Risk of parkinsonism induced by flunarizine or cinnarizine: a population-based study.

PURPOSE: This retrospective cohort study used a population-based dataset to test the risk for parkinsonism in patients receiving flunarizine and cinnarizine, compared with matched controls. METHODS: Data were obtained from the National Health Insurance Research Dataset of Taiwan. Patients receiving flunarizine or cinnarizine for more than 1 month between 2000 and 2005 were enrolled. Exclusion criteria included receiving flunarizine, cinnarizine, or antipsychotics for more than 1 month during 1997-1999, a history of neurodegenerative diseases, and an age of less than 30 years. One matched control for each patient was selected. Each participant was followed for diagnosis of parkinsonism within a 3-year observation period. Stroke, diabetes mellitus, total prescription days, and doses of flunarizine or cinnarizine were recorded. RESULTS: The study and control groups consisted of 9830 subjects. In the study group, 280 patients (2.9 %) were diagnosed with parkinsonism with a median observation period of 1.2 years, and 49 participants (0.5 %) were diagnosed in the control group with a median observation period of 1.9 years. The adjusted hazard ratio for parkinsonism among patients receiving flunarizine and cinnarizine was 5.117 (95 % CI = 3.758-6.967). Age, stroke, and diabetes mellitus were significant risk factors, but female sex and total doses of the study drugs were not. CONCLUSIONS: This study demonstrates that flunarizine and cinnarizine significantly increase the risk for parkinsonism. The treatment benefits of these two agents should be balanced with this adverse effect. Physicians must look carefully for early signs of parkinsonism in patients treated with flunarizine and cinnarizine.

Inverse Association Between Cancer and Dementia: A Population-based Registry Study in Taiwan.

Dementia and cancer are 2 common diseases in the elderly. This retrospective cohort study used a population-based insurance claim dataset, merged with a cancer registry, to test whether risk reduction of cancers occurs at various primary sites after diagnosis of dementia. The study included a cohort of 3282 patients who were first diagnosed with dementia between 2001 and 2002. A control cohort consisted of 13,128 subjects matched for age, sex, and year of enrollment. The site of cancer and duration between the diagnosis of dementia and cancer were analyzed. Among the dementia cases, 169 patients (5.2%) were diagnosed with cancer during a median observation period of 40 months. In the control group, 976 subjects (7.4%) were diagnosed with cancer, during a median observation period of 46 months. During a 7-year follow-up period, the adjusted hazard ratio for cancer among dementia patients was 0.77 (95% confidence interval, 0.65-0.91), and significantly lower for colon (0.54, 0.29-0.99) and prostate cancers (0.44, 0.20-0.98). This study showed an inverse association between cancer and dementia. Further studies focusing on colon and prostate cancers may help elucidate the underlying mechanism and expand the therapeutic strategies.

The association of anthropometry indices with gout in Taiwanese men.

BACKGROUND: To examine the association of anthropometry indices with gout and to compare the performance of indices to predict gout in Taiwanese men. METHODS: There were 1443 male subjects aged more than 20 years who participated in the Nutrition and Health Survey in Taiwan (NAHSIT, 1993-1996). Anthropometric evaluation consisted of weight, height, hip and waist circumference (WC) with later body mass index (BMI), waist to height (WHtR) and waist to hip (WHR) estimations. We conducted 4 logistic models to determine the relationships between anthropometric indices and gout. Receiver operating characteristic (ROC) curve were used to compare the predictive performance and to identify the optimal cut-off points, sensitivity and specificity of these indices for gout in men. RESULTS: After controlling for other covariables, the adjusted odds ratios for the mid and top tertiles of WHtR were 2.55 (95% CI: 1.16, 5.59) and 3.01 (95% CI: 1.13, 7.99), respectively, but no linear association was found for BMI, WHR and WC. In ROC curve, the greatest area under curve was 0.684 for WHtR and the cut-off point of WHtR was 0.57. CONCLUSIONS: WHtR had a significant linear association with gout in Taiwanese men and was superior to BMI, WHR and WC.

Geographic patterns of hepatocellular carcinoma mortality with exposure to iron in groundwater in Taiwanese population: an ecological study.

BACKGROUND: Many studies have examined the risk factors for HCC (including hepatitis B virus, hepatitis C virus, aflatoxin, retinol, cigarette smoking, and alcohol consumption). However, data from previous studies on the association between iron exposure, land subsidence, and HCC mortality/incidence were limited, especially in Taiwanese population. We aimed to explore the geographical distribution of HCC mortality rates by township-specific data and to evaluate the association between HCC mortality, land subsidence, and iron levels in groundwater in Taiwan. METHODS: We conducted an ecological study and calculated the HCC age-standardized mortality/incidence rates according to death certificates issued in Taiwan from 1992 to 2001 and incidence data from 1995-1998. The land subsidence dataset before 2005 and iron concentrations in groundwater in 1989 are also involved in this study. Both geographical information systems and Pearson correlation coefficients were used to analyze the relationship between HCC mortality rates, land subsidence, and iron concentrations in groundwater. RESULTS: Township-specific HCC mortality rates are higher in southwestern coastal townships where serious land subsidence and higher township-specific concentrations of iron in groundwater are present. The Pearson correlation coefficients of iron concentrations in groundwater and ASRs of HCC were 0.286 (P = 0.004) in males and 0.192 (P = 0.058) in females for mortality data; the coefficients were 0.375 (P < 0.001) in males and 0.210 (P = 0.038) in females for incidence data. CONCLUSIONS: This study showed that HCC mortality is clustered in southwestern Taiwan and the association with the iron levels in groundwater in Taiwanese population warrant further investigation.

Cell-type specificity of lung cancer associated with low-dose soil heavy metal contamination in Taiwan: an ecological study.

BACKGROUND: Numerous studies have examined the association between heavy metal contamination (including arsenic [As], cadmium [Cd], chromium [Cr], copper [Cu], mercury [Hg], nickel [Ni], lead [Pb], and zinc [Zn]) and lung cancer. However, data from previous studies on pathological cell types are limited, particularly regarding exposure to low-dose soil heavy metal contamination. The purpose of this study was to explore the association between soil heavy metal contamination and lung cancer incidence by specific cell type in Taiwan. METHODS: We conducted an ecological study and calculated the annual averages of eight soil heavy metals (i.e., As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) by using data from the Taiwan Environmental Protection Administration from1982 to 1986. The age-standardized incidence rates of lung cancer according to two major pathological types (adenocarcinoma [AC] and squamous cell carcinoma [SCC]) were obtained from the National Cancer Registry Program conducted in Taiwan from 2001 to 2005. A geographical information system was used to plot the maps of soil heavy metal concentration and lung cancer incidence rates. Poisson regression models were used to obtain the adjusted relative ratios (RR) and 95% confidence intervals (CI) for the lung cancer incidence associated with soil heavy metals. RESULTS: For males, the trend test for lung SCC incidence caused by exposure to Cr, Cu, Hg, Ni, and Zn showed a statistically significant dose-response relationship. However, for lung AC, only Cu and Ni had a significant dose-response relationship. As for females, those achieving a statistically significant dose-response relationship for the trend test were Cr (P = 0.02), Ni (P = 0.02), and Zn (P= 0.02) for lung SCC, and Cu (P < 0.01) and Zn (P = 0.02) for lung AC. CONCLUSION: The current study suggests that a dose-response relationship exists between low-dose soil heavy metal concentration and lung cancer occurrence by specific cell-type; however, the relevant mechanism should be explored further.

A simple method for increasing levels of high-density lipoprotein cholesterol: a pilot study of combination aerobic- and resistance-exercise training.

Evidence suggests that physical activity has a beneficial effect of elevated high-density lipoprotein cholesterol (HDL-C) on reducing coronary artery risk. However, previous studies show contrasting results for this association between different types of exercise training (i.e., aerobic, resistance, or combined aerobic and resistance training). The aim of this study was to determine which type of exercise training is more effective in increasing HDL-C levels. Forty obese men, age 18-29 yr, were randomized into 4 groups: an aerobic-training group (n = 10), a resistance-training group (n = 10), a combined-exercise-training group (n = 10), and a control group (n = 10). After a 12-wk exercise program, anthropometrics, blood biochemical variables, and physical-fitness components were compared with the data obtained at the baseline. Multiple-regression analysis was used to evaluate the association between different types of exercise training and changes in HDL-C while adjusting for potential confounders. The results showed that with the control group as the comparator, the effects of combined-exercise training (ß = 4.17, p < .0001), aerobic training (ß = 3.65, p < .0001), and resistance training (ß = 2.10, p = .0001) were positively associated with increase in HDL-C after adjusting for potential confounders. Our findings suggested that a short-term exercise program can play an important role in increasing HDL-C levels; either aerobic or resistance training alone significantly increases the HDL-C levels, but the improvements are greatest with combined aerobic and resistance training.

Interleukin-27 and interleukin-12 augment activation of distinct cord blood natural killer cells responses via STAT3 pathways.

BACKGROUND/PURPOSE: Umbilical cord blood is rich in primitive natural killer (NK) cells, which are activated by interleukin (IL)-12. It was previously reported that a novel IL-12 family cytokine, IL-27 comprised of EBI3 and p28, was elevated in maternal serum during normal pregnancy. Thus, we compared the immune regulatory functions of IL-27 and IL-12 on mononuclear cells derived from cord blood and adult peripheral blood. METHODS: After stimulation with IL-27, IL-12, and IL-27 combined with IL-12, the cytotoxicity against BJAB lymphoma cells by blood mononuclear cells was performed. Then immunofluorescence staining, reverse transcriptase-polymerase chain reaction and Western blotting were used to detect the effects of IL-27 and IL-12 in isolated NK cells. RESULTS: IL-27, IL-12, and IL-27 combined with IL-12 enhanced the cytotoxicity of adult peripheral blood cells and cord blood cells, but the proliferation of distinct subpopulations of cells was not evident. Similar results were also obtained with purified cord blood NK cells. Interestingly, distinct from IL-12, IL-27 could induce aggregation and morphological changes of umbilical cord blood cells. Finally, IL-27 combined with IL-12 could stimulate increased IL-27 receptor (gp130 and WSX-1) transcripts in purified cord blood NK cells. However, the activation of signal transducer and activator of transcription 3 (STAT3) in NK cells was only detected in the presence of IL-27, but not IL-12 alone. CONCLUSION: From previous results, we summarize our current understanding of the augmentation of distinct regulation of NK cells by IL-27 and IL-12.

Cross-generation link between inactive behavior of schoolchildren and metabolic disease category of parents.

In this study, we determined the cross-generation link between sedentary behavior of schoolchildren with their 6-year BMI progression pattern and metabolic disease category of their parents. Anthropometric data of 11,190 elementary schoolchildren (aged 13) were retrospectively tracked from 2003 to 2009, and classified into two groups: Normal (N = 9793) and Metabolic Disorders (N = 1397), based on the disease category of their parents (under at least one medication for stroke, coronary heart disease (CAD), diabetes, and hypertension). Schoolchildren's weekly time spending on reading, computer use, video game, music listening, radio listening, TV watching, and movie watching, was reported with parental assistance via questionnaires. Baseline BMI and 6 years BMI progression rate in Metabolic Disorders group were significantly higher than those in Normal group. In particular, offsprings from stroke parents exhibited the greatest baseline BMI across 6 years compared to the rest of the disease categories. For Metabolic Disorders group, time spending on computer use, video game, TV watching, and music listening of schoolchildren was significantly longer than Normal group. Reading, which occupied the largest portion of weekly sedentary time, was not contributed to the group difference on the BMI status of schoolchildren. The current study demonstrates that schoolchildren from family with at least one parent having metabolic disorders, particularly stroke, tend to be more sedentary and heavior than their age-matched normal peers. School-based obesity prevention programs are suggested for this specific group by restricting time spent on technology-associated sedentary behaviors and promoting sport activities.

A Simple Method for Increasing High-Density Lipoprotein Cholesterol Levels: A Pilot Study of Combination Aerobic and Resistance Exercise Training.

Evidence suggests that physical activity has a beneficial effect of elevated high-density lipoprotein cholesterol (HDL-C) on reducing coronary artery risk. However, previous studies show contrasting results for this association between different types of exercise training (i.e., aerobic, resistance or combined aerobic and resistance training).The aim of this study was to determine which type of exercise training is more effective in increasing HDL-C levels. A total of 40 obese males, aged 18-29 years old, were randomized into four groups: an aerobic training group (n= 10), a resistance training group (n= 10), a combined exercise training group (n= 10), and a control group(n= 10). After 12-week of exercise program, anthropometrics, blood biochemical variables and physical fitness components were compared with the data obtained at the baseline. The multiple regression analysis was used to evaluate the association between different types of exercise training and changes in HDL-C while adjusting for potential confounders. The results showed that with the control group as the comparator, the effects of combined exercise training group (ß= 4.17, P< 0.0001), aerobic training group (ß= 3.65, P< 0.0001) and resistance training group (ß= 2.10, P=0.0001) were positively associated with increase in HDL-C after adjusting for potential confounders. Our findings suggested that a short-term exercise program can play an important role in increasing the HDL-C level, either aerobic or resistance training alone increase significantly the HDL-C levels, but the improvements are greatest with combined aerobic and resistance training.

Anthropometric Characteristics in Taiwanese Adults: Age and Gender Differences.

Population aging is creating critical issues in Taiwan, and adults are being forced to maintain productivity at work; in other words, they need to work longer. Therefore, their fitness and health warrant immediate attention. Although the association between health and anthropometric characteristics has been reported, few profiles on Taiwanese adults can be found. The purpose of this study was to provide a suitable reference on the anthropometric data of Taiwanese adults. We recruited 60,056 anthropometric measurements from a representative database. Significant differences were found in every measurement for each gender and age group. Statistically, our results indicated anthropometric differences in different ages. However, CVs showed that the dispersions are minor. This study presents a sufficient profile on Taiwanese adults from a representative database to practitioners and other potential users.

Integrating the Public Health Services Model into Age-Friendly Pharmacies: A Case Study on the Pharmacies in Taiwan.

Taiwan is expected to become a superaged society by 2026. Community pharmacies have recently joined Taiwan's primary care system; they have great potential to provide professional healthcare services. This study examined whether the services provided by community pharmacists enhance medication adherence, enable the identification and solution of drug therapy problems, and are accepted by community residents. The Department of Public Health, Taoyuan City, collaborated with the Taoyuan Pharmacist Association over 11 months in 2018 in enabling pharmacists to dispense prescriptions and provide medication adherence consultations, cognitive services, and home and institutional medical care services. This study designed four satisfaction questionnaires to assess the feasibility and performance of these services. Regarding the services related to medication knowledge and adherence, 92.10% of the patients reported overall satisfaction, and all understanding and ability scores were improved in more than 95% of patients. The number of patients highly cooperative regarding their medication had risen from 14 to 234 after the intervention, and the number with low medication adherence had dropped from 533 to 33. More than 90% of respondents indicated that the institutional medical care services had significantly improved their medication knowledge and behaviors. The feasibility of the incorporation of integrated the public health services model into age-friendly pharmacies was confirmed by this study.

Association of Regular Leisure-Time Physical Activity with Self-Reported Body Mass Index and Obesity Risk among Middle-Aged and Older Adults in Taiwan.

Through this study, we aimed to determine the association of regular leisure-time physical activity (LTPA) with self-reported body mass index (BMI) and obesity risk among middle-aged and older adults in Taiwan. We conducted a cross-sectional study and reviewed the data derived from the Taiwan National Physical Activity Survey (TNPAS). Responses from 12,687 participants aged 45-108 years from the database were collected in this study. All the participants completed a standardized structured questionnaire that solicitated information regarding their demographic characteristics (age, gender, education, occupation, and self-reported health status), physical activity behaviors (regular/nonregular LTPA), and self-reported anthropometrics (height, weight, and BMI). Multiple linear and logistic regressions were used to examine the association between regular LTPA and BMI, and between regular LTPA and obesity status, respectively. Regular LTPA was associated with male gender, normal weight, excellent or good self-reported health status, and a lower rate of being underweight compared with nonregular LTPA. Regular LTPA was significant negatively associated with being underweight (OR = 0.71, p < 0.05), whereas it had no significant relationship with BMI and obesity (p > 0.05). Regular LTPA was associated with a reduced risk of being underweight among middle-aged and elderly adults in Taiwan. Further research on the relevant mechanism underlying this phenomenon is warranted.

Effects of one-year swimming training on blood pressure and insulin sensitivity in mild hypertensive young patients.

UNLABELLED: Swimming is a lifestyle intervention recommended by many clinicians in the prevention and treatment of hypertension. Yet, not all studies have agreed that swimming training can reduce blood pressure (BP). Inclusion of normotensive subjects could be a confounder for discrepancies among studies. In this one-year longitudinal study, long-term effects of swimming training on BP were investigated in 7 mild hypertensive patients (systolic BP (SBP) > 140 mmHg) and 16 normotensive controls. At baseline, these subjects (aged 21.5 +/- 0.1 years) did not participate in any form of sport training activity for the previous 3 months before enrollment into the training program. The training distance progressed from 0 (baseline) to 7 kilometers per week. BP and the homeostasis model assessment for insulin resistance (HOMA-IR) were determined under fasted condition at baseline and 48 h after the last swimming bout. The hypertensive patients displayed significantly greater HOMA-IR than age-matched normotensive controls. When data of all subjects were pooled, plasma glucose concentration was only slightly lowered after training, but weight, height, body mass index, SBP, diastolic BP (DBP) and HOMA-IR values were not significantly altered. However, when observation was restricted to the hypertensive patients, swimming training significantly lowered SBP by approximately 17 mmHg, concurrent with 41% reduction in HOMA-IR. Intriguingly, SBP in the normotensive subjects was elevated by approximately 6 mmHg after training. CONCLUSIONS: The present study found normalization rather than universal reduction effect of swimming training on BP. Furthermore, the BP-lowering effect of training in hypertensive patients appears to be associated with improvement in insulin sensitivity.

Exploration of the association between obesity and semen quality in a 7630 male population.

This study aimed to explore the association between body mass index (BMI), other anthropometric indexes and semen quality in a general male population in Taiwan. In this cross-sectional cohort study, the study cohort consisted of 7941 healthy male individuals aged 18 years or older who participated in a standard medical screening program run by a private firm from January 2008 to May 2013. Semen parameters including sperm concentration (SC), total sperm motility (TSM), progressive motility (PRM), and normal sperm morphology (NSM) were recorded. Anthropometric indexes including BMI, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and body fat percentage were measured. A total of 7630 men were enrolled for the final analysis, of whom 68.5% had a normal weight distribution and 31.4% were overweight or obese. Total sperm motility, progressive motility, normal sperm morphology and sperm concentration showed a statistically linear decline with increasing age (p < 0.001, p < 0.001, p < 0.001 and p = 0.004). Sperm concentration showed a significantly negatively linear association with BMI (p = 0.005), and normal sperm morphology showed an inverse association with BMI and waist-to-height ratio (p < 0.001 and p = 0.004). The prevalence of abnormal total sperm motility, progressive motility, normal sperm morphology and sperm concentration increased with increasing age (p = 0.011, p < 0.001, p < 0.001 and p = 0.002). Lower normal sperm morphology and sperm concentration were associated with increasing body adiposity (p<0.05). No relationship between obesity and sperm motility was identified.

Effect of composition on the stability of liposomal irinotecan prepared by a pH gradient method.

Liposomal irinotecan was prepared by pH gradient loading. The parameters that govern this process, including drug loading time, incubation temperature, buffer composition for hydration, and deltapH, were studied. The uptake of irinotecan into liposomal systems in response to the magnitude of the pH gradient was examined. The drug uptake was maximum when the magnitude of deltapH approached 3.7. The effect of the formulation of the liposomes on the stability of the drug delivery system was also studied. Liposomes composed of lipids with a high phase transition temperature, L-alpha-distearoyl-phosphatidyl-choline and hydrogenated soy phosphatidylcholine, were more stable than those composed of lipids with lower phase transition temperatures. Incorporating distearoyl phosphatidylethanolamine-poly (ethylene glycol)2000 into liposomes helped to reduce the size of the liposomes. In addition, the retention of a drug within liposomes was found to be slightly enhanced by including dimyristoylphosphatidylglycerol or dextran sulfate in the liposome formulation.

Artificial neural network for predicting pathological stage of clinically localized prostate cancer in a Taiwanese population.

BACKGROUND: We developed an artificial neural network (ANN) model to predict prostate cancer pathological staging in patients prior to when they received radical prostatectomy as this is more effective than logistic regression (LR), or combined use of age, prostate-specific antigen (PSA), body mass index (BMI), digital rectal examination (DRE), trans-rectal ultrasound (TRUS), biopsy Gleason sum, and primary biopsy Gleason grade. METHODS: Our study evaluated 299 patients undergoing retro-pubic radical prostatectomy or robotic-assisted laparoscopic radical prostatectomy surgical procedures with pelvic lymph node dissection. The results were intended to predict the pathological stage of prostate cancer (T2 or T3) after radical surgery. The predictive ability of ANN was compared with LR and validation of the 2007 Partin Tables was estimated by the areas under the receiving operating characteristic curve (AUCs). RESULTS: Of the 299 patients we evaluated, 109 (36.45%) displayed prostate cancer with extra-capsular extension (ECE), and 190 (63.55%) displayed organ-confined disease (OCD). LR analysis showed that only PSA and BMI were statistically significant predictors of prostate cancer with capsule invasion. Overall, ANN outperformed LR significantly (0.795 ± 0.023 versus 0.746 ± 0.025, p = 0.016). Validation using the current Partin Tables for the participants of our study was assessed, and the predictive capacity of AUC for OCD was 0.695. CONCLUSION: ANN was superior to LR at predicting OCD in prostate cancer. Compared with the validation of current Partin Tables for the Taiwanese population, the ANN model resulted in larger AUCs and more accurate prediction of the pathologic stage of prostate cancer.

Effect of a prolonged altitude expedition on glucose tolerance and abdominal fatness.

In the present study, we investigated the effect of a long-term mountain expedition on glucose tolerance and insulin action. Twelve registered mountaineers ages 31 years (SD = 1.1) participated in a 25-day expedition at a 2,200-3,800-m altitude with an average duration of 8 hr per day. Arterial oxygen saturation (SaO2) was substantially reduced during hiking. Glucose tolerance and insulin responses were measured prior to and twice during the expedition period. Maximal oxygen consumption increased from 43.0 +/- 2.7 to 49.1 +/- 2.2 mL/kg/min. Percentage of body fat decreased from 19.4 +/- 6.8% to 16.9 +/- 5.9%. The area under the curves for insulin and glucose during the oral glucose tolerance test were also reduced in Days 3 and 25. The present study demonstrated that altitude hiking activity is an effective lifestyle intervention to improve insulin action.