Statin Use and Influenza Vaccine Effectiveness in Persons >65 Years of Age, Taiwan.

Debates on whether statin use reduces the effectiveness of influenza vaccines against critical illness and death among persons >65 years of age continue. We conducted a study of 9,427,392 persons >65 years of age who did and did not receive influenza vaccinations during 12 consecutive influenza seasons, 2000-01 through 2011-12. Using data from Taiwan's National Health Insurance Research Database, we performed propensity score-matching to compare vaccinated persons with unvaccinated controls. After propensity score-matching, the vaccinated group had lower risks for in-hospital death from influenza and pneumonia and for hospitalization for pneumonia and influenza, circulatory conditions, and critical illnesses compared with the unvaccinated group. We stratified the 2 groups by statin use and analyzed data by interaction analysis and saw no statistically significant difference. We found that influenza vaccine effectively reduced risks for hospitalization and death in persons >65 years of age, regardless of statin use.

U-Shaped Association Between Serum Uric Acid Levels With Cardiovascular and All-Cause Mortality in the Elderly: The Role of Malnourishment.

BACKGROUND: The link between elevated serum uric acid (SUA) levels and cardiovascular disease (CVD)-related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA-predicted mortality and the effect-modifying roles of malnourishment in older people. METHODS AND RESULTS: A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1-mg/dL increment of SUA. Low SUA (<4 mg/dL) strata was categorized by malnourishment status defined as Geriatric Nutritional Risk Index <98, serum albumin <38 g/L, or body mass index <22 kg/m2. Study outcomes were all-cause and CVD-related mortality. Cox models were used to estimate hazard ratios (HRs) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow-up of 5.8 years, there were 16 439 all-cause and 3877 CVD-related deaths. Compared with the reference SUA strata of 4 to <5 mg/dL, all-cause mortality was significantly higher at SUA <4 mg/dL (HR, 1.16; 95% confidence interval, 1.07-1.25) and ≥8 mg/dL (HR, 1.13; confidence interval, 1.06-1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD-related mortality was found at the SUA level <4 mg/dL (HR, 1.19; confidence interval, 1.00-1.40) and ≥7 mg/dL (HR, 1.17; confidence interval, 1.04-1.32). Remarkably, among the low SUA (<4 mg/dL) strata, only malnourished participants had greater all-cause and CVD-related mortality. This modifying effect of malnourishment remained consistent across subgroups. CONCLUSIONS: SUA ≥8 or <4 mg/dL independently predicts higher all-cause and CVD-related mortality in the elderly, particularly in those with malnourishment.

Association between influenza vaccination and reduced risks of major adverse cardiovascular events in elderly patients.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: Results of this study suggest that influenza vaccination is associated with reduced primary MACE risks in the elderly population, including those with ILI.

Impact of physical activity on the association between lipid profiles and mortality among older people.

High serum lipid levels are independent predictors of mortality risk in the general population. Recent data suggest that this may not apply in the older populations, and even acts in the opposite direction. In consideration of the frail state, minimum amount of physical activity (60-100 minutes each week) may be more suitable for older individuals but its role in lipid profiles has never been explored. Between 2006 and 2010, we conducted a cohort study of 83,820 participants aged ≥65 years using the Taipei City Elderly Health Examination Database. Participants were classified as inactive, low or high in their level of physical activity. Older individuals with lowest quintile of total cholesterol, non-HDL and HDL were associated with increased risk of all-cause mortality compared to those with other quintile of these lipid profiles. Compared to inactive older individuals, both low (adjusted hazard ratios [aHR] 0.75, 95% confidence interval [CI] 0.70-0.81) and high active older individuals (aHR 0.55, 95% CI 0.51-0.59) were associated with lower risks of mortality. Physical activity, even minimum volume of exercise, in older people has to be encouraged to reduce the increased risk of mortality from low serum lipid levels.

Association of pre-hospital theophylline use and mortality in chronic obstructive pulmonary disease patients with sepsis.

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.

Long-Term Risk of Cardiovascular Events in Patients With Chronic Kidney Disease Who Have Survived Sepsis: A Nationwide Cohort Study.

BACKGROUND: Long-term cardiovascular outcomes after sepsis in patients with chronic kidney disease are not well known. We aimed to examine the risk of subsequent cardiovascular events in patients with chronic kidney disease discharged after hospitalization for sepsis in Taiwan. METHODS AND RESULTS: Using complete claims data for patients with chronic kidney disease from Taiwan's National Health Insurance Research Database, we identified patients with sepsis who survived hospitalization between 2000 and 2010. Each sepsis survivor was propensity score-matched to one nonsepsis hospitalized control patient. Cox regression models were used to estimate the hazard ratios (HRs) of clinical outcomes, including major adverse cardiovascular events (myocardial infarction and ischemic stroke), hospitalization for heart failure, and all-cause death. Among 66 961 sepsis survivors, the incidence rates of all-cause mortality and major adverse cardiovascular events during the study period were 288.51 and 47.05 per 1000 person-years, respectively. In comparison with matched hospitalized nonsepsis control patients, sepsis survivors had greater risks of major adverse cardiovascular events (HR, 1.42; 95% CI, 1.37-1.47), myocardial infarction (HR, 1.39; 95% CI, 1.32-1.47), ischemic stroke (HR, 1.46; 95% CI, 1.40-1.52), hospitalization for heart failure (HR, 1.55; 95% CI, 1.51-1.59), and all-cause mortality (HR, 1.56; 95% CI, 1.54-1.58). The results remained unchanged in analyses of several subgroups of patients, and were similar in analyses accounting for the competing risk of death. CONCLUSIONS: Our findings highlight the association of sepsis with a significantly increased long-term risk of cardiovascular events among survivors in the chronic kidney disease population.

Dual Antiplatelet Therapy and Clinical Outcomes after Coronary Drug-Eluting Stent Implantation in Patients on Hemodialysis.

BACKGROUND AND OBJECTIVES: We aimed to investigate the benefits and risks of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent (DES) implantation in patients undergoing hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A nested case-control analysis of patients on hemodialysis after receipt of DES and DAPT treatment was conducted using data from Taiwan's National Health Insurance Research Database for the period 2007-2011. Cases of myocardial infarction or death within 1 year after DES implantation were matched one-to-one with control patients. Odds ratios were calculated to compare DAPT continuation with discontinuation. Additionally, a propensity score-adjusted 6-month landmark cohort analysis was also conducted to evaluate the long-term benefits and risks of prolonged (>6 months) compared with ≤6 months of DAPT use. The primary outcomes were death and myocardial infarction. The secondary outcomes were ischemic stroke, revascularization, and major bleeding. RESULTS: In the nested case-control analysis, patients who continued DAPT had a lower rate of death or myocardial infarction within 1 year after receipt of a DES (adjusted odds ratio, 0.54; 95% confidence interval, 0.36 to 0.81; P=0.003), whereas this association became statistically nonsignificant when compared with patients who discontinued DAPT for the period between 6 and 12 months after receipt of a DES (adjusted odds ratio, 1.51; 95% confidence interval, 0.75 to 3.04). In the propensity score-adjusted cohort analysis, >6 months of DAPT use was not associated with different primary or secondary outcomes than shorter-term use. CONCLUSIONS: Our findings support that the clinical effectiveness of extended DAPT in a hemodialysis population may be tempered after 6 months post-DES implantation.

Association of weekend effect with early mortality in severe sepsis patients over time.

BACKGROUND: The aim of this study is to investigate the "weekend effect" and early mortality of patients with severe sepsis. METHODS: Using the Taiwanese National Healthcare Insurance Research Database, all patients who were hospitalized for the first time with an episode of severe sepsis between January 2000 and December 2011 were identified and the short-term mortality of patients admitted on weekdays was compared to those admitted on weekends. The primary endpoint was 7-day mortality. The secondary endpoints were 14 and 28-day mortality. RESULTS: A total of 398,043 patients were identified to have had the diagnosis of severe sepsis. Compared with patients admitted on weekends, patients admitted on weekdays had a lower 7-day mortality rate (adjusted odds ratio [OR] 0.89, 95% confidential interval [CI] 0.87-0.91), 14-day mortality rate (adjusted OR 0.92, 95% CI 0.90-0.93), and 28-day mortality rate (adjusted OR 0.97, 95% CI 0.95-0.98). This "weekend effect" was maintained every year throughout the 11-year study period. CONCLUSIONS: Patients with severe sepsis are more likely to die in the hospital if they were admitted on weekends than if they were admitted on weekdays.

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 Taiwan's 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 estimated glomerular filtration rate with all-cause and cardiovascular mortality: the role of malnutrition-inflammation-cachexia syndrome.

BACKGROUND: Previous studies have demonstrated that high estimated glomerular filtration rate (eGFR) is paradoxically associated with an increased risk of mortality, and the association becomes more predominant in older people. However, the role of malnutrition-inflammation-cachexia syndrome (MICS) in the association between eGFR and mortality has never been explored. METHODS: We conducted a community-based cohort study using data from the Taipei City Elderly Health Examination Database, collected during the period 2001-10. All participants aged ≥65 years were included and stratified by the absence or presence of MICS, which is defined as the presence of at least one of the following markers: body mass index <22 kg/m(2), serum albumin <3.0 mg/dL, or Geriatric Nutritional Risk Index (GNRI) <98. The study endpoints were all-cause and cardiovascular mortality. RESULTS: A total of 131 354 participants were identified and categorized according to the chronic kidney disease stage based on eGFR. Compared with the reference eGFR of 60-89 mL/min/1.73 m(2), the overall and cardiovascular mortality risks were markedly high in the groups with eGFR of <30 mL/min/1.73 m(2) [overall: adjusted hazard ratio (aHR), 1.86; 95% confidence interval (CI), 1.72-2.00; cardiovascular: aHR, 1.87; 95% CI, 1.60-2.19] and ≥90 mL/min/1.73 m(2) (overall: aHR, 1.23; 95% CI, 1.13-1.34; cardiovascular: aHR, 1.28; 95% CI, 1.06-1.54). In the absence of MICS, high eGFR was associated with lower mortality risk (aHR, 0.71; 95% CI, 0.62-0.80), and the U-shaped relationship disappeared. Subgroup analyses produced consistent results. CONCLUSIONS: MICS could influence the association observed between high eGFR and mortality in older people, particularly in those with low body mass index, albumin level, GNRI, and very low serum creatinine level.

Observed Blood Pressure and Mortality Among People Aged 65 Years and Older: A Community-Based Cohort Study.

OBJECTIVES: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. RESULTS: As compared to participants with systolic BP at 130 to 139 mm Hg, the risk of all-cause mortality was significantly higher among those with <110 (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. CONCLUSIONS: 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.

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.

Association of Genetic Polymorphisms of Renin-Angiotensin-Aldosterone System-Related Genes with Arterio-Venous Fistula Malfunction in Hemodialysis Patients.

Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001), lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025), right-sided (31.8% vs. 18.4%, p = 0.002) and upper arm AVF (26.6% vs. 9.7%, p < 0.001), and higher mean dynamic venous pressure (DVP) (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021). In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs), rs275653 (Odds ratio 1.90, p = 0.038) and rs1492099 (Odds ratio 2.29, p = 0.017) of angiotensin II receptor 1 (AGTR1), were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA) of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005). In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could be a potential genetic risk factor of AVF malfunction in male HD patients.

Effects of DPP-4 inhibitors on cardiovascular outcomes in patients with type 2 diabetes and end-stage renal disease.

BACKGROUND: Recent clinical trials have evaluated the cardiovascular outcomes of dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM), but those with end-stage renal disease (ESRD) were ineligible for participation in these trials. We aimed to characterize the impact of DPP-4 inhibitors on major adverse cardiovascular events (MACEs) in patients with T2DM and ESRD undergoing chronic dialysis. METHODS: This nationwide observational study utilized data from 3556 patients aged ≥20years with T2DM and ESRD who initiated treatment with DPP-4 inhibitors between 1 March 2009 and 31 June 2013, retrieved from Taiwan's National Health Insurance Research Database. Each DPP-4 inhibitor user was matched to a non-user control subject using propensity scores. The primary outcomes were all-cause mortality and MACEs (ischemic stroke and myocardial infarction). The secondary outcomes were hospitalization for heart failure and hypoglycemia. All subjects were followed until death or 31 December 2013. RESULTS: Compared with non-users, DPP-4 inhibitor users had lower risks of all-cause mortality (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.39-0.47), MACEs (HR 0.76, 95% CI 0.65-0.90), and ischemic stroke (HR 0.77, 95% CI 0.61-0.97); the risks of myocardial infarction and hospitalization for heart failure and hypoglycemia did not differ. This treatment effect remained consistent in subgroup analyses according to age, sex, comorbidities, dialysis modality, and insulin use. CONCLUSIONS: In this nationwide ESRD cohort, DPP-4 inhibitor use was associated with reduced risks of all-cause mortality and ischemic stroke.

Comparative effectiveness of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers in patients with type 2 diabetes and retinopathy.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective treatments for diabetic retinopathy, but randomized trials and meta-analyses comparing their effects on macrovascular complications have yielded conflicting results. We compared the effectiveness of these drugs in patients with pre-existing diabetic retinopathy in a large population-based cohort. METHODS: We conducted a propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. We included adult patients prescribed an ACE inhibitor or ARB within 90 days after diagnosis of diabetic retinopathy between 2000 and 2010. Primary outcomes were all-cause death and major adverse cardiovascular events (myocardial infarction, ischemic stroke or cardiovascular death). Secondary outcomes were hospital admissions with acute kidney injury or hyperkalemia. RESULTS: We identified 11 246 patients receiving ACE inhibitors and 15 173 receiving ARBs, of whom 9769 patients in each group were matched successfully by propensity scores. In the intention-to-treat analyses, ARBs were similar to ACE inhibitors in risk of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87-1.01) and major adverse cardiovascular events (HR 0.95, 95% CI 0.87-1.04), including myocardial infarction (HR 1.03, 95% CI 0.88-1.20), ischemic stroke (HR 0.94, 95% CI 0.85-1.04) and cardiovascular death (HR 1.01, 95% CI 0.88-1.16). They also did not differ from ACE inhibitors in risk of hospital admission with acute kidney injury (HR 1.01, 95% CI 0.91-1.13) and hospital admission with hyperkalemia (HR 1.01, 95% CI 0.86-1.18). Results were similar in as-treated analyses. INTERPRETATION: Our study showed that ACE inhibitors were similar to ARBs in risk of all-cause death, major adverse cardiovascular events and adverse effects among patients with pre-existing diabetic retinopathy.

Adverse Effects of Oral Nonselective and cyclooxygenase-2-Selective NSAIDs on Hospitalization for Acute Kidney Injury: A Nested Case-Control Cohort Study.

To investigate the association between the use of nonselective or cyclooxygenase (COX)-2-selective nonsteroidal antiinflammatory drugs (NSAIDs) and risk of acute kidney injury (AKI) in a general Asian population. We conducted an observational, nationwide, nested case-control cohort study using Taiwan's National Health Insurance Research Database between 2010 and 2012. AKI cases were defined as hospitalization with a principle diagnosis of AKI. Each case was matched to 4 randomly selected controls based on age, sex, and the month and year of cohort entry. Odds ratios (ORs) were used to demonstrate the association between hospitalization for AKI and current, recent, or past use of an oral NSAID. During the study period, we identified 6199 patients with AKI and 24,796 matched controls. Overall, current users (adjusted OR 2.73, 95% confidence interval [CI] 2.28-3.28) and recent users (adjusted OR 1.17, 95% CI 1.01-1.35) were associated with increased risk of hospitalization for AKI. The risk was also similar for nonselective NSAIDs. However, neither current nor recent use of COX-2 inhibitors was significantly associated with AKI events. Our study supported that the initiation of nonselective NSAIDs rather than COX-2 inhibitors is associated with an increased risk of AKI requiring hospitalization. Future randomized trials are needed to elucidate these findings.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: Data were retrieved from Taiwan's National Health Insurance Research Database during the period between 2000 and 2010 for this retrospective cohort study. The cohorts are composed of patients (age ≥ 20 years) newly diagnosed with SA and matched subjects without SA. The two cohorts were followed until the occurrence of CKD, death or the end of 2010. RESULTS: The sample is composed of 43,434 individuals (8687 patients with SA and 34,747 matched non-SA subjects). A total of 157 new CKD events in patients with SA and 298 events in the matched non-SA cohort were recorded during a mean follow-up period of 3.9 years (incidence rates, 4.5 and 2.2/per 1000 person-years). The risk of CKD development was greater among patients with SA than in the matched non-SA cohort (adjusted hazard ratio (aHR) 1.58, 95% confidence interval ( CI): 1.29-1.94). The contribution of SA to the CKD hazard was similar to that of hypertension (aHR 1.17, 95% CI: 0.68-2.01, P = 0.56), whereas that of diabetes remained significantly higher (aHR 2.17, 95% CI: 1.21-3.90, P = 0.01). CONCLUSION: SA was associated with an increase in the risk of CKD incidence similar to that of hypertension. See article, page 578.

Long-Term Outcomes in Critically Ill Septic Patients Who Survived Cardiopulmonary Resuscitation.

OBJECTIVE: To evaluate the long-term survival rate of critically ill sepsis survivors following cardiopulmonary resuscitation on a national scale. DESIGN: Retrospective and observational cohort study. SETTING: Data were extracted from Taiwan's National Health Insurance Research Database. PATIENTS: A total of 272,897 ICU patients with sepsis were identified during 2000-2010. Patients who survived to hospital discharge were enrolled. Post-discharge survival outcomes of ICU sepsis survivors who received cardiopulmonary resuscitation were compared with those of patients who did not experience cardiopulmonary arrest using propensity score matching with a 1:1 ratio. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Only 7% (n = 3,207) of sepsis patients who received cardiopulmonary resuscitation survived to discharge. The overall 1-, 2-, and 5-year postdischarge survival rates following cardiopulmonary resuscitation were 28%, 23%, and 14%, respectively. Compared with sepsis survivors without cardiopulmonary arrest, sepsis survivors who received cardiopulmonary resuscitation had a greater risk of all-cause mortality after discharge (hazard ratio, 1.38; 95% CI, 1.34-1.46). This difference in mortality risk diminished after 2 years (hazard ratio, 1.11; 95% CI, 0.96-1.28). Multivariable analysis showed that independent risk factors for long-term mortality following cardiopulmonary resuscitation were male sex, older age, receipt of care in a nonmedical center, higher Charlson Comorbidity Index score, chronic kidney disease, cancer, respiratory infection, vasoactive agent use, and receipt of renal replacement therapy during ICU stay. CONCLUSION: The long-term outcome was worse in ICU survivors of sepsis who received in-hospital cardiopulmonary resuscitation than in those who did not, but this increased risk of mortality diminished at 2 years after discharge.