Long-Term Effects of Spironolactone on Kidney Function and Hyperkalemia-Associated Hospitalization in Patients with Chronic Kidney Disease

Background: Spironolactone, a non-selective mineralocorticoid receptor antagonist, can protect against cardiac fibrosis and left ventricular dysfunction, and improve endothelial dysfunction and proteinuria. However, the safety and effects of spironolactone on patient-centered cardiovascular and renal endpoints remain unclear. Methods: We identified predialysis stage 3⁻4 chronic kidney disease (CKD) patients between 2000 and 2013 from the Longitudinal Health Insurance Database 2005 (LHID 2005). The outcomes of interest were end-stage renal disease (ESRD), major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), hyperkalemia-associated hospitalization (HKAH), all-cause mortality and cardiovascular mortality. The Fine and Gray sub-distribution hazards approach was adopted to adjust for the competing risk of death. Results: After the propensity score matching, 693 patients with stage 3⁻4 CKD were spironolactone users and 1386 were nonusers. During the follow-up period, spironolactone users had a lower incidence rate for ESRD than spironolactone non-users (39.2 vs. 53.69 per 1000 person-years) and a higher incidence rate for HKAH (54.79 vs. 18.57 per 1000 person-years). The adjusted hazard ratios for ESRD of spironolactone users versus non-users were 0.66 (95% CI, 0.51⁻0.84; p value < 0.001) and 3.17 (95% CI, 2.41⁻4.17; p value < 0.001) for HKAH. A dose-response relationship was found between spironolactone use and risk of ESRD and HKAH. There were no statistical differences in MACE, HHF, all-cause mortality and cardiovascular mortality between spironolactone users and non-users. Conclusion: Spironolactone represented a promising treatment option to retard CKD progression to ESRD amongst stage 3⁻4 CKD patients, but strategic treatments to prevent hyperkalemia should be enforced

An Inverse Relationship between Hyperuricemia and Mortality in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Background: The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Methods: Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 ± 15.3 years, with 52% being female (n = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus (n = 179, 34.6%), hypertension (n = 419, 85.2%), and cardiovascular disease (n = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Results: Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24⁻0.68, p = 0.001), 0.4 (95% CI 0.2⁻0.81, p = 0.01), and 0.47 (95% CI 0.19⁻1.08, p = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69⁻0.9, p = 0.07), 0.79 (95% CI, 0.61⁻1.01, p = 0.06), and 0.79 (95% CI, 0.48⁻1.21, p = 0.32) for men and 0.57 (95% CI, 0.44⁻0.73, p < 0.001), 0.6 (95% CI, 0.41⁻0.87, p = 0.006), and 0.41 (95% CI, 0.26⁻0.6, p < 0.001) for women, respectively. Conclusions: Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis

Menopausal symptoms and risk of coronary heart disease in middle-aged women: A nationwide population-based cohort study.

OBJECTIVE:To assess the relationship between coronary heart disease (CHD) and menopausal symptoms in middle-aged women in Taiwan. PATIENTS AND METHODS:The present study identified 14,340 symptomatic menopausal women without a history of CHD from the Taiwan National Health Insurance Research Database from January 1, 2000, to December 31, 2013. A total of 14,340 age- and Charlson-comorbidity-index-score-matched asymptomatic women were used as controls. Possible comorbidity-attributable risks of CHD were surveyed to assess whether the symptomatic menopausal cohort had a higher incidence of CHD. RESULTS:The incidence of CHD was higher in the symptomatic menopausal cohort than in the control cohort (17.18 vs. 12.05 per 1000 person-years). After adjustment in multivariate Cox analysis, the risk of CHD was significantly higher in the symptomatic menopausal cohort (adjusted hazard ratio = 1.344, 95% confidence interval [CI] = 1.262-1.43, P < 0.001) than in the control cohort. In the symptomatic menopausal cohort, the risk of CHD was significantly higher in all subgroups, except for the hormone therapy (HT) subgroup. Patients undergoing HT had a nonsignificantly higher risk of CHD, regardless of the presence or absence of menopausal symptoms. CONCLUSION:This large-scale longitudinal retrospective cohort study revealed that menopausal symptoms are an independent risk factor for CHD. Moreover, our findings indicate that HT has a nonsignificant effect on the risk of CHD

Serum globulin is a novel predictor of mortality in patients undergoing peritoneal dialysis

Abstract Serum globulin, which is composed mainly of immunoglobulins and acute phase proteins, can be considered as reflecting the inflammatory state. We conducted the present study to investigate the role of globulin in mortality risk in patients undergoing peritoneal dialysis (PD). The study participants were categorized by the median globulin value (2.8 g/dL) as the high globulin group (≥ 2.8 g/dL), and low globulin group (< 2.8 g/dL). Serum globulin is calculated by the equation: (serum total protein-serum albumin). The area under the curve (AUC) by the receiver operating characteristics curve analysis was calculated to compare the mortality prediction capacity of globulin with that of ferritin, and WBC counts. Among the 554 patients, 265 (47.83%) were men, the mean age was 52.91 ± 15.54 years and the body mass index was 23.44 ± 3.88 kg/m2. Multivariate Cox models showed the high globulin group had higher mortality risks of all-cause and cardiovascular disease (CVD), compared with the low globulin group with adjusted HRs of 2.06 (95% CI 1.39–3.05) and 1.94 (95% CI 1.18–3.16), respectively. The AUC of univariate and multivariate models for all-cause mortality resulted in higher AUC values for globulin than for ferritin and white blood cell (WBC) counts. In patients undergoing PD, the serum globulin can serve as a novel and independent determinant of predicting overall and CVD- associated mortality

Effects of Prevalent and Incident Chronic Kidney Disease on Cardiovascular Events in Patients with Atrial Fibrillation

Background: Chronic kidney disease (CKD) is a well-known complication of atrial fibrillation (AF) but how the incident CKD affects the clinical outcomes amongst AF patients is not clear. Methods: Our study data were retrieved from National Health Insurance Research Data for the period from 1996 to 2013. Incident AF patients were classified as non-CKD group (n = 7272), prevalent CKD group (n = 2104), and incident CKD group (n = 1507) based on administrative codes. Patients with prevalent CKD were those participants who already had CKD ahead of the index date of AF, whereas patients with incident CKD were those who developed CKD after the index date and the remaining patients were designated as non-CKD. Multivariate-adjusted time-dependent Cox models were conducted to estimate the associations of CKD status with the outcomes of interest, including heart failure (HF), acute myocardial infarction (AMI), stroke or systemic thromboembolism, all-cause mortality, and cardiovascular (CV) mortality, expressed as hazard ratio (HR) and 95% confidence interval (CI). Results: The mean age was 70.8 &plusmn; 13.3 years, and 55.4% of the studied population were men. In Cox models, the adjusted rate of HF, AMI, all-cause mortality, and CV mortality was greater in the prevalent and incident CKD groups, ranging from 1.31-fold to 4.28-fold, compared with non-CKD group. Notably, incident CKD was associated with higher rates of HF (HR, 1.8; 95% CI, 1.67&ndash;1.93), stroke or systemic thromboembolism (HR, 1.33; 95% CI, 1.22&ndash;1.45), AMI (HR, 1.46; 95% CI, 1.25&ndash;1.71), all-cause mortality (HR, 1.76; 95% CI, 1.68&ndash;1.85), and CV mortality (HR, 2.13; 95% CI, 1.92&ndash;2.36) compared with prevalent CKD. Conclusion: The presence of CKD was associated with higher risks of subsequent adverse clinical outcomes in patients with AF. Our study was even highlighted by the finding that incident CKD was linked to higher risks of outcome events compared with prevalent CKD

Self-monitoring of blood glucose in association with glycemic control in newly diagnosed non-insulin-treated diabetes patients: a retrospective cohort study

Abstract The benefits of self-monitoring of blood glucose (SMBG) on glycemic control among type 2 diabetes (T2DM) patients not receiving insulin remains controversial. This study aimed to examine the association between SMBG and glycemic control in these patients. This retrospective longitudinal study enrolled 4987 eligible patients from a medical center in Taiwan. Data were collected from electronic medical records at 0 (baseline), 3, 6, 9, and 12 (end-point) months after enrollment. Patients were assigned to the early SMBG group or to the non-user group depending on whether they performed SMBG at baseline. Differences in glycated hemoglobin (HbA1c) reduction between groups at each time-point were assessed using SMBG group-by-time interaction in generalized estimating equations models, which were established using backward elimination method for multivariate regression analysis. Subgroup analyses for patients using non-insulin and insulin secretagogues were performed additionally. The estimated maximal difference in HbA1c reduction between groups (early SMBG users vs. non-users) was 0.55% at 3 months. Subgroup analyses showed maximal differences of 0.61% and 0.52% at 3 months in the non-insulin and insulin secretagogues groups, respectively. SMBG group-by-time interaction was statistically significant at 3 months and lasted for 12 months. The finding suggests that performing SMBG at disease onset was positively associated with better glycemic control in newly diagnosed non-insulin-treated T2DM patients, regardless whether non-insulin secretagogues or insulin secretagogues were used

Ventilator Parameters in the Diagnosis and Prognosis of Acute Respiratory Distress Syndrome in Postoperative Patients: A Preliminary Study

This study investigated the usefulness of ventilator parameters in the prediction of development and outcome of acute respiratory distress syndrome (ARDS) in postoperative patients with esophageal or lung cancer on admission to the surgical intensive care unit (SICU). A total of 32 post-operative patients with lung or esophageal cancer from SICU in a tertiary medical center were retrospectively analyzed. The study patients were divided into an ARDS group (n = 21) and a non-ARDS group (n = 11). The ARDS group contained the postoperative patients who developed ARDS after lung or esophageal cancer surgery. The ventilator variables were analyzed in this study. Principal component analysis (PCA) was performed to reduce the correlated ventilator variables to a small set of variables. The top three ventilator variables with large coefficients, as determined by PCA, were considered as sensitive variables and included in the analysis model based on the rule of 10 events per variable. Firth logistic regression with selective stepwise elimination procedure was performed to identify the most important predictors of morbidity and mortality in patients with ARDS. Ventilator parameters, including rapid shallow breath index during mechanical ventilation (RSBIv), rate pressure product of ventilation (RPPv), rate pressure volume index (RPVI), mechanical work (MW), and inspiration to expiration time ratio (IER), were analyzed in this study. It was found that the ARDS patients had significantly greater respiratory rate (RR), airway resistance (Raw), RSBIv, RPPv, RPVI, positive end-expiratory pressure (PEEP), and IER and significantly lower respiratory interval (RI), expiration time (Te), flow rate (V˙), tidal volume (VT), dynamic compliance (Cdyn), mechanical work of ventilation (MW), and MW/IER ratio than the non-ARDS patients. The non-survivors of ARDS had significantly greater peak inspiratory pressure above PEEP (PIP), RSBIv, RPPv, and RPVI than the survivors of ARDS. By using PCA, the MW/IER was found to be the most important predictor of the development of ARDS, and both RPPv and RPVI were significant predictors of mortality in patients with ARDS. In conclusion, some ventilator parameters, such as RPPv, RPVI, and MW/IER defined in this study, can be derived from ventilator readings and used to predict the development and outcome of ARDS in mechanically ventilated patients on admission to the SICU

Impact of age at appendectomy on development of type 2 diabetes: A population-based cohort study.

AIM:Diabetes is a complex metabolic disease characterized by chronic low-grade inflammation in which genetic and environmental factors are involved. Growing evidence implicates that alterations of the gut microbiota potentially contribute to the emergence of metabolic diseases. The human appendix has more recently been recognized as a microbial reservoir for repopulating the gastrointestinal tract and an important part of the immune system. Thus, appendectomy may influence microbial ecology and immune function. This study investigated the association between appendectomy and type 2 diabetes risk. METHODS:We analyzed a cohort of 10954 patients who underwent appendectomy between 1998 and 2013 based on the Taiwan National Health Insurance Program database. A comparison cohort of 43815 persons without appendectomy was selected randomly and matched by sex, age, comorbidities, and index year. To ensure reliability of the results, a sensitivity analysis using a propensity score-matched study was performed. We observed the subsequent development of type 2 diabetes in both cohorts. RESULTS:Although the overall incidence of type 2 diabetes in the appendectomy patients was 7.9% higher than that in the non-appendectomy patients, it was not statistically significant (95% confidence interval [CI], 0.997-1.168) after the adjustment of confounding factors. Multivariate regression analysis revealed that the adjusted hazard ratio (HR) of type 2 diabetes was 1.347 for appendectomy patients < 30 years of age (95% CI, 1.009-1.798) compared to non-appendectomy patients. The incidence of type 2 diabetes was higher within 3 years of post-appendectomy follow-up than for non-appendectomy patients (HR, 2.017; 95% CI, 1.07-3.802). Age impacted the association between appendectomy and type 2 diabetes risk (Pinteraction = 0.002); in contrast, sex did not affect the association between appendectomy and type 2 diabetes risk (Pinteraction = 0.88). CONCLUSIONS:Our study results suggest that appendectomy increases type 2 diabetes risk, particularly when performed prior to middle age

The Predictive Role of Red Cell Distribution Width in Mortality among Chronic Kidney Disease Patients.

Recently, accumulating evidence has demonstrated that RDW independently predicts clinically important outcomes in many populations. However, the role of RDW has not been elucidated in chronic kidney disease (CKD) patients. We conducted the present study with the aim to evaluate the predictive value of RDW in CKD patients.A retrospective observational cohort study of 1075 stage 3-5 CKD patients was conducted in a medical center. The patients' baseline information included demographic data, laboratory values, medications, and comorbid conditions. The upper limit of normal RDW value (14.9%) was used to divide the whole population. Multivariate Cox regression analysis was used to determine the independent predictors of mortality.Of the 1075 participants, 158 patients (14.7%) died over a mean follow-up of approximately 2.35 years. The crude mortality rate was significantly higher in the high RDW group (high RDW group, 22.4%; low RDW group 11%, p <0.001). From the adjusted model, the high RDW group was correlated with a hazard ratio of 2.19 for overall mortality as compared with the low RDW group (95% CI = 1.53-3.09, p<0.001). In addition, the high RDW group was also associated with an increased risk for cardiovascular disease (HR = 2.28, 95% CI = 1.14-4.25, p = 0.019) and infection (HR = 1.9, 95% CI = 1.15-3.14, p = 0.012)) related mortality in comparison with the low RDW group.In stage 3-5 CKD patients, RDW was associated with patient mortality of all-cause, cardiovascular disease and infection. RDW should be considered as a clinical predictor for mortality when providing healthcare to CKD patients

Explainable Machine Learning Model for Predicting First-Time Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease

Background: The study developed accurate explainable machine learning (ML) models for predicting first-time acute exacerbation of chronic obstructive pulmonary disease (COPD, AECOPD) at an individual level. Methods: We conducted a retrospective case&ndash;control study. A total of 606 patients with COPD were screened for eligibility using registry data from the COPD Pay-for-Performance Program (COPD P4P program) database at Changhua Christian Hospital between January 2017 and December 2019. Recursive feature elimination technology was used to select the optimal subset of features for predicting the occurrence of AECOPD. We developed four ML models to predict first-time AECOPD, and the highest-performing model was applied. Finally, an explainable approach based on ML and the SHapley Additive exPlanations (SHAP) and a local explanation method were used to evaluate the risk of AECOPD and to generate individual explanations of the model&rsquo;s decisions. Results: The gradient boosting machine (GBM) and support vector machine (SVM) models exhibited superior discrimination ability (area under curve [AUC] = 0.833 [95% confidence interval (CI) 0.745&ndash;0.921] and AUC = 0.836 [95% CI 0.757&ndash;0.915], respectively). The decision curve analysis indicated that the GBM model exhibited a higher net benefit in distinguishing patients at high risk for AECOPD when the threshold probability was &lt;0.55. The COPD Assessment Test (CAT) and the symptom of wheezing were the two most important features and exhibited the highest SHAP values, followed by monocyte count and white blood cell (WBC) count, coughing, red blood cell (RBC) count, breathing rate, oral long-acting bronchodilator use, chronic pulmonary disease (CPD), systolic blood pressure (SBP), and others. Higher CAT score; monocyte, WBC, and RBC counts; BMI; diastolic blood pressure (DBP); neutrophil-to-lymphocyte ratio; and eosinophil and lymphocyte counts were associated with AECOPD. The presence of symptoms (wheezing, dyspnea, coughing), chronic disease (CPD, congestive heart failure [CHF], sleep disorders, and pneumonia), and use of COPD medications (triple-therapy long-acting bronchodilators, short-acting bronchodilators, oral long-acting bronchodilators, and antibiotics) were also positively associated with AECOPD. A high breathing rate, heart rate, or systolic blood pressure and methylxanthine use were negatively correlated with AECOPD. Conclusions: The ML model was able to accurately assess the risk of AECOPD. The ML model combined with SHAP and the local explanation method were able to provide interpretable and visual explanations of individualized risk predictions, which may assist clinical physicians in understanding the effects of key features in the model and the model&rsquo;s decision-making process