Epidemiology of cancer in end-stage renal disease dialysis patients: a national cohort study in Taiwan.

The incidence and mortality of site-specific cancers in patients with end-stage renal disease (ESRD) on maintenance dialysis have been rarely studied for Asian populations. We tapped Taiwan`s National Health Insurance Research Database to identify and recruit patients starting maintenance dialysis between 1999 and 2004. They were followed from initiation of dialysis until death, discontinuation of dialysis, or the end of 2008. We calculated the survival rate and mortality risk of dialysis patients with cancer. Of 40,833 dialysis patients, 2352 (5.8%) had been newly diagnosed with cancer. Being older, being male, and having chronic liver disease were factors associated with a higher risk for new cancer in ESRD dialysis patients. In men, liver cancer (20.63%) was the most frequent, followed by cancers of the bladder (16.88%) and kidney (11.61%). In women, bladder cancer (25.57%) was the most frequent, followed by cancers of the kidney (16.31%) and breast (11.20%). The 5-year survival rates for kidney and bladder cancer were higher than for other cancers; the survival rates for lung, stomach, and liver cancer were lower. In conclusion, the distribution of site-specific cancer was different between men and women in patients with ESRD on dialysis. More attention should be paid to teaching dialysis patients how to avoid the well-known cancer risks and carcinogens and individualized regular cancer screenings.

Increased risk of mortality among haemodialysis patients with or without prior stroke: a nationwide population-based study in Taiwan.

BACKGROUND & OBJECTIVES: Patients with prior stroke (PS) undergoing chronic dialysis are at a high risk of mortality. However, little is known about the cumulative risk and survival rate of dialysis patients with long-term follow up. The aim of this study was to assess risks for mortality between patients with and without PS undergoing chronic haemodialysis (HD). METHODS: The Taiwan National Health Insurance Research Database (NHRI-NHIRD-99182) was used and all adult patients (≥18 yr) with end stage renal disease (ESRD) who started maintenance HD between January 1, 1999, and December 31, 1999, were selected. The patients were followed from the first reported date of HD to the date of death, end of dialysis or December 31, 2008. A Cox's proportional hazard model was applied to identify the risk factors for all-cause mortality. RESULTS: Among 5672 HD patients, 650 patients (11.5%) had PS. A higher proportion of stroke history at baseline was found in men (52.8%) and those aged ≥ 55 yr (80.9%). After adjusting for age, sex and other covariates, the patients with PS were found to have a 36 per cent increased risk of mortality compared to those without PS (HR 1.36, 95% CI: 1.22-1.52). The cumulative survival rates among HD patients without PS were 96.0 per cent at the first year, 68.4 per cent at the fifth year, and 46.7 per cent at the ninth year, and 92.9, 47.3 and 23.6 per cent, respectively, in those with PS (log-rank: P<0.001). INTERPRETATION & CONCLUSIONS: Our findings showed that PS was an important predictor for all-cause mortality and poor outcome in patients undergoing chronic HD.

The new comorbidity index for predicting survival in elderly dialysis patients: a long-term population-based study.

BACKGROUND: The worldwide elderly (≥ 65 years old) dialysis population has grown significantly. This population is expected to have more comorbid conditions and shorter life expectancies than the general elderly population. Predicting outcomes for this population is important for decision-making. Recently, a new comorbidity index (nCI) with good predictive value for patient outcomes was developed and validated in chronic dialysis patients regardless of age. Our study examined the nCI outcome predictability in elderly dialysis patients. METHODS AND FINDINGS: For this population-based cohort study, we used Taiwan's National Health Insurance Research Database of enrolled elderly patients, who began maintenance dialysis between January 1999 and December 2005. A total of 21,043 incident dialysis patients were divided into 4 groups by nCI score (intervals ≤ 3, 4-6, 7-9, ≥ 10) and followed nearly for 10 years. All-cause mortality and life expectancy were analyzed. During the follow-up period, 11272 (53.55%) patients died. Kaplan-Meier curves showed significant group difference in survival (log-rank: P<0.001). After stratification by age, life expectancy was found to be significantly longer in groups with lower nCI scores. CONCLUSION: The nCI, even without the age component, is a strong predictor of mortality in elderly dialysis patients. Because patients with lower nCI scores may predict better survival, more attention should paid to adequate dialysis rather than palliative care, especially in those without obvious functional impairments.

Epidemiology and mortality of new-onset diabetes after dialysis: Taiwan national cohort study.

OBJECTIVE: We examined the predictors and risks associated with pre-existing versus new-onset diabetes mellitus (DM) after initiation of chronic dialysis therapy in end-stage renal disease (ESRD) patients. RESEARCH DESIGN AND METHODS: In the Taiwan National Health Insurance Research Database, we examined records of ESRD patients who initiated dialysis between 1999 and 2005. Patients were followed until death, transplant, dialysis withdrawal, or 31 December 2008. Predictors of new-onset DM and mortality were calculated using Cox models. RESULTS: A total of 51,487 incident dialysis patients were examined in this study, including 25,321 patients with pre-existing DM, 3,346 with new-onset DM, and 22,820 without DM at any time. Patients' age (mean±SD) was 61.8±11.5, 61.6±13.7, and 56.5±16.6 years in pre-existing, new-onset DM, and without DM groups, respectively. The cumulative incidence rate of new-onset DM was 4% at 1 year and 21% at 9 years. Dialysis modality was not a risk factor for new-onset DM (peritoneal dialysis to hemodialysis hazard ratio [HR] of new-onset DM, 0.94 [95% CI 0.83-1.06]). Pre-existing DM was associated with 80% higher death risk (HR 1.81 [95% CI 1.75-1.87]), whereas the new-onset DM was associated with 10% increased death risk (HR 1.10 [95% CI 1.03-1.17]). CONCLUSIONS: Whereas dialysis modality does not appear to associate with new-onset DM, both pre-existing and new-onset DM are related to higher long-term mortality in maintenance dialysis patients.

Epidemiology and mortality among dialysis patients with acute coronary syndrome: Taiwan National Cohort Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) on dialysis have poor outcomes after acute coronary syndrome (ACS). Epidemiological data for Asian patients are scarce. METHODS: This longitudinal cohort study investigated the incidence, risk factors, and outcomes of ACS in 19,974 ESRD incident dialysis patients in the Taiwan National Health Insurance research Database between January 1999 and December 2001. The follow-up period was from the start of dialysis to the date of death, end of dialysis, or December 31, 2008. RESULTS: ACS was diagnosed in 1785 patients during follow-up (1.78/100 person-years): 832 (46.6%) had acute myocardial infarction (AMI), 681 (38.2%) underwent cardiac catheterization, 398 (22.3%) underwent percutaneous transluminal coronary angioplasty (PTCA), and 50 (2.8%) underwent coronary artery bypass grafting. Male (HR 1.35, 95% CI: 1.23-1.49) and elderly (HR 3.289, 95% CI: 2.71-4.00) patients had a high rate of ACS. Patients with baseline comorbidities (diabetes mellitus, hypertension, congestive heart failure, coronary artery disease, dysrhythmia, and other cardiac and chronic obstructive lung diseases) had a higher incidence of ACS than did those without. Overall in-hospital mortality was 9.7%. The cumulative 6-month post-hospitalization survival rate was 79.3%; the 1-year rate was 72.3%. Being elderly (≥ 65 years old), and having DM or AMI were associated with an increased risk for mortality; PTCA was associated with a decreased risk (HR 0.77, 95% CI: 0.66-0.91). CONCLUSION: ESRD dialysis patients had a high incidence of ACS and mortality. Being male, elderly and having baseline comorbidities were independent risk factors for ACS. Coronary intervention is the possible benefits for dialysis patients.

Influence of water quality parameters on occurrence of polybrominated diphenyl ether in sediment and sediment to biota accumulation.

Polybrominated diphenyl ether (PBDE) concentrations in sediment and fish from 12 principal rivers in Taiwan were investigated to determine their association with water quality parameters as well as the biota-sediment accumulation factor (BSAF) in fish with different living patterns. The highest PBDE concentration in sediment was found in the Bajhang River (261 ng g(-1) dryweight (d.w.)) and the lowest in the Beinan River and the Da-an River (0.17 ng g(-1) d.w.). The PBDE concentrations in fish samples ranged from 1.28 ng g(-1) d.w. (Oreochromis niloticus niloticus) in the Yanshuei River to 33.7 ng g(-1) d.w. (Varico rhinos barbatulus) in the Da-an River. We conclude that PBDEs contamination in sediment was significantly affected by NH(3)-N, pH, and DO. The BSAF results showed a parabolic trend from low- to high-brominated BDEs. Fish easily accumulated the congeners BDE-47, -100, -119, -126, and -154 from sediment. The BSAF decreased in the following order: PeBDE>HxBDE>TeBDE>other BDEs. Principle component analysis showed that demersal fish have different PBDE sources than do pelagic fish. We conclude that living and feeding habits are critical factors affecting PBDE accumulation in fish.

Long-term survival and predictors for mortality among dialysis patients in an endemic area for chronic liver disease: a national cohort study in Taiwan.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at a higher risk for chronic hepatitis, liver cirrhosis (LC) and mortality than the general population. Optimal modalities of renal replacement therapy for ESRD patients with concomitant end-stage liver disease remain controversial. We investigated the long-term outcome for chronic liver disease among dialysis patients in an endemic area. METHODS: Using Taiwan's National Health Insurance claim data (NHRI-NHIRD-99182), We performed a longitudinal cohort study to investigate the impact of comorbidities on mortality in dialysis patients. We followed up 11293 incident hemodialysis (HD) and 761 peritoneal dialysis (PD) patients from the start of dialysis until the date of death or the end of database period (December 31, 2008). A Cox proportional hazards model was used to identify the risk factors for all-cause mortality. RESULTS: Patients receiving PD tended to be younger and less likely to have comorbidities than those receiving HD. At the beginning of dialysis, a high prevalence rate (6.16 %) of LC was found. Other than well-known risk factors, LC (hazard ratio [HR] 1.473, 95 % CI: 1.329-1.634) and dementia (HR 1.376, 95 % CI: 1.083-1.750) were also independent predictors of mortality. Hypertension and mortality were inversely associated. Dialysis modality and three individual comorbidities (diabetes mellitus, chronic lung disease, and dementia) interacted significantly on mortality risk. CONCLUSIONS: LC is an important predictor of mortality; however, the effect on mortality was not different between HD and PD patients.

Effects of gene-environmental interaction on noise-induced hearing threshold levels for high frequencies (HTLHF).

In this study we assessed the interaction between glutathione S-transferase (GST) genetic polymorphisms and noise exposures, with regard to their effect on the hearing threshold levels for high frequencies (HTLHF). Research participants comprised 347 male workers, and each participant's cumulative noise exposure was determined using a job-exposure matrix. Approximately 64.6% of the participants' exposure in L(eq-8 h) was above 90 dBA. The mean HTLHF was 32.1 dB. A significant dose-response relationship was found between noise exposure and HTLHF. We further converted the estimated total noise exposure level over each participant's job history to a noise exposure level that corresponded to a 40-year exposure (L(eq-40y)). After we had adjusted the results for age, we found that workers carrying GSTM1 null, GSTT1 null, and GSTP1 Ile(105)/Ile(105) genotypes were susceptible to the HTLHF when their L(eq-40y) were above 90 dBA. Therefore, GST genetic polymorphisms might affect HTLHF only when workers are exposed to high noise levels.

N-Acetyl-cysteine against noise-induced temporary threshold shift in male workers.

Previous animal studies showed protective effects of antioxidant medicines against noise-induced hearing loss (NIHL). It is unclear whether antioxidants would protect humans from NIHL. We conducted a study to determine whether N-Acetyl-cysteine (NAC) protected men against noise-induced temporary threshold shift (TTS), and whether subgroups with genetic polymorphisms of glutathione S-transferase (GST) T1 and M1 responded to NAC differently. In this prospective, double-blind, crossover study, 53 male workers were randomly assigned to receive either NAC (1200 mg/day, 14 days) during the first period and placebo during the second period, or placebo during the first period and NAC during the second period. Dosing periods were separated by a washout period of 2 weeks. The hearing threshold changes were determined before and after each dosing period. Pre-shift hearing threshold for high frequencies was 19.1 dB. Daily exposure to noise ranged from 88.4 to 89.4 dB. The noise levels of different frequencies ranged from 80.0 to 89.4 dB with a peak-value at 4 kHz. NAC significantly reduced TTS (p = 0.03). When the participants were grouped by GST M1/T1 genotypes, the NAC effect was only significant among workers with null genotypes in both GSTM1 and GSTT1 (p = 0.004). NAC may prevent noise-induced TTS among occupationally noise-exposed men. The protective effect of NAC was more prominent in subjects with both GSTM1-null and GSTT1-null genotypes. (clinicaltrials.gov Identifier: NCT00552786).

Biosorption of lead, Mercury, and cadmium ions by Aspergillus terreus immobilized in a natural matrix.

Our aim was to investigate the biosorption of Pb2+, Hg2+, Cd2 from aqueous solution by Aspergillus terreus (both free and immobilized on loofa sponge discs). Our results show that the adsorption capacity of fungal biomass on loofa sponge (FBLS) is superior to free fungal biomass (FFB). The adsorption selectivity by FBLS was in the order Pb2+>Hg2+>Cd2+. The maximum metal ions adsorbed was 247.2, 37.7, 23.8 mg/g FBLS for Pb2+, Hg2+ and Cd2+, respectively. Metal uptake by FBLS was affected by the pH of the metal solution, but independent of temperature (10-50 degrees C). The Langmuir model was more suitable than the Freundlich model to describe the biosorption process of FBLS. The regenerated FBLS was found to be effective for repeated use for five cycles without significant loss in adsorption capacity. This research demonstrates that FBLS possesses excellent capacity for Pb2+ biosorption from aqueous solution and industrial wastewaters.

Glutathione S-transferase M1, T1, and P1 polymorphisms as susceptibility factors for noise-induced temporary threshold shift.

The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione is an important cellular antioxidant that limits cell damage by ROS. We aimed to determine the effect of genetic polymorphisms of glutathione S-transferase (GST) T1, GSTM1, and GSTP1, on temporary threshold shift (TTS) in 58 noise-exposed male workers from a steel factory. The pre-shift hearing impairment at high frequency (HF, average of 3, 4, and 6kHz) was 30.7dB HL (S.D.=19.3). The amount of daily noise exposure was 83.0dBA (S.D.=5.0). Noise-induced TTS at HF by pure-tone audiometry (PTA) was related to the daily noise exposure (p<0.05). Based on combinatory analysis, we found that individuals carrying all genotypes with GSTT1 null, GSTM1 null, and GSTP1 Ile(105)/Ile(105) were more susceptible to NIHL. These results suggest that pre-shift hearing impairment and daily noise exposure had impacts on TTS at HF by PTA. In addition, GST genetic polymorphisms may modify the susceptibility to noise-induced TTS.

Work fatigue and physiological symptoms in different occupations of high-elevation construction workers.

The objective of this study is to investigate whether work fatigue and physiological symptoms that high-elevation construction workers experience would be affected by the occupations. Questionnaires of demographic data and subjective fatigue symptoms as well as some physiological measurements were carried out, pre- and post-shift, on scaffolders, steel fixers, formworkers, electrician-plumbers, concreters and miscellaneous workers at a high-rise building construction site. This study found that some subjective fatigue symptoms coincide with the life style of some workers and that the extent of fatigue symptoms and physiological strains varies among different occupations of construction workers. Scaffolders, steel fixers and formworkers are categorized as physically demanding fatigue type of workers, while concreters, electrician-plumbers and miscellaneous workers as general type. The prevalence and occurrence of subjective fatigue symptoms indicate high-elevation workers have more complaints of "projection of physical impairment" than "drowsiness and dullness" and "difficulty in concentration". Some unexpected changes (i.e., post-shift measurements are greater than pre-shift ones) in some strength tests in scaffolders and concreters were consistent with the observations of how they exercised their bodies during work shift. Considerable variation of average heart rate among occupations was found, with scaffolders the highest and concreters the lowest. This study concludes that questionnaires of subjective fatigue symptoms and some physiological measurements can be used as indicators to predict the extent of strains or hazards which construction workers encounter. In terms of management program of safety and health, more attention should be paid to those physically demanding workers, such as scaffolders, workers with lower sense of safety and health, such as miscellaneous workers, and workers with older age, such as concreters.

Occurrence of phthalates in sediment and biota: relationship to aquatic factors and the biota-sediment accumulation factor.

Phthalate compounds in sediments and fishes were investigated in 17 Taiwan's rivers to determine the relationships between phthalate levels in sediment and aquatic factors, and biota-sediment accumulation factor (BSAF) for phthalates. Mean concentrations (range) of di(2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBzP) and di-n-butyl phthalate (DBP) in sediment at low-flow season were 4.1 (<0.05-46.5), 0.22 (<0.05-3.1) and 0.14 (<0.05-1.3)mgkg(-1)dw; those at high-flow season were 1.2 (<0.05-13.1), 0.13 (<0.05-0.27) and 0.09 (<0.05-0.22)mgkg(-1)dw, respectively. Trace levels of dimethyl phthalate (DMP), diethyl phthalate (DEP) and di-n-octyl phthalate (DOP) in sediment were found in both seasons. Concentrations of DEHP in sediments were significantly affected by temperature, suspended solids, ammonia-nitrogen, and chemical oxygen demand. The highest concentration of DEHP in fish samples were found in Liza subviridis (253.9mgkg(-1)dw) and Oreochromis miloticus niloticus (129.5mgkg(-1)dw). BSAF of DEHP in L. subviridis (13.8-40.9) and O. miloticus niloticus (2.4-28.5) were higher than those in other fish species, indicating that the living habits of fish and physical-chemical properties of phthalates, like logKow, may influence the bioavailability of phthalates in fish. Our data suggested that DEHP level in river sediments were influenced by water quality parameters due to their effects on the biodegradation processes, and that the DEHP level in fish was affected by fish habitat and physiochemical properties of polluted contaminants.

Evaluation of auditory fatigue in combined noise, heat and workload exposure.

This study was performed in a climatic chamber to evaluate the combined effects of noise intensity, heat stress, workload, and exposure duration on both noise-induced temporary threshold shift (TTS) and the recovery time by adopting Taguch's method. Fourteen subjects without previous significant noise exposure and smoking history were recruited to participate in this study. All hearing threshold levels at eight different frequencies (250 to 8,000 Hz) of better ear were measured in an audiometric booth by using the ascending method in 2 dB steps before each exposure condition. The test was also carried out after exposure to evaluate TTS at various times. The TTS recovery time was assessed using an audiometric test on all subjects at post-exposure times of 2, 20, 40, 60, 80 and 120 min, respectively. It was found that TTS depended mainly on the exposed noise dose and was enhanced by workload and heat stress. The TTS recovery time is dependent upon the magnitude of the initial hearing loss. In conclusion, TTS driven by noise exposure is enhanced by heat and workload. Further studies are required to evaluate the effects of workload with extreme temperature in a workplace environment.

Phosphorylated and hypoacetylated mutant p53 enhances cisplatin-induced apoptosis through caspase-9 pathway in the absence of transcriptional activation or translation.

It is not completely understood how certain epithelial cells harboring mutant p53 have better response to chemotherapy. We investigate the mechanism of cisplatin-induced apoptosis in two resistant cell lines (parental TCCSUP and R273L mutant p53 transfectant) and two sensitive cell lines (V143A and N247I mutant p53 transfectants). Activation of caspase 9 was demonstrated by Western blotting, and specific inhibitor for caspase 9 could inhibit apoptosis. Inhibitors for caspases 1, 2, 6, and 8 had no effect on apoptosis. Transcriptional repression of Bcl-2 occurred during apoptosis and could be reversed by the treatment of histone deacetylase inhibitor trichostatin A (TSA). The expression of Noxa, p53 inducible ribonucleotide reductase subunit 2 (p53R2), and p53 inducible death domain (PIDD) gene were not elevated with treatment of cisplatin (CDDP). Surface trafficking of Fas or Fas-L was not observed. Ser15 of wild-type p53 and mutant p53 was phosphorylated in response to cisplatin. Acetylation of wild-type p53 increased, while acetylation of mutant p53 decreased during cisplatin treatment. Both transcriptional inhibitor actinomycin D and translational inhibitor cycloheximide did not inhibit apoptosis. These results indicated that phosphorylated and hypoacetylated mutant p53 could enhance cisplatin-induced apoptosis through activation of caspase 9 independent of transcriptional activation and translation.

Evaluating the efficacy of a thermal exposure chamber designed for assessing workers' thermal hazard.

This study was conducted on a thermal exposure chamber designed for assessing workers' thermal hazard. In order to assess the efficacy of the studied chamber, three environmental conditions were selected to simulate high, middle and low thermal impact situations, with air temperatures (Ta) of 43.12, 36.23 and 25.77 masculine C, globe temperatures (Tg) of 44.41, 41.07 and 29.24 masculine C, relative humidity (RH) of 77, 59 and 39%, and air flow velocities (Va) of 1.70, 0.91 and 0.25 m/s, respectively. For the three specified thermal impact conditions, results show that the coefficients of variation (CVs) for Ta, Tg, RH and Va measured in the chamber studied were consistently less than 10%, except for Va under the low thermal impact condition (=50%). For each specified thermal impact condition, we generated 1,000 environmental combinations by using the Monte Carlo simulation approach according to the variations obtained from the four environmental factors. We directly adopted the ISO 7933 approach to estimate the allowable exposure time (AET) for each simulated environmental condition. This study yielded a range in the 95% confidence interval (95% CI) of the estimated AETs for the three specified thermal impact conditions which were consistently less than 5 min. We further conducted the sensitivity analysis to examine the effect of the four environmental factors on estimating AETs. We found Va was the least important factor in estimating AETs for any specified thermal impact condition. In conclusion, although Va was found with great variation for the chamber specified in the low thermal impact condition, the exposure chamber studied can still be regarded as a feasible one for assessing workers' thermal hazard.

The feasibility study of the octane-enhancing process: isobutylene dimerization using C4 mixture.

The dimerization of isobutylene to diisobutylene in C4 mixture was evaluated using various catalysts such as nickel salts system, zeolite system and acidic ion exchange resin. There were shown that the strong acidic type ion exchange resin (Amberlyst 15) under 6 kg/cm2 and 60 degrees C gave rise to 90% conversion and more than 60% selectivity to diisobutylene with acceptable amounts of oligomer as a best catalyst. Therefore, Amberlyst 15 was employed to investigate the optimum reaction condition. In the batch reaction, since the catalyst activity was increased with the increasing reaction temperature, the reaction time should be shortened appropriately to prevent a high yield of oligomer. The reaction rate was increased by the increased amount of catalyst without much change in the product composition. The formation of oligomer was inhibited when a small amount of organic solvents (methyl tert-butyl ether) are attended. In the fixed-bed study, the results indicate that the increase in reaction temperature was accompanied by the increase in reaction rate, however, the selectivity to the dimer was affected. Higher WHSV will enhance the selectivity but reduce the conversion. Conclusively, the appropriate reaction condition was 45 degrees C with WHSV of 10.