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1.  Peptic Ulcer Disease Risk in Chronic Kidney Disease: Ten-Year Incidence, Ulcer Location, and Ulcerogenic Effect of Medications 
PLoS ONE  2014;9(2):e87952.
We aimed at determining peptic ulcer disease (PUD) incidence among chronic kidney disease (CKD) patients during 1998–2008, compared to patients without CKD, and at examining associations between CKD and PUD.
Data for 1998–2008 were extracted from the National Health Insurance Research Database in Taiwan. The annual PUD incidence (cases per thousand persons per year) was calculated separately for patients with and without CKD. Characteristics of patients with newly diagnosed PUD (n = 16322) were compared to those of a control group without PUD (n = 32644). The 2 groups were matched for age, sex, and index year. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression.
Over the 10-year period, the PUD incidence was ∼10–12 times higher in CKD patients than in those without CKD. Its incidence in elderly CKD patients increased rapidly over time. For CKD patients, most PUD events (>95%) were managed during hospitalization. Peptic ulcer risk, adjusted for all potential confounders, was much higher in CKD patients undergoing hemodialysis (adjusted OR, 9.74; 95% CI, 7.11–13.31). Maintenance hemodialysis patients were 2 times more likely to have gastric ulcers than duodenal ulcers, while CKD patients not on dialysis had similar risks for both. There were no significant interactions between medications and CKD status on the peptic ulcer risk. Unlike CKD patients on nonsteroidal anti-inflammatory drugs and clopidogrel, those on aspirin did not have a higher peptic ulcer risk (adjusted OR, 0.88; 95% CI, 0.44–1.77).
CKD patients have a substantially increased PUD risk, and the majority of CKD patients with PUD require hospital management. Further, peptic ulcer risk is affected by hemodialysis therapy, patient status (inpatient vs. outpatient), and ulcerogenic medications.
PMCID: PMC3912161  PMID: 24498412
2.  Outcomes of patients with acetaminophen-associated toxic hepatitis at a far east poison center 
SpringerPlus  2013;2:674.
There is an overall paucity of data regarding the outcomes of patients with acetaminophen-associated toxic hepatitis in Taiwan. Therefore, the purpose of this study was to recruit a larger number of patients and to examine the clinical features, the degrees of toxic hepatitis, the physiological markers, and the clinical outcomes after intentional acetaminophen poisoning, and to determine what association, if any, might exist between these findings.
We examined the medical records of 187 patients with intentional acetaminophen poisoning who were examined at Chang Gung Memorial Hospital between 2000 and 2011. Patients were categorized into 2 groups according to hepatic complications, i.e. with (n = 15) or without (n = 172) toxic hepatitis. Demographic, clinical, and laboratory data were collected, and the mortality rate was analyzed.
It was found that patients with toxic hepatitis had higher serum acetaminophen level (P = 0.007), but they also arrived to the hospital later (P < 0.001) than patients without toxic hepatitis. Furthermore, patients with toxic hepatitis showed higher incidences of acute respiratory failure (P = 0.012) than those shown by patients who did not have hepatitis. The laboratory examinations also revealed greater degrees of granulocytosis (P < 0.001) and poorer liver function tests (P < 0.001) in patients with hepatitis than in patients without hepatitis. Nevertheless, a univariate logistic regression model failed to identify any significant risk factors for toxic hepatitis complication after ingestion (P > 0.05). At the end of the analysis, 1 patient with toxic hepatitis died of liver failure. Finally, there was no significant difference in mortality between patients with and without hepatitis (P = 0.080).
The analytical data revealed that toxic hepatitis was not uncommon (15/187 or 8.0%) after acetaminophen overdose. Further studies are warranted.
PMCID: PMC3870054  PMID: 24386620
Acetaminophen; Poisoning; Suicide; Toxic hepatitis; N-acetylcysteine
3.  Spectrum of corrosive esophageal injury after intentional paraquat or glyphosate-surfactant herbicide ingestion 
Data on the spectrum of corrosive injury to the esophagus after paraquat or glyphosate-surfactant ingestion are sparse in the literature and confined to case studies and brief reports. Therefore, this study aimed to examine the clinical features, degrees of esophageal injury, and clinical outcomes after paraquat or glyphosate herbicide ingestion, and sought to determine what association, if any, may exist between these findings.
We performed an observational study on 47 patients with paraquat or glyphosate ingestion who underwent endoscopic evaluation over a period of 11 years (2000–2011).
Corrosive esophageal injuries were classified as grade 1 in 14 (glyphosate-surfactant) and three (paraquat), grade 2a in nine (glyphosate-surfactant) and 18 (paraquat), and grade 2b in one (glyphosate-surfactant) and two (paraquat) patients. No patients had grade 0, 3a, or 3b esophageal injuries. Therefore, the severity of corrosive injury was more severe in the paraquat group (P = 0.005). After toxin ingestion, systemic toxicity occurred, with rapid development of systemic complications in many cases. Neurologic complications occurred more frequently in the glyphosate-surfactant group (29.2% versus 0%, P = 0.005), although respiratory failure (4.2% versus 34.8%, P = 0.008), hepatitis (12.5% versus 52.2%, P = 0.004), and renal failure (20.8% versus 52.2%, P = 0.025) developed more frequently in the paraquat group. Patients with glyphosate poisoning had shorter hospital stays than patients with paraquat poisoning (13.3 ± 15.1 days versus 26.8 ± 10.2 days, P = 0.001). Nevertheless, there was no significant difference in mortality rate between the glyphosate-surfactant and paraquat groups (8.3% versus 13.0%, P = 0.601). We ultimately found that patients with grade 2b esophageal injury suffered from a greater incidence of respiratory (100.0% versus 5.9%, P = 0.001) and gastrointestinal (66.7% versus 11.8%, P = 0.034) complications than patients with grade 1 injury, regardless of herbicide type.
Paraquat and glyphosate are mild caustic agents that produce esophageal injuries of grades 1, 2a, and 2b only. Our data also suggest a potential relationship between the degree of esophageal injury and systemic complications.
PMCID: PMC3747816  PMID: 23983484
paraquat; glyphosate-surfactant; poisoning; suicide; esophageal injury
4.  Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study 
PLoS ONE  2013;8(3):e58317.
Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.
We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.
The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.
ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.
PMCID: PMC3596393  PMID: 23516462
5.  Association between hypertensive disorders during pregnancy and end-stage renal disease: a population-based study 
Studies into the association between hypertensive disorders during pregnancy and end-stage renal disease are limited. We investigated the risk of end-stage renal disease after delivery among women with hypertensive disorders during pregnancy.
We used insurance claims data from 1998 to 2009 to identify 26 651 women aged 19–40 years old who experienced hypertensive disorders during pregnancy; these women had no history of hypertension, diabetes, kidney disease or lupus. We also randomly selected 213 397 women without hypertensive disorders during pregnancy as a comparison cohort; the frequency was matched by age and index year of pregnancy. We compared the incidence of end-stage renal disease in the 2 cohorts. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) after controlling for demographic and clinical factors.
Women with hypertensive disorders during pregnancy had a greater risk of chronic kidney disease and end-stage renal disease, with adjusted HRs of 9.38 (95% CI 7.09–12.4) and 12.4 (95% CI 8.54–18.0), respectively, after controlling for urban status, coronary artery disease, congestive heart failure, hyperlipidemia and abruption. The HR for end-stage renal disease was 2.72 (95% CI 1.76–4.22) after we also controlled for hypertension and diabetes. Women with preeclampsia or eclampsia had a higher risk of end-stage renal disease (adjusted HR 14.0, 95% CI 9.43–20.7) than women who had gestational hypertension only (adjusted HR 9.03, 95% CI 5.20–15.7).
Women with hypertensive disorders during pregnancy were at a high risk of end-stage renal disease. The risk was much greater for women who had preeclampsia or eclampsia than those who had gestational hypertension only.
PMCID: PMC3576438  PMID: 23339156
6.  Comparing Survival between Peritoneal Dialysis and Hemodialysis Patients with Subclinical Peripheral Artery Disease: a 6-Year Follow-Up 
Peripheral artery disease (PAD) is known to be an increased mortality risk in patients with end-stage renal disease (ESRD). The aim of this study was to compare patient survival between patients with subclinical PAD undergoing peritoneal dialysis (PD) and hemodialysis (HD). Subclinical peripheral artery was defined as an ankle-brachial index of less than 0.9. This study was conducted from April 2005, and the observation period ended on 30 June 2011. At the end of the follow-up, the status of all patients was assessed and data on mortality were obtained for the entire cohort. A total of 91 patients (61 HD and 30 PD) were included for analyses in this study. Mortality rate was 60.0% (18/30) for PD and 52.5% (32/61) for HD. Kaplan-Meier estimate demonstrate that PD patients had a higher mortality rate than those underwent HD (log-rank p = 0.0039). Cox regression model demonstrated that PD was an independent predictor for further mortality in ESRD patients with subclinical peripheral artery disease.(p = 0.012, HR: 1.776, 95% CI: 1.136-2.775). In multivariate analysis, the HD group still had a greater survival than PD group (p = 0.005, HR:1.916, 95% CI: 1.218-3.015). In patients with subclinical peripheral artery disease, the patient survival is better in HD patients as compared with PD patients.
PMCID: PMC3590604  PMID: 23471522
Survival; hemodialysis; peritoneal dialysis; peripheral artery disease.
7.  Association of response to hepatitis B vaccination and survival in dialysis patients 
BMC Nephrology  2012;13:97.
The status of immunocompromised patients is well recognized in end stage renal disease (ESRD). As described recently, this acquired immune dysfunction in the uremic milieu may be one of the main pathogenic factors for mortality in ESRD. The aim of this study was to determine the relationship between the immune response following a hepatitis B vaccination (HBV vaccination) and the survival of maintenance dialysis patients.
A total of 156 patients (103 on hemodialysis and 53 on continuous ambulatory peritoneal dialysis) were recruited. After receiving a full dose of the HBV vaccination, all patients were followed up for to 5 years to evaluate the association of patient survival, cause of mortality, and immune response.
The response rate to the hepatitis B vaccination was 70.5%. There was no significant association between the immune response and the 5-year survival rate (p =0.600) or between the post-vaccination anti-HBs titers and the 5-year survival rate (p = 0.201). The logistic prediction model with the coefficient as non-response following HBV vaccination, diabetes mellitus, old age, and low albumin level could significantly predict infection-cause mortality (sensitivity = 0.842, specificity = 0.937).
There was no significant association between the immune response to HBV vaccination and the 5-year survival rate. However, non-response following HBV vaccination might be associated with infection-cause mortality in dialysis patients.
PMCID: PMC3471045  PMID: 22935561
Hepatitis B vaccination; Immune response; Post-vaccination anti-HBs titers
8.  Real-Time PCR Analysis of the Intestinal Microbiotas in Peritoneal Dialysis Patients 
Bifidobacterium and Lactobacillus can beneficially affect the host by producing acetic acid and lactic acid, which lower pH and thereby inhibit the growth of pathogens or allow the probiotic bacteria to compete with pathogens for epithelial adhesion sites and nutrients. The transmural migration of enteric organisms into the peritoneal cavity can cause peritonitis in peritoneal dialysis (PD) patients. We hypothesized that the composition of the intestinal microbiota with regard to Lactobacillus species and Bifidobacterium species differed between PD patients and healthy controls. The aim of the study was to investigate these differences by real-time PCR analysis of fecal samples. From 1 August 2009 to 31 March 2010, a total of 29 nondiabetic PD patients and 41 healthy controls from China Medical University Hospital were recruited after giving their informed consent. Fecal samples were collected from the PD patients and their age-matched counterparts in the morning using a standardized procedure. DNA extracted from these samples was analyzed by real-time PCR. All bifidobacteria, Bifidobacterium catenulatum, B. longum, B. bifidum, Lactobacillus plantarum, L. paracasei, and Klebsiella pneumoniae were less frequently detected in the patient samples. Dysbiosis (microbial imbalance) may impair intestinal barrier function and increase host vulnerability to pathogen invasion. Further studies are necessary to confirm our findings before clinical trials with probiotic supplementation in PD patients.
PMCID: PMC3273023  PMID: 22179250
9.  Acute large-dose exposure to organophosphates in patients with and without diabetes mellitus: analysis of mortality rate and new-onset diabetes mellitus 
Environmental Health  2014;13:11.
We investigated the mortality rates of patients with and without diabetes mellitus after acute large-dose exposure to organophosphate insecticides. All patients without diabetes mellitus were traced to examine the long-term risk of new-onset diabetes mellitus. Previous reports indicated that organophosphate exposure might increase the risk of new-onset diabetes mellitus.
We analyzed the records of 118 patients referred to Chang Gung Memorial Hospital for management of intentional organophosphate poisoning between 2000 and 2011. Patients were stratified by diabetes mellitus status. Demographic, clinical, laboratory and mortality data were analyzed.
Most patients were middle aged (53.45 ± 16.20 years) and male (65.3%) and were referred to our hospital after a relatively short amount of time had elapsed since poisoning (median 3.0 hours). 18 (15.2%) of 118 patients died, including 15 (13.8%) of 109 patients without diabetes mellitus and 3 (33.3%) of 9 with diabetes mellitus. There was no significant difference in mortality between these groups (P = 0.117). In a multivariate Cox regression model, hypotension (P = 0.000), respiratory failure (P = 0.042), coma (P = 0.023), and corrected QT interval prolongation (P = 0.002) were significant risk factors for mortality. Conversely, diabetes mellitus status was not a significant variable in this model. At routine outpatient follow up a median of 1.25 months post exposure, random blood glucose measurements gave no evidence of new-onset diabetes in patients without pre-existing diabetes.
Diabetes mellitus status might not increase mortality risk following acute large-dose exposure to organophosphates, and the risk of new-onset diabetes mellitus also might be minimal in the short term. Larger prospective studies with formal testing for diabetes at later times post-exposure are required.
PMCID: PMC3975839  PMID: 24597539
Organophosphate poisoning; Suicide; Diabetes mellitus; Mortality; New-onset diabetes mellitus
10.  Increased Risk of Stroke after Septicaemia: A Population-Based Longitudinal Study in Taiwan 
PLoS ONE  2014;9(2):e89386.
Inflammation and infection have been noted to increase stroke risk. However, the association between septicaemia and increased risk of stroke remains unclear. This population-based cohort study, using a National Health Insurance database, aimed to investigate whether patients with septicaemia are predisposed to increased stroke risk. The study included all patients hospitalised for septicaemia for the first time between 2000 and 2003 without prior stroke. Patients were followed until the end of 2010 to evaluate incidence of stroke. An age-, gender- and co-morbidities-matched cohort without prior stroke served as the control. Cox’s proportional hazards regressions were used to assess differences in stroke risk between groups. Based on hazard ratios (HRs), patients with septicaemia had greater stroke risk, especially in the younger age groups (age <45: HR = 4.16, 95% CI: 2.39–7.24, p<0.001; age 45–64: HR = 1.76, 95% CI: 1.41–2.19, p<0.001; age ≥65: HR = 1.05, 95% CI: 0.91–1.22, p>0.05). Haemorrhagic stroke was the dominant type (ischaemic stroke: HR = 1.20, 95% CI: 1.06–1.37, p<0.01; haemorrhagic stroke: HR = 1.82, 95% CI: 1.35–2.46, p<0.001) and patients without co-morbidities were at slightly higher risk (without co-morbidities: HR = 1.49, 95% CI: 1.02–2.17, p<0.05; with co-morbidities: HR = 1.24, 95% CI: 1.10–1.41, p<0.001). The impact of septicaemia on stroke risk was highest within 6 months of the event and gradually declined over time. Our results suggest that septicaemia is associated with an increase in stroke risk, which is greatest in haemorrhagic stroke. Closer attention to patients with history of septicaemia may be warranted for stroke preventive measures, especially for younger patients without co-morbidities.
PMCID: PMC3931764  PMID: 24586739
11.  Comparing Risk of New Onset Diabetes Mellitus in Chronic Kidney Disease Patients Receiving Peritoneal Dialysis and Hemodialysis Using Propensity Score Matching 
PLoS ONE  2014;9(2):e87891.
Chronic kidney disease (CKD) patients are at risk for developing new-onset diabetes mellitus (NODM) even after hemodialysis (HD) and peritoneal dialysis (PD) treatment. It is not clear if the incidence for NODM is different in CKD patients receiving HD and PD. This study compared the risk of NODM in PD patients and HD patients.
All HD and PD patients in Taiwan Renal Registry Database from 1997 to 2005 were included and all patients were followed to December 31, 2008. The risk of NODM was analyzed in PD patients and propensity score matched HD patients using logistic regression for early type NODM (< = 6 months after dialysis) and Cox regression for late type NODM (>6 months after dialysis).
A total of 2548 PD patients and 10192 HD patients who had no diabetes on the initiation of dialysis were analyzed. The incidence for NODM was 3.7 per 100 patient/year for HD and 2.4 for PD patients. HD patients are more at risk for developing early type NODM (p<0.001) with an adjusted odds ratio of 1.41 [95% confidence interval (CI) 1.12–1.78)]. HD patients are more at risk for late type NODM (p<0.001) with an adjusted hazard ratio of 2.01 (95% CI: 1.77–2.29). Patient’s age was negatively associated with risk of early type of NODM (p<0.001) but positively associated with risk of late type NODM (p<0.001).
Chronic kidney disease patients receiving hemodialysis are more at risk for developing new-onset diabetes mellitus compared to those receiving peritoneal dialysis.
PMCID: PMC3913687  PMID: 24504072
12.  Early utilization of hypertonic peritoneal dialysate and subsequent risks of non-traumatic amputation among peritoneal dialysis patients: a nationwide retrospective longitudinal study 
BMC Nephrology  2013;14:128.
The hemodialysis (HD) population has a particularly high incidence of amputation, which is likely associated with decreased tissue oxygenation during HD. However, information about the risk factors leading to amputation in peritoneal dialysis (PD) patients is limited. Here, we have investigated the association between the use of hypertonic peritoneal dialysate (HPD) and subsequent amputation in PD patients.
Based on the data from the Taiwan National Health Insurance research database, this observational cohort study enrolled 203 PD patients who had received HPD early during treatment and had not undergone amputation and 296 PD controls who had not undergone amputation. Subjects were followed through until the end of 2009 and the event rates of new non-traumatic amputation were compared between groups.
The incidence of amputation was 3 times higher for the HPD cohort than for the comparison cohort (23.68 vs. 8.01 per 1000 person-years). The hazard ratio (HR) for this group, estimated using a multivariable Cox model, was 2.48 (95% confidence interval [CI] = 1.06–5.79). The HR for patients with both diabetes and early adoption of HPD increased to 44.34 (95% CI = 5.51-357.03), compared to non-HPD non-diabetic PD controls.
Early utilization of HPD in PD patients is associated with increasing risk of amputation; this risk considerably increases for those with concomitant diabetes.
PMCID: PMC3691767  PMID: 23786634
Non-traumatic amputation; Hypertonic dialysate; Peritoneal dialysis

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