Changes in Plasma Amyloid and Tau in a Longitudinal Study of Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Changes in cerebrospinal fluid, neuroimaging, and cognitive functions have been used as diagnostic biomarkers of Alzheimer's disease (AD). This study aimed to investigate the temporal trajectories of plasma biomarkers in subjects with mild cognitive impairment (MCI) and patients with AD relative to healthy controls (HCs). METHODS: In this longitudinal study, 82 participants (31 HCs, 33 MCI patients, and 18 AD patients) were enrolled. After 3 years, 7 HCs had transitioned to MCI and 10 subjects with MCI had converted to AD. We analyzed plasma amyloid beta (Aß) and tau proteins at baseline and annually to correlate with biochemical data and neuropsychological scores. RESULTS: Longitudinal data analysis showed an evolution of Aß-related biomarkers over time within patients, whereas tau-related biomarkers differed primarily across diagnostic classifications. An initial steady increase in Aß42 in the MCI stage was followed by a decrease just prior to clinical AD onset. Hyperphosphorylated tau protein levels correlated with cognitive decline in the MCI stage, but not in the AD stage. CONCLUSION: Plasma Aß and tau levels change in a dynamic, nonlinear, nonparallel manner over the AD continuum. Changes in plasma Aß concentration are time-dependent, whereas changes in hyperphosphorylated tau protein levels paralleled the clinical progression of MCI. It remains to be clarified whether diagnostic efficiency can be improved by combining multiple plasma markers or combining plasma markers with other diagnostic biomarkers.

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.

Long-Term Mortality and Major Adverse Cardiovascular Events in Sepsis Survivors. A Nationwide Population-based Study.

RATIONALE: Patients with sepsis who survive to hospital discharge may present with ongoing high morbidity and mortality. However, little is known about the risk of long-term, all-cause mortality and cardiovascular outcomes after sepsis. OBJECTIVES: Our study aimed to investigate the long-term clinical outcomes in sepsis survivors. METHODS: In this nationwide population-based study, data from patients with sepsis were retrieved from Taiwan's National Health Insurance Research Database between 2000 and 2002. Each sepsis survivor was 1:1 propensity-matched to control subjects from two different control populations: subjects who were in the general population and subjects who were hospitalized for a nonsepsis diagnosis. The primary outcomes were all-cause mortality, major adverse cardiovascular events, myocardial infarction, heart failure, stroke, and sudden cardiac death or ventricular arrhythmia. MEASUREMENTS AND MAIN RESULTS: Compared with matched population control subjects, sepsis survivors had higher risks of all-cause mortality (hazard ratio [HR], 2.18; 95% confidence interval [CI], 2.14-2.22), major adverse cardiovascular events (HR, 1.37; 95% CI, 1.34-1.41), ischemic stroke (HR, 1.27; 95% CI, 1.23-1.32), hemorrhagic stroke (HR, 1.36; 95% CI, 1.26-1.46), myocardial infarction (HR, 1.22; 95% CI, 1.14-1.30), heart failure (HR, 1.48; 95% CI, 1.43-1.53), and sudden cardiac death or ventricular arrhythmia (HR, 1.65; 95% CI, 1.57-1.74). Similar results, although slightly attenuated risks, were found when comparisons were made with hospitalized control subjects without sepsis. CONCLUSIONS: These data indicate that sepsis survivors had substantially increased risks of subsequent all-cause mortality and major adverse cardiovascular events at 1 year after discharge, which persisted for up to 5 years after discharge.

Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Recent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce. OBJECTIVE: To compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM. DESIGN: Nationwide study using Taiwan's National Health Insurance Research Database. SETTING: Taiwan. PATIENTS: All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined. MEASUREMENTS: Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013. RESULTS: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure. LIMITATION: Observational study design. CONCLUSION: Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy. PRIMARY FUNDING SOURCE: None.

Long-term clinical outcome of major adverse cardiac events in survivors of infective endocarditis: a nationwide population-based study.

BACKGROUND: Substantial infective endocarditis (IE)-related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors. METHODS AND RESULTS: A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40-1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90-2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17-1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05-2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44-1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14-2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE. CONCLUSION: Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors.

Association of postdischarge rehabilitation with mortality in intensive care unit survivors of sepsis.

RATIONALE: Intensive care unit (ICU)-acquired weakness is a common issue for sepsis survivors that is characterized by impaired muscle strength and causes functional disability. Although inpatient rehabilitation has not been found to reduce in-hospital mortality, the impact of postdischarge rehabilitation on sepsis survivors is uncertain. OBJECTIVES: To investigate the benefit of postdischarge rehabilitation to long-term mortality in sepsis survivors. METHODS: We conducted a nationwide, population-based, high-dimensional propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. The rehabilitation cohort comprised 15,535 ICU patients who survived sepsis and received rehabilitation within 3 months after discharge between 2000 and 2010. The control cohort consisted of 15,535 high-dimensional propensity score-matched subjects who did not receive rehabilitation within 3 months after discharge. The endpoint was mortality during the 10-year follow-up period. MEASUREMENTS AND MAIN RESULTS: Compared with the control cohort, the rehabilitation cohort had a significantly lower risk of 10-year mortality (adjusted hazard ratio, 0.94; 95% confidence interval, 0.92-0.97; P < 0.001), with an absolute risk reduction of 1.4 per 100 person-years. The frequency of rehabilitation was inversely associated with 10-year mortality (≥3 vs. 1 course: adjusted hazard ratio, 0.82; P < 0.001). Compared with the control cohort, improved survival was observed in the rehabilitation cohort among ill patients who had more comorbidities, required more prolonged mechanical ventilation, and had longer ICU or hospital stays, but not among those with the opposite conditions (i.e., less ill patients). CONCLUSIONS: Postdischarge rehabilitation may be associated with a reduced risk of 10-year mortality in the subset of patients with particularly long ICU courses.

Nonsteroidal anti-inflammatory drug use is associated with cancer risk reduction in chronic dialysis patients.

Previous studies have shown that nonsteroidal anti-inflammatory drug (NSAID) use might be associated with a lower risk of developing cancer in the general population. Patients on dialysis have increased risk for cancer, but there are no studies to determine the relationship between NSAID use and cancer risk in these patients. To identify any association between NSAID use and cancer risk in patients with end-stage renal disease on dialysis, we used Taiwan's National Health Insurance database to conduct a nationwide population-based, propensity score-matched cohort study. All cancers between groups were compared by Cox proportional hazards models. Compared to nonuse of NSAIDs, the use of non-COX-2-selective inhibitors (hazard ratio 0.81, 95% confidence interval 0.67-0.97) or COX-2-selective inhibitors (0.78, 0.62-0.98) was associated with a lower risk of developing cancer. NSAID use reduced the risk of respiratory (0.39, 0.19-0.79), breast (0.41, 0.19-0.89), kidney (0.58, 0.38-0.88), digestive tract (0.64, 0.49-0.85), and bladder cancers (0.73, 0.55-0.96). NSAID use, however, significantly increased risk for upper gastrointestinal bleeding (odds ratio, 1.15, 1.07-1.23) but not adverse cardiac or cerebrovascular events. Thus, NSAID use was associated with a lower risk of developing cancer in chronic dialysis patients; however, they should still be used with caution due to the side effects of gastrointestinal bleeding.

Does Alzheimer's disease protect against cancers? A nationwide population-based study.

BACKGROUND: Previous studies suggested a decreased risk of cancer among patients with Alzheimer's disease (AD). There is still a lack of data on the specific types of cancer, the risk factors, and the impact of cholinesterase inhibitors on developing cancer in AD. METHODS: We performed a nationwide population-based study of 6,960 patients with AD between 1997 and 2006 using Taiwan's National Health Insurance database. Patterns of cancer incidence in AD patients were compared with those of the general population using standardized incidence ratios (SIRs). RESULTS: Patients with AD had a reduced risk of developing overall cancer [SIR = 0.88, 95% confidence interval (CI) = 0.80-0.97]. Specifically, patients with AD were protected from lung cancers (SIR = 0.75, 95% CI = 0.57-0.98), especially men (SIR = 0.61, 95% CI = 0.40-0.88). In subgroup analyses, women, patients aged 60-79 years, and those diagnosed as having AD for more than 1 year were more likely to be protected from cancers. CONCLUSIONS: Our study demonstrates a decreased incidence of overall cancers in patients with AD, a finding lower than but consistent with Western countries. Patients with AD had a significantly decreased risk of lung cancer. Further investigation of genetic evidence linking AD to cancer is warranted.

Hyperlactatemia is associated with increased risks of long-term mortality and major adverse cardiovascular events in sepsis survivors.

INTRODUCTION: Serum lactate is a potentially valuable biomarker for risk assessment for patients with sepsis, as hyperlactatemia is associated with elevated short-term mortality risks. However, the associations between hyperlactatemia and long-term clinical outcomes in sepsis survivors remain unknown. The objective of this study was to investigate whether hyperlactatemia at the time of hospitalisation for sepsis was associated with worse long-term clinical outcomes in sepsis survivors. METHODS: In total, of 4983 sepsis survivors aged ≥ 20 years were enrolled in this study between January 1, 2012, and December 31, 2018. They were divided into low (≤18 mg/dL; n = 2698) and high (>18 mg/dL; n = 2285) lactate groups. The high lactate group was then matched 1:1 by propensity-score method to the low lactate group. The outcomes of interest were all-cause mortality, major adverse cardiac events (MACEs), ischaemic stroke, myocardial infarction, hospitalisation for heart failure, and end-stage renal disease. RESULTS: After propensity score matching, the high lactate group had greater risks of all-cause mortality (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.41-1.67), MACEs (HR 1.53, 95% CI 1.29-1.81), ischaemic stroke (HR 1.47, 95% CI 1.19-1.81), myocardial infarction (HR 1.52, 95% CI 1.17-1.99), and end-stage renal disease (HR 1.42, 95% CI 1.16-1.72). Subgroup analyses stratified by baseline renal function revealed almost similarity across groups. CONCLUSION: We found that hyperlactatemia is associated with long-term risks of mortality and MACEs in sepsis survivors. Physicians may consider more aggressive and prompter management of sepsis in patients who present with hyperlactatemia to improve long-term prognoses.

The Clinical Course of Early and Late Mild Cognitive Impairment.

Introduction: Amnestic mild cognitive impairment (MCI) can be classified as either early MCI (EMCI) or late MCI (LMCI) according to the severity of memory impairment. The aim of this study was to compare the prognosis and clinical course between EMCI and LMCI. Methods: Between January 2009 and December 2017, a total of 418 patients with MCI and 146 subjects with normal cognition were recruited from a memory clinic. All the patients received at least two series of neuropsychological evaluations each year and were categorized as either EMCI or LMCI according to Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) criteria. Results: In total, our study included 161 patients with EMCI, 258 with LMCI, and 146 subjects with normal cognition as controls (NCs). The mean follow-up duration was 3.55 ± 2.18 years (range: 1-9). In a first-year follow-up assessment, 54 cases (32.8%) of EMCI and 16 (5%) of LMCI showed a normal cognitive status. There was no significant difference between the first year EMCI reverter and NCs in terms of dementia-free survival and further cognitive decline. However, first-year LMCI reverters still had a higher risk of cognitive decline during the following evaluations. Until the last follow-up, annual dementia conversion rates were 1.74, 4.33, and 18.6% in the NC, EMCI, and LMCI groups, respectively. The EMCI and LMCI groups showed a higher rate of progression to dementia (log-rank test, p < 0.001) than normal subjects. Compared with NCs, patients in the LMCI group showed a significantly faster annual decline in global cognition [annual rate of change for the mini-mental status examination (MMSE) score: -1.035, p < 0.001]) and all cognitive domains, while those in the EMCI group showed a faster rate of decline in global cognitive function (annual rate of change for the MMSE score: -0.299, p = 0.001). Conclusion: It is important to arrange follow-up visits for patients with MCI, even in the EMCI stage. One-year short-term follow-up may provide clues about the progression of cognitive function and help to identify relatively low-risk EMCI subjects.

The Flexibility of Physio-Cognitive Decline Syndrome: A Longitudinal Cohort Study.

The mutual presence of impairments in physical and cognitive functions in older adults has been reported to predict incident disability, dementia, and mortality. The longitudinal transitions of phenotypes between these functional impairments, either individually or in combination, remain unclear. To investigate the natural course and prevalence of physical and/or cognitive impairments (CIs), we enrolled participants from a community-based population. Data were retrieved from the first (August 2011 and December 2012) and second wave (August 2013 and June 2015) of the I-Lan Longitudinal Aging Study (ILAS). All participants were classified into four groups: robust, mobility impairment (MI), CI, and physio-cognitive decline syndrome (PCDS). MI was diagnosed with weakness and/or slowness. CI was diagnosed if a subject met a cutoff below 1.5 standard deviations (SDs) of age-, sex-, and education-matched norms of any neuropsychological assessments. PCDS was combined with MI and CI. Our results showed that 38, 14, 30, and 18% of the participants were on the robust, MI, CI, and PCDS at the first wave, respectively. After 2.5 years, 17% robust, 29% MI, and 37% CI progressed to PCDS. In contrast, 33% of PCDS was reversed to non-PCDS. Predictors of conversion to PCDS included worse memory and language functions, older age, lower muscle mass, and the presence of diabetes. In PCDS, a stronger hand-grip strength, younger age, and better memory functions predicted reversion to non-PCDS status. In summary, we probed the transition of PCDS. The skeletal muscle mass/function and memory function are crucial factors associated with PCDS reversion or progression.

Effects of Renin-Angiotensin-Aldosterone System Inhibitors on Long-Term Major Adverse Cardiovascular Events in Sepsis Survivors.

Background Sepsis is known to increase morbidity and duration of hospital stay and is a common cause of mortality worldwide. Renin-angiotensin-aldosterone system inhibitors (RAASis) are commonly used to treat hypertension but are usually discontinued during hospitalization for sepsis because of concerns about renal hypoperfusion. The aim of our study was to investigate whether RAASis should be continued after discharge in sepsis survivors and to identify the effects on the clinical outcomes. Methods and Results A total of 9188 sepsis survivors aged 20 years and older who were discharged from January 1, 2012 to December 31, 2019 were included in our analyses. We further divided sepsis survivors into RAASi users and nonusers. These groups were matched by propensity scores before the outcomes of interest, including all-cause mortality and major adverse cardiac events (MACE), were examined. After propensity score matching, 3106 RAASi users and 3106 RAASi nonusers were included in our analyses. Compared with RAASi nonusers, RAASi users had lower risks of all-cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.62-0.75), MACEs (HR, 0.87; 95% CI, 0.81-0.94), ischemic stroke (HR, 0.85; 95% CI, 0.76-0.96), myocardial infarction (HR, 0.74; 95% CI, 0.61-0.90), and hospitalization for heart failure (HR, 0.84; 95% CI, 0.77-0.92). Subgroup analyses stratified by admission to the ICU and the use of inotropes showed similar results. Conclusions In our study, we found that RAASi users had reduced risks of all-cause mortality and MACEs. These findings suggested a beneficial effect of RAASi use by sepsis survivors after discharge.

Prediction of Cerebral Amyloid Pathology Based on Plasma Amyloid and Tau Related Markers.

Background and Purpose: Pyroglutamate-modified ß-amyloid peptide (AßpE) is crucial for AD pathophysiological process. The potential associations of plasma AßpE and total tau (t-tau) with brain Aß burden and cognitive performance remain to be clarified. Methods: Forty-six subjects with unimpaired cognition, mild cognitive impairment, or very mild dementia were enrolled. Plasma levels of AßpE3-40, t-tau, and Aß42 were quantified by immunomagnetic reduction (IMR) assays. We analyzed individual and combined biomarker correlations with neuropsychological scores and Aß positivity determined by 18F-florbetapir positron emission tomography (PET). Results: Both plasma AßpE3-40 levels and AßpE3-40/t-tau ratios correlated negatively with short-term memory and global cognition scores, while correlating positively with PET standardized uptake value ratios (SUVRs). Among the biomarkers analyzed, the combination of AßpE3-40 in a ratio with t-tau had the best discriminatory ability for Aß PET positivity. Likewise, logistic regression analysis showed that AßpE3-40/t-tau was a highly robust predictor of Aß PET positivity after controlling for relevant demographic covariates. Conclusion: Plasma AßpE3-40/t-tau ratios correlate with cognitive function and cerebral Aß burden. The suitability of AßpE3-40/t-tau as a candidate clinical biomarker of AD pathology in the brain should be examined further in larger studies.

Plasma Aß42 and Total Tau Predict Cognitive Decline in Amnestic Mild Cognitive Impairment.

Levels of amyloid-ß (Aß) and tau peptides in brain have been associated with Alzheimer disease (AD). The current study investigated the abilities of plasma Aß42 and total-tau (t-tau) levels in predicting cognitive decline in subjects with amnestic mild cognitive impairment (MCI). Plasma Aß42 and t-tau levels were quantified in 22 participants with amnestic MCI through immunomagnetic reduction (IMR) assay at baseline. The cognitive performance of participants was measured through neuropsychological tests at baseline and annual follow-up (average follow-up period of 1.5 years). The predictive value of plasma Aß42 and t-tau for cognitive status was evaluated. We found that higher levels of Aß42 and t-tau are associated with lower episodic verbal memory performance at baseline and cognitive decline over the course of follow-up. While Aß42 or t-tau alone had moderate-to-high discriminatory value in the identification of future cognitive decline, the product of Aß42 and t-tau offered greater differential value. These preliminary results might suggest that high levels of plasma Aß42 and t-tau in amnestic MCI are associated with later cognitive decline. A further replication with a larger sample over a longer time period to validate and determine their long-term predictive value is warranted.

Association between influenza vaccination and the reduced risk of acute kidney injury among older people: A nested case-control study.

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.

Association Between Use of Dipeptidyl Peptidase-4 Inhibitors and the Risk of Acute Kidney Injury: A Nested Case-Control Study.

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.

Bidirectional association between the risk of comorbidities and the diagnosis of retinal vein occlusion in an elderly population: a nationwide population-based study.

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.

Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Terms of Major Cardiovascular Disease Outcomes in Elderly Patients: A Nationwide Population-Based Cohort Study.

Renin and aldosterone activity levels are low in elderly patients, raising concerns about the benefits and risks of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARB) use. However, data from direct comparisons of the effects of ACEIs on ARBs in the elderly population remain inconclusive.In this nationwide study, all patients aged ≥ 70 years were retrieved from the Taiwan National Health Insurance database for the period 2000 to 2009 and were followed up until the end of 2010. The ARB cohort (12,347 patients who continuously used ARBs for ≥ 90 days) was matched to ACEI cohort using high-dimensional propensity score (hdPS). Intention-to-treat (ITT) and as-treated (AT) analyses were conducted.In the ITT analysis, after considering death as a competing risk, the ACEI cohort had similar risks of myocardial infarction (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.79-1.06), ischemic stroke (HR 0.98, 95% CI 0.90-1.07), and heart failure (HR 0.93, 95% CI 0.83-1.04) compared with the ARB cohort. No difference in adverse effects, such as acute kidney injury (HR 0.99, 95% CI 0.89-1.09) and hyperkalemia (HR 1.02, 95% CI 0.87-1.20), was observed between cohorts. AT analysis produced similar results to those of ITT analysis. We were unable to demonstrate a survival difference between cohorts (HR 1.03, 95% CI 0.88-1.21) after considering drug discontinuation as a competing risk in AT analysis.Our study supports the notion that ACEI and ARB users have similar risks of major adverse cardiovascular events (MACE), even in elderly populations.

Effect of the use of low and high potency statins and sepsis outcomes.

INTRODUCTION: Although statins have been shown to have cholesterol-lowering effects, their pleiotropic benefits on sepsis remain a matter of debate. In addition, the influence of statin potency on sepsis-related mortality has never been explored. The aim of our study was to determine the sepsis outcomes of low- and high-potency statin users and non-users. METHODS: This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients were hospitalized for sepsis between 2000 and 2010. All-cause mortality and major adverse consequences of sepsis, such as in-hospital death, intensive care unit admission, shock events, and the use of mechanical ventilation, were assessed. Patients were divided into high-potency statin users (at least 10 mg rosuvastatin, at least 20 mg atorvastatin, or at least 40 mg simvastatin), low-potency statin users (all other statin treatments), and non-users. RESULTS: A propensity score-matched cohort of 27,792 statin users and 27,792 non-users was included. Of 27,792 statin users, 9,785 (35.2 %) were treated with high-potency statins and 18,007 (64.8 %) were treated with low-potency statins. The 1-year mortality risk was significantly lower among both low-potency [adjusted hazard ratio (aHR) 0.89, 95 % confidence interval (CI) 0.85-0.93] and high-potency (aHR 0.80, 95 % CI 0.75-0.86) statin users compared with non-users. The risks of mortality and adverse consequences of sepsis were lower among high-potency than among low-potency statin users. CONCLUSIONS: High-potency statin use is associated with a lower risk of sepsis-related mortality compared with low-potency statin use.

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.