[Show abstract][Hide abstract] ABSTRACT: The impact of ribavirin (RBV) dosage on sustained virologic response (SVR) rates remains elusive in hepatitis C virus genotype 2 (HCV-2) rapid responders receiving 16 weeks of peginterferon (Peg-IFN) plus RBV. Treatment-naïve HCV-2 patients with rapid virologic response (RVR) received Peg-IFN alfa-2a 180 μg/week plus weight-based RBV (1,000 or 1,200 mg/day; cut-off body weight: 75 kg) for 6 weeks, and then randomly received Peg-IFN alfa-2a 180 μg/week plus weight-based (1,000 or 1,200 mg/day; n = 247) or flat-dose (800 mg/day; n = 246) RBV for additional 10 weeks. The primary endpoint was SVR24. Patients receiving weight-based and flat-dose RBV therapies had comparable SVR24 rates (93.5% versus 91.9%, P = 0.49). The risk differences (RDs) of SVR24 receiving weight-based and flat-dose RBV arms were 7.1% [95% CI: 0.7% to 13.6%] in males, and -5.8% [95% CI: -12.1% to 0.5%] in females (interaction P = 0.01). The SVR24 rate was higher in males receiving ≥13 mg/kg/day than those receiving <13 mg/kg/day (96.3% versus 85.1%, P = 0.001). In conclusion, Peg-IFN alfa-2a plus weight-based or flat-dose RBV for 16 weeks provides comparable SVR24 rates in treatment-naïve HCV-2 rapid responders. However, males should receive weight-based RBV to achieve a high SVR24 rate.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus genotype 2 (HCV-2) slow responders poorly respond to 24 weeks of peginterferon (Peg-IFN) plus ribavirin (RBV). We evaluated the efficacy of extended 48-week regimen and the role of interleukin-28B (IL-28B) genotype in this clinical setting. Treatment-naïve HCV-2 patients not achieving rapid virologic response (RVR) by Peg-IFN alfa-2a 180 μg/week plus weight-based RBV (1,000-1,200 mg/day, cutoff body weight of 75 kg) were randomly assigned to receive a total duration of 48 (n = 94) or 24 (n = 93) weeks of therapy. The primary endpoint was sustained virologic response (SVR). Baseline patient characteristics to predict SVR were analyzed. Patients receiving 48 weeks of treatment had a greater SVR rate than those receiving 24 weeks of treatment (70.2% versus 46.2%, P = 0.001). Compared to patients treated for 24 weeks, the SVR rate in those treated for 48 weeks increased by 10.9% [95% CI: -5.9% to 27.7%] and 65.6% [95% CI: 44.5% to 86.7%] if they had IL-28B rs8099917 TT genotype, and GT/GG genotype, respectively (interaction P = 0.002). In conclusion, 48-week treatment with Peg-IFN plus weight-based RBV provides a greater SVR rate than 24-week treatment in treatment-naïve HCV-2 patients with unfavorable IL-28B genotypes who fail to achieve RVR.
[Show abstract][Hide abstract] ABSTRACT: Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). We examined the relationship between LVDD, major adverse cardiovascular events (MACE), and mortality in PD patients. A total of 149 patients undergoing PD with preserved left ventricular systolic function were included and followed for 3.5 years. LVDD was diagnosed (according to the European Society of Cardiology guidelines) by conventional and tissue Doppler echocardiography. Serum high-sensitivity C-reactive protein (hsCRP) was measured. The location and volume of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, and more visceral and peritoneal fat than controls. The relationship between adjusted visceral adipose tissue and LVDD became nonsignificant when hsCRP and baseline demographic data were introduced into the logistic regression model (odds ratio = 1.52, P = 0.07). Subsequent hierarchical multivariate Cox regression analysis showed that LVDD was one of the most powerful determinants of MACE and mortality after adjusting for all confounding factors (hazard ratio [HR]: 1.71, 95% confidence interval [CI]: 1.43-3.51, P = 0.02 and HR: 2.25, 95% CI: 1.45-2.91, P = 0.04, respectively). Systemic inflammation (hsCRP) was also significantly associated with MACE and mortality (HR: 2.03, P = 0.03 and HR: 2.16, P = 0.04, respectively). LVDD is associated with systemic inflammation and increased visceral fat in patients undergoing PD. LVDD is also a sensitive, independent indicator of future MACE and mortality in PD patients.
Medicine 05/2015; 94(20):e819. DOI:10.1097/MD.0000000000000819 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a prior history of stroke.
-Patients initiating statin therapy between 2005 and 2009 without a prior history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥ 70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (ICD-9-CM codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio (HR) of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1,096,547 statin initiators with an average follow-up of 3.3 years. The adjusted HR for ICH between the highest the lowest quartile was non-significant at 1.06 with a 95% confidence interval [CI] spanning 1.00 (0.94-1.19). Similar non-significant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted HR 1.36 [1.11-1.67]).
-Generally, no association was observed between cumulative statin use and risk of ICH among subjects without a prior history of stroke. An increased risk was identified among the non-hypertensive cohort, but this finding should be interpreted with caution.
[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: Three dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored.
We studied 200 subjects (mean age: 60.2±16 years, 54% female, female n = 107) with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis (Artida, Toshiba Medical Systems, Tokyo, Japan). We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes.
The global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all p<0.001). Global twist measurements were estimated to be 9.49°, 9.77°, 8.32°, and 4.56°, respectively. We observed significant differences regarding 3D-derived longitudinal, radial, and global 3D strains between the different disease categories (p<0.05), even when age, gender, BMI and heart rate were matched. In addition, 3D-derived longitudinal, circumferential, and 3D strains were all highly correlated with brain natriuretic peptide levels (p<0.001). At a mean 567.7 days follow-up (25th-75th IQR: 197-909 days), poorer 3D-derived longitudinal, radial, and global 3D strain measurements remained independently associated with a higher risk of cardiovascular related death or hospitalization due to heart failure, after adjusting for age, gender, and left ventricular ejection fraction (all p<0.05).
3D-based strain analysis may be a feasible and useful diagnostic tool for discriminating the extent of myocardial dysfunction. Furthermore, it is able to provide a prognostic value beyond traditional echocardiographic parameters in terms of ejection fraction.
PLoS ONE 12/2014; 9(12):e115260. DOI:10.1371/journal.pone.0115260 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The objective was to evaluate time-trend bias in the context of a series of studies reporting that a national hepatitis B virus vaccination program (launched in mid-1980s) substantially reduced childhood hepatocellular carcinoma (HCC) incidence.
Study design and setting:
We applied an age-period-cohort model to evaluate the relative importance of age, time-trend (period), and vaccination (cohort) effect, respectively, on the incidence and mortality rate of HCC in boys and girls in Taiwan from 1980 to 2009.
HCC incidence increased with age. The period effect analysis revealed that the incidence of HCC started to decrease in 1980s, leveled off in mid-1990s, and declined again in mid-2000s among boys. The period effect was flat among girls. Cohort effect analysis demonstrated that among boys, the incidence of HCC started to decrease by those born in 2000-2004, which was 15 years later than the first vaccinated cohort. Among girls, the incidence rate started to decline before the mass vaccination program was initiated. The analysis showed a decline in mortality for boys and girls born in 1980s.
Time trend may play a more important role than the universal vaccination program in interpretation of the observed early decreasing trend in HCC in children, especially among boys.
[Show abstract][Hide abstract] ABSTRACT: 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.
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. The outcomes of interest were hospitalization for pneumonia and pneumonia-related mortality. Participants were followed from treatment initiation to the earliest of outcome occurrence, death or disenrollment, treatment discontinuation, switching to other ACE inhibitors or ARBs, or study termination (31 December 31 2010). Proportional-hazards regression model was used to calculate the hazard ratios and their 95% confidence intervals (CIs), adjusted on baseline characteristics.
A total of 1 192 082 ACE inhibitors and 175 668 losartan initiators were included. The risk of hospitalization for pneumonia was significantly higher for captopril (hazard ratio 1.94, 95% CI 1.82-2.07), enalapril (hazard ratio 1.14, 95% CI 1.07-1.22), fosinopril (hazard ratio 1.11, 95% CI 1.02-1.21), perindopril (hazard ratio 1.14, 95% CI 1.04-1.25), and ramipril (hazard ratio 1.11, 95% CI 1.02-1.22), as compared with losartan. Captopril was associated with a significantly increased risk of pneumonia mortality (hazard ratio 2.43, 95% CI 1.79-3.31).
Treatment with ACE inhibitors is not associated with a lower risk of pneumonia incidence and mortality as compared with losartan.
Journal of Hypertension 12/2014; 33(3). DOI:10.1097/HJH.0000000000000438 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Whether retroperitoneal fat should be included in the measurement of visceral fat remains controversial. We compared the relationships of fat areas in peritoneal, retroperitoneal, and subcutaneous compartments to metabolic syndrome, adipokines, and incident hypertension and diabetes.
We enrolled 432 adult participants (153 men and 279 women) in a community-based cohort study. Computed tomography at the umbilicus level was used to measure the fat areas.
Retroperitoneal fat correlated significantly with metabolic syndrome (adjusted odds ratio (OR), 5.651, p<0.05) and the number of metabolic abnormalities (p<0.05). Retroperitoneal fat area was significantly associated with blood pressure, plasma glycemic indices, lipid profile, C-reactive protein, adiponectin (r = −0.244, P<0.05), and leptin (r = 0.323, p<0.05), but not plasma renin or aldosterone concentrations. During the 2.94±0.84 years of follow-up, 32 participants developed incident hypertension. Retroperitoneal fat area (hazard ration (HR) 1.62, p = 0.003) and peritoneal fat area (HR 1.62, p = 0.009), but not subcutaneous fat area (p = 0.14) were associated with incident hypertension. Neither retroperitoneal fat area, peritoneal fat area, nor subcutaneous fat areas was associated with incident diabetes after adjustment.
Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in terms of its relationship with metabolic syndrome and incident hypertension. Retroperitoneal fat area should be included in the measurement of visceral fat for cardio-metabolic studies in human.
PLoS ONE 11/2014; 9(11):e112355. DOI:10.1371/journal.pone.0112355 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Constipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample.
551,324 participants free of PD, dementia, and stroke were retrospectively ascertained between January 1, 2005 and December 31, 2005 using the Taiwan National Health Insurance Research Database. The association between constipation at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities and concomitant medications use was adjusted in the proportional hazards models.
After an average follow-up of 5.5 years, 2336 incident PD cases were diagnosed. The crude incidence rate of PD per 1,000,000 person-days was 1.57 for subjects without constipation and 4.04, 5.28, and 12.67 for mild, moderate, and severe constipation, respectively. After adjusting for age, sex, comorbidities, and concomitant medication use, patients with constipation were more likely to develop PD than subjects without constipation; the adjusted hazard ratio (aHR) was 3.28 (95% CI: 2.14–5.03), 3.83 (2.51–5.84), and 4.22 (2.95–6.05) for individual constipation severity categories. Constipation severity was also associated with an increased likelihood of PD in the time-varying analysis; the aHR was 2.84 (2.43–3.33), 5.22 (4.61–5.92), and 10.47 (9.46–11.58) for mild, moderate, and severe constipation, respectively (P < 0.0001). After excluding PD patients diagnosed within 3 years of constipation, the association remained significant.
Our study suggests that the severity of constipation is associated with a future diagnosis of PD in a dose-dependent manner.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The aim was to investigate the effects of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) and compare the results with those of in-hospital cardiac arrest (IHCA).
We analyzed our extracorporeal membrane oxygenation (ECMO) results for patients who received ECPR for OHCA or IHCA in the last 5 years. Pre-arrest, resuscitation, and post-resuscitative data were evaluated.
In the last 5 years, ECPR was used 230 times for OHCA (n=31) and IHCA (n=199). The basic demographic data showed significant differences in age, cardiomyopathy, and location of the initial CPR. Duration of ischemia was shorter in the IHCA group (44.4±24.7 min vs. 67.5±30.6 min, p<0.05). About 50% of each group underwent a further intervention to treat the underlying etiology. ECMO was maintained for a shorter duration in the OHCA patients (61±48 h vs. 94±122 h, p<0.05). Survival to discharge was similar in the two groups (38.7% for OHCA vs. 31.2% for IHCA, p>0.05), as was the favorable outcome rate (25.5% for OHCA vs. 25.1% for IHCA, p>0.05). Survival was acceptable (about 33%) in both groups when the duration of ischemia was no longer than 75 min.
In addition to having a beneficial effect in IHCA, ECPR can lead to survival and a positive neurological outcome in selected OHCA patients after prolonged resuscitation. Our results suggest that further investigation of the use of ECMO in OHCA is warranted.
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose
Hypertension has been associated with Parkinson's disease (PD), but data on antihypertensive drugs and PD are inconclusive. We aim to evaluate antihypertensive drugs for an association with PD in hypertensive patients.
Hypertensive patients who were free of PD, dementia and stroke were recruited from 2005–2006 using Taiwan National Health Insurance Database. We examined the association between the use of calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and the incidence of PD using beta-blockers as the reference. Cox regression model with time-varying medication use was applied.
Among 65,001 hypertensive patients with a mean follow-up period of 4.6 years, use of dihydropyridine CCBs, but not non-dihydropyridine CCBs, was associated with a reduced risk of PD (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.57–0.90). Additionally, use of central-acting CCBs, rather than peripheral-acting ones, was associated with a decreased risk of PD (aHR = .69 [55–0.87]. Further decreased association was observed for higher cumulative doses of felodipine (aHR = 0.54 [0.36–0.80]) and amlodipine (aHR = 0.60 [0.45–0.79]). There was no association between the use of ACEIs (aHR = 0.80 [0.64–1.00]) or ARBs (aHR = 0.86 [0.69–1.08]) with PD. A potentially decreased association was only found for higher cumulative use of ACEIs (HR = 0.52 [0.34–0.80]) and ARBs (HR = 0.52 [0.33–0.80]).
Our study suggests centrally-acting dihydropyridine CCB use and high cumulative doses of ACEIs and ARBs may associate with a decreased incidence of PD in hypertensive patients. Further long-term follow-up studies are needed to confirm the potential beneficial effects of antihypertensive agents in PD.
PLoS ONE 06/2014; 9(6):e98961. DOI:10.1371/journal.pone.0098961 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Angiotensin receptor blockers (ARBs) have been shown to exert various peroxisome proliferator-activated receptor gamma (PPARγ) binding activities and insulin-sensitizing effects. The objective of this study was to investigate the association of different ARBs with new-onset diabetes mellitus.
In the respective cohort, a total of 492,530 subjects who initiated ARB treatment between January 2004 and December 2009 were identified from Taiwan National Health Insurance Database. The primary outcome was newly diagnosed diabetes, defined as at least one hospital admission or two or more outpatient visits within a year with an ICD-9-CM code 250. Cox proportional regression was used to estimate the risk of diabetes associated with each ARB, using losartan as the reference.
A total of 65,358 incident diabetes cases were identified out of 1,771,173 person-years. Olmesartan initiators had a small but significantly increased risk of developing diabetes after adjusting for baseline characteristics and mean daily dose (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03-1.12). After excluding those followed for less than one year, the increase in diabetes risk are more pronounced (HR, 1.09; 95% CI, 1.05-1.14). This association was consistent across all subgroup analyses. Similar results were observed when a more strict definition of diabetes combining both diabetes diagnosis and anti-diabetic treatment was used. On the other hand, there was no difference in diabetes risk between telmisartan and losartan.
Among all ARBs, olmesartan might be associated with a slightly increased risk of diabetes mellitus. Our data suggest differential diabetes risks associated with ARBs beyond a class effect.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to construct a framework of core competency indicators of medical doctors who teach in the clinical setting in Taiwan and to evaluate the relative importance of the indicators among these clinical teachers.
The preliminary framework of the indicators was developed from an in-depth interview conducted with 12 clinical teachers who had previously been recognized and awarded for their teaching excellence in university hospitals. The framework was categorized into 4 dimensions: 1) Expertise (i.e., professional knowledge and skill); 2) Teaching Ability; 3) Attitudes and Traits; and 4) Beliefs and Values. These areas were further divided into 11 sub-dimensions and 40 indicators. Subsequently, a questionnaire built upon this qualitative analysis was distributed to another group of 17 clinical teachers. Saaty's eigenvector approach, or the so-called analytic hierarchy process (AHP), was applied to perform the pairwise comparisons between indicators and to determine the ranking and relative importance of the indicators.
Fourteen questionnaires were deemed valid for AHP assessment due to completeness of data input. The relative contribution of the four main dimensions was 31% for Attitudes and Traits, 30% for Beliefs and Values, 22% for Expertise, and 17% for Teaching Ability. Specifically, 9 out of the 10 top-ranked indicators belonged to the "Attitudes and Traits" or "Beliefs and Values" dimensions, indicating that inner characteristics (i.e., attitudes, traits, beliefs, and values) were perceived as more important than surface ones (i.e., professional knowledge, skills, and teaching competency).
We performed a qualitative analysis and developed a questionnaire based upon an interview with experienced clinical teachers in Taiwan, and used this tool to construct the key features for the role model. The application has also demonstrated the relative importance in the dimensions of the core competencies for clinical teachers in Taiwan.
BMC Medical Education 04/2014; 14(1):75. DOI:10.1186/1472-6920-14-75 · 1.22 Impact Factor
[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; 435. DOI:10.1016/j.cca.2014.03.030 · 2.82 Impact Factor