Chiz-Tzung Chang

Association between hypertensive disorders during pregnancy and end-stage renal disease: a population-based study

Background: 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. Methods: 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. Results: 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). Interpretation: 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.

Effectiveness of influenza vaccination in elderly diabetic patients: a retrospective cohort study.

PURPOSE Studies regarding the clinical benefits of influenza vaccination in diabetic patients are limited. This study evaluated if the elderly diabetic patients who have had influenza vaccination would have benefits such as reduced medical care and mortality. METHODS We used the universal insurance claims data from 2001 to 2009 in Taiwan to identify annual elderly patients with diabetes cohorts with (N=4454) and without (N=4571) influenza vaccination. The risk of developing pneumonia or influenza, respiratory failure, intensive care, hospitalization, and mortality were measured and compared between cohorts within one year of follow-up. RESULTS The vaccine cohort had lower incidences of pneumonia or influenza and respiratory failure compared with the non-vaccine cohort. More importantly, the vaccine cohort had a hospitalization rate that was 11% less than the non-vaccine cohort (29.6 vs. 33.1 per 100 person-years) with an adjusted hazard ratio (HR) of 0.88 (95% CI 0.81-0.96). The vaccine cohort was also less likely to be admitted to the intensive care unit (ICU) [0.58 vs. 2.05 per 100 person-year; adjusted HR 0.30 (95% CI 0.19-0.47)] and less likely to expire [3.13 vs. 7.96 per 100 person-year; adjusted HR 0.44 (95% CI 0.36-0.54)]. Influenza vaccination reduced the hospitalization cost by 1282.6 USD, compared with patients without influenza vaccination (95% CI -2210.3, -354.8). CONCLUSION Influenza vaccination is associated with a reduced risk of morbidity, hospitalization, ICU admissions, and mortality. In addition, the hospitalization cost is reduced.

Real-Time PCR Analysis of the Intestinal Microbiotas in Peritoneal Dialysis Patients

ABSTRACT 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.

Effectiveness of influenza vaccination in patients with end-stage renal disease receiving hemodialysis: a population-based study.

Background 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. Methods 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. Results 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. Conclusions 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.

Hypertensive Disorders in Pregnancy and Preterm Delivery and Subsequent Stroke in Asian Women A Retrospective Cohort Study

Background and Purpose— Few studies exist concerning the risk of stroke associated with hypertensive disorders in pregnancy (HDP) in Asian women. This study investigates whether preterm delivery further complicates this risk in women with HDP in Taiwan. Methods— Based on universal insurance claims data, 1092 pregnant women with newly diagnosed HDP from 2000 to 2004 and aged 15 to 40 years were identified as the HDP cohort. Then, 4715 randomly selected persons without HDP frequency matched with the index year were designated as the non-HDP controls. Both cohorts were followed-up until the end of 2008 to measure the incidence of stroke. Results— The HDP cohort had a higher incidence of stroke than the non-HDP cohort (30.1 vs 12.8 per 10 000 person-years), with an overall adjusted hazard ratio of 2.04 (95% CI, 1.18- 3.51) for stroke. Preterm delivery increased the risk of stroke to 3.22-fold (95% CI, 1.48–6.99; P for trend=0.002). The age-specific V-shape risk association showed that the highest risk of stroke was noted among subjects 15 to 18 years old in the HDP group (hazard ratio, 13.4; 95% CI, 1.54–116.7) and followed by women aged 35 years and older (hazard ratio, 5.56; 95% CI, 1.47–21.0). Conclusions— Pregnant women with HDP have an increased risk of subsequent stroke. Preterm delivery and older ages increase the risk of subsequent stroke. Adolescents with HDP also have an elevated risk of stroke. Early identification of women with HDP is needed for prevention.

Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation

L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aβ, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P < .01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphate-buffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefold after focal cerebral ischemia in mice, illustrating the importance of LOX-1 in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Aβ release via IκB kinase 2 (IKK2). Furthermore, L5+Aβ synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IκBα, p65, and c-Jun N-terminal kinase 1; and platelet aggregation. These effects were blocked by inhibiting IKK2, LOX-1, or nuclear factor-κB (NF-κB). Injecting L5+Aβ shortened tail-bleeding time by 50% (n = 12; P < .05 vs L1-injected mice), which was prevented by the IKK2 inhibitor. Our findings suggest that, through LOX-1, atherogenic L5 potentiates Aβ-mediated platelet activation, platelet aggregation, and hemostasis via IKK2/NF-κB signaling. L5 elevation may be a risk factor for cerebral atherothrombosis, and downregulating LOX-1 and inhibiting IKK2 may be novel antithrombotic strategies.

Peptic Ulcer Disease Risk in Chronic Kidney Disease: Ten-Year Incidence, Ulcer Location, and Ulcerogenic Effect of Medications

Objectives 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. Methods 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. Results 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). Conclusions 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.

Hypertensive Disorders in Pregnancy and Subsequent Diabetes Mellitus: A Retrospective Cohort Study

BACKGROUND Cohort study on the association between hypertensive disorders in pregnancy (HDP) and postpartum diabetes is limited. This retrospective cohort study investigated the incidence of diabetes mellitus after delivery among women with HDP using claims data of a universal insurance system. METHODS We defined the HDP group as women aged 19-40 years with their first HDP in 2003, excluding those with a history of gestational diabetes mellitus, diabetes mellitus, or hypertension before the date of diagnosis with HDP. Women who had normal pregnancy without HDP were randomly chosen as our comparison group, frequency matched with age and index year of the HDP group. Both groups were followed until December 31, 2008 to evaluate the occurrence of diabetes. RESULTS This study consisted of 1139 women with HDP cases and 4527 non-HDP pregnant women. Overall, the subsequent incidence of diabetes mellitus was 5.08-fold higher in the HDP group than in the non-HDP group, with an adjusted hazard ratio of 3.42 (95% confidence interval [CI], 2.07-5.64) after controlling for age, occupation, income, and comorbidity. The hazard ratio of developing diabetes increased to 39.5 (95% CI, 13.0-120.6) for women having HDP, hyperlipidemia, and obesity simultaneously. CONCLUSIONS Women with HDP have a high risk of subsequent diabetes. HDP women with obesity and hyperlipidemia are at an extremely high risk of diabetes mellitus. Early identification of women with HDP is needed for prevention, particularly those with other comorbidities.

Atrial fibrillation associated with increased risk of venous thromboembolism. A population-based cohort study.

Whether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR]= 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.

Paraquat poisoning in pediatric patients.

Objective This observational study examined the outcome of Taiwanese pediatric patients with paraquat poisoning and compared these data with the published data on paraquat poisonings from other international poisoning centers. Methods We performed a retrospective study on children with acute paraquat poisoning that were admitted to the Chang Gung Memorial Hospital during a period of 10 years (2000–2010). Of the 193 paraquat poisoning patients, only 6 were children. Results The mean age was 8.85 ± 5.55 (1–15.6) years. Younger patients had accidentally swallowed paraquat, whereas older patients had intentionally ingested paraquat. Most patients were referred within a relatively short period (0.5–2.0 hours). Paraquat poisoning was associated with high morbidity and often resulted in severe complications, including acute respiratory distress syndrome and multiple-organ failure. The complications included shock (50.0%), hypoxemia (33.3%), respiratory failure (33.3%), nausea/vomiting (16.7%), abdominal pain (33.3%), hepatitis (66.7%), gastrointestinal tract bleeding (33.3%), acute renal failure (33.3%), and seizures (16.7%). Patients were treated aggressively with a standard detoxification protocol consisting of gastric lavage, active charcoal, charcoal hemoperfusion, and cyclophosphamide and steroid pulse therapies. Secondary bacterial infections were common after hospitalization and included sepsis (33.3%), pneumonia (33.3%), and urinary tract infection (50.0%). In the end, 2 patients (33.3%) died from multiple-organ failure, despite intensive resuscitation. Conclusions Our data (mortality rate, 33.3%) are comparable to the data of other published reports from other international poison centers. Evidently, a prompt diagnosis of paraquat poisoning and an immediate institution of a detoxification protocol is a prerequisite for a favorable outcome.