An Approach for Personalized Dynamic Assessment of Chronic Kidney Disease Progression Using Joint Model.

Chronic kidney disease (CKD) poses significant challenges to public health and healthcare systems, demanding a comprehensive understanding of its progressive nature. Prior methods have often fallen short in capturing the dynamic and individual variability of renal function. This study aims to address this gap by introducing a novel approach for the individualized assessment of CKD progression. A cohort of 1042 patients, comprising 700 with stage 3a and 342 with stage 3b to stage 5 CKD, treated at a veteran general hospital in Taiwan from 2006 to 2019, was included in the study. A comprehensive dataset spanning 12 years, consisting of clinical measurements, was collected and analyzed using joint models to predict the progression to hemodialysis treatment. The study reveals that the estimated glomerular filtration rate (eGFR) can be considered an endogenous factor influenced by innate biochemical markers. Serum creatinine, blood pressure, and urinary protein excretion emerged as valuable factors for predicting CKD progression. The joint model, combining longitudinal and survival analyses, demonstrated predictive versatility across various CKD severities. This innovative approach enhances conventional models by concurrently incorporating both longitudinal and survival analyses and provides a nuanced understanding of the variables influencing renal function in CKD patients. This personalized model enables a more precise assessment of renal failure risk, tailored to each patient's unique clinical profile. The findings contribute to improving the management of CKD patients and provide a foundation for personalized healthcare interventions in the context of renal diseases.

Improved Survival Analyses Based on Characterized Time-Dependent Covariates to Predict Individual Chronic Kidney Disease Progression.

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 497 patients with stage 3-5 chronic kidney disease (CKD) who were treated at the ward of Taipei Veterans General Hospital from January 2006 to 2019 in Taiwan. The patients underwent 3-year-long follow-up sessions for clinical measurements, which occurred every 3 months. Three time-dependent survival models, namely the Cox proportional hazard model (Cox PHM), random survival forest (RSF), and an artificial neural network (ANN), were used to process patient demographics and laboratory data for predicting progression to renal failure, and important features for optimal prediction were evaluated. The individual prediction of CKD progression was validated using the Kaplan-Meier estimation method, based on patients' true outcomes during and beyond the study period. The results showed that the average concordance indexes for the cross-validation of the Cox PHM, ANN, and RSF models were 0.71, 0.72, and 0.89, respectively. RSF had the best predictive performances for CKD patients within the 3 years of follow-up sessions, with a sensitivity of 0.79 and specificity of 0.88. Creatinine, age, estimated glomerular filtration rate, and urine protein to creatinine ratio were useful factors for predicting the progression of CKD patients in the RSF model. These results may be helpful for instantaneous risk prediction at each follow-up session for CKD patients.

Novel Application of Multiscale Cross-Approximate Entropy for Assessing Early Changes in the Complexity between Systolic Blood Pressure and ECG R-R Intervals in Diabetic Rats.

Cardiac autonomic neuropathy (CAN) is a common complication of diabetes mellitus, and can be assessed using heart rate variability (HRV) and the correlations between systolic blood pressure (SBP) and ECG R-R intervals (RRIs), namely baroreflex sensitivity (BRS). In this study, we propose a novel parameter for the nonlinear association between SBP and RRIs based on multiscale cross-approximate entropy (MS-CXApEn). Sixteen male adult Wistar Kyoto rats were equally divided into two groups: streptozotocin-induced diabetes and age-matched controls. RRIs and SBP were acquired in control rats and the diabetic rats at the onset of hyperglycemia and insulin-treated euglycemia to determine HRV by the ratio of low-frequency to high-frequency power (LF/HF) and Poincaré plot as SSR (SD1/SD2), BRS, and MS-CXApEn. SSR and BRS were not significantly different among the three groups. The LF/HF was significantly higher in the hyperglycemic diabetics than those in the controls and euglycemic diabetic rats. MS-CXApEn was higher in the diabetic hyperglycemic rats than the control rats from scales 2 to 10, and approached the values of controls in diabetic euglycemic rats at scales 9 and 10. Conclusions: We propose MS-CXApEn as a novel parameter to quantify the dynamic nonlinear interactions between SBP and RRIs that reveals more apparent changes in early diabetic rats. Furthermore, changes in this parameter were related to correction of hyperglycemia and could be useful for detecting and assessing CAN in early diabetes.

Static and Dynamic Prediction of Chronic Renal Disease Progression Using Longitudinal Clinical Data from Taiwan's National Prevention Programs.

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 1042 chronic kidney disease (CKD) patients with Stage 3-5 kidney disease who were treated at a public veteran's hospital through the national prevention program. A total of 12.5 years of records of clinical measurements were collected and analyzed using dynamic and static Cox hazard models to predict the progression to dialysis treatment. The results showed that the statistical significance of several variables in patients with Stage 3-5 CKD was attenuated while the dynamic model was being used. The estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (PCR) had the powerful ability to predict the progression of CKD patients with Stage 3a and Stage 3b-5 kidney disease, whereas serum calcium was also predictive for the progression of Stages 3b-5 CKD. Because these two sub-stages of Stage 3 CKD are often associated with differences in routine measurements and the risk analysis of renal dialysis, future research can use this predictive model as a reference while similar prevention programs are implemented.

Adjusting Quality Control Chart Limits for WBC, RBC, Hb, and PLT Counts to Reduce Daily Control Risks in Hospital Laboratory.

BACKGROUND: To continuously improve medical quality and provide clinicians with more accurate blood test reports, this study collected blood quality control data in 2017 from a medical examination laboratory in a teaching level hospital located in Taoyuan City, Taiwan. MATERIAL AND METHODS: The quality control data were arranged and analyzed from daily complete blood count (CBC), including white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and platelets (PLT) recorded by a laboratory blood analyzer. Using the empirical Bayesian method, we estimated the variation of concentrations of the last and current batches to establish a novel control chart with adjusted upper and lower limits for the current batch, and then compared results with the traditional Shewhart method. The average run length (ARL) and sensitivity of the empirical Bayesian method were explored. RESULTS: The study found that ARL showed a qualified capability for the four blood routine tests when using the empirical Bayesian method. Compared to the Levey-Jennings control chart, the novel control chart presents an alert earlier when a deviation occurs and shows a fake alert later when there is no deviation. CONCLUSION: The parallel tests showed that the longer the time is, the better the test's proficiency. We concluded that the empirical Bayesian method could be applied effectively to improve the capability of daily control in CBC laboratory tests.

Economic fluctuations and cardiovascular diseases: A multiple-input time series analysis.

OBJECTIVES: Little is known about the gender and age differences associated with the effects of economic fluctuations on hospitalization for cardiovascular diseases. This paper investigates the impact of economic fluctuations on hospitalization for ischemic heart disease (IHD), stroke, and hypertension by age and gender between January 1996 and December 2012 in Taiwan. METHODS: We adopted a multiple-input time series analysis to examine the strength of the immediate and latent effects of the 17-year quarterly unemployment rates (UR), air pollution exposure (APE), gross domestic product (GDP), per capita consumption expenditure in cigarette and alcohol (ECA), and per capita healthcare expenditure (HE) on the adjusted quarterly incidence rate of hospitalization. The data used in this paper were retrieved from the National Health Insurance Research Database and the website of the Directorate-General of Budget, Accounting and Statistics (DGBAS), Executive Yuan. RESULTS: Our findings indicate that higher UR increased IHD hospitalization in young men and women and middle-aged women but reduced stroke hospitalization in young men. Higher APE increased IHD hospitalization in young men but reduced it for young women, increased stroke hospitalization in old men and middle-aged women but reduced it for young men, and increased hypertension hospitalization in middle-aged men and young women. Higher ECA reduced IHD hospitalization in middle-aged men, increased stoke hospitalization in middle-aged and old men and middle-aged women. Higher HE reduced IHD hospitalization in old men, young and old women, reduced stroke hospitalization in old women, and reduced hypertension hospitalization in young and middle-aged women. CONCLUSIONS: Overall, we found that the economic fluctuations caused increased harmful effects in certain population subgroups but also brought some soothing effects to some groups.

Life Course Effects of Socioeconomic and Lifestyle Factors on Metabolic Syndrome and 10-Year Risk of Cardiovascular Disease: A Longitudinal Study in Taiwan Adults.

The objective of the study was to explore the dynamic effects of socioeconomic status (SES) and lifestyle behaviors on the risks of metabolic syndrome (MS) or cardiovascular disease (CVD) in life course. The data of 12,825 subjects (6616 males and 6209 females) who underwent repeated examinations and answered repeated questionnaires from 2006 to 2014 at the Major Health Screening Center in Taiwan, was collected and analyzed. The trajectory of trends in the subjects' SES and lifestyle mobility over time was observed, and the effects of factors with potential impacts on health were tested and analyzed using multiple logistic regression and a generalized estimated equation model. A 10% increase in MS prevalence was observed over the nine-year period. The average Framingham CVD score for people with MS was estimated to be about 1.4% (SD = 1.5%). Except for middle-aged women, marriage was found to raise the risk of CVD, whereas increasing education and work promotions independently reduced CVD risk for the majority of subjects. However, the risk of CVD was raised by half for young men who had a job or lost a job in comparison to continuously unemployed young men. Physical activity was only found to be advantageous for disease prevention in those aged less than 40 years; increased exercise levels were useless for reducing CVD risk among older men. Alcohol drinking and betel chewing caused increased CVD risk in the old and young subjects, respectively, whereas vegetarian diets and vitamin C/E intake were helpful in preventing CVD, even if those habits were ceased in later life. For middle-aged women, getting sufficient sleep reduced CVD risk. We concluded that SES and lifestyle behaviors may have different effects on health over time, among various populations. Accordingly, suggestions can be provided to healthcare workers in designing health promotion courses for people at different life stages.

The impacts of the global financial crisis on hospitalizations due to depressive illnesses in Taiwan: A prospective nationwide population-based study.

BACKGROUND: In the third quarter of 2008, a major financial crisis hit many developed countries. Taiwan suffered its own share: a rise in unemployment and a severe decline in gross domestic product. This study is to address the health consequences of this crisis on different socioeconomic populations in Taiwan. METHODS: A sample of 6,225,766 men and 5,417,651 women, was obtained and their admissions data over 2007-2012 were retrieved. Stratified into three income levels, the sample was examined on the 147,921 episodes of hospitalization due to depressive illnesses (DIs) over that period by an interrupted time series analysis for monthly incidence rates of DI hospitalizations RESULTS: The adjusted incidence rates of hospitalization (AIRH) for DIs among the low income were 10 times that of the high income group. The AIRHs were generally higher in all of three female income groups than they were in the three male income groups. The low income men and women showed increases (of 18.0% and 14.2%, respectively) beginning in April 2008 that sustained for two years. The high income women exhibited a 5.0% monthly rise in the rate of DI hospitalizations. LIMITATIONS: Our time series models can control some confounding factors, but the ecological fallacy remained. CONCLUSIONS: This study provides evidence that the economic recession resulted in increased rates of DI hospitalization in Taiwan, especially among the low income population. Women of higher incomes may have suffered a more enduring impact.

The Effects of the Global Economic Recession and a Reduced Alcohol Tax on Hospitalizations Due to Alcohol-Attributed Diseases in Taiwan.

This study is to assess the effects of the 2008 economic crisis and a 2009 alcohol tax reduction on alcohol-related morbidity for men of different socioeconomic statuses in Taiwan. Admissions data for the period from 2007 to 2012 for men aged 24-59 years in 2007 was retrieved from the National Health Insurance Research Database. With stratification over three income levels, an interrupted time-series analysis examining the effects of the crisis and taxation reduction on incidence rates of hospitalization for alcohol-attributed diseases (AADs) was employed. The low income group showed a significant (p < 0.05) change in the rate of AAD-related hospitalizations in July 2008; specifically, an abrupt 7.11% increase that was then sustained for several months thereafter. In contrast, while the middle income group exhibited a significant 22.9% decline in the rate of AAD-related hospitalizations over the course of the crisis, that downward trend was gradual. The reduction of the alcohol tax resulted in increased rates of AADs among both the low and high income groups. The economic recession and the reduction of the alcohol tax resulted in an increased rate of AAD among low income men.

Improvement of the quality of work in a biochemistry laboratory via measurement system analysis.

An adequate and continuous monitoring of operational variations can effectively reduce the uncertainty and enhance the quality of laboratory reports. This study applied the evaluation rule of the measurement system analysis (MSA) method to estimate the quality of work conducted in a biochemistry laboratory. Using the gauge repeatability & reproducibility (GR&R) approach, variations in quality control (QC) data among medical technicians in conducting measurements of five biochemical items, namely, serum glucose (GLU), aspartate aminotransferase (AST), uric acid (UA), sodium (Na) and chloride (Cl), were evaluated. The measurements of the five biochemical items showed different levels of variance among the different technicians, with the variances in GLU measurements being higher than those for the other four items. The ratios of precision-to-tolerance (P/T) for Na, Cl and GLU were all above 0.5, implying inadequate gauge capability. The product variation contribution of Na was large (75.45% and 31.24% in normal and abnormal QC levels, respectively), which showed that the impact of insufficient usage of reagents could not be excluded. With regard to reproducibility, high contributions (of more than 30%) of variation for the selected items were found. These high operator variation levels implied that the possibility of inadequate gauge capacity could not be excluded. The analysis of variance (ANOVA) of GR&R showed that the operator variations in GLU measurements were significant (F=5.296, P=0.001 in the normal level and F=3.399, P=0.015 in the abnormal level, respectively). In addition to operator variations, product variations of Na were also significant for both QC levels. The heterogeneity of variance for the five technicians showed significant differences for the Na and Cl measurements in the normal QC level. The accuracy of QC for five technicians was identified for further operational improvement. This study revealed that MSA can be used to evaluate product and personnel errors and to improve the quality of work in a biochemical laboratory through proper corrective actions.

Geographical Inequalities in Alcohol-Related Mortality Rates in Taiwan due to Socio-Demographic Differences.

AIMS: To assess the relationships between alcohol-related mortality and socio-demography in Taiwan. METHODS: Using 2002-2006 data from the national death-diagnosis registration system, we calculated the alcohol-attributed disease mortality of those aged 15 and older in 348 townships in Taiwan. This study provides spatial clustering of alcohol-attributed disease mortality rates and area socio-demographic conditions across townships, examining the relationship between the two using a spatial autoregressive model. RESULTS: The relative risk of death due to alcohol-attributed diseases was estimated to increase by 2.1 and 0.9% as a result of a 1% increase in the percentage of men and aboriginal residents, respectively. The risk of death was estimated to decrease by 25% for every 1 year increase in education level. Industrialization and labor participation were also found to be predictors of the outcome measure in areas with differing levels of urbanization. CONCLUSIONS: This study provides significant evidence that township-level relationships between alcohol-related mortality and socioeconomic variables exist in Taiwan. Public health policymakers should better prioritize the specific areas in which comprehensive intervention should be undertaken accordingly.

Alcohol tax policy in relation to hospitalization from alcohol-attributed diseases in Taiwan: a nationwide population analysis of data from 1996 to 2010.

BACKGROUND: The effects of alcohol taxes and prices on drinking and mortality are well established, but the effects of alcohol taxes on measures of alcohol-related morbidity from noninjury health outcomes have not been fully elucidated. We assess the 2 opposing effects of alcohol tax policy interventions (tax rate increase in 2002 and decrease in 2009) on alcohol-attributed diseases (AADs) in Taiwan. METHODS: Admissions data from 1996 to 2010 were retrieved from the National Health Insurance Research Database (NHIRD) claims file and analyzed in this study. Data on 430,388 men and 34,874 women aged 15 or above who had an admission due to an AAD were collected. An interrupted time series analysis examining the effects of the implementation of alcohol tax policy on quarterly age- and sex-specific incidence rates of hospitalization for AADs was employed. The same method was also used to analyze hospitalizations for alcoholic liver disease. RESULTS: The teen/adult groups all showed significant (p < 0.05) changes in the adjusted incidence rate of hospitalization (AIRH) for AADs and alcoholic liver disease in 2002. Men aged 15 to 64 years showed an abrupt decline in the rate of AADs (9.1%) and in the rate of alcoholic liver disease (10.3%). A 16% reduction in the AAD rate was found in teen/adult women after the alcohol tax increase. In contrast, a 17.4% increase in the same rate was seen in the first quarter of 2010 for this group. A similar pattern was presented for the AIRH for alcoholic liver disease among women. The effect of tax intervention was not significant among the elderly. CONCLUSIONS: This study provides evidence that alcohol taxation in response to international trade liberalization has resulted in an immediate reduction of AADs in Taiwan. The policy of increasing alcohol tax rates may have favorable influences on the time trend for the rate of AADs, most notably among young and middle-aged men and women.

A time-series analysis of alcohol tax policy in relation to mortality from alcohol attributed causes in Taiwan.

It is known that taxation on alcohol products may effectively reduce the alcohol consumption. However, whether alcohol taxation may lead to a decrease in alcohol attributed disease mortality (ADM) has been inclusively. We conducted this time-series analysis to assess the effect of alcohol tax policy intervention in 2002 on rate of ADM in Taiwan. Mortality data were retrieved from Taiwan's Death Registry. We employed the autoregression integrated moving average technique to examine secular patterns of quarterly rate of ADM in residents aged 15 or above between 1991 and 2007, and to determine whether alcohol tax policy intervention, imposed in January 2002, had affected the time trend in rate of ADM in subsequent years. We observed a statistically significant reduction in the rate of ADM following the implementation of alcohol tax policy for all sex- and age-specific segments of population. Further analyses revealed that the effect was most obvious in men aged 15-64 years, who showed an abrupt decline in AMD rate (10.9%) in the first quarter of 2002. For elderly men and women, the tax intervention was followed by a gradually declining trend of ADM, with a magnitude ranging from 0.53% per season (elderly women) to 0.63% per season (elderly men). This study demonstrated that alcohol taxation policy may pose favorite influences on the time trend of ADM rate in Taiwan, and such influence was most noteworthy in young and middle aged men.

Temperature-dependent association between mortality rate and carbon monoxide level in a subtropical city: Kaohsiung, Taiwan.

The objective of this study was to explore the combined effect of temperature and air pollutant levels on daily non-accidental deaths and cardiovascular causes of mortality. In this study, associations were assessed by means of time-series analyses over the period 1995-1999 for Kaohsiung, Taiwan's largest industrial city, which has a subtropical climate. Ambient exposures to various air pollutants, including carbon monoxide (CO), sulfur dioxide (SO(2)), ozone (O(3)), nitrogen dioxide (NO(2)), and particulate matter (PM(10)), were estimated from the arithmetic means of all daily measurements taken by an air quality monitoring station nearest to the residential district. Generalized additive models with non-parametric spline were used to identify associations between daily mortality and air pollutants as well as the air pollutant-temperature interaction correlation. Our findings indicate that CO is associated with increased risks of non-accidental and cardiovascular mortality. For a 0.2 ppm increase in CO, the increased relative daily risk of non-accidental death is at least 4% on the same day, when the mean temperature is above 24.8 degrees C, while the increased relative risk of mortality due to cardiovascular diseases is 7% two days later at 19.7 degrees C. The study also suggests a statistically significant interaction between CO concentration and daily mean temperature, with non-accidental mortality increasing with a warm outdoor temperature and the effect of CO on cardiovascular mortality being modified by a cold climate. Further reduction of CO pollution is thus deemed crucial for the benefit of public health.