The trend of direct medical costs and associated factors in patients with chronic hepatitis B in Guangzhou, China: an eight-year retrospective cohort study.

BACKGROUND: Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the medical costs associated with hepatitis B virus (HBV) related diseases is not well addressed. In order to provide evidence to address the problem, we investigated the trend of direct medical costs and associated factors in patients with chronic HBV infection. METHODS: A retrospective cohort study of 65,175 outpatients and 12,649 inpatients was conducted using a hospital information system database for the period from 2008 to 2015. Generalized estimating equations (GEE) were applied to explore associations between annual direct medical costs and corresponding factors, meanwhile quantile regression models were used to evaluate the effect of treatment modes on different quantiles of annual direct medical costs stratified by medical insurances. RESULTS: The direct medical costs increased with time, but the proportion of antiviral costs decreased with CHB progression. Antiviral costs accounted 54.61% of total direct medical costs for outpatients, but only 6.17% for inpatients. Non-antiviral medicine costs (46.06%) and lab tests costs (23.63%) accounted for the majority of the cost for inpatients. The direct medical costs were positively associated with CHB progression and hospitalization days in inpatients. The direct medical costs were the highest in outpatients with medical insurance and in inpatients with free medical service, and treatment modes had different effects on the direct medical costs in patients with and without medical insurance. CONCLUSIONS: CHB patients had a heavy economic burden in Guangzhou, China, which increased over time, which were influenced by payment mode and treatment mode.

Renewable and robust biomass waste-derived Co-doped carbon aerogels for PMS activation: Catalytic mechanisms and phytotoxicity assessment.

Developing monolithic carbon-based catalyst with low cost, easy separation and high performance to degrade pollutants via PMS activation is crucial. In this work, a series of novel monolithic Me-CA catalysts based on biomass derived carbon aerogel were prepared by hydrothermal method using waste watermelon peel as raw material. Co-CA catalyst showed excellent performance to activate PMS for 2, 4-DCP degradation in different temperature and different water matrices. Different pollutants, such as ciprofloxacin (CIP), bisphenol A (BPA), and 2, 4-dichlorophenoxyacetic acid (2, 4-D) could also be removed in the Co-CA/PMS system. As expected, Co-CA could be easily separated from degraded solution, and show high stability and reusability for PMS activation with a lower cobalt leaching. Based on the results of the quenching tests, electron paramagnetic resonance (EPR) spectra, Chronoamperometric test (i-t curves) and electro-chemical impedance spectroscopy (EIS), the PMS activation mechanism was proposed. The phytotoxicity assessment determined by germination situation of mung bean indicated that PMS activation could eliminate the hazards of 2, 4-D. Therefore, this study provides a low cost, efficient and environmental-friendly monolithic biomass carbon aerogel catalyst for different pollutants degradation, which further advances monolithic catalyst for practical wastewater treatment.

Antiviral drug utilization and annual expenditures for patients with chronic HBV infection in Guangzhou, China, in 2008-2015.

BACKGROUND: The aims of this study were to describe antiviral drug (AD) utilization and costs in patients with chronic HBV infection. METHODS: We conducted a retrospective study of patients in the hospital and calculated annual proportions of AD utilization and costs among patients. A two-part model was used to estimate adjusted odds ratio (OR) for antiviral therapy and cost ratios for antiviral costs associated with demographics. RESULTS: Of a total of 14,920 records, 143,658 records were involved in the analysis. The annual proportions of AD utilization were 56.99% (45.65%) for inpatients (outpatients) during 2008-2015 and increased annually. Entecavir (ETV), in particular, increased from 11.08% to 70.26% (11.05% to 49.35%) for inpatients (outpatients). The patients with medical insurance were more likely to use AD than patients without insurance, and the adjusted OR was 1.11 (95% CI: 1.03, 1.19) for inpatients and 1.66 (1.59, 1.73) for outpatients. With the disease progressing, the proportion of antiviral costs in total direct medical costs decreased from 13.91% to 4.07% (71.29% to 49.29%) for inpatients (outpatients). CONCLUSIONS: The use of AD for chronic HBV infection was less than expected based on established guidelines, and only half of patients received antiviral treatment. However, the AD utilization, especially ETV, increased annually. Reimbursement policy was the most important factor affecting antiviral treatment. Antiviral therapy was an important part of the direct medical costs, especially in the early stage of disease.

Assessment of relationship on excess arsenic intake from drinking water and cognitive impairment in adults and elders in arsenicosis areas.

In this study, the relationships between high water arsenic exposure and cognitive impairment were investigated. A total of 483 residents aged 40 or older were randomly recruited and were divided into four groups according to the concentrations of arsenic in their water. Consumption levels (̄x¯±sd) of drinking water arsenic for normal, mild, moderate, and high exposure groups were 4±2µg/L, 25±11µg/L, 73±15µg/L, and 183±88µg/L, respectively. The average scores (̄x¯±sd) of the Chinese version Mini-Mental State Examination (MMSE) for females in each group were 21.49±3.14, 19.04±5.87, 16.18±8.14, and 15.82±7.78, and the average scores (̄x¯±sd) for males were 24.50±3.97, 23.16±4.45, 21.00±6.57, and 18.92±7.99, respectively. Significant differences among the average scores of MMSE for males or females in the four groups were found (p<0.05). The prevalence of cognitive impairment for females in each group was 10.86%, 29.63%, 53.48%, and 55.29%, and the prevalence of cognitive impairment for males was 10.71%, 12.00%, 35.71%, and 50.89%, respectively. Significant differences between all groups were observed (p<0.05). In the multivariable regress model, high water was closely associated with the MMSE score (Standardized Coefficient=-0.021) and cognitive impairment (arsenic ˃100 µg/L PR4/1=4.01). The findings of our research suggested a significant positive relationship between arsenic exposure from drinking water and cognitive impairment.

Cost-Effectiveness Comparison Between the Response-Guided Therapies and Monotherapies of Nucleos(t)ide Analogues for Chronic Hepatitis B Patients in China.

BACKGROUND AND OBJECTIVE: Nucleos(t)ide analogue (NA) monotherapies are typically used as the primary treatment for chronic hepatitis B (CHB) patients, including lamivudine (LAM), telbivudine (TBV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF). For high-resistance NAs (LAM, TBV, ADV), they can generate excellent clinical outcomes by using response-guided therapy; however, their pharmacoeconomic profiles remain unclear in China. We aimed to evaluate the cost effectiveness between response-guided therapies and monotherapies of NAs for Chinese hepatitis B e-antigen (HBeAg)-positive and -negative CHB patients. METHODS: We constructed a Markov model to simulate CHB progression associated with 12 treatment strategies using effectiveness and cost data from the published literature. We measured the lifetime costs, quality adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity (especially to extend the range of the TDF price) and probabilistic sensitivity analyses were used to explore the uncertainties of the model. RESULTS: For both HBeAg-positive and -negative patients, no treatment strategy generated the lowest lifetime costs (US$31,185-US$31,338) and QALYs (7.54-7.58). ETV and TDF monotherapies were not dominated by other treatments, whereas, the ICER of ETV monotherapy was the lowest (US$6112/QALY-US$8533/QALY). For each high-resistance NA, compared with its monotherapy, the ICERs of its response-guided therapies were below the willingness-to-pay threshold of US$22,833/QALY. Additionally, TDF monotherapy was the preferred treatment when its price dropped to US$1820/year or lower. CONCLUSION: Among 12 treatment strategies evaluated, ETV monotherapy is the most cost-effective treatment for treatment-naive CHB patients in China. The response-guided therapies of high-resistance NAs are more cost-effective than their monotherapies.

Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. METHODS: Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. RESULTS: In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. CONCLUSIONS: For Chinese chronic hepatitis B patients, ETV is still the most cost-effective strategy over TDF and other nucleos(t)ide analogs, with a threshold of $20,466 USD/QALY gained.

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

BACKGROUND/AIM: Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). METHODS: To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. RESULTS: In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. CONCLUSION: ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

Cost-effectiveness analysis of antiviral therapies for hepatitis B e antigen-positive chronic hepatitis B patients in China.

BACKGROUND AND OBJECTIVE: Several antiviral therapies are now available for patients with chronic hepatitis B (CHB), but the most cost-effective strategy for Chinese patients is unclear. The aim of this study was to estimate the long-term cost effectiveness of the antiviral treatments (lamivudine, adefovir, telbivudine and entecavir) for hepatitis B e antigen (HBeAg)-positive CHB patients in China. METHODS: A Markov model was used to simulate the life-time (41-year time span) costs and effectiveness associated with antiviral treatments from the perspective of Chinese healthcare. Relative model parameters were derived from Chinese population studies. Costs and effectiveness were discounted at 5 %. The highest retail prices for generic and branded drug prices were also considered. Probabilistic sensitivity analysis and one-way sensitivity analysis were used to explore model uncertainties. RESULTS: In the base-case analysis, the least quality-adjusted life years (QALYs) were obtained with adefovir as the reference strategy. Lamivudine generated the highest incremental cost-effectiveness ratio (ICER), with an additional US$35,000 needed to gain one additional QALY for generic drugs and US$36,000 for branded drugs. Entecavir had the lowest ICER of US$7,600 and US$9,100, respectively. The projected 10-year cumulative incidences of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and mortality for entecavir were lower than the other strategies. In probabilistic sensitivity analyses, entecavir was the preferred option at a threshold of US$18,924 per QALY. CONCLUSIONS: In patients with HBeAg-positive CHB in China, entecavir is a cost-effective option compared with other therapies for CHB.

Status and determinants of health literacy among adolescents in Guangdong, China.

BACKGROUND: Previous studies for non-communicable disease cotrol, including cancer, have mostly relied on health literacy in adults. However, limited studies are available for adolescents. This study aimed to assess the status and determinants of health literacy in in-school adolescents in Guangdong, China. MATERIALS AND METHODS: A total of 3,821 students aged 13-25 years were selected by multi-stage cluster sampling. After the questionnaire of health literacy was answered, the total scores for health knowledge (18 questions), skills (5 questions) and behaviors (14 questions) were determined. The total scores for health literacy and each subscale were recoded into adequate and inadequate subgroups, and logistic regression models were used to identify factors associated with each outcome variable. RESULTS: The prevalence of adequate health literacy was 14.4%, and the prevalences for adequate knowledge, skills and behavior were 22.4%, 64.7% and 6.6%, respectively. Students coming from prestigious schools and having parents with higher education had higher odds of having adequate knowledge, skills and behaviors. Female students had higher odds of having adequate knowledge and behaviors. Students in grade 7-8 had higher odds of having adequate knowledge and skills. The health knowledge was positive associated with health skills (odds ratio [OR]=2.1, 95% confidence interval [CI] 1.7-2.5) and behaviors (OR=3.0, 95% CI 2.3-4.0), and health skills were positive associated with health behaviors (OR=2.6, 95% CI 1.8-3.8). CONCLUSIONS: Further efforts should be made to increase adolescents' health knowledge and behaviors, especially for low grade and male students in non-prestigious schools.

Assessment of relationship on excess fluoride intake from drinking water and carotid atherosclerosis development in adults in fluoride endemic areas, China.

Cross-sectional analysis was conducted to access the relationships between developing carotid artery atherosclerosis through consuming high fluoride in drinking water and its possible mechanism, using the baseline data collected from 585 study subjects. In the cross sectional analysis, subjects were divided into four groups based on the concentrations of fluoride in their drinking water. The range of fluoride concentrations was: normal group (less than 1.20 mg/L), mild group (1.21-2.00 mg/L), moderate group (2.01-3.00 mg/L), and high concentration group (more than 3.01 mg/L). The prevalence rate of carotid artery atherosclerosis in the subjects in each group was found to be 16.13%, 27.22%, 27.10%, and 29.69%, respectively. Significant difference between the prevalence of carotid artery atherosclerosis in the mild, moderate and high fluoride exposure group and in the normal group was observed (P<0.05). In addition, it was found that elevated intercellular cell adhesion molecule-1 (ICAM-1) and reduced glutathione peroxidases (GPx) was associated with carotid artery atherosclerosis in fluoride endemic areas. The findings of the research study revealed a significant positive relationship between excess fluoride exposure from drinking water and prevalence of carotid artery atherosclerosis in adults living in fluoride endemic areas. The possible mechanism was the excess fluoride induced the decreasing level of GPx causing the systemic inflammation and endothelial activation by oxidative stress.

An assessment of the relationship between excess fluoride intake from drinking water and essential hypertension in adults residing in fluoride endemic areas.

In this study, the relationships between high water fluoride exposure and essential hypertension as well as plasma ET-1 levels were investigated. A total of 487 residents aged 40 to 75 were randomly recruited from eight villages in Zhaozhou County from Heilongjiang Province in China and were divided into 4 groups according to the concentrations of fluoride in their water. Consumption levels of drinking water fluoride for normal, mild, moderate, and high exposure groups were 0.84±0.26 mg/L, 1.55±0.22 mg/L, 2.49±0.30 mg/L, and 4.06±1.15 mg/L, respectively. The prevalence of hypertension in each group was 20.16%, 24.54%, 32.30%, and 49.23%, respectively. There were significant differences between all the groups; namely, with the increase in water fluoride concentrations, the risk of essential hypertension in adults grows in a concentration-dependent manner. Significant differences were observed in the plasma ET-1 levels between the different groups (P<0.0001). In the multivariable logistic regression model, high water fluoride concentrations (F(-)≥3.01 mg/L, OR(4/1)=2.84), age (OR(3/1)=2.63), and BMI (OR(2/1)=2.40, OR(3/1)=6.03) were closely associated with essential hypertension. In other words, the study not only confirmed the relationship between excess fluoride intake and essential hypertension in adults, but it also demonstrated that high levels of fluoride exposure in drinking water could increase plasma ET-1 levels in subjects living in fluoride endemic areas.

[Using log-binomial model for estimating the prevalence ratio].

To estimate the prevalence ratios, using a log-binomial model with or without continuous covariates. Prevalence ratios for individuals' attitude towards smoking-ban legislation associated with smoking status, estimated by using a log-binomial model were compared with odds ratios estimated by logistic regression model. In the log-binomial modeling, maximum likelihood method was used when there were no continuous covariates and COPY approach was used if the model did not converge, for example due to the existence of continuous covariates. We examined the association between individuals' attitude towards smoking-ban legislation and smoking status in men and women. Prevalence ratio and odds ratio estimation provided similar results for the association in women since smoking was not common. In men however, the odds ratio estimates were markedly larger than the prevalence ratios due to a higher prevalence of outcome. The log-binomial model did not converge when age was included as a continuous covariate and COPY method was used to deal with the situation. All analysis was performed by SAS. Prevalence ratio seemed to better measure the association than odds ratio when prevalence is high. SAS programs were provided to calculate the prevalence ratios with or without continuous covariates in the log-binomial regression analysis.

The combination effects of phenolic compounds and fluconazole on the formation of ergosterol in Candida albicans determined by high-performance liquid chromatography/tandem mass spectrometry.

A liquid chromatography/tandem mass spectrometry (LC/MS) with atmospheric pressure chemical ionization (APCI) for the quantification of ergosterol, lanosterol, and squalene was developed to evaluate the combination effects of phenolic compounds with fluconazole on ergosterol biosynthesis in Candida albicans. The three analytes were separated by a column of C18 and were quantified without interference with each other using positive mode tandem mass spectrometry (MS/MS). Molecular ions of ergosterol and lanosterol were detected as the [M+H-H2O]+ ion species at m/z 380 and 410, whereas squalene appeared as the [M+H]+ ion species at m/z 412. On fragmentation of ergosterol, lanosterol, and squalene, the product ions at m/z 69, 149, and 109, respectively, were present as major fragments. These product ions were used for the quantification of them in multiple reaction monitoring acquisition mode. The relationship between signal intensity and the analytes' concentration was linear over the concentration range of 0.05-10 microg/ml. Following the treatment of C. albicans with fluconazole in combination with albicanyl caffeate, resveratrol, and 3,4'-difluorostilbene, respectively, the content of ergosterol in both the sensitive and resistant C. albicans showed depletion, whereas the squalene showed accumulation especially in the sensitive isolates determined with the method developed.