scientific World Journal 01/2013; 2013:364236. · 1.73 Impact Factor