A multi-trait GWAS identifies novel genes influencing albuminuria.

BACKGROUND: Albuminuria is common and associated with increased risks of end-stage kidney disease and cardiovascular diseases, yet its underlying mechanism remains obscure. Previous genome-wide association studies (GWAS) for albuminuria did not consider gene pleiotropy and primarily focused on European ancestry populations. This study adopted a multi-trait analysis of GWAS (MTAG) approach to jointly analyze two vital kidney traits, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) to identify and prioritize the genes associated with UACR. METHODS: Data from the Taiwan Biobank from 2012 to 2023 were analyzed. GWAS of UACR and eGFR were performed separately and the summary statistics from these GWAS were jointly analyzed using MTAG. The polygenic risk scores (PRS) of UACR were constructed for validation. The UACR-associated loci were further fine-mapped and prioritized based on their deleteriousness, eQTL associations, and relatedness to Mendelian kidney diseases. RESULTS: MTAG analysis of the UACR revealed 15 genetic loci, including 12 novel loci. The PRS for UACR was significantly associated with urinary albumin level (P < 0.001) and microalbuminuria (P = 0.001 ∼ 0.045). A list of priority genes was generated. Twelve genes with high priority included the albumin endocytic receptor gene LRP2 and ciliary genes  IFT172. CONCLUSIONS: The findings of this multi-trait GWAS suggest that primary cilia play a role in sensing mechanical stimuli, leading to albumin endocytosis. The priority list of genes warrants further translational investigation to reduce albuminuria.

Clinical implications of frailty in peritoneal dialysis patients - A prospective observational study.

BACKGROUND: Frailty is an age-related condition that predicts adverse outcomes. The study was aimed to investigate the clinical implications of frailty evolution in patients undergoing peritoneal dialysis (PD). METHOD: In this prospective study, all new-onset (<6 months) and prevalent (≧6 months) PD patients completed frailty assessment at entry and 6 months by a semiautomated frailty index of 80 risk factors (FI80) which also contained the 5 components of Fried frailty phenotype. A score ≧13/80 (FI80 > 0.16) or ≧3/5 (frailty phenotype) was designated to define frailty. RESULT: 337 PD patients were recruited (new-onset 23.4%, prevalent 76.6%). Two hundred (59.3%) and 163 (48.4%) patients were frail by FI80 and frailty phenotype, respectively. Predictors for frailty were old age, dialysis, diabetes mellitus, gout and sleep disorder. New-onset patients aged <55 years displayed the best evolution of frailty over 6 months (stable or improved, n = 29/47, 61.7% by FI80, p = 0.0293), compared with other groups. Survival analysis found that frail patients exhibited the worse outcomes (overall death and hospitalization). Poisson regression showed frailty was associated with increased utilizations of outpatient and ER services; however multivariate Cox models identified only diabetes, gout and low body mass index (<19 kg/m2), but not frailty, predicted overall death and hospitalizations. CONCLUSION: Frailty is a common medical condition in PD patients, and the status of which can be stabilized or improved in new-onset, young patients at least over the short term. Compared with frailty, certain comorbidities (diabetes and gout) and undernutrition appeared to be more robust in the prediction of adverse outcomes.

A competing risk predictive model for kidney failure in patients with advanced chronic kidney disease.

BACKGROUND/PURPOSE: Predictive modeling aids in identifying patients at high risk of adverse events. Using routinely collected data, we report a competing risk prediction model for kidney failure. METHODS: A total of 5138 patients with CKD stages 3b-5 were included and randomized into the development and validation cohorts at a ratio of 7:3. The outcome was end-stage kidney disease, defined as the initiation of dialysis or kidney transplantation. All patients were followed-up until December 31, 2020. A Fine and Gray model was applied to estimate the sub-hazard ratio of kidney failure, with death as a competing event. RESULTS: In the development cohort, the mean age was 67.6 ± 13.9 years and 60 % were male. The mean index eGFR and median urinary protein-creatinine ratio (UPCR) were 26.5 ± 12.8 mL/min/1.73 m2 and 1051 mg/g, respectively. The median follow-up duration was 1051 days. The proportion of patients with kidney failure and death was 25.4 % and 14.1 %, respectively. Four models were applied, including eGFR, age, sex, UPCR, systolic and diastolic blood pressure, serum albumin, phosphate, uric acid, haemoglobin, and potassium levels had the best goodness of fit. All models had good discrimination with time-to-event c statistics of 0.89-0.95 in the development cohort and 0.86-0.95 in the validation cohort. The prediction models showed excellent and fairly good calibration at 2 and 5-year risk, respectively. CONCLUSION: Using real-world data, our competing risk model can accurately predict progression to kidney failure over 2 years in patients with advanced CKD.

Effect of Lipid-Lowering Drugs on Renal and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Dyslipidemia: A Retrospective Cohort Study.

The effects of lipid-lowering drugs (LLDs) on cardiovascular and renal outcomes in patients with advanced chronic kidney disease (CKD) and dyslipidemia are not completely understood. We conducted a retrospective cohort study to evaluate the effect of LLDs on end-stage kidney disease (ESKD), major adverse cardiovascular events (MACEs), and mortality in adult patients with CKD stage 3b, 4, or 5, and dyslipidemia. Participants were recruited between January 1, 2008, and December 31, 2018, and classified as LLD or non-LLD users; the final follow-up date was December 31, 2020. The primary outcome was time to ESKD or death due to renal failure. Sub-distribution hazard regression models adjusted for multivariables, including time-varying lipid profile covariates, were used for the analysis. Among the 6,740 participants, 4,280 patients with CKD and dyslipidemia, including 872 using LLDs and 3,408 not using LLDs, completed the primary analysis. The multivariable analyses showed that LLD users had a significantly lower risk of time to the composite renal outcome (adjusted hazard ratio [aHR], 0.76, 95% confidence interval [CI], 0.65-0.89), and MACE incidence (aHR, 0.75, 95% CI, 0.62-0.93) than did non-LLD users. After adjusting for time-varying covariates of the lipid profile, there was a significant difference in the composite renal outcome (aHR, 0.78, 95% CI, 0.65-0.93) and MACEs (aHR, 0.77, 95% CI, 0.60-0.98). Among adult patients with advanced CKD and dyslipidemia, LLD users had a significantly lower risk of composite renal outcomes and MACEs than non-LLD users. In addition to reducing lipid profile, the use of LLD is associated with renal and cardiovascular protective effects.

Predialysis trajectories of estimated GFR and concurrent trends of Chronic Kidney Disease-relevant biomarkers.

Background: The glomerular filtration rate (GFR) decline varies in patients with advanced chronic kidney disease (CKD), and the concurrent changes in CKD-related biomarkers are unclear. Objectives: This study aimed to examine the changes in CKD-related biomarkers along with the kidney function decline in various GFR trajectory groups. Design: This study was a longitudinal cohort study originated from the pre-end-stage renal disease (pre-ESRD) care program in a single tertiary center between 2006 and 2019. Methods: We adopted a group-based trajectory model to categorize CKD patients into three trajectories according to estimated glomerular filtration rate (eGFR) changes. A repeated-measures linear mixed model was used to estimate the concurrent biomarker trends in a 2-year period before dialysis and to examine the differences among trajectory groups. A total of 15 biomarkers were analyzed, including urine protein, serum uric acid, albumin, lipid, electrolytes, and hematologic markers. Results: Using longitudinal data from 2 years before dialysis initiation, 1758 CKD patients were included. We identified three distinct eGFR trajectories: persistently low eGFR levels, progressive loss of eGFR, and accelerated loss of eGFR. Eight of the 15 biomarkers showed distinct patterns among the trajectory groups. Compared with the group with persistently low eGFR values, the other two groups were associated with a more rapid increase in the blood urea nitrogen (BUN) level and urine protein-creatinine ratio (UPCR), especially in the year before dialysis initiation, and a more rapid decline in hemoglobin and platelet counts. A rapid eGFR decline was associated with lower levels of albumin and potassium, and higher levels of mean corpuscular hemoglobin concentration (MCHC) and white blood cell (WBC). The albumin level in the group with an accelerated loss of eGFR was below the normal range. Conclusion: Using longitudinal data, we delineated the changes in CKD biomarkers with disease progression. The results provide information to clinicians and clues to elucidate the mechanism of CKD progression.

Serum Urate and Risk of Chronic Kidney Disease: A Mendelian Randomization Study Using Taiwan Biobank.

OBJECTIVE: To evaluate the association between serum urate and risk of incident chronic kidney disease (CKD) and to assess whether serum urate plays a causal role in CKD. PATIENTS AND METHODS: We conducted a prospective cohort study and Mendelian randomization analysis that analyzed longitudinal data from the Taiwan Biobank between January 1, 2012, and December 31, 2021. RESULTS: A total of 34,831 individuals met the inclusion criteria, of which 4697 (13.5%) had hyperuricemia. After a median (interquartile range) follow-up of 4.1 (3.1-4.9) years, 429 participants developed CKD. After adjustment for age, sex, and comorbid conditions, each mg/dL increase in serum urate was associated with a 15% higher risk of incident CKD (HR, 1.15; 95% CI, 1.08 to 1.24; P<.001). The genetic risk score and seven Mendelian randomization methods revealed no significant association between serum urate levels and the risk of incident CKD (HR, 1.03; 95% CI, 0.72 to 1.46; P=0.89; all P>.05 for 7 Mendelian randomization methods). CONCLUSION: This prospective, population-based cohort study showed that elevated serum urate is a significant risk factor for incident CKD; however, Mendelian randomization analyses failed to provide evidence that serum urate had a causal effect on CKD in the East Asian population.

Prepregnancy Endocrine, Autoimmune Disorders and the Risks of Gestational Hypertension-Preeclampsia in Primiparas: A Nationwide Population-Based Study in Taiwan.

(1) Objective: To assess the risks of gestational hypertension/preeclampsia (GH-PE) in women with prepregnancy endocrine and autoimmune disorders such as polycystic ovarian syndrome (PCOS) and systemic lupus erythematosus (SLE). (2) Methods: In a nationwide population-based longitudinal study, data were retrieved from the 1998 to 2012 Taiwan National Health Insurance Research Database. ICD9-CM codes 256.4, 710.0, and 642.X were identified for the corresponding diagnoses of PCOS, SLE, and GH-PE, respectively, which were further confirmed by inspection of medical claims data for ultrasonography findings, laboratory tests, blood pressure measurements and examinations of urine protein to ensure the accuracy of the diagnoses. To clarify the risks of primiparous GH-PE, the study excluded women diagnosed with PCOS or SLE at <15 or >45 years of age, pre-existing chronic hypertension, GH-PE before PCOS and SLE, and abortion or termination before 20 weeks' gestation. For women affected by prepregnancy PCOS or SLE individually, each pregnant woman was age-matched to four pregnant women without PCOS or SLE. Logistic regression analyses were applied to report odds ratios (ORs) for the risks of GH-PE after adjustment for age, occupation, urbanization, economic status, and other co-morbidities. (3) Results: Among 8070 and 2430 women with prepregnancy PCOS and SLE retrieved from a population of 1,000,000 residents, 1953 (24.20%) and 820 (33.74%) had subsequent primiparous pregnancies that were analyzable and compared with 7812 and 3280 pregnancies without prepregnancy PCOS and SLE, respectively. GH-PE occurred more frequently in pregnancies with prepregnancy PCOS (5.79% vs. 2.23%, p < 0.0001) and SLE (3.41% vs. 1.80%, p < 0.01) as compared to those without PCOS and SLE. Further analysis revealed that prepregnancy PCOS (adjusted OR = 2.36; 95%CI: 1.83-3.05) and SLE (adjusted OR = 1.95; 95%CI: 1.23-3.10) were individually associated with GH-PE. The risk of GH-PE was not reduced in women with prepregnancy PCOS receiving metformin treatment (p = 0.22). (4) Conclusions: Prepregnancy PCOS and SLE are independent and significant risk factors for the occurrence of GH-PE. Because the peripartum complications are much higher among pregnancies with GH-PE, the at-risk woman should be informed and well-prepared during her pregnancy and delivery.

Risk of gestational hypertension-preeclampsia in women with preceding endometriosis: A nationwide population-based study.

OBJECTIVE: To investigate the association between preceding endometriosis and gestational hypertension-preeclampsia (GH-PE). METHODS: In this nationwide population-based longitudinal study, data from 1998-2012 Taiwan National Health Insurance Research Database were used. We used ICD9-CM codes 617.X and 642.X respectively for the diagnoses of endometriosis and GH-PE, which were further confirmed by examining medical records of surgeries, blood pressure and urine protein to ensure the accuracy of the diagnoses. The study excluded women diagnosed with endometriosis at < 15 or > 45 years of age, chronic hypertension, and GH-PE prior to endometriosis. Each pregnant woman with a prior diagnosis of endometriosis was matched to 4 pregnant women without endometriosis by age. Logistic regression analysis was used to calculate odds ratios (ORs) for the risk of GH-PE with adjustment for age, occupation, urbanization, economic status and comorbidities. RESULTS: Among 6,300 women with a prior endometriosis diagnosis who were retrieved from a population of 1,000,000 residents, 2,578 (40.92%) had subsequent pregnancies that were eligible for further analysis and were compared with 10,312 pregnant women without previous endometriosis. GH-PE occurred more in women with prior endometriosis as compared to those without endometriosis (3.88% vs. 1.63%, p<0.0001). Further analysis revealed prior endometriosis was associated with GH-PE (adjusted OR = 2.27; 95% CI:1.76-2.93). For danazol-treated and non-danazol-treated subgroups, the incidences of GH-PE were 3.13% (15/480) and 4.05% (85/2,098), respectively. Although the risk for subsequent GH-PE was lower (adjusted OR = 1.49; 95% CI:0.86-2.56) after receiving danazol treatment than average (adjusted OR = 2.27; 95% CI:1.76-2.93) for women with preceding endometriosis, the reduction of risk was not statistically remarkable for danazol-treated (adjusted OR = 1.49) vs. non-danazol-treated (adjusted OR = 2.48) subgroups (p heterogeneity = 0.12). CONCLUSIONS: Preceding endometriosis is an independent and significant risk factor for the occurrence of GH-PE.

Iron Deficiency Anemia as a Risk Factor for Osteoporosis in Taiwan: A Nationwide Population-Based Study.

The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012. Taiwan National Health Insurance Research Database, patients with IDA (case group (n = 35,751)) and individuals without IDA (control group (n = 178,755)) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to five individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p < 0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio (HR) = 1.74; 95% CI = 1.61-1.88) and remained similar after adjustment for covariates (adjusted HR = 1.81; 95% CI = 1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR = 2.21; 95% CI = 1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR = 1.47; 95% CI = 1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis.

Polycystic ovarian syndrome and the risk of subsequent primary ovarian insufficiency: a nationwide population-based study.

OBJECTIVE: To evaluate the risk of subsequent primary ovarian insufficiency (POI) amongst patients with a history of polycystic ovarian syndrome (PCOS). METHODS: This nationwide, population-based study is an inspection and review of data from the 1998 to 2012 Taiwan National Health Insurance Research Database. In a sample of 1,000,000 randomly sampled individuals, women with PCOS (exposure group; n = 7,049) and women without PCOS (contrast group; n = 70,490) were compared. Women initially diagnosed with PCOS at less than 15 or more than 35 years of age were excluded. Each woman with PCOS was age-matched to 10 women without PCOS. The diagnoses of PCOS and POI (coded using International Classification of Diseases, 9th Revision, Clinical Modification) were further confirmed with blood test results and ultrasonographic findings to ensure the accuracy of the diagnoses. RESULTS: POI occurred more among women with PCOS compared with women without PCOS (3.73% vs 0.44%; P < 0.001). Using Kaplan-Meier survival analysis, the POI-free survival rates were significantly different between the exposure and contrast groups (P < 0.001). During 10 years of follow-up, Cox proportional-hazard analysis revealed that the risk for POI was significantly higher in the exposure than in the contrast group (hazard ratio [HR] 8.64, 95% confidence interval [CI] 7.33-10.18) and remained similar after adjustment for covariates (adjusted HR 8.31, 95% CI 7.05-9.81). Compared with that of women without PCOS, the risk of POI was even higher for women with PCOS who did not receive metformin treatment (adjusted HR 9.93, 95% CI 8.28-11.90). However, the risk for POI was significantly reduced for women with PCOS who received metformin treatment (adjusted HR 5.66, 95% CI 4.36-7.35). CONCLUSIONS: As a possible precursor stage, prior PCOS is a significant and independent risk factor for development of POI. The use of metformin reduces the risk of POI.

Toward Automatic Reporting of Infectious Diseases.

Accurate, complete, and timely disease surveillance data are vital for disease control. We report a national scale effort to automatically extract information from electronic medical records as well as electronic laboratory systems. The extracted information is then transferred to the centers of disease control after a proper confirmation process. The coverage rates of the automated reporting systems are over 50%. Not only is the workload of surveillance greatly reduced, but also reporting is completed in near real-time. From our experiences, a system sustainable strategy, well-defined working plan, and multifaceted team coordination work effectively. Knowledge management reduces the cost to maintain the system. Training courses with hands-on practice and reference documents are useful for LOINC adoption.

Bidirectional association between obstructive sleep apnea and depression: A population-based longitudinal study.

An association may exist between obstructive sleep apnea (OSA) and depression. However, results regarding this association are inconsistent, and the direction of the association between OSA and depression remains unknown. Therefore, we used the Taiwan National Health Insurance Research Database to investigate the bidirectional association between OSA and depression.A total of 6427 OSA patients and 32,135 age and sex-matched control subjects were enrolled to analyze the risk of depression among patients with OSA, where 27,073 patients with depression and 135,365 control subjects were enrolled to address the risk of OSA among patients with depression. All subjects were followed to identify their outcomes of interest from January 1, 1997 to December 31, 2012.Cox proportional-hazards models, after adjusting for potential confounders, demonstrated that patients with OSA had an increased risk (adjusted hazard ratio 2.48, 95% confidence interval 2.20-2.79) of developing depression, whereas those with depression were associated with an increased risk of future OSA (adjusted hazard ratio 2.30, 95% confidence interval 2.11-2.50).Our results suggested that a strong bidirectional relationship exists between OSA and depression, with each disease influencing the development of the other. Health providers are recommended to ensure the early detection and management of depression among patients with OSA and vice versa.

Relationship between Polycystic Ovarian Syndrome and Subsequent Gestational Diabetes Mellitus: A Nationwide Population-Based Study.

OBJECTIVE: This nationwide population-based study aims to explore the relationship between polycystic ovarian syndrome (PCOS) and subsequent gestational diabetes mellitus (GDM). METHODS: Data from 1998-2012 Taiwan National Health Insurance Research Database were used for this study. ICD9-CM codes 256.4X and 648.X were used separately for the diagnoses of PCOS and GDM, which were further confirmed by records of blood tests or ultrasonography to ensure the accuracy of the diagnoses. Women diagnosed at < 15 or > 45 years of age, and those diagnosed with overt diabetes mellitus or GDM prior to PCOS were excluded. During pregnancy, each woman with a previous diagnosis of PCOS was age-matched to 10 women without PCOS. Odds ratios (ORs) for risk of GDM were calculated by logistic regression analysis with adjustment for economic status and co-morbidities. RESULTS: Among 7,629 eligible women with a valid PCOS diagnosis, 3,109 (42.87%) had subsequent pregnancies. GDM occurred frequently among women with a history of PCOS as compared to those without PCOS (20.46% vs. 10.54%, p<0.0001). Logistic regression analysis revealed that PCOS was associated with GDM (adjusted OR = 2.15; 95% CI:1.96-2.37). Among 3,109 affected patients, 1,160 (37.31%) had used medications for PCOS and 261 (8.39%) were treated with an oral hypoglycemic agent (OHA). There was no significant difference in development of GDM between the medication and no medication sub-groups (p>0.05). If not used after conception, OHAs did not reduce the risk of GDM (adjusted OR = 1.20; 95% CI:0.88-1.62). CONCLUSIONS: A history of PCOS is a significant and independent risk factor for development of GDM. Medication for PCOS or pre-pregnancy use of OHAs does not reduce the risk of GDM. When at-risk women become pregnant, they require closer surveillance for maternal and fetal well-being, and should follow a strict diet and adhere to weight gain control to avoid obstetric complications due to GDM.

A rational approach to estimating the surgical demand elasticity needed to guide manpower reallocation during contagious outbreaks.

BACKGROUND: Emerging infectious diseases continue to pose serious threats to global public health. So far, however, few published study has addressed the need for manpower reallocation needed in hospitals when such a serious contagious outbreak occurs. AIM: To quantify the demand elasticity of the major surgery types in order to guide future manpower reallocation during contagious outbreaks. MATERIALS AND METHODS: Based on a nationwide research database in Taiwan, we extracted the monthly volumes of major surgery types for the period 1998-2003, which covered the SARS period, in order to carry out a time series analysis. The demand elasticity of each surgery type was then estimated by autoregressive integrated moving average (ARIMA) analysis. RESULTS: During the study period, the surgical volumes of most selected surgery types either increased or remained steady. We categorized these surgery types into low-, moderate- and high-elastic groups according to their demand elasticity. Appendectomy, 'open reduction of fracture with internal fixation' and 'free skin graft' were in the low demand elasticity group. Transurethral prostatectomy and extracorporeal shockwave lithotripsy (ESWL) were in the high demand elasticity group. The manpower of the departments carrying out the surgeries with low demand elasticity should be maintained during outbreaks. In contrast, departments in charge of surgeries mainly with high demand elasticity, like urology departments, may be in a position to have part of their staff reallocated. CONCLUSIONS: Taking advantage of the demand variation during the SARS period in 2003, we adopted the concept of demand elasticity and used a time series approach to figure out an effective index of demand elasticity for various types of surgery that could be used as a rational reference to carry out manpower reallocation during contagious outbreak situations.

Noncancer hospice care in taiwan: a nationwide dataset analysis from 2005 to 2010.

UNLABELLED: Abstract Background: The National Health Insurance program (NHI) in Taiwan has provided hospice services since 2000, and it was expanded to noncancer illnesses in September 2009. The issues of noncancer hospice care and the impact of the expanded hospice policy remain unclear. METHODS: Data were collected retrospectively from claims data of hospice admissions using the NHI Research Database of 2005-2010. RESULTS: A total of 359 noncancer subjects and 412 hospice admissions were enrolled; 1795 age- and gender-matched cancer patients and 2578 hospice admissions were selected as a comparison group. Noncancer hospice care increased markedly after the third quartile of 2009. The most common noncancer diagnosis was "other diseases of the lung" (23.9%). The noncancer subjects had a significantly lower frequency of admissions, lower Charlson Comorbidity Index (CCI) scores, shorter hospice stay, and higher mortality rate than the cancer subjects. Family physicians provided the majority of hospice services in both groups. Acute low respiratory conditions (ALRC) were the most common acute comorbidity in deceased subjects. The noncancer decedents had more ALRC, sepsis/bacteremia, nontraumatic shock, acute myocardial infarctions, and esophageal varicose bleeding than the comparison group. The mean inpatient charges differed insignificantly between both groups. The noncancer subjects correlated negatively with CCI (odds ratio [OR] 0.59 in all hospice admissions; 0.63 in decedents), but positively with a hospice stay ≤3 days, mortality, sepsis/bacteremia, ALRC, nontraumatic shock, and acute myocardial infarctions compared with the cancer subjects (OR 1.42, 1.98, 2.24, 2.36, 2.17, and 11.68, respectively, adjusted by CCI). CONCLUSIONS: The expanded palliative care policy has impacted positively on noncancer hospice care in Taiwan. The terminal noncancer patients had higher risks for short hospice stay, sepsis, nontraumatic shock, and respiratory and heart problems than the cancer subjects. Early referral to hospices is required for terminal patients in Taiwan. The CCI had a limited role for cost/severity evaluations of hospice care.