Recovery Dynamics and Prognosis After Dialysis for Acute Kidney Injury.

Importance: The interplay among baseline kidney function, severity of acute kidney disease (AKD), and post-AKD kidney function has significant associations with patient outcomes. However, a comprehensive understanding of how these factors are collectively associated with mortality, major adverse cardiac events (MACEs), and end-stage kidney disease (ESKD) in patients with dialysis-requiring acute kidney injury (AKI-D) is yet to be fully explored. Objective: To investigate the associations of baseline kidney function, AKD severity, and post-AKD kidney function with mortality, MACEs, and ESKD in patients with AKI-D. Design, Setting, and Participants: This nationwide, population-based cohort study of patients with AKI-D was conducted between January 1, 2015, and December 31, 2018, using data from various health care settings included in the Taiwan nationwide population-based cohort database. Data analysis was conducted from April 28, 2022, to June 30, 2023. Exposure: Exposure to severe AKI and baseline and post-AKD kidney function. Main Outcomes and Measures: The primary outcomes were all-cause mortality and incident MACEs, and secondary outcomes were risks of permanent dialysis and readmission. Results: A total of 6703 of 22 232 patients (mean [SD] age, 68.0 [14.7] years; 3846 [57.4%] male) with AKI-D with post-AKD kidney function follow-up and AKD stage data were enrolled. During a mean (SD) 1.2 (0.9) years of follow-up, the all-cause mortality rate was 28.3% (n = 1899), while the incidence rates of MACEs and ESKD were 11.1% (n = 746) and 16.7% (n = 1119), respectively. After adjusting for known covariates, both post-AKD kidney function and baseline kidney function, but not AKD severity, were independently associated with all-cause mortality, MACEs, ESKD, and readmission. Moreover, worse post-AKD kidney function correlated with progressive and significant increases in the risk of adverse outcomes. Conclusions and Relevance: In this cohort study of patients with AKI-D, more than one-quarter of patients died after 1.2 years of follow-up. Baseline and post-AKD kidney functions serve as important factors associated with the long-term prognosis of patients with AKI-D. Therefore, concerted efforts to understand the transition from post-AKD to chronic kidney disease are crucial.

Percutaneous Coronary Intervention With a Drug-Eluting Stent Versus Coronary Artery Bypass Grafting in Patients Receiving Dialysis: A National Study From Taiwan.

Rationale & Objective: We aimed to study the comparative effectiveness of percutaneous coronary intervention with drug-eluting stent and coronary artery bypass grafting in patients receiving dialysis. Study Design: This was a retrospective observational cohort study. Setting & Participants: This population-based study identified patients receiving dialysis hospitalized for coronary revascularization between January 1, 2009 and December 31, 2015, in the Taiwan National Health Insurance Research Database. Exposures: Patients received percutaneous coronary intervention with drug-eluting stent versus coronary artery bypass grafting. Outcomes: The study outcomes were all-cause mortality, in-hospital mortality, and repeat revascularization. Analytical Approach: Propensity scores were used to match patients. Cox proportional hazards models and logistic regression models were constructed to examine associations between revascularization strategies and mortality. Interval Cox models were fitted to estimate time-varying hazards during different periods. Results: A total of 1,840 propensity score-matched patients receiving dialysis were analyzed. Coronary artery bypass grafting was associated with higher in-hospital mortality (coronary artery bypass grafting vs percutaneous coronary intervention with drug-eluting stent; crude mortality rate 12.5% vs 3.3%; adjusted OR, 5.22; 95% CI, 3.42-7.97; P < 0.001) and longer hospitalization duration (median [IQR], 20 [14-30] days vs 3 [2-8] days; P < 0.001). After discharge, repeat revascularization, acute coronary syndrome, and repeat hospitalization all occurred more frequently in the percutaneous coronary intervention with drug-eluting stent group. Importantly, with a median follow-up of 2.8 years, coronary artery bypass grafting was significantly associated with a higher risk of all-cause overall mortality (adjusted HR, 1.19; 95% CI, 1.05-1.35; P = 0.006) in the multivariable Cox proportional hazard model. Sensitivity and subgroup analyses yielded consistent results. Limitations: This was an observational study with mainly Asian ethnicity. Conclusions: Percutaneous coronary intervention with drug-eluting stent may be associated with better survival than coronary artery bypass grafting in patients receiving dialysis. Future studies are warranted to confirm this finding.

Although coronary artery bypass grafting offers better long-term survival in the general population than percutaneous coronary intervention with drug-eluting stent, patients receiving dialysis may be too frail to tolerate the increased perioperative mortality risk of coronary artery bypass grafting. In this retrospective study in a national cohort of patients receiving dialysis from Taiwan, percutaneous coronary intervention with drug-eluting stent is associated with lower in-hospital mortality and better long-term survival when compared with coronary artery bypass grafting. Subsequent acute coronary syndrome, repeat revascularization, and rehospitalization were noted more frequently in the percutaneous coronary intervention with drug-eluting stent group. These findings may suggest percutaneous coronary intervention with drug-eluting stent as a safe revascularization strategy for patients receiving dialysis.

Premorbid use of selective beta-blockers improves sepsis incidence and course: Human cohort and animal model studies.

Introduction: Beta-blockers are widely prescribed to manage hypertension and cardiovascular diseases and have been suggested as an attractive therapy to improve the prognosis of sepsis. Herein, we investigated the potential benefits of premorbid selective beta-blocker use in sepsis with a real-world database and explored the underlying mechanism by in vivo and in vitro experiments. Methods: A total of 64,070 sepsis patients and 64,070 matched controls who were prescribed at least one anti-hypertensive drug for more than 300 days within 1 year were selected for the nested case-control study. Female C57BL/6 J mice and THP-1 cells stimulated with lipopolysaccharide (LPS) were used for studying systemic responses during sepsis to validate our clinical findings. Results: The risk of sepsis was lower in current selective beta-blocker users than in non-users (adjusted OR (aOR), 0.842; 95% CI, 0.755-0.939), and in recent users than in non-users (aOR, 0.773; 95% CI, 0.737-0.810). A mean daily dose of ≥0.5 DDD was associated with a lower risk of sepsis (aOR, 0.7; 95% CI, 0.676-0.725). Metoprolol, atenolol, and bisoprolol users had lower risk of sepsis than non-users. In a LPS-induced sepsis mouse model, mice pre-fed with atenolol had significantly reduced mortality. While atenolol had some mild effects on LPS-induced release of inflammatory cytokines in septic mice, it significantly reduced serum soluble PD-L1 levels. Notably, atenolol treatment reversed the negative correlation of sPD-L1 with inflammatory cytokines in septic mice. Moreover, atenolol markedly downregulated the PD-L1 expression on LPS-stimulated THP-1 monocytes/macrophages via targeting ROS-induced NF-κB and STAT3 activation. Conclusion: Atenolol pretreatment can reduce sepsis mortality in mice, and in vivo and in vitro studies of PD-L1 expression suggest a role for atenolol in the modulation of immune homeostasis. These findings may contribute to the reduced incidence of sepsis in hypertensive patients with premorbid treatment with selective beta-blockers, especially atenolol.

Incidence, subtypes, sex differences and trends of stroke in Taiwan.

BACKGROUND: Chinese populations have been reported higher incidence of all strokes and intracerebral hemorrhage. However, few large-scale studies have evaluated changes of stroke epidemiology in the 21st century. METHODS: We explored the rates of incidence of all first-ever strokes, subtypes, and 1-month case fatality by using data from the Taiwan National Health Insurance Research Database since 2004. Also, we investigated sex differences in stroke. Time-trend analysis was performed for incidence and case fatality rates of all strokes and subtypes in both sexes. RESULTS: The age-adjusted incidence of all strokes per 100,000 person-years decreased by 16%, from 251 (95% confidence interval [CI] 249-253) in 2004 to 210 (95% CI 209-212) in 2011 (p<0.001); it was always higher in Chinese men than in women. Among pathological subtypes, the incidence of intracerebral hemorrhage markedly decreased by 26% over the years (p<0.001), while that of ischemic stroke slightly decreased by 8%. However, when stratified by sex, the incidence of ischemic stroke decreased significantly in only women, not in men (men: p = 0.399, women: p = 0.004). Regarding the incidence of subarachnoid hemorrhage, it remained unchanged. Furthermore, the rate of 1-month case fatality decreased significantly for all strokes in both sexes (p<0.001). CONCLUSIONS: In Taiwan, the incidence rate of first-ever stroke decreased in both Chinese men and women in the early 21st century. Men had a higher incidence rate than women. Furthermore, a marked decrease was noted in the incidence of intracerebral hemorrhage, while a slight decrease was noted in that of ischemic stroke; however, the decreased incidence of ischemic stroke was significant in only women.

Angiotensin II Receptor Blocker Associated With Less Outcome Risk in Patients With Acute Kidney Disease.

Objective: The aim of this study was to explore the respective use of angiotensin-converting-enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) on the outcomes of patients who could be weaned from dialysis-requiring acute kidney injury (AKI-D). Methods: This case-control study enrolled 41,731 patients who were weaned from AKI-D for at least 7 days from Taiwan's National Health Insurance Administration. We further grouped AKI-D patients according to ACEi and ARB use to evaluate subsequent risks of all-cause mortality and re-dialysis. The outcomes included the all-cause mortality and new-onset of end-stage kidney disease (ESKD; re-dialysis) following withdraw from AKI-D. Results: A total of 17,141 (41.1%) patients surviving AKI-D could be weaned from dialysis for at least 7 days. The overall events of mortality were 366 (48.9%) in ACEi users, 659 (52.1%) in ARB users, and 6,261 (41.3%) in ACEi/ARB nonusers, during a mean follow-up period of 1.01 years after weaning from AKI-D. In regard to all-cause of mortality, pre-dialysis ARB users had lower incidence than ACEi users [hazard ratio (HR 0.82), p = 0.017]. Compared with ACEi/ARB nonusers, continuing ARB users had a significantly low risk of long-term all-cause mortality (adjusted hazard ratio 0.51, p = 0.013) after propensity score matching. However, new users of ACEi at the acute kidney disease (AKD) period had a higher risk of re-dialysis after weaning than ACEi/ARB nonusers (aHR 1.82, p < 0.001), whereas neither ACEi nor ARB users confronted significantly increased risks of hyperkalemia after weaning. Conclusions: Compared with patients without ACEi/ARB, those continuing to use ARB before the event and after weaning had low all-cause mortality, while new users of ACEi at AKD had increased risk of re-dialysis. AKI-D patients continuing to use ACEi or ARB did not have higher risk of hyperkalemia. Future prospective randomized trials are expected to confirm these findings.

Dynamic Changes in Prognosis with Elapsed Time on Ventilators among Mechanically Ventilated Patients.

Rationale: Previous outcome studies of mechanical ventilation usually adopted a static timeframe to observe the outcome and reported prognosis from the standpoint of the first ventilator day. However, patients and their families may repeatedly inquire about prognosis over time after the initiation of mechanical ventilation.Objectives: We aimed to describe dynamic changes in prognosis according to the elapsed time on a ventilator among mechanically ventilated patients.Methods: For this cohort study we used the entire population dataset of Taiwan's National Health Insurance database. We enrolled adults who newly received invasive mechanical ventilation for at least two consecutive days between March 1, 2010, and August 31, 2011. For every single ventilator day after the initiation of mechanical ventilation, we estimated the cumulative probabilities of weaning success and death in the subsequent 90 days.Results: A total of 162,200 episodes of respiratory failure requiring invasive mechanical ventilation were included. The median age of the subjects was 72 years (interquartile range 57-81 yr) and the median follow-up time was 250 days (interquartile range 30-463 d). The probability curve of weaning success against the time on ventilation showed a unidirectionally decreasing trend, with a relatively sharp slope in the initial 2 months. The probabilities of weaning success in 90 days after the 2nd, 7th, 21st, and 60th ventilator days were 68.3% (95% confidence interval [CI], 68.1-68.5%), 62.6% (95% CI, 62.2-62.9%), 46.3% (95% CI, 45.8-46.8%), and 21.0% (95% CI, 20.3-21.8%), respectively. In contrast, the death curve showed an initial increase and then a decreasing trend after the 19th ventilator day. We also reported tailored prognosis information according to the age, sex, and ventilator day of a mechanically ventilated patient.Conclusions: This study provides ventilator-day-specific prognosis information obtained from a large cohort of unselected patients on invasive mechanical ventilation. The probability of weaning success decreased with the elapsed time on mechanical ventilation, and the decline was particularly remarkable in the first 2 months of ventilatory support.

The secular trends in the incidence rate and outcomes of out-of-hospital cardiac arrest in Taiwan--a nationwide population-based study.

OBJECTIVE: This study investigated the trends in incidence and mortality of out-of-hospital cardiac arrest (OHCA), as well as factors associated with OHCA outcomes in Taiwan. METHODS: Our study included OHCA patients requiring cardiopulmonary resuscitation (CPR) upon arrival at the hospital. We used national time-series data on annual OHCA incidence rates and mortality rates from 2000 to 2012, and individual demographic and clinical data for all OHCA patients requiring mechanical ventilation (MV) care from March of 2010 to September of 2011. Analytic techniques included the time-series regression and the logistic regression. RESULTS: There were 117,787 OHCAs in total. The overall incidence rate during the 13 years was 51.1 per 100,000 persons, and the secular trend indicates a sharp increase in the early 2000s and a decrease afterwards. The trend in mortality was also curvilinear, revealing a substantial increase in the early 2000s, a subsequent steep decline and finally a modest increase. Both the 30-day and 180-day mortality rates had a long-term decreasing trend over the period (p<0.01). For both incidence and mortality rates, a significant second-order autoregressive effect emerged. Among OHCA patients with MV, 1-day, 30-day and 180-day mortality rates were 31.3%, 75.8%, and 86.0%, respectively. In this cohort, older age, the female gender, and a Charlson comorbidity index score ≥ 2 were associated with higher 180-day mortality; patients delivered to regional hospitals and those residing in non-metropolitan areas had higher death risk. CONCLUSIONS: Overall, both the 30-day and the 180-day mortality rates after OHCA had a long-term decreasing trend, while the 1-day mortality had no long-term decline. Among OHCA patients requiring MV, those delivered to regional hospitals and those residing in non-metropolitan areas tended to have higher mortality, suggesting a need for effort to further standardize and improve in-hospital care across hospitals and to advance pre-hospital care in non-metropolitan areas.

Idiopathic pulmonary fibrosis in Taiwan - a population-based study.

BACKGROUND: This study took advantage of a large population-based database of the Taiwan National Health Insurance (NHI) to investigate the epidemiology of idiopathic pulmonary fibrosis (IPF) in Taiwan. METHODS: This is a retrospective cohort study based on secondary analysis of prospectively collected data in the NHI system and governmental data on death registry in Taiwan during 1997-2007. By using the broad and narrow definitions for IPF, we estimated incidence and prevalence rates of IPF, and its associated clinical outcomes. RESULTS: The estimates of annual IPF incidence rates became more stable after 2000, ranging between 0.9 and 1.6 cases per 100,000 persons. The prevalence rates became more than twofold from 2000 to 2007 (from 2.8 to 6.4 cases per 100,000 persons for the broad definition, and from 2.0 to 4.9 cases per 100,000 persons for the narrow definition). Men of age older than 75 years had markedly higher incidence and prevalence rates than other groups. Around 40% of all incidences and about 30% of prevalent cases occurred in this population group. The median survival time after IPF diagnosis was 0.9 year (interquartile range (IQR), 0.2-2.5 years) and 0.7 year (IQR, 0.1-2.3 years) for the broad and narrow definitions, respectively. Progression of IPF was the leading cause of death, followed by cancer. CONCLUSIONS: In Taiwan, elderly men were the major group suffering from IPF. Survival time was short after IPF diagnosis, and the poor survival was largely attributable to quick IPF progression after diagnosis.

Imputed food insecurity as a predictor of disease and mental health in Taiwanese elementary school children.

This study investigated the association between food insecurity and Taiwanese children's ambulatory medical care use for treating eighteen disease types linked to endocrine and metabolic disorders, nutrition, immunity, infections, asthma, mental health, injury, and poisoning. We used longitudinal data in the Taiwan National Health Insurance scheme (NHI) for 764,526 elementary children, and employed approximate NHI data to construct three indicators imputed to food insecurity: low birth weight status, economic status (poverty versus non-poverty), and time of year (summer break time versus semester time). We compared ambulatory care for these diseases between children with low birth weight and those not, and between children living in poverty and those not. A difference-in-differences method was adopted to examine the potential for a publicly- funded lunch program to reduce the harmful health effects of food insecurity on poor children. We found that children in poverty were significantly more likely to have ambulatory visits linked with diabetes, inherited disorders of metabolism, iron deficiency anemias, ill-defined symptoms concerning nutrition, metabolism and development, as well as mental disorders. Children with low birth weight also had a significantly higher likelihood of using care for other endocrine disorders and nutritional deficiencies, in addition to the above diseases. The study failed to find any significant effect of the semester school lunch program on alleviating the harmful health effects of food insecurity for poor children, suggesting that a more intensive food program or other program approaches might be required to help poor children overcome food insecurity and its related health outcomes.