Immediate knowledge improvement and long-term teaching confidence after general medicine faculty training program.

BACKGROUND/PURPOSE: This study analyzed the effects of the General Medicine Faculty Training Program (GMFTP), which was implemented in 2009. The training program includes a 7-hour basic training (BT) to introduce ways of teaching and assessing the 6 core competencies identified by the Accreditation Council for Graduate Medical Education, and a 40-hour clinical training program. METHODS: Physicians from different hospitals attended the GMFTPs. Since 2010, we have been using quick tests to assess trainees' familiarity of core competencies. Knowledge improvement (KI) was defined as the difference between post-BT and pre-BT test scores. Since 2013, we have been annually mailing questionnaires to assess trainees' teaching confidence (TC) of core competencies. We analyzed the correlations between trainees' characteristics, KIs, and TCs. RESULTS: Between year 2009 and 2017, a total of 319 attending physicians (257 male, 62 female), with a mean age of 39.1 ± 6.2 years, completed the GMFTPs. Significant KI (32.6-55.4) was noted. There were no correlations between trainees' characteristics and KIs. The mean TCs for the 6 core competences were all above 4.0 (based on a 5-point Likert scale). TCs were positively correlated with age during GMFTP training, age when responding to the questionnaire, and duration between training and the last time responding to the questionnaire. TC showed no correlation with sex, hospitals, departments, or KI. CONCLUSION: Knowledge of teaching core competencies improved immediately after BT, but KIs did not correlate with TCs in long-term follow-up. After the training program, physicians' teaching confidence increased over time.

Old age is a positive modifier of renal outcome in Taiwanese patients with stages 3-5 chronic kidney disease.

BACKGROUND: The incidence of end-stage renal disease (ESRD) is increasing in elderly patients with chronic kidney disease (CKD). This contradicts the general notion that elderly people are more likely to die than to ever reach ESRD. And racial disparity in relation to age on kidney disease outcomes has always been a subject of research interest. AIMS: We investigated the effect of age on outcome in a cohort with stages 3-5 CKD patients by age category. METHODS: A total of 430 patients with a mean age of 65.6 years were enrolled and followed till death, ESRD, or end of 2015. Multivariable Cox regression was used to identify predictors of all-cause mortality. Competing risk-adjusted Cox regression was used to identify determinants of ESRD. The median follow-up was 7.3 (interquartile range 8.8) years. RESULTS: Cox regression showed old age and low mean arterial pressure were predictors of mortality before and after onset of ESRD. Competing risk analysis revealed patients aged 20-39 years and 40-64 years exhibited greater risks of ESRD, compared to those aged over 75 years. These effects of age on outcomes occurred independently of traditional risk factors such as low estimated glomerular filtration rate and high proteinuria. CONCLUSIONS: Age over 75 years is associated with decreased risk for ESRD even after adjustment for competing mortality. Given the global trends in population aging, there is a need to develop age-specific strategies, on top of the existing stage-based measures, to optimize the management of CKD in the elderly.

Diabetes mellitus, superoxide dismutase and peroxisome proliferator activated receptor gamma polymorphisms modify the outcome of end-stage renal disease patients of Han Chinese origin.

AIM: Increased oxidative stress significantly modifies the outcome of patients with diabetes mellitus (DM) and end-stage renal disease (ESRD), and is counteracted by antioxidative capacity. We aimed to investigate whether antioxidant single nucleotide polymorphisms (SNPs) influence the outcome of ESRD individuals and the influences exerted by DM, which has not been tested before. METHODS: We prospectively enrolled multi-centre ESRD patients of Han Chinese origin between 2002 and 2003, recording their antioxidant (superoxide dismutase [SOD2], glutathione peroxidase [GPX1]) and peroxisome proliferator activated receptor-γ (PPAR-γ) genotyping results, and stratified based on DM. They were followed up until 2008, with risk factors for mortality analyzed by Cox proportional hazard regression. RESULTS: We discovered that diabetic ESRD carriers of CC genotype of SOD2 exon 2 had an increased risk of mortality compared to non-diabetic ones with other genotypes (hazard ratio [HR] 4.04, P = 0.04), while GPX1 SNPs had no influence. Interactions between SOD2 and PPAR-γ SNPs regarding the mortality influence were also detected (for SOD2 CC genotype x PPAR-γ exon 6 CT genotype, HR 3.19, P = 0.008), suggesting the importance of considering a combination panel of SNPs on patient survival. CONCLUSION: This might be the largest study focusing on the relationship between antioxidant SNPs and the outcomes of diabetic ESRD patients of Han Chinese origin. More studies are needed to validate our findings.

Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against oxidative stress.

The phenomenon that heme oxygenase-1 (HO-1) protects cell from injury yet its enzymatic product, iron, may facilitate generation of free radical has been long puzzling. Here we establish a functional connection between ferritin heavy chain (FHC) and HO-1. In human lupus nephritis HO-1 and FHC are colocalized within the glomeruli. In rodent anti-Thy1 (thymocyte antigen 1) induced glomerulonephritis, heme oxygenase blockade lowers the expression of FHC and accelerates mesangial cell death. Stimulation of heme oxygenase in cultured rat mesangial cell enhances its resistance to hydrogen peroxide, whereas FHC knockdown by RNA interference compromises this salutary effect. RNA interference of HO-1 makes the cell more susceptible to hydrogen peroxide, which can be rescued by forced expression of wild-type FHC but not mutants that lose the capacity of iron storage and ferroxidase activity. Phosphorylation of JunD was not sustained in these cells. Microarray analysis identifies four candidate transcriptional factors that may regulate the HO-1-induced transcription of FHC. Our results support the role of FHC in neutralizing the iron toxicity as well as mediating the protective effect of HO-1 in response to oxidative stress.

Citrobacter peritoneal dialysis peritonitis: rare occurrence with poor outcomes.

INTRODUCTION: Non-Pseudomonas gram-negative bacteria are responsible for an increasing proportion of cases of peritoneal dialysis (PD)-related peritonitis. The role of Citrobacter species in the etiology of PD-related peritonitis is often underestimated. In the present study, we aimed to describe the clinical features, laboratory findings, and short- and long-term outcomes in PD-related peritonitis caused by Citrobacter. METHODS: A retrospective review of all episodes of PD-related peritonitis caused by Citrobacter from a single center between 1990 and 2010 was performed. Clinical features, microbiological data, and outcomes of these episodes were analyzed. RESULTS: Citrobacter species was responsible for 11 PD-related episodes (1.8% of all peritonitis episodes) in 8 patients. Citrobacter freundii was the most common etiologic species (73%), and mixed growth was found in the other 3 episodes (27%). Approximately half (46%) of the episodes were associated with constipation and/or diarrhea. Of the Citrobacter isolates from all episodes, 54% were resistant to cefazolin, and only 18% were susceptible to cefmetazole. All isolates were susceptible to ceftazidime, cefepime, carbapenem, and aminoglycosides. More than half of the patients (54%) were hospitalized for index peritonitis, and 27% of the episodes involved a change in antibiotic medication. One patient had relapsing peritonitis caused by C. koseri (9%). The mortality rate of PD-related peritonitis caused by Citrobacter was 18%, and 89% of surviving patients developed technique failure requiring a modality switch after an average of 12 months of follow-up (range 1.2-31.2 months). CONCLUSION: PD-related peritonitis caused by Citrobacter is associated with poor outcomes, including high rates of antibiotic resistance, a high mortality rate, and a high rate of technique failure among survivors during the follow-up period.

Peritoneal dialysis peritonitis by anaerobic pathogens: a retrospective case series.

BACKGROUND: Bacterial infections account for most peritoneal dialysis (PD)-associated peritonitis episodes. However, anaerobic PD peritonitis is extremely rare and intuitively associated with intra-abdominal lesions. In this study, we examined the clinical characteristics of PD patients who developed anaerobic peritonitis. METHODS: We retrospectively identified all anaerobic PD peritonitis episodes from a prospectively collected PD registry at a single center between 1990 and 2010. Only patients receiving more than 3 months of PD were enrolled. We analyzed clinical features as well as outcomes of anaerobic PD peritonitis patients. RESULTS: Among 6 patients, 10 episodes of PD-associated peritonitis were caused by anaerobic pathogens (1.59% of all peritonitis episodes during study the period), in which the cultures from 5 episodes had mixed growth. Bacteroides fragilis was the most common species identified (4 isolates). Only 3 episodes were associated with gastrointestinal lesions, and 4 episodes were related to a break in sterility during exchange procedures. All anaerobic pathogens were susceptible to clindamycin and metronidazole, but penicillin resistance was noted in 4 isolates. Ampicillin/sulbactam resistance was found in 2 isolates. In 5 episodes, a primary response was achieved using the first-generation cephalosporin and ceftazidime or aminoglycoside. In 3 episodes, the first-generation cephalosporin was replaced with aminoglycosides. Tenckhoff catheter removal was necessary in 2 episodes. Only one episode ended with mortality (due to a perforated bowel). CONCLUSION: Anaerobic PD-associated peritonitis might be predominantly caused by contamination, rather than intra-abdominal events. Half of anaerobic PD-associated peritonitis episodes had polymicrobial growth. The overall outcome of anaerobic peritonitis is fair, with a high catheter survival rate.

Effect of age on febrile response in patients with healthcare-associated bloodstream infection.

OBJECTIVE: This study aimed to determine the effect of age on febrile response in patients with healthcare-associated bloodstream infection (BSI). METHODS: This was a retrospective observational study using medical records as the primary source of data. Three indicators measured body temperature changes: basal body temperature (BBT), body temperature at infection onset (onset T), and maximum temperature (max T) during the infection period. RESULTS: In a sample of 230 patients there was no significant correlation between BBT or onset T and age. Max T was significantly correlated with age (r = -.191, p = .004). There was wide variation in onset T in all age groups. CONCLUSIONS: Age showed no effect on BBT and onset T, but blunted max T in patients with bacteremia. This variability in onset T in all age groups emphasizes the need for early recognition of subtle signs of infection and the need to use an individualized definition of fever.

Tamoxifen downregulates connective tissue growth factor to ameliorate peritoneal fibrosis.

Peritoneal fibrosis (PF), including simple sclerosis and encapsulating peritoneal sclerosis (EPS), is a serious complication in patients on long-term peritoneal dialysis. Tamoxifen has successfully been used in treating EPS; however, the mechanism of tamoxifen in treating EPS fibrosis disorders remains unclear. This study demonstrates a possible antifibrotic mechanism of tamoxifen. A bleach-induced PF rat model was applied as the in vivo treatment target. Tamoxifen was intraperitoneally injected daily to treat PF. The PF scores and thickness of the submesothelial zone over the liver surface were measured as indicators for the severity of PF. Human peritoneal mesothelial cells (HPMC) were used as an in vitro model to test the antifibrotic effect of tamoxifen. Gene expressions of transforming growth factors-ß (TGF-ß), connective tissue growth factor (CTGF) and collagen were investigated using quantitative polymerase chain reactions. In HPMC, tamoxifen showed paradoxical effects between collagen I and TGF-ß. Tamoxifen also inhibited TGF-ß-induced collagen and CTGF. The possible antifibrotic effect of tamoxifen is through inhibiting CTGF to block collagen synthesis, although it enhances TGF-ß which increases fibrosis. These results provide a possible molecular mechanism for tamoxifen.

Life expectancy, expected years of life lost and survival of hemodialysis and peritoneal dialysis patients.

BACKGROUND: Expected years of life lost (EYLL) in dialysis patients are rarely discussed. This study compared life expectancy, EYLL and survival between hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Adults who underwent maintenance dialysis at National Taiwan University Hospital from 1995 to 2006 were followed up until December 2007. Kaplan-Meier analysis and a constant excess hazard model were used to estimate and project long-term survival. EYLL was calculated by subtracting the life expectancy of patients from that of age- and sex-matched referents. HD patients were then matched with PD patients on age, sex and diabetes mellitus (DM). Life expectancy, EYLL and survival between the 2 groups were compared. Mortality risks were determined by the Cox model. RESULTS: Before matching, the 305 HD patients were older than the 428 PD patients (62.4 ± 13.7 vs. 53.1 ± 16.7 years; p<0.0001). More HD patients had DM (HD vs. PD, 29.2% vs. 20.6%; p=0.0072). Life expectancy and EYLL of HD patients were 8.8 and 11.5 years, compared with those of PD patients (19.9 and 7.4 years). After matching, life expectancy (p=0.790) and EYLL (p=0.793) of both groups (236 patients each) were similar. Age (adjusted hazard ratio [AHR] = 1.07; 95% confidence interval [95% CI], 1.05-1.09) and DM (AHR=3.81; 95% CI, 2.28-6.36) were independent mortality predictors. For diabetic patients who underwent HD, a better survival rate was observed (AHR=0.24; 95% CI, 0.11-0.53). CONCLUSIONS: After matching, HD and PD patients had similar life expectancy and EYLL. Survival was better for diabetic patients if they received HD.

Shared risk factors for distinct geriatric syndromes in older Taiwanese inpatients.

BACKGROUND: Identifying shared common risk factors of geriatric syndromes is clinically useful in designing a unified approach to optimizing geriatric care. OBJECTIVES: The purpose of this study was to identify older Taiwanese inpatients' common shared risk factors among seven distinct geriatric syndromes: malnutrition, depression, cognitive impairment, functional dependence, incontinence, pressure ulcers, and dehydration. METHOD: A cross-sectional, hospital-wide survey was conducted to enroll inpatients (N = 455) older than 65 years and admitted to 24 medical and surgical units in a 2,200-bed urban academic medical center in northern Taiwan. Malnutrition was defined as a Mini-Nutritional Assessment score less than 17.5, depression was defined as a Geriatric Depression Scale score more than 10, cognitive impairment was considered a Mini-Mental State Examination score less than 20, and functional dependence was defined as a Barthel Index score less than 50. Incontinence, pressure ulcers, and dehydration were extracted from patients' medical records. RESULTS: Participants had a mean age of 75.3 years (SD = 6.1 years, range = 65-92 years). The prevalence of geriatric syndromes ranged from 5% (pressure ulcers) to 33% (malnutrition). The selected geriatric syndromes were shown through logistic regression analysis to be predicted by female gender (odds ratio [OR] = 1.57-2.75), functional status (OR = 0.94-0.99), cognitive status (OR = 0.82-0.95), nutritional status (OR = 0.74-0.93), and depressive symptoms (OR = 1.07-1.26), supporting the notion of shared risk factors in geriatric syndromes. CONCLUSIONS: The findings support the theory that common geriatric syndromes have a shared set of risk factors-female gender, depressive symptoms, and functional, cognitive, and nutritional status. Revising care to target these shared risk factors in preventing common geriatric syndromes is theoretically sound.

Benefits of sevelamer on markers of bone turnover in Taiwanese hemodialysis patients.

BACKGROUND/PURPOSE: Sevelamer hydrochloride is a recently developed phosphate binder, which is a quaternary amine anion exchanger without calcium or aluminum. Sevelamer is effective in controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis (HD) patients. We investigated whether sevelamer restored bone metabolism in chronic HD patients. METHODS: An 8-week, prospective, open-label, randomized study was conducted after a 2-week washout period in chronic hyperphosphatemic HD patients. This study compared the effect of sevelamer on markers of bone turnover with that of calcium acetate, as stratified by baseline serum intact parathyroid hormone (iPTH) level. RESULTS: There was no difference in the changes of serum phosphorus, calcium-phosphorus product and serum iPTH between the sevelamer and the calcium acetate groups. However, more hypercalcemic events (12%) were documented under calcium acetate treatment. In patients with hypoparathyroidism, calcium acetate treatment decreased serum iPTH at the end of the study, while sevelamer did not. Increased serum alkaline phosphatase levels were found among patients receiving sevelamer treatment compared with those who received calcium acetate treatment. In those patients receiving sevelamer, the serum alkaline phosphatase level was also positively correlated to the sevelamer dosage (r = 0.246, p = 0.013). CONCLUSION: Sevelamer effectively reduces serum phosphorus with a lower incidence of hypercalcemic effects in HD patients. Sevelamer is an effective means of treatment for chronic hyperphosphatemic HD patients, especially those with hypoparathyroidism.

Hyperuricemia associated with rapid renal function decline in elderly Taiwanese subjects.

BACKGROUND/PURPOSE: Hyperuricemia is encountered frequently in patients with chronic kidney disease (CKD). We tested the hypothesis that uric acid influences glomerular filtration rate (GFR) and is associated with renal function decline in elderly Taiwanese subjects. METHODS: We enrolled 800 elderly Taiwanese subjects for a health checkup. Estimated GFR (eGFR) was measured using the Modification of Diet in Renal Disease Study equation. eGFR < 60 mL/min/1.73 m2 was used to analyze the prevalence and incidence of CKD. Significant renal function decline was defined as a decrease in eGFR of > or = 3 mL/min/1.73 m2 per year. RESULTS: The prevalence of CKD was 18.0% in the elderly subjects. Mean serum uric acid level was 6.6 mg/dL in male and 5.6 mg/dL in female subjects, and eGFR was 71.7 mL/min/1.73 m2. Uric acid levels were associated independently and negatively with eGFR after adjusting for conventional factors of renal function decline. One hundred and sixty-two individuals (31.2%) had a significant decline in renal function. As uric acid level increased by 1 mg/dL, the odds of a significant eGFR decline increased by 1.208. CONCLUSION: Serum uric acid level was associated with eGFR and decline in renal function in elderly Taiwanese subjects. Whether hypouricemic therapy could retard the progression of CKD deserves further in-depth study.

10-Year Renal Function Trajectories in Community-Dwelling Older Adults: Exploring the Risk Factors for Different Patterns.

Longitudinal changes of renal function help inform patients' clinical courses and improve risk stratification. Rare studies address risk factors predicting changes in estimated glomerular filtration rate (eGFR) over time in older adults, particularly of Chinese ethnicity. We identified prospectively enrolled community-dwelling older adults (≥65 years) receiving annual health examinations between 2005 and 2015 with serum creatinine available continuously in a single institute, and used linear regression to derive individual's annual eGFR changes, followed by multivariate logistic regression analyses to identify features associated with different eGFR change patterns. Among 500 elderly (71.3 ± 4.2 years), their mean annual eGFR changes were 0.84 ± 1.67 mL/min/1.73 m²/year, with 136 (27.2%) and 238 (47.6%) classified as having downward (annual eGFR change <0 mL/min/1.73 m²/year) and upward eGFR (≥1 mL/min/1.73 m²/year) trajectories, respectively. Multivariate logistic regression showed that higher age (odds ratio (OR) 1.08), worse renal function (OR 13.2), and more severe proteinuria (OR 9.86) or hematuria (OR 3.39) were predictive of a declining eGFR while greater waist circumference (OR 1.06) and higher leukocyte counts (OR 1.21) were predictive of an uprising 10-year eGFR. These findings elucidate important features associated with geriatric renal function variations, which are expected to improve their renal care.

Relationship of homocysteine levels to quadriceps strength, gait speed, and late-life disability in older adults.

BACKGROUND: Elevated homocysteine, causing tissue injury by such mechanisms as oxidative stress, endothelial damage, and protein homocysteinylation, is associated with multiple age-related problems including cardiovascular diseases, dementia, and osteoporotic fracture. Disability is one of the most common features in older adults. However, little is known about the role of homocysteine in physical disability among older adults. METHODS: Participants (>60 years, N = 1677) were from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Nineteen questionnaires in five major domains were administered to assess the level of difficulty in performing various tasks: activities of daily living (ADL), instrumental ADL (IADL), leisure and social activities (LSA), lower extremity mobility (LEM), and general physical activities (GPA). Peak quadriceps strength was obtained by using an isokinetic dynamometer. Habitual gait speed was obtained from a 20-foot timed walk. Homocysteine levels were measured by the Abbott homocysteine assay, an automated fluorescence polarization immunoassay (FPIA). RESULTS: Elevated homocysteine was associated with disability in ADL, IADL, LSA, and GPA after multivariate adjustment. The odds ratios (ORs) for disability in these domains comparing participants in the highest quartile of homocysteine to those in the lowest were 2.18 (95% confidence interval [CI], 1.32-3.59) for ADL; 1.62 (95% CI, 1.02-2.57) for IADL; 2.00 (95% CI, 1.14-3.51) for LSA; and 1.52 (95% CI, 1.05-2.21) for GPA. The strength of associations weakened somewhat after additional adjustment of quadriceps strength and/or gait speed, suggesting a mediating role of quadriceps strength and gait speed in the association between homocysteine and disability. Homocysteine had an inverse relationship to quadriceps strength and gait speed. Likewise, quadriceps strength seemed to mediate the inverse association between homocysteine and gait speed. CONCLUSIONS: Elevated homocysteine is associated with multiple domains of disability mediated in part by muscle strength and gait speed. The results suggest that homocysteine levels may be important indicators of performance status in older adults.

Seroprevalence of hepatitis B viral markers among freshmen--20 years after mass hepatitis B vaccination program in Taiwan.

BACKGROUND/PURPOSE: The nationwide hepatitis B vaccination program in Taiwan was well known for its efficacy in reducing the carrier rate of hepatitis B and the morbidity and mortality of hepatitis B-related diseases among children. The aim of this study was to investigate the seroprevalence of hepatitis B 20 years after this program was implemented. METHODS: A total of 7592 freshmen from one university in Northern Taiwan participated in this study during their school entry health exam in September 2003 and September 2004. Basic data including gender, birthday, family history and vaccination history of hepatitis B by self-reported questionnaire were collected. Hepatitis B serum markers, including hepatitis B surface antigen, antibody against hepatitis B surface antigen, and antibody against hepatitis B core antigen were all checked. The differences in the seroprevalence of hepatitis B between two groups of subjects born before July 1984 and after July 1984 were examined. Multiple logistic analyses were performed for identifying the odds ratio (OR) of family history and other variables for each hepatitis B serum marker. RESULTS: Subjects born after July 1984 were found to have a lower rate of hepatitis B surface antigen of 2.2% (95% confidence interval [CI], 1.8-2.6%) vs. 7.4% (95% CI, 5.9-8.9%), and core antibody against hepatitis B of 6.7% (95% CI, 6.0-7.3%) vs. 23.5% (95% CI, 21.1-25.9%), but a higher rate of surface antibody against hepatitis B of 74.3% (95% CI, 73.2-75.4%) vs. 69.1% (95% CI, 66.5-71.7%) compared with those born before July 1984 (all p < 0.001). Subjects with a family history of hepatitis B had higher risk of being infected by hepatitis B (OR, 4.07; 95% CI, 3.18-5.12) and becoming carriers (OR, 7.26; 95% CI, 5.05-10.44) after adjustment for sex, age, birth year, and self-reported hepatitis B vaccination history. CONCLUSION: The seroprevalence of hepatitis B surface antigen continued to decline 20 years after neonatal hepatitis B vaccination program. It is strongly recommended that those who have a family history of hepatitis B should receive early check-up of hepatitis B status after complete vaccination or closely follow up their hepatitis B status after neonatal hepatitis B vaccination.

Effect of Kidney Dysfunction on Cerebral Cortical Thinning in Elderly Population.

Chronic kidney disease has been linked to cognitive impairment and morphological brain change. However, less is known about the impact of kidney functions on cerebral cortical thickness. This study investigated the relationship between kidney functions and global or lobar cerebral cortical thickness (CTh) in 259 non-demented elderly persons. Forty-three participants (16.7%) had kidney dysfunction, which was defined as either a glomerular filtration rate (GFR) of <60 ml/min/1.73 m2 or presence of proteinuria. Kidney dysfunction was associated with lower global (ß = -0.05, 95% CI = -0.08 to -0.01) as well as frontal, parietal, temporal, occipital, and insular lobar CTh. In the stratified analysis, the associations were more pronounced in women, APOEε4 non-carriers, and participants with a lower cognitive score. Besides, kidney dysfunction significantly increased the risk of cortical thinning, defined as being the lowest CTh tertile, in the insular lobe (adjusted odds ratio = 2.74, 95% CI = 1.31-5.74). Our results suggested that kidney dysfunction should be closely monitored and managed in elderly population to prevent neurodegeneration.

Linking C-reactive protein to late-life disability in the National Health and Nutrition Examination Survey (NHANES) 1999-2002.

BACKGROUND: Chronic inflammation, measured by interleukin-6, predicts incident disability among elderly people. However, little is known about the relation of C-reactive protein (CRP) to disability. METHOD: Participants (>60 years old, N = 1680) were from the National Health and Nutrition Examination Survey 1999-2002. Disability in activities of daily living (ADL), instrumental activities of daily living (IADL), leisure and social activities (LSA), lower extremity mobility (LEM), and general physical activities (GPA) was obtained by self-report. Peak muscle power was the product of isokinetic peak leg torque and peak force velocity. Functional limitations were evaluated via habitual walking speed, which was obtained from a 20-foot timed walk. CRP levels were quantified by using latex-enhanced nephelometry. RESULTS: Elevated CRP levels were associated with disability in IADL, LSA, LEM, and GPA, independent of basic demographics, chronic medical diseases, health behaviors, as well as nutritional markers. The corresponding odds ratios of disability for each standard-deviation increase in natural-log-transformed CRP were 1.18 (95% confidence interval [CI], 1.02-1.35), 1.18 (95% CI, 1.00-1.39), 1.17 (95% CI, 1.03-1.33), and 1.17 (95% CI, 1.05-1.31), respectively. The relationship diminished after additional adjustment of leg power and/or walking speed, meaning that impairment in leg power and limitations in gait speed likely mediate the association between CRP and disability. CRP had an inverse relationship to leg power and walking speed. Likewise, additional adjustment for leg power substantially diminished the association between CRP and walking speed, suggesting a mediating effect of power between CRP and gait speed. CONCLUSIONS: Independent of chronic diseases, elevated CRP is associated with multiple domains of disability through mediation of muscle power, habitual gait speed, or both. Future research is needed to understand CRP as a risk factor for disability in older populations.

Interplay between Superoxide Dismutase, Glutathione Peroxidase, and Peroxisome Proliferator Activated Receptor Gamma Polymorphisms on the Risk of End-Stage Renal Disease among Han Chinese Patients.

Background. Single nucleotide polymorphisms (SNPs) of antioxidants, including superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1), play an important role in the risk for cancer and metabolic disorders. However, little is known regarding the effect of antioxidant SNPs on renal events. Methods. We prospectively enrolled multicenter patients with end-stage renal disease (ESRD) and those without chronic kidney disease (CKD) of Han Chinese origin, with SOD2 (Val16Ala), GPX1 (Pro197Leu), and PPAR-γ (Pro12Ala, C161T) genotyped. Multiple regression analyses were conducted to evaluate the significant risk determinants for ESRD. Results. Compared to ESRD patients, non-CKD subjects were more likely to have T allele at SOD2 Val16Ala (p = 0.036) and CC genotype at PPAR-γ Pro12Ala (p = 0.028). Regression analysis showed that TT genotype of SOD2 Val16Ala conferred significantly lower ESRD risk among patients without diabetes (odds ratio 0.699; p = 0.018). GPX1 SNP alone did not alter the risk. We detected significant interactions between SNPs including PPAR-γ Pro12Ala, C161T, and GPX1 regarding the risk of ESRD. Conclusion. This is the first and largest study on the association between adverse renal outcomes and antioxidant SNPs among Han Chinese population. Determination of SOD2 and PPAR-γ SNPs status might assist in ESRD risk estimation.

Antihypertensive agents and the risk of breast cancer in women aged 55 years and older: a nested case-control study.

OBJECTIVE: The study aimed to investigate the association of long-term use of different antihypertensive agents with incident breast cancer. METHODS: A total of 794 ,533 women aged at least 55 years were identified from Taiwan National Health Insurance claims database during 2001-2011. As of 31 December 2011, incident breast cancer patients were included as cases, and 1 : 4 age-matched controls were selected by risk-set sampling scheme. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer incidence associated with different durations of use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, and dihydropyridine calcium channel blockers (DHP CCBs). Different restriction rules were applied to reveal the potential effects of confounding by indication. RESULTS: Among the 9397 incident breast cancer patients and 37 ,588 controls, a significantly elevated risk was found for relatively short-term use of DHP CCBs (<6 years) but not in those observed for more than 6 years. There was no association between either angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or ß-blockers use and breast cancer. Although restricting our analyses to those with any prescription of antihypertensive medications in 2001 or those with diagnosis of hypertension, there was no longer a statistically significant association between any use of DHP CCBs and breast cancer (OR: 1.21, 95% CI: 0.88-1.67 for the former, and OR: 1.71, 95% CI: 0.99-2.95 for the latter). CONCLUSION: The results demonstrated the potential effect of confounding by indication, and thus, did not suggest any association of the use of antihypertensive medication and breast cancer risk.

Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis.

Evidence suggests that a high concentration of C-reactive protein (CRP) is a cardiovascular risk factor and an important correlate of cognitive disorders and depression. Recently, population-based studies examining the association between CRP and stroke, cognitive impairment, or depression have been done but have not yet been systematically reviewed. Here we present a systematic review of the associations between CRP and stroke, cognitive impairment, and depression. Hospital or clinic-based studies were excluded because the inferences might not be easily applicable to the general population. 19 eligible studies of CRP were selected: seven for stroke, six for cognitive disorders, and six for depression. Raised CRP concentrations were associated with history of stroke and increased risk of incident stroke. Meta-analysis of studies with long follow-up (>8 years) showed that the risk for stroke in healthy individuals with the highest quartile of CRP concentrations increased nearly 70% compared to those with the lowest quartile. High concentrations of CRP were predictive of cognitive decline and dementia. The relations of CRP to depression were all cross-sectional and were not consistent. We conclude that high concentrations of CRP are associated with increased risk of stroke and cognitive impairment. The association between CRP and depression should be studied prospectively.