Association and mediation analyses among multiple metals exposure, plasma folate, and community-based impaired estimated glomerular filtration rate in central Taiwan.

BACKGROUND: Chronic kidney disease (CKD) is increasing, with heavy metal exposure an important risk factor. Additionally, the antioxidant folic acid has been studied for reducing blood arsenic levels and related tissue damage. Therefore, we explored the association and mediation effects among various heavy metal levels in blood, plasma folate, other CKD risk factors, and impaired estimated glomerular filtration rate (eGFR). METHODS: We constructed a community-based cross-sectional study from the Human Biomonitoring and Environmental Health Program in central Taiwan. A total of 1643 participants had lived locally for > 5 years, > 40 years old, and completely received health examinations and biospecimen collections. Impaired eGFR was defined as one single eGFR < 60 mL/min/1.73 m2. Plasma folate and metal levels in blood were determined, as well as urinary 8-hydroxy-2'-deoxyguanosine as an oxidative stress marker. Generalized weighted quantile sum (WQS) regression analysis was used to calculate a WQS score, reflecting overall body-burden of multiple metals (arsenic, cadmium, chromium, nickel, and lead) in blood. RESULTS: Impaired eGFR was identified in 225 participants. Participants with high WQS scores had increased risk of impaired eGFR (odds ratio = 1.67; 95% confidence interval [CI]: 1.34, 2.07). Of five metals, arsenic, lead, and cadmium were weighted highly in impaired eGFR. Participants with high WQS and folate insufficiency (< 6 ng/mL) had 2.38-fold risk of impaired eGFR compared to those with low WQS and high folate (≥6 ng/mL) (95% CI: 1.55, 5.17). Similar increased 4.16-fold risk of impaired eGFR was shown in participants with high WQS and uric acid levels (95% CI: 2.63, 6.58). However, there were no significant WQS-folate (p = 0.87) or WQS-uric acid (p = 0.38) interactions on impaired eGFR risk. As a mediator, uric acid contributed 24% of the association between WQS score and impaired eGFR risk (p < 0.0001). However, no mediation effect of plasma folate was observed. CONCLUSION: WQS analysis could be applied to evaluate the joint effects of multiple metals exposure. High WQS scores may influence impaired eGFR risk through increased uric acid levels. A large-scale and prospective cohort study is necessary to validate these results and demonstrate any causal relationship.

Effects of ambient PM2.5 and particle-bound metals on the healthy residents living near an electric arc furnace: A community- based study.

Fine particulate matter (PM2.5) emitted from electric arc furnaces (EAFs) poses health concerns. However, little research has been done on the impact of EAF on the health of community residents. This cross-sectional study conducted a PM2.5 exposure assessment and health examination of community residents living near an EAF. A total of 965 residents aged 40-90 years were recruited. The residents' exposure to PM2.5 was categorized according to the distance of their residence from the EAFs (<500, 500-1000, 1000-1500, 1500-2000, and > 2000 m). Average ambient PM2.5 concentrations were estimated using a hybrid kriging/land-use regression (LUR) model. In addition, we selected two air-sampling sites to monitor the 2-year levels of PM2.5 and particle-bound metals. A spot urine sample and blood samples were collected and ten heavy metal concentrations in the blood were analyzed. Inflammation- and oxidative stress-related biomarkers were measured. The associations between environmental factors and a biochemical examination were estimated using a generalized linear model. Active air sampling and hybrid kriging/LUR model simulation indicated increased levels of PM2.5 near the EAF. The metal concentrations in PM2.5 included Fe, Pb, Mn, Ni, As, Cu, Ni, Zn, and Al, which also significantly increased near the EAF. PM2.5 levels were significantly associated with an increased total cholesterol-high-density lipoprotein (TC/HDL) ratio. High levels of PM2.5 and malondialdehyde were associated with a 1.72-fold increased risk of TC/HDL ratio ≥ 4 (95% CI: 1.12-2.65) after adjusting for potential confounding factors. Blood Pb levels were significantly associated with increased systolic and diastolic blood pressure and decreased estimated glomerular filtration rate but negatively associated with distance from the EAF. The results show that people living near EAFs should pay more attention to adverse health problems, including atherogenic dyslipidemia, hypertension, and chronic kidney disease associated with exposure to PM2.5 and particle-bound metals.

Objective palliative prognostic score among patients with advanced cancer.

CONTEXT: The accurate prediction of survival is one of the key factors in the decision-making process for patients with advanced illnesses. OBJECTIVES: This study aimed to develop a short-term prognostic prediction method that included such objective factors as medical history, vital signs, and blood tests for use with patients with advanced cancer. METHODS: Medical records gathered at the admission of patients with advanced cancer to the hospice palliative care unit at a tertiary hospital in Taiwan were reviewed retrospectively. The records included demographics, history of cancer treatments, performance status, vital signs, and biological parameters, Multivariate logistic regression analyses and receiver operating characteristic curves were used for model development. RESULTS: The Objective Palliative Prognostic Score was determined by using six objective predictors identified by multivariate logistic regression analysis. The predictors include heart rate >120/min, white blood cells >11,000/mm(3), platelets <130,000/mm(3), serum creatinine level >1.3 mg/dL, serum potassium level >5 mg/dL, and no history of chemotherapy. The area under the receiver operating characteristic curve used to predict seven-day survival was 82.0% (95% confidence interval 75.2%-88.8%). If any three predictors of the six were reached, death within seven days was predicted with 68.8% sensitivity, 86.0% specificity, 55.9% positive predictive value, and 91.4% negative predictive value. CONCLUSION: The Objective Palliative Prognostic Score consists of six objective predictors for the estimation of seven-day survival among patients with advanced cancer and showed a relatively high accuracy, specificity, and negative predictive value. Objective signs, such as vital signs and blood test results, may help clinicians make decisions at the end of life.

Hospice shared-care saved medical expenditure and reduced the likelihood of intensive medical utilization among advanced cancer patients in Taiwan--a nationwide survey.

PURPOSE: Hospice shared care (HSC) is a new care model that has been adopted to treat inpatient advanced cancer patients in Taiwan since 2005. Our aim was to assess the effect of HSC on medical expenditure and the likelihood of intensive medical utilization by advanced cancer patients. METHODS: This is a nationwide retrospective study. HSC was defined as using "Hospice palliative care (HPC) teams to provide consultation and service to advanced cancer patients admitted in the nonhospice care ward." There were 120,481 deaths due to cancer between 2006 and 2008 in Taiwan. Patients receiving HSC were matched by propensity score to patients receiving usual care. Of the 120,481 cancer deaths, 12,137 paired subjects were matched. Medical expenditures for 1 year before death were assessed between groups using a database from the Bureau of National Health Insurance. Paired t and McNemar's tests were applied for comparing the medical expenditure and intensive medical utilization before death between paired groups. RESULTS: Compared to the non-HSC group, subjects receiving HSC had a lower average medical expenditure per person (US$3,939 vs. US$4,664; p<0.001). The HSC group had an adjusted net savings of US$557 (13.3%; p<0.001) in inpatient medical expenditure per person compared with the non-HSC group. Subjects that received different types of HPC had 15.4-44.9% less average medical expenditure per person and significantly lower likelihood of intensive medical utilization than those that did not receive HPC. CONCLUSIONS: HSC is associated with significant medical expenditure savings and reduced likelihood of intensive medical utilization. All types of HPC are associated with medical expenditure savings.

Subclinical hypothyroidism is associated with elevated high-sensitive C-reactive protein among adult Taiwanese.

Subjects with subclinical hypothyroidism (SCH) are at increased risk for cardiovascular disease (CVD). High-sensitivity C-reactive protein (hsCRP) is one of the inflammatory markers related to CVD. It is unclear whether inflammation is a mechanistic intermediary between SCH and CVD. We aimed to investigate the association between SCH and hsCRP in a Taiwanese population. A baseline cohort of 2,494 participants over the age of 19 was recruited in Taiwan from 2006 to 2008. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.61-19.9 mIU/L with normal thyroxine concentrations (a total T4 level of 4.9-12.0 µg/dL). Euthyroidism was defined as a serum TSH level of 0.34-5.60 mIU/L. HsCPR was grouped using quartiles. Multiple logistic and linear regression analyses were used to evaluate the relationship between hsCRP and SCH. After adjusting for gender and betel nut chewing, stepwise multiple logistic regression analyses revealed that hsCRP groups were significantly associated with SCH. Compared to the lowest hsCRP quartile, the adjusted odds ratio of having SCH for hsCRP quartile II, III, and IV were 1.38 (0.48-3.98), 1.48 (0.56-3.96), and 2.59 (1.01-6.67), respectively. The significant increase in odds ratios for SCH in progressive hsCRP quartiles reveals a dose-response effect (p < 0.05). Moreover, stepwise multiple linear regression analyses showed that hsCRP was significantly positively associated with serum TSH level after adjusting for potential confounders. Adult Taiwanese with SCH were associated with elevated hsCRP quartiles.

In addition to malnutrition and renal function impairment, anemia is associated with hyponatremia in the elderly.

Hyponatremia is the most common electrolyte abnormality among the elderly living in long-term care facilities. In this study, we investigate the associated factors of hyponatremia, and its association with anemia in the institutionalized elderly in Taiwan. A total of 414 participants aged 65 years and above were recruited from eight long-term care facilities in 2002-2003. Baseline characteristics, medical records, and biomarkers were obtained. Hyponatremia was defined as a serum Na-concentration<135 mmol/l. Relationships between hyponatremia and the demographic and laboratory characteristics were tested using multiple logistic and linear regression analyses. The prevalence of hyponatremia and anemia was 14.7% and 56.0%, respectively. Anemia, hypouricemia, and the placement of tubes (including nasogastric tube, tracheostomy tube, and Foley catheter) were significantly associated with hyponatremia after adjustment for potential confounders using multiple logistic regression analysis. The adjusted odds ratios (OR) and 95% confidence interval (95%CI) for these three factors were 3.28 (1.40-7.69), 4.98 (2.18-11.36), 9.15 (3.33-25.12), respectively. Multiple linear regression analyses also showed that serum Na concentration was significantly associated with hemoglobin, uric acid, and number of tubes. In conclusion, it was found that anemia, the placement of tubes, and hypouricemia were associated with hyponatremia in the institutionalized elderly. In those with the above conditions, serum Na concentration should be monitored.

Certain bio-psychosocial-spiritual problems associated with dyspnea among advanced cancer patients in Taiwan.

PURPOSE: Dyspnea is a multidimensional phenomenon among advanced cancer patients. We aim to explore the association between bio-psychosocial-spiritual problems and dyspnea among advanced cancer patients in Taiwan. METHODS: We retrospectively analyzed advanced cancer patients admitted to the hospice palliative ward in a tertiary hospital in Taiwan from 2002 to 2005. A total of 687 consecutive advanced cancer patients were enrolled. Physical, psychosocial, and spiritual problems for each patient were collected. Multiple logistic regression analyses were used to evaluate the association between dyspnea and other physical, psychosocial, and spiritual problems. RESULTS: The top four primary sites of cancer among these patients are the liver/biliary tract (19.9%), lung (15.6%), colon/rectum (12.8%), and head/neck (9.9%). During admission period, 260 (37.8%) patients experienced dyspnea. For primary cancer types and metastatic locations, subjects with dyspnea tended to have lung cancer, lung metastasis, or brain metastasis. The clinical symptoms/signs related to dyspnea are pain, anorexia, constipation, nausea/vomiting, coughing, pleural effusion, edema, anxiety, and propriety preparation problem, that is, arranging one's will, feelings of isolation, fear of death, and survival. After further adjustments for potential confounders, subjects with problems of propriety preparation were found to be strongly associated with dyspnea. The adjusted odds ratio of having dyspnea caused by the problem of propriety preparation was 1.91 (95% confidence interval, 1.15-3.19). CONCLUSIONS: Advanced cancer patients with certain psychosocial and spiritual problems, such as, the problem of propriety preparation, fear of death, and anxiety, tended to have dyspnea. Among these factors, propriety preparation plays an important role among dyspnea patients. Advanced cancer patients with dyspnea have greater needs for propriety preparation.

Arterial stiffness is strongly associated with insulin resistance in Chinese--a population-based study (Taichung Community Health Study, TCHS).

AIM: Few studies have investigated the association between insulin resistance and arterial stiffness in Chinese. We aimed to investigate this relationship in a population-based study of middle-aged Chinese. METHODS: A total of 2,188 subjects aged 40 years and older were recruited in 2004 in Taiwan. The association between arterial stiffness (measured by brachial-ankle pulse wave velocity (baPWV)) and insulin resistance (represented by homeostasis model assessment (HOMA-IR) and fasting glucose levels) was studied by multiple logistic and linear regression analyses. RESULTS: The respective prevalence of diabetes and impaired fasting glucose (IFG) was 13.9% and 30.6% in males and 10.4% and 20.8% in females. Using multiple linear regression analyses, we found baPWV to be strongly associated with age, gender, body mass index (BMI), waist circumference (WC), systolic blood pressure (BP), diastolic BP, fasting glucose, and triglycerides. Compared to the lowest HOMA-IR tertile I and adjusting for age, BMI, WC, gender, triglycerides, systolic BP, diastolic BP, smoking, alcohol drinking, betel nut chewing, and physical activity, the odds ratios (95% confidence interval) of arterial stiffness for the higher HOMA-IR tertiles II and III were 1.15 (0.77-1.71) and 1.60 (1.05-2.46), respectively. Using a general linear model with adjustment for age, systolic BP, diastolic BP, BMI, WC, and triglycerides, baPWV was significantly lower in the diabetic group by 90.3 cm/sec in males and 100.5 cm/sec in females compared to the IFG group. When comparing the IFG group to the normal glucose group, baPWV was 28.5 cm/sec lower in males and 14.4 cm/sec lower in females. CONCLUSIONS: Arterial stiffness is independently associated with insulin resistance in Chinese middle-aged adults. Subjects with diabetes or IFG have higher baPWV than normoglycemic subjects.

Predictive equation of resting energy expenditure in obese adult Taiwanese.

OBJECTIVE: To examine the accuracy of present resting energy expenditure (REE) predictive equations among obese adult Taiwanese, and obtain new predictive equations for this population. METHOD: A total of 80 participants (men = 42, women = 38) aged 18-64 years (mean 41.5 ± 13.1 years) with body mass index (BMI) ≥30 kg/m(2) were recruited from obesity clinic of a tertiary hospital. Anthropometric data including weight, height, waist circumference (WC), hip circumference (HipC) were collected. Body fat and fat free mass (FFM) were measured using bioelectric impedance analysis. Indirect calorimeter (Vmax 29n) was used for measurement of REE. The commonly used predictive equations (Harris-Benedict equation, Bernstein equation, Mifflin equation, Owen equation, Schofield equation, Cunningham equation, Wang equation, and Liu equation) were tested for group means and individual prediction accuracy for our target population. New predictive equations were formulated using multiple linear regression analyses. RESULT: The mean BMI was 34.3 ± 4.6 kg/m(2). All of the commonly used predictive equations showed statistically significant differences with the measured REE values. As for individual prediction accuracy, these predictive equations showed poor performance and only Mifflin equation provided an individual accuracy over 40%. The new predictive equation recommended for obese adult Taiwanese is below: REE (kcal/d) = 11.6 × weight (kg) - 204.84 × gender - 4.8 × height (cm) + 1594.6 (gender: men = 1; women = 2). CONCLUSION: The previous commonly used predictive equations were less accurate in obese Taiwanese. For this specific population, the newly developed equation should be applied for better prediction of REE.

Impact of the new lung cancer staging system for a predominantly advanced-disease patient population.

INTRODUCTION: To investigate the feasibility and clinical impact of the 7th edition of the "Tumor, Node, Metastasis" (TNM) classification scheme in lung cancer as proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer. METHODS: We evaluated the feasibility of the new staging system in our routine biweekly multidisciplinary lung cancer staging conference compared with the 6th TNM staging in a prospective manner from April 2008 to June 2009. The impact of IASLC staging versus the 6th TNM staging was observed at three levels: change in substaging, staging, and clinical management (based on the discussion within the staging conference). RESULTS: From 348 patients discussed during these conferences, 226 eligible non-small cell lung cancer patients newly diagnosed within the study period were reviewed and clinically staged. The majority were elderly (median age, 67 years) and men (58%). Of these, 23 patients had different staging, and four patients had different substaging in the IASLC staging compared with the 6th TNM staging. An impact on clinical management was seen in 2.7% (6 of 226) of these patients because of coding ipsilateral different-lobe metastasis as T4 instead of M1. CONCLUSIONS: The new staging system was clinically feasible and resulted in some (27 of 226, 12%) differences in staging. An impact on clinical decision making was occasionally seen within our institutional practice. Further studies are needed to investigate the comprehensive and long-term impact of the new staging system.