Chia-Jen Shih

Proton pump inhibitor use represents an independent risk factor for myocardial infarction

BACKGROUND There is substantial debate regarding the development of acute coronary syndrome in patients using proton pump inhibitors (PPIs) combined with clopidogrel. However, data remain limited to address the effect of PPIs alone on the subsequent risk of myocardial infarction (MI). We aimed to explore the subsequent risk of MI in PPI users who had no previous history of MI. METHODS The records of inpatients and outpatients with PPI prescriptions were retrieved from the Taiwan National Health Insurance Research Database between 2000 and 2009. We conducted two different study designs, the first using propensity score (PS)-matching analyses and the second using case-crossover analyses. The risk of developing MI for PPI users was analyzed in the PS-matched study. The association between risk of MI and prior PPI exposure was further validated in the case-crossover study. RESULTS In the PS-matched study, we included 126,367 PPI users and 126,367 PS-matched PPI non-users. After 120 days of follow-up, PPI use was associated with a 1.58-fold greater risk of MI (adjusted hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.11 to 2.25). In the case-crossover study, adjusted odds ratios of PPI for MI risk were 4.61 (95% CI = 1.76 to 12.07) for the 7-day window and 3.47 (95% CI = 1.76 to 6.83) for the 14-day window. CONCLUSIONS Use of PPIs may be independently associated with an increased risk of MI. However, the benefits of PPIs may greatly outweigh the risks of adverse cardiovascular effects, with number needed to harm of 4357.

Risks of Death and Stroke in Patients Undergoing Hemodialysis With New-Onset Atrial Fibrillation A Competing-Risk Analysis of a Nationwide Cohort

Background— Whether oral anticoagulant use should be considered in patients undergoing hemodialysis with atrial fibrillation (AF) remains controversial because of the uncertainty regarding risk-benefit assessments. The purpose of this study was to investigate the risk of ischemic stroke in patients undergoing hemodialysis with new-onset AF, in comparison with those without arrhythmia. Methods and Results— This nationwide, population-based, propensity score–matched cohort study used data from Taiwan’s National Health Insurance Research Database during 1998 to 2011 for patients on hemodialysis with new-onset nonvalvular AF and matched subjects without arrhythmia. The clinical end points were ischemic stroke (fatal or nonfatal), all-cause death, and other serious adverse cardiovascular events. In comparison with the matched cohort, patients with AF (n=6772) had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.13–1.43), all-cause death (aHR, 1.59; 95% CI, 1.52–1.67), in-hospital cardiovascular death (aHR, 1.83; 95% CI, 1.71–1.94), myocardial infarction (aHR, 1.33; 95% CI, 1.17–1.51), and hospitalization for heart failure (aHR, 1.90; 95% CI, 1.76–2.05). After considering in-hospital death as a competing risk, AF significantly increased the risk of heart failure (HR, 1.56; 95% CI, 1.45–1.68), but not those of ischemic stroke and myocardial infarction. Additionally, the predictive value of the CHA2DS2–VASc score for ischemic stroke was diminished in the competing-risk model. Conclusions— The risk of stroke was only modestly higher in patients undergoing hemodialysis with new-onset AF than in those without AF, and it became insignificant when accounting for the competing risk of in-hospital death.

The impact of dialysis therapy on older patients with advanced chronic kidney disease: a nationwide population-based study

BackgroundOlder patients with advanced chronic kidney disease (CKD) face the decision of whether to undergo dialysis. Currently available data on this issue are limited because they were generated by small, short-term studies with statistical drawbacks. Further research is urgently needed to provide objective information for dialysis decision making in older patients with advanced CKD.MethodsThis nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database. Data from 2000 to 2010 were extracted. A total of 8,341 patients ?70 years old with advanced CKD and serum creatinine levels >6 mg/dl, who had been treated with erythropoiesis-stimulating agents were included. Cox proportional hazard models in which initiation of chronic dialysis was defined as the time-dependent covariate were used to calculate adjusted hazard ratios for mortality. The endpoint was all-cause mortality.ResultsDuring a median follow-up period of 2.7 years, 6,292 (75.4%) older patients chose dialysis therapy and 2,049 (24.6%) received conservative care. Dialysis was initiated to treat kidney failure a median of 6.4 months after enrollment. Dialysis was associated with a 1.4-fold increased risk of mortality compared with conservative care (adjusted hazard ratio 1.39, 95% confidence interval 1.30 to 1.49). In subgroup analyses, the risk of mortality remained consistently increased, independent of age, sex and comorbidities.ConclusionsIn older patients, dialysis may be associated with increased mortality risk and healthcare cost compared with conservative care. For patients who are ?70 years old with advanced CKD, decision making about whether to undergo dialysis should be weighted by consideration of risks and benefits.

Risk of tuberculosis among healthcare workers in an intermediate-burden country: A nationwide population study

OBJECTIVE The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear. METHODS A nationwide, population-based cohort study was performed by using Taiwan National Health Insurance Database during 2000-2010. We included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio according to age, sex, monthly income, underlying comorbidities, and concomitant medications. All subjects were followed from the date of enrollment until TB occurrence, death, or 31 December 2010. RESULTS The study population comprised 11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control subjects developed TB during a median follow-up period of 9.4 years. The incidence of TB was higher among HCWs than among matched subjects (61.08 vs. 37.81 per 100,000 person-years). The risk of TB was also greater among HCWs (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08-2.43), particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56; 95% CI, 1.02-2.39). Among different job categories of HCWs, we found that only nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI, 1.37-4.72) compared to the matched cohort. CONCLUSIONS HCWs are associated independently with a higher risk of developing TB in this intermediate-burden country. Therefore, the importance of TB surveillance among HCWs should be emphasized.

Dipeptidyl peptidase-4 inhibitors and cardiovascular risks in patients with pre-existing heart failure

Background Although recent clinical trials raised concerns about the risk for heart failure (HF) in dipeptidyl peptidase-4 (DPP-4) inhibitor use, data on the cardiovascular risks in the patients with pre-existing HF are still lacking. Methods We used Taiwans National Health Insurance Research Database to identify 196 986 patients diagnosed with type 2 diabetes mellitus (T2DM) who had previous history of HF between 2009 and 2013. This population included 30 204 DPP-4 inhibitor users and 166 782 propensity score-matched DPP-4 inhibitor non-users. The outcomes of interest were all-cause mortality, combination of myocardial infarction (MI) and ischaemic stroke, and hospitalisation for HF. Results The incidence in DPP-4 users compared with non-users was 67.02 vs 102.85 per 1000 person-years for all-cause mortality, 37.89 vs 47.54 per 1000 person-years for the combination of MI and ischaemic stroke, 12.70 vs 16.18 per 1000 person-years for MI and 26.37 vs 32.46 per 1000 person-years for ischaemic stroke. The risk of all-cause mortality was lower in DPP-4 inhibitor users (HR 0.67, 95% CI 0.64 to 0.70), combination of MI and stroke (HR 0.81, 95% CI 0.76 to 0.87), MI (HR 0.80, 95% CI 0.71 to 0.89) and ischaemic stroke (HR 0.83, 95% CI 0.76 to 0.89) than in non-users. Notably, the risk of hospitalisation for HF did not differ significantly between groups. The results were similar after accounting for death as a competing risk. Conclusions In this nationwide T2DM cohort, the risks of mortality and the combination of MI and ischaemic stroke were lower for patients receiving DPP-4 inhibitors than for those who did not receive such treatment. DPP-4 inhibitor use was not associated with a higher risk of hospitalisation for HF even in patients with pre-existing HF.

Association of Hypoglycemia With Incident Chronic Kidney Disease in Patients With Type 2 Diabetes: A Nationwide Population-Based Study

AbstractThis article aims to investigate the long-term risk of incident chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) patients with hypoglycemia.This nationwide, population-based, propensity score (PS)-matched cohort study involved 2 cohorts: a hypoglycemic cohort and a matched cohort without hypoglycemia. Data from 1.3 million patients with newly diagnosed T2DM between 2000 and 2010 were extracted from Taiwans National Health Insurance Research Database. Hypoglycemic events were collected using inpatient, outpatient, and emergency department diagnoses. Patients aged <20 years and those with previous histories of CKD were excluded. The association between hypoglycemia and subsequent CKD risk in patients with T2DM was examined using Cox regression analysis after PS matching.During the mean follow-up period of 4.2 years, a total of 15,036 (1.7 %) patients experienced at least 1 episode of hypoglycemia and 15,036 matched controls without hypoglycemia were identified among 906,368 eligible patients. The incidence rates of subsequent CKD were 26.1 and 14.8 events per 1000 person-years in the hypoglycemic and matched cohorts, respectively. The hazard ratio (HR) of hypoglycemia for incident CKD was 1.77 (95% confidence interval [CI], 1.63–1.92; P < 0.001). Compared with those without hypoglycemia, HRs for 1 to 3 and ≥4 episodes of hypoglycemia for CKD were 1.65 (95% CI, 1.50–1.81) and 1.75 (95% CI, 1.34–2.29), respectively (P for trend <0.001).Our study supports the association of hypoglycemia with CKD development among patients with T2DM, possibly in a dose-dependent relationship.

Urinary Calculi and Risk of Cancer: A Nationwide Population-Based Study

AbstractPrevious studies have shown that urinary calculi are associated with increased risks of urinary tract cancers. However, the association between urinary calculi and overall cancers is a largely undefined body of knowledge.We conducted a nationwide population-based cohort study using Taiwans National Health Insurance Research Database from 2000 and 2009. Patients were excluded if they had antecedent cancers or urinary calculi before the enrollment. All study subjects were followed until the occurrence of cancer, dropout from the NHI program, death, or the end of 2010. Patterns of cancer incidence in patients with urinary calculi were compared with those of the general population using standardized incidence ratio (SIR).A total of 43,516 patients with urinary calculi were included. After a median follow-up of 5.3 years, 1891 patients developed cancer. The risk of overall cancers was significantly increased (SIR, 1.75; 95% confidence interval [CI], 1.68–1.83). We observed that urinary calculi was associated with higher risk of cancers of kidney (4.24; 95% CI, 3.47–5.13), bladder (3.30; 95% CI, 2.69–4.00), thyroid (2.50; 95% CI, 1.78–3.40), hematologic origin (2.41; 95% CI, 1.92–2.99), breast (1.84; 95% CI, 1.54–2.20), lung (1.82; 95% CI, 1.59–2.07), digestive tract (1.69; 95% CI, 1.57–1.82), and head and neck (1.54; 95% CI, 1.32–1.79), respectively.Our study shows that urinary calculi are associated with higher risk of systemic cancers in addition to urinary tract cancers. Further study is required to validate this association.

Parathyroidectomy reduces intradialytic hypotension in hemodialysis patients with secondary hyperparathyroidism.

Background: Secondary hyperparathyroidism is associated with vascular calcification and arterial stiffness in patients with end-stage renal disease. The aim of this study was to analyze the frequency of intradialytic hypotension (IDH) and cardiovascular function before and after parathyroidectomy (PTX) in maintenance hemodialysis patients. Methods: We compared predialytic and intradialytic blood pressure, left and right ventricular ejection fraction (LVEF and RVEF), and cardiothoracic ratio 1 month before PTX, and 6 and 12 months after PTX. IDH was defined as a decrease in systolic blood pressure ≥ 20 mmHg or a decrease in mean arterial pressure ≥ 10 mmHg. Results: At the time of PTX, the mean age of the patients was 57.4 ± 12.0 years, and the mean dialysis vintage was 12.2 ± 5.8 years. At baseline, 6 months, and 12 months after PTX, the average numbers of sessions disturbed by IDH during 13 dialysis sessions (1 month) were 6.4, 3.9 (p < 0.016 vs. baseline), and 4.0 sessions (p < 0.037 vs. baseline, p = 0.801 vs. 6 months), respectively. LVEF and RVEF were improved significantly after PTX. Furthermore, volume status was also improved, as evidenced by the significantly greater ultrafiltration volume and reduced cardiothoracic ratio. Conclusions: Hemodialysis patients with severe secondary hyperparathyroidism are more likely to achieve normotensive and euvolemic status after PTX, probably through improved heart function and reduced IDH episodes.

Association of sleep apnoea with chronic kidney disease in a large cohort from Taiwan

Recent observational studies have shown that sleep apnoea (SA) is associated with increased risk of incident CKD. However, the contribution of SA relative to common traditional CKD risk factors remains unknown. The aims of this study were to investigate the long‐term risk of incident CKD events following SA diagnosis and compare the relative contributions of SA, diabetes and hypertension.

Cardiovascular Outcomes of Dipeptidyl Peptidase-4 Inhibitors in Elderly Patients With Type 2 Diabetes: A Nationwide Study.

OBJECTIVES The elderly (aged ≥65 years) population with type 2 diabetes (T2D) is growing substantially, but evidence for associations between the use of dipeptidyl peptidase-4 inhibitors (DPP-4is), novel incretin-based antidiabetic drugs, and clinical hard endpoints in this group remains inconclusive. We aimed to assess the safety and cardiovascular effects of DPP-4i use in a nationally representative sample of elderly adults with T2D. DESIGN, SETTING, AND PARTICIPANTS We conducted a nationwide, observational, propensity score-matched study using Taiwans National Health Insurance Research Database. Of a total of 414,213 patients aged ≥65 years with T2D, 58,485 patients receiving initial DPP-4i prescriptions between March 1, 2009, and June 31, 2013, were included. Each DPP-4i user was matched with a nonuser control using propensity scores. The endpoints were all-cause mortality and major adverse cardiovascular events (MACEs), including ischemic stroke and myocardial infarction. Potential adverse effects of hospitalization for heart failure and hypoglycemia were also evaluated. RESULTS Compared with the matched control cohort, the risks of all-cause mortality (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.52-0.56), MACEs (HR 0.79, 95% CI 0.75-0.83), myocardial infarction (HR 0.79, 95% CI 0.72-0.87), and ischemic stroke (HR 0.79, 95% CI 0.75-0.84) were lower in the DPP-4i cohort. DPP-4i use did not affect the risks of hospitalization for heart failure and hypoglycemia. Stratified analyses produced consistent results across age, sex, and comorbidity subgroups. CONCLUSIONS Prescription of DPP-4is was associated with reduced risks of all-cause mortality and MACEs in patients aged ≥65 years with T2D.