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Objectives: The aim of this study was to determine the long-term incidence of cryptococcosis in kidney transplant recipients (KTRs) and to analyze its risk factors. Methods: This retrospective population-based cohort study analyzed data obtained from Taiwan’s National Health Insurance Research Database for KTRs during 2000–2012 and matched cohorts. Both populations were followed until death, development of cryptococcosis, or December 2013. Results: A total of 4,933 KTRs and 49,930 matched patients were included. The cryptococcosis incidence rates for the KTR cohort and matched cohort were 10.59 and 0.4 per 10,000 person-years, respectively. The hazard ratio for cryptococcosis among KTRs was 26.65 (p

Objective The objective of this study is to determine whether vaccination against influenza is associated with a reduced risk of acute kidney injury (AKI) in a nationwide cohort of adults aged ≥65 years. Methods We investigated a total of 13,270 patients aged ≥65 years who were hospitalized for AKI between 2000 and 2013 from Taiwan's National Health Insurance Research Database. Each AKI case was matched with one control subject according to duration of follow-up, age, sex, monthly income, urbanization level, and baseline comorbidities. Odds ratios (ORs) for AKI associated with exposure to the influenza vaccine in the previous year were calculated in a nested case-control analysis. Results Influenza vaccination in the previous year was associated with a lower risk of AKI (adjusted OR 0.67, 95% confidence interval [CI] 0.63–0.72). Compared with a reference group of unvaccinated individuals with no influenza infection, vaccination with no influenza infection was associated with a lower risk of AKI (adjusted OR 0.68, 95% CI 0.64–0.73). Lack of vaccination and presence of influenza infection was associated with a higher risk of AKI (adjusted OR 1.78, 95% CI 1.57–2.01), whereas the risk of AKI was insignificant in vaccinated patients who developed influenza (adjusted OR 1.01, 95% CI 0.69–1.18). Conclusions The risk of AKI was 37% lower among older people who received vaccination against influenza in a real-world setting. Further work is required to clarify causality.

This study was conducted to determine the protective effect of influenza vaccine against primary major adverse cardiovascular events (MACEs) in elderly patients, especially those with influenza-like illness (ILI).This retrospective, population-based case-control study of an elderly population (age≥65 years) was conducted using Taiwan's National Health Insurance Research Database (2000-2013). One control was selected for each MACE case (n=80,363 each), matched according to age, year of study entry, and predisposing factors for MACEs. ILI and MACEs (myocardial infarction [MI] and ischemic stroke) were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Odds ratios (ORs) were calculated for the association between MACEs and vaccination.Influenza vaccination received in the previous year was associated with reduced risks of primary MACEs overall (adjusted OR [aOR] 0.80, 95% CI 0.78-0.82, P.001), MI (aOR 0.80, 95% CI 0.76-0.84, P.001), and ischemic stroke (aOR 0.80, 95% CI 0.77-0.82, P.001). ILI diagnosed in the previous year was associated with increased risks of MACEs (aOR 1.24, 95% CI 1.18-1.29, P.001), MI (aOR 1.46, 95% CI 1.34-1.59, P.001), and ischemic stroke (aOR 1.16, 95% CI 1.10-1.22, P.001). Vaccination attenuated the heightened risks associated with ILI (MACEs: aOR 0.99, 95% CI 0.92-1.07, P=.834; MI: aOR 1.05, 95% CI 0.92-1.21, P=.440; ischemic stroke: aOR 0.96, 95% CI 0.89-1.05, P=.398).Results of this study suggest that influenza vaccination is associated with reduced primary MACE risks in the elderly population, including those with ILI.

Background Although theophylline has been shown to have anti-inflammatory effects, the therapeutic use of theophylline before sepsis is unknown. The aim of our study was to determine the effect of theophylline on COPD patients presenting with sepsis. Methods This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients with COPD who were hospitalized for sepsis between 2000 and 2011 were divided into theophylline users and non-users. The primary outcome was 30-day mortality. The secondary outcome was in-hospital death, intensive care unit admission, and need for mechanical ventilation. Cox proportional hazard model and conditional logistic regression were used to calculate the risk between groups. Results A propensity score-matched cohort of 51,801 theophylline users and 51,801 non-users was included. Compared with non-users, the 30-day (HR 0.931, 95% CI 0.910–0.953), 180-day (HR 0.930, 95% CI 0.914–0.946), 365-day (HR 0.944, 95% CI 0.929–0.960) and overall mortality (HR 0.965, 95% CI 0.952–0.979) were all significantly lower in theophylline users. Additionally, the theophylline users also had lower risk of in-hospital death (OR 0.895, 95% CI 0.873–0.918) and need for mechanical ventilation (OR 0.972, 95% CI 0.949–0.997). Conclusions Theophylline use is associated with a lower risk of sepsis-related mortality in COPD patients. Pre-hospital theophylline use may be protective to COPD patients with sepsis.

Objective To examine the risk of acute kidney injury (AKI) in a nationwide cohort of patients with type 2 diabetes initiating dipeptidyl peptidase-4 (DPP-4) inhibitors. Patients and Methods This nested case-control study of a cohort of adult DPP-4 inhibitor users with type 2 diabetes who were hospitalized for AKI between January 1, 2010, and December 31, 2013, was conducted using Taiwan's National Health Insurance Research Database. Each AKI case was matched with one control subject according to duration of follow-up, age, sex, urbanization level, monthly income, comorbidity severity, and well-known predisposing factors for AKI. Odds ratios (ORs) for AKI were calculated according to current, recent, or past use of DPP-4 inhibitors. Results A total of 6752 cases with AKI and 6752 matched controls were analyzed. The exposure prevalence of DPP-4 inhibitor use in the previous year was higher among patients with AKI (adjusted OR, 1.20; 95% CI, 1.05-1.36; P =.006). In a stratified analysis, the association was significant for current DPP-4 inhibitor use (adjusted OR, 1.26; 95% CI, 1.08-1.48; P =.004), but not for recent or past use. Conclusion In this large contemporary cohort, DPP-4 inhibitor users had an increased risk of AKI development compared with nonusers. Further research is warranted to investigate the mechanism underlying this association.

The 2014 Eighth Joint National Committee guidelines for hypertension management emphasize the upper limit of blood pressure (BP) as the target for treatment in the elderly population. Given the uncertainty regarding optimal BP range, we aimed to investigate the association between observed BP and subsequent mortality in older people.We extracted data from 128,765 participants ≥65 years of age who underwent annual health examinations in a retrospective, observational community-based study from 2001 to 2010. Seated BP was measured using an oscillometric device. The outcomes were all-cause and cardiovascular mortality.As compared to participants with systolic BP at 130 to 139 mm Hg, the risk of all-cause mortality was significantly higher among those with110 (adjusted hazard ratios [aHRs], 1.12; 95% confidence interval [CI], 1.05-1.20), 140 to 149 (aHR, 1.08; 95% CI, 1.03-1.14), 150 to 159 (aHR, 1.07; 95% CI, 1.01-1.17), 160 to 169 (aHR, 1.11; 95% CI, 1.04-1.19), and ≥170 mm Hg (aHR, 1.25; 95% CI, 1.17-1.33), whereas the differences were not significant for those with 110 to119 (aHR, 1.06; 95% CI, 1.00-1.12) and 120 to 129 mm Hg (aHR, 1.03; 95% CI, 0.97-1.08). Similarly, diastolic BP at 40 to 79 mm Hg was associated with the lowest risk of all-cause mortality. The J-shaped curve relationship between BP and cardiovascular mortality was also observed.Observed systolic and diastolic BP other than 110 to 139 and 40 to 79 mm Hg, respectively, were associated with a worse outcome. Our large cohort study supports the J-shaped mortality with observed BP in older people.

Purpose To determine whether migraine is associated with an increased risk of developing ocular motor cranial nerve palsies (OMCNP). Design Nationwide retrospective cohort study. Participants Medical records of patients with migraine who were entered in the National Health Insurance Research Database (NHIRD) between 2005 and 2009 were retrieved from the NHIRD in Taiwan. Two cohorts were selected: patients with migraine (n = 138 907) and propensity score–matched controls (n = 138 907). Main Outcome Measures Cohorts were followed until the end of 2010, death, or occurrence of cranial nerve (CN)3, CN4, or CN6 palsies. A Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), which were used to compare to the risk of developing CN3, CN4, and CN6 palsy between cohorts. Results After a mean follow-up period of 3.1 years (range, 1–6 years), the migraine cohort exhibited a greater risk of developing subsequent CN3, CN4, and CN6 palsies compared with the control cohort (HR, 2.67, P P P Conclusions Migraine is an unrecognized risk factor for OMCNP development in adults. Further studies are needed to validate our findings and to delineate the exact pathophysiologic mechanisms linking migraine and OMCNP.

Background The comorbidity profile, especially cancer risk, of narcoleptic patients has seldom been explored. We used a nationwide database to evaluate the risk of cancer among adult narcoleptic patients. Methods We conducted the cohort study using National Health Insurance Research Database from 2000 to 2009. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. Results 2833 narcoleptic patients were identified after excluding patients with antecedent malignancy and age younger than 18 years old. The study cohort was observed for 15,913 person-years during a 10-year period. The median follow-up interval was 5.6 ± 3.0 years. Seventy-four cancers occurred in during the follow-up. The risk of all cancers was found significantly increased in adult narcoleptic patients (SIR 1.32; 95% CI, 1.04–1.66, p = 0.0248). Regarding sex, the overall cancer risk was increased in female patients (SIR 1.52; 95% CI, 1.05–2.13, p = 0.026). Furthermore, females were found to have more head and neck cancers (SIR 6.17; 95% CI, 1.66-15.80, p = 0.009) and gastric cancers (SIR 4.87; 95% CI, 1.31–12.48, p = 0.02). For males, the incidence of overall and specific cancer types was not significantly increased. Conclusions Adult narcoleptic patients had a higher risk for cancer. Further research is warranted to elucidate the mechanism underlying its association.

Objective Gastro-esophageal reflux disease (GERD) is a highly prevalent disorder; however, important questions remain regarding the link between GERD and extra-esophageal cancers. This nationwide cohort study investigated the risk of developing head and neck cancers (HNCs) among patients with GERD. Methods Newly diagnosed GERD patients aged ≥20 years without antecedent cancer were included. Case data were obtained from the National Health Insurance Research Database covering period from 1998 to 2010. We compared the standardized incidence ratios (SIRs) of cancer among GERD patients with those of the general population. Results A total of 98 cancers were identified among the 39,845 GERD patients in the study, representing 128,361 person-years. The SIR for all cases of cancer was 1.59 (95% CI 1.29–1.93). GERD patients exhibited significantly higher SIRs for oropharyngeal (SIR 3.58, 95% CI 1.85–6.25) and hypopharyngeal (SIR 3.96, 95% CI 2.35–6.26) cancers. Male patients had a significantly higher risk of HNCs (SIR 1.70, 95% CI 1.36–2.10), particularly oropharyngeal (SIR 4.01, 95% CI 2.00–7.17) and hypopharyngeal (SIR 3.91, 95% CI 2.28–6.26) cancers. Following adjustment for age and co-morbidities, the hazard ratio was 9.06 (95% CI 4.70–17.44) for males compared to females. Conclusion There may be a potential association between GERD and risk of HNCs, which however merits further studies to confirm the causal relationship. Our observations indicate a need for careful extra-esophageal examination of patients with acid reflux. Our findings also underline the importance of raising awareness among clinicians regarding the possibility of concurrent HNCs in GERD patients with refractory laryngo-pharyngeal symptoms.

Background The association between periodontal disease and chronic kidney disease in older people is controversial, and evidence for a causal link between kidney function decline and subsequent mortality risk is limited. Study Design Longitudinal, observational, community-based cohort study. Setting & Participants Participants were citizens 65 years or older who received the Taipei City Government–sponsored Annual Elderly Health Examination Program during 2005 to 2010, including dental status assessment and biochemical examinations. Predictors Participants with periodontal disease defined by the World Health Organization Community Periodontal Index of Treatment Need criteria. Outcomes All-cause and cardiovascular mortality and estimated glomerular filtration rate (eGFR) decline ≥ 30% over 2 years. Results Of 100,263 study participants, 13,749 (13.7%) had periodontal disease. In a mean follow-up of 3.8 years, all-cause and cardiovascular mortality rates in those with periodontal disease (11.5% and 2.6%, respectively) were higher compared with those without periodontal disease (6.7% and 1.6%, respectively). After adjustment for demographic characteristics, comorbid conditions, and biochemistry data, adjusted HRs for all-cause and cardiovascular mortality were 1.34 (95% CI, 1.26-1.42) and 1.25 (95% CI, 1.13-1.41), respectively. The frequency of eGFR decline ≥ 30% over 1-, 2-, and 3-years' follow-up in those with periodontal disease was 1.8%, 3.7%, and 4.0%, respectively. In a logistic regression model, adjusted ORs of the detrimental effect of periodontal disease on 30% eGFR decline in participants over 1-, 2-, or 3-years' follow-up were 1.03 (95% CI, 0.85-1.25), 1.62 (95% CI, 1.41-1.87), and 1.59 (95% CI, 1.37-1.86), respectively. In subgroup analyses according to age, sex, and comorbid conditions, risks for eGFR decline and mortality remained consistent. Limitations Results may not be generalizable to other non-Asian ethnic populations. Conclusions The results indicate that periodontal disease is a risk factor for all-cause and cardiovascular mortality and eGFR decline ≥ 30% over 2 to 3 years in older people.

Background Retinal vein occlusion (RVO) is the second most common retinal vascular disease, with peak incidence at 70years of age. However, the bidirectional association between the risk of comorbidities and the diagnosis of RVO in this population is uncertain. Methods A population-based cohort of 1,784,960 patients 70years of age and older retrieved from the Taiwan National Health Insurance Research Database between 2000 and 2010. Risks of comorbidities were assessed 5years before and after the diagnosis of RVO. Results In our study, 3393 subjects had central RVO (CRVO) and 6688 subjects had branch RVO (BRVO). Before the diagnosis of RVO, patients showed increased risks for the following comorbidities: hypertension (odds ratio [OR]=1.83, 95% confidence interval [CI], 1.74–1.93), dyslipidemia (OR=1.29, [1.23–1.35]), DM (OR=1.29, [1.23–1.35]), liver disease (OR=1.22, [1.16–1.29]), renal disease (OR=1.30, [1.23–1.37]), and cerebrovascular disease (OR=1.16, [1.11–1.21]). After the diagnosis of RVO, patients were at greater risk of developing DM (adjusted hazard ratio [AHR]=1.12, [1.06–1.19]), PAD (AHR=1.17, [1.08–1.27]), and MACE (AHR=1.35, [1.25–1.46]); however, the risk of all-cause mortality was unchanged. Elderly patients with CRVO had a significantly higher risk of all-cause mortality (AHR=1.09, [1.02–1.17]), whereas patients with BRVO showed no significant differences in mortality. Conclusion This study suggests bidirectional association between the risk of comorbidities and the diagnosis of RVO in an elderly population.

Summary 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.

The objective of this study was to evaluate the risks of acute cholecystitis among end-stage renal disease patients and compare the incidence between two dialysis modality.In this retrospective cohort study, records of fifty thousand end-stage renal disease patients older than 20 years of age from 1998 to 2007 and an age, gender, Charlson's score, diabetes, and dyslipidemia matched control cohort were retrieved from Taiwan National Health Insurance Research Database. Hospitalizations for acute cholecystitis were retrieved using ICD-9-CM diagnosis codes and ICD-9-CM operation codes from in-patient claims.The incidence rates were 5.8 per 1000 patient-years in the end-stage renal disease patients and 0.92 per 1000 patient-years in the control group. End-stage renal disease was an independent risk factor for acute cholecystitis. In the end-stage renal disease patients, independent risk factors were old age, higher Charlson's score, diabetes, severe liver disease, atrial fibrillation, and haemodialysis (all p0.05). However, the peritoneal dialysis patients had a higher mortality rate after developing acute cholecystitis.Acute cholecystitis is not uncommon in end-stage renal disease patients. The independent risk factors were older age, higher Charlson's score, atrial fibrillation, severe liver disease, diabetes, and dialysis modality. Haemodialysis patients had a higher risk of acute cholecystitis than PD patients.

Urolithiasis is a worldwide disease which has affected humans from ancient eras to modern times. Recently, societal changes have altered the epidemiology of urinary calculi. The incidence of urolithiasis is higher in industrialized countries. Obese people are known to have a higher risk of stone formation. Metabolic syndrome has resulted in an increasing rate of nephrolithiasis among women. There are many useful tools for diagnosing urolithiasis, including conventional plain radiography, intravenous urography, ultrasonography, computed tomography (CT), and nuclear medicine. Nonenhanced CT has high sensitivities and specificities. It can be rapidly performed without intravenous administration of contrast material and can therefore be used in patients with severely impaired renal function. Beyond that, it can reveal extraurinary causes of flank pain. However, concerns about radiation exposure and costs remain. Since ancient times, hundreds of natural plant extracts and more recently, synthetic chemicals have been proposed to eliminate urinary calculi. Clinical trials demonstrated that calcium channel blockers and adrenergic antagonists are effective in enhancing stone passage. Shock wave lithotripsy (SWL) can successfully treat renal calculi. A meta-analysis study revealed that SWL is more effective in treating urinary calculi with a lower-frequency mode. Highly dense stones are more refractory to SWL. The stone composition can be evaluated by preoperative CT attenuation values. Patients with preoperative Houndsfield units (HUs) of >750 have a 10.5-times greater chance of needing three or more sessions of SWL treatment compared to patients whose HUs are

• The risk of hypoglycemia within a very short time in patients co-prescribed antimicrobials and sulfonylureas were analyzed.