Evaluating omadacycline dosing regimens against drug-resistant pathogens including Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and ß-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

[Potential Ecological Risk Characteristics and Source Apportionment of Heavy Metals in Farmland Soils around Typical Factories in Hunan Province Based on Monte-Carlo Simulation].

In order to explore the pollution characteristics， ecological risks， and pollution sources of heavy metals in farmland soils around typical factories in Hunan Province， the content characteristics of eight heavy metals in farmland soils around fluoride factories， leather factories， and plating plants were analyzed. The geo-accumulation index and potential ecological risk index were used to evaluate the pollution and environmental risk of heavy metals. The correlation analysis， hierarchical cluster analysis， and principal component analysis were used to analyze the sources of heavy metals. The Monte-Carlo model was used to evaluate the probability risk of regional ecological risk. The results showed that the main pollution elements in the soil were Cd and Zn， and their mean values were 4.46 and 2.73 times the background values， respectively. Zn was at a mild pollution level in the soil of the three typical factories， and Cd was at a moderate pollution level in the whole fluoride factory. The pollution sources of heavy metals in the typical factories were mainly natural sources， industrial activity sources （industrial waste discharge， mineral mining， and smelting activities）， traffic sources， etc. The results of potential ecological risk assessment showed that the ecological risk of the fluoride factory was at a high risk level， and the ecological risk of the leather factory and plating plants was at a high risk level. Cd was the main contributing element. The results of Monte-Carlo probabilistic ecological risk assessment reduced the uncertainty of deterministic assessment， which could provide scientific basis for accurate risk management and control in the regions.

The influence mechanism of self-transcendence on green consumption: The chain-mediating effect of construction of meaning in life and connectedness.

A transition to a more sustainable society is occurring worldwide and necessitates a change in people's ways of consuming. Self-transcendence (ST) is recognized as a key predictor of green consumption. Thus, a multiple intermediary model was developed to clarify the psychological mechanisms underlying ST and its influence on consumption. The model was tested using data from a nationally representative sample of 428 Chinese participants. The results show that ST's overall positive effect on green consumption is realized via four indirect paths: (1) the simple mediating role of nature connectedness between ST and green consumption, (2) the simple mediating role of social connectedness between ST and green consumption; (3) the chain-mediating role of construction of meaning in life (CoMIL) and nature connectedness, and (4) the chain-mediating role of CoMIL and social connectedness. Among these paths, nature connectedness plays the most critical mediating role for the Chinese, accounting for the greatest proportion of the total indirect effect. The study advances understanding of the influence and path of ST on green consumption, and provides theoretical and practical support for guiding people toward sustainable lifestyles.

Tracking progress towards equitable maternal and child health in Yunnan: a systematic assessment for the Health Programme for Poverty Alleviation in China during 2015-2020.

OBJECTIVES: To inform the impacts of health programmes which aimed at preventing women and children from being trapped in or returning to poverty because of illness in Yunnan, the main battlefield against poverty in China. DESIGN: The longitudinal comparative evaluation design. DATA COLLECTION AND ANALYSIS: National and Yunnan policy documents related to maternal and child health programmes for poverty alleviation during 2015-2020 were analysed. The changes in disparities in maternal and child health system inputs, service coverage, and health outcomes between poor and non-poor areas, as well as out-of-pocket payments between poor and non-poor populations were assessed before and after 2017. RESULTS: In total 12 policies and 15 programmes related to poverty alleviation for poor women and children in Yunnan were summarised. As a result of health system strengthening in Yunnan, the densities of licensed doctors, nurses, obstetricians, midwives, township health workers and female village doctors had been increased substantially in poor areas, with the annual rates of 14.3%, 22.5%, 21.8%, 23.9%, 14.1% and 7.1% separately. Although disparities existed in some of service coverage between poor and non-poor areas, the health programmes had narrowed the gaps in utilisation of facility birth, caesarean section, prenatal screening and newborn screening across Yunnan (p<0.01). The out-of-pocket payments for inpatient care for serious illnesses among women and children with poverty registration had been considerably decreased to 10.0%. Paralleling the universal coverage, maternal deaths per 100 000 livebirths and child deaths per 1000 livebirths had further declined in both poor and non-poor areas, and the impacts of health programmes on closing the gaps in child survivals across Yunnan were significant (p<0.01). CONCLUSIONS: Remarkable progress in equitable maternal and child survival has been achieved in Yunnan. The practices in Yunnan have shown the Chinese model in ending poverty by strengthening health system and implementing universal coverage with firm commitment, determined leadership, detailed blueprint and social participation.

Assessment of micafungin dosage regimens against Candida spp. in pediatric patients undergoing hematopoietic stem cell transplantation: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various micafungin dosing regimens against Candida spp. in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration targets of micafungin. Current standard clinical micafungin dosing regimens of 1 and 2 mg/kg/day were appropriate for the prevention and treatment of Candida glabrata infection in pediatric patients undergoing HSCT, respectively. Moreover, the high-dose prophylactic dosage (2 mg/kg/day) and therapeutic dosage (4 mg/kg/day) should be the preferred option to optimize efficacy against Candida albicans. However, none of the simulated regimens was effective against Candida parapsilosis in pediatric HSCT patients. These PK/PD-based simulations rationalize and optimize the micafungin dosing regimens against Candida spp. in pediatric patients undergoing HSCT.

[Risk Assessment and Source Analysis of Heavy Metal Pollution in Surface Sediments from Major River Systems in Maoming City, Guangdong Province].

In order to understand the spatial distribution and sources of heavy metals in surface sediments of MaoMing city and to reasonably evaluate the ecological risk of heavy metals in sediments of the study area, the contents of heavy metals (As, Hg, Cd, Co, Cr, Cu, Mn, Ni, Pb, and Zn) in surface sediments of eight rivers and three reservoirs were detected, and the risks of heavy metals were assessed using the geo-accumulation index (Igeo), potential ecological disk index (RI), and potential adverse biological impacts (ΣTUs). The sources of heavy metals were analyzed via correlation, principal component analysis (PCA), and positive matrix factorization (PMF). The results showed that the ω(Zn) (147.56 mg·kg-1) and ω(Hg) (0.20 mg·kg-1) were 3.72 and 2.25 times the background value, respectively, and the spatial distributions of Cd, Co, Cu, Mn, Ni, and Zn were in the order of northern>central>western>southeast. The geo-accumulation index results showed that Zn was at a moderate pollution level, 76.6% of the sampling sites of Hg were at a light-heavy pollution level, and other heavy metals were at a non-light pollution level. The results of potential ecological risk and potential adverse biological impacts indicated that the potential ecological risk index and toxicity effect of Gaozhou Reservoir were higher than those of other rivers, and Hg was the major contributor to heavy metal pollution. The three factors extracted from principal component analysis and positive matrix factorization represented natural sources, agricultural sources, and industrial sources, respectively. Therefore, in order to reduce the health hazards caused by heavy metals in sediments, a prevention and control system for the Hg element should be established.

[Pollution Characteristics and Ecological Risk Assessment of Antibiotics in Vegetable Field in Kaizhou, Chongqing].

The accumulation of antibiotics in farmland and its ecological risk have become a research hotspot at home and abroad. The objective of this study was to investigate the occurrence and accumulation of antibiotics and their potential environmental and ecological risks in vegetable fields in Kaizhou district of Chongqing country. The occurrence characteristics of antibiotics including tetracyclines, sulfonamides, quinolones, macrolides, and chloramphenicols were detected using experimental analysis. The results showed that there was an accumulation of antibiotics in the vegetable soil, and 18 antibiotics in five categories were detected (0-42.88 µg·kg-1), mainly for tetracyclines and quinolones. The detection rate of quinolone antibiotics was the highest (15.38%-100%), especially for norfloxacin and ofloxacin (100%), whereas the tetracyclines presented the highest concentration (0-42.88 µg·kg-1). The amount of total antibiotics in the vegetable soil was 1.64-233.11 µg·kg-1, whereas different vegetable soils showed the following trend:water spinach soil (89.73 µg·kg-1)>cabbage soil (32.53 µg·kg-1)>pepper soil (32.16 µg·kg-1)>tomato soil (32.13 µg·kg-1)>cucumber soil (26.46 µg·kg-1)>grassland (7.32 µg·kg-1). The correlation results showed that there was a significantly positive correlation between total antibiotic residues and organic fertilizer application (P<0.05) but a significantly negative correlation with soil pH (P<0.05). Quinolones and sulfonamides were negatively correlated with soil water content (P<0.05), whereas quinolones positively correlated with soil available phosphorus and organic matter content (P<0.05). The potential eco-environmental risk assessment results showed that tetracyclines and quinolones in vegetable soil in Kaizhou district had certain ecological risks, of which 62%-92% and 62%-100% of soil samples with quinolones had potential toxicity to soil animals and microorganisms.

Comparison of Fitness Cost, Stability, and Conjugation Frequencies of tet(X4)-Positive Plasmids in Chicken and Pig Escherichia coli.

The large-scale epidemic of the tet(X4) gene in the livestock and poultry industry is threatening public health; however, there is still a lack of comparative studies on tet(X4)-bearing plasmids in chicken and pig Escherichia coli. To evaluate the prevalence trend of tet(X4)-bearing plasmids and the factors influencing their persistence in the livestock and poultry industry, we examined the fitness cost, stability under tetracyclines pressure, and conjugation frequencies at various temperatures of six tet(X4)-bearing plasmids in four representative pig E. coli isolates and chicken E. coli isolates. Compared with pig E. coli, the plasmid in chicken E. coli showed lower fitness cost, and stronger ability to promote bacterial biofilm formation and motility. Meanwhile, the presence of tetracycline may favor the stability of tet(X4)-bearing plasmids, which was more common in chicken E. coli. Furthermore, the optimal temperature for IncX1 tet(X4)-bearing plasmid conjugation was 42 °C, and its conjugation frequency in chicken E. coli was higher than that in pig E. coli, whereas the optimal temperature for IncFII tet(X4)-bearing plasmid conjugation was 37 °C and it performed better in pig E. coli, suggesting the predominant plasmid types circulating in chicken E. coli and pig E. coli may be distinct. Collectively, although tet(X4) currently appears to be more prevalent in pig E. coli, this is probably independent of the fitness cost caused by tet(X4)-plasmids. To curb the future spread of the tet(X4) gene, reduced tetracyclines usage and tailored interventions should be applied in different breeding industries.

Estimation of the fraction of soil-borne particulates in indoor air by PMF and its impact on health risk assessment of soil contamination in Guangzhou, China.

The fraction of soil-borne particulates in indoor air (fspi), a principal exposure factor in health risk assessment of soil, is used to calculate the inhaled dose of contaminants in air particulates (PM10) from soil. To investigate the fspi, consecutive 24-h PM10 samples (n = 180) of indoor ambient were collected from September 2019 to January 2020 in Guangzhou main urban areas, China. The concentrations of twenty-six metal elements, five anions, organic carbon (OC) and elemental carbon (EC) in samples were measured. The sources of indoor ambient PM10 and the value of fspi were identified by the method of Positive Matrix Factor analysis (PMF). Results showed that the main sources contributing to indoor PM10 content were combustion sources (50.53%) and vehicular sources (28.17%). The soil sources (the local fspi) were 19.96%. The soil contents of indoor PM10 in Guangzhou main urban areas were in accordance with those in similar monsoon climate regions, such as Malaysia. The health risks of the inhalation route were dropped by about 62% for some common brownfield contaminants (Cr (VI), Ni, Be and Cd) with the investigated local fspi in Guangzhou main urban areas, compared with using the fspi (0.8) recommended by the C-RAG model in China. The results supplied a new effective methodology for estimation of the local fspi value in health risk assessment of soil contamination in urban areas.

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Optimization of dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus in neutropenic patients with cancer by Monte Carlo simulations.

The objective of this study was to evaluate the efficacy of various dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) in neutropenic patients with cancer. Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to determine cumulative fraction of response (CFRs) in terms of area under the concentration-time curve/minimum inhibition concentration target. Currently clinical standard dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin were insufficient to provide expected CFRs against MRSA for neutropenic patients with cancer. The high dosing regimens of vancomycin (3500 mg/d), teicoplanin (800 mg/d) and daptomycin (8 mg/kg/d) could provide CFRs of ≥ 80%, showing a higher treatment success. However, the majority of CFRs with linezolid simulated dosing regimens reached < 80% against MRSA. Therefore, a strategy of high dosages of vancomycin, teicoplanin and daptomycin may be needed to attain optimal therapeutic efficacy against MRSA in neutropenic patients with cancer.

Prospective assessment of a nasopharyngeal carcinoma risk score in a population undergoing screening.

Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction.

Evaluating posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults. Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probability of target attainment (PTA) and cumulative fraction of response (CFR) in terms of area under the concentration-time curve/minimum inhibition concentration (AUC/MIC) targets of posaconazole. According to the results of the PTA analysis, currently recommended clinical dosing regimens of the delayed-release tablet and intravenous (i.v.) solution were appropriate in prophylaxis against Aspergillus spp. with MICs ≤ 0.125 µg/mL. However, only high-dose regimens of the delayed-release tablet could achieve the target PTA in the treatment against Aspergillus spp. at an MIC of 0.125 µg/mL. Furthermore, the CFR was calculated for each dosing regimen. For the oral suspension, none of the simulated dosing regimens was effective against Aspergillus spp. For the delayed-release tablet and i.v. solution, the recommended dosing regimens were effective for prophylaxis of invasive fungal infections by four Aspergillus spp. (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans and Aspergillus terreus). However, these recommended dosing regimens were only effective for the treatment of A. terreus infection. Therefore, the high-dose regimen (200 mg oral every 12 h) of the delayed-release tablet should be recommended to achieve optimal therapeutic efficacy against four Aspergillus spp. (A. flavus, A. fumigatus, A. nidulans and A. terreus). These PK/PD-based simulations rationalise and optimise the dosing regimens of the different posaconazole formulations against Aspergillus spp. in adults.

[Contrast-enhanced Ultrasonography and Color Doppler Ultrasonography for Dynamic Assessment of Intracranial Changes in Early MCAO Rats Models].

OBJECTIVE: To assess the value of contrast-enhanced ultrasound (CEUS) and color Doppler ultrasound (DUS) on hemodynamic changes and cerebral perfusion quantitative analyses in Sprague-Dawley (SD) rats with focal permanent ischemic stroke. METHODS: Sixteen SD rats with thin skulls were subjected to establish middle cerebral artery occlusion (MCAO) model. CEUS images were performed before modeling (T 0), immediately after modeling (5-15 min after modeling, T 1), 3 h after modeling (T 2), followed by the measurement of bilateral middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA) using DUS. The peak systolic velocity (PSV), end-diastolic velocity (EDV) and mean velocity (MV) of these arteries were obtained. The brain time-intensity curve was taken as interest region of the whole right brain, and the quantitative parameters of CEUS were obtained, including peak intensity (PI), area under the curve ( AUC), wash in slope (WIS), time to peak (TTP), rise time (RT) and time from peak to one half (TPH). The modified neurological deficit score (mNSS) of the rats was performed 3 h after the modeling, and the data of the rats with a score of 9-11 were statistically analyzed. RESULTS: A total of 12 rats were successfully modeled and completed with mNSS score 9-11. No blood flow signals were observed on the right MCA and ACA in the 12 rats at T 1 and T 2. From T 0 to T 1, PI, AUC and WIS of the right hemisphere decreased sharply with TTP and RT significantly prolonged, and the differences were statistically significant. However, there was no significant difference in hemodynamic parameters at that period of time. From T 1 to T 2, there were no significant changes in CEUS quantitative parameters (except AUCand TPH), while PSV, EDV, MV of LMCA and bilateral PCA showed significant acceleration, and the differences were statistically significant. CONCLUSION: CEUS and DUS can reveal the intracranial hemodynamics and brain tissue perfusion trends of MCAO rats, which could be new methods in assessment of ischemic stroke model at multiple time points.

Pharmacokinetic/Pharmacodynamic Analysis of Daptomycin Against Staphylococcus aureus and Enterococcus faecium in Pediatric Patients by Monte Carlo Simulation.

The objective of this study was to evaluate the efficacy of various daptomycin dosing regimens against Staphylococcus aureus and Enterococcus faecium in pediatric patients with proven/suspected gram-positive infection. Monte Carlo simulations (MCSs) were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (MIC) targets of daptomycin. According to the results of the MCSs, currently approved pediatric dosage regimens were sufficient against Staphylococcus aureus with MIC ≤ 0.5 µg/mL for all pediatric patients, but poor when MIC ≥ 1 µg/mL except for adolescents (12-17 years) who need a dosage of ≥10 mg/kg/day at MIC = 1 µg/mL. For Enterococcus faecium with MIC ≤ 4 µg/mL, the recommended dosage of 8-12 mg/kg/day in adults was enough for adolescents, but not subjected to younger pediatric patients. Furthermore, based on MIC distributions obtained from the European Committee on Antimicrobial Susceptibility Testing, the approved high-dose regimen should be recommended for infants aged 3-12 months, children (2-11 years), and adolescents to achieve better clinical efficacy against methicillin-resistant Staphylococcus aureus. In addition, the dosage of 8-12 mg/kg/day was powerful against Enterococcus faecium for adolescents; however, only the highest dosage of 12 mg/kg/day was effective for infants aged 3-12 months and children. All the simulated regimens were not optimal for infants aged 13-24 months. These PK/PD-based simulations rationalize and optimize the dosage regimens of daptomycin against Staphylococcus aureus and Enterococcus faecium in pediatric patients.

Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies: a systematic review and meta-analysis.

BACKGROUND: Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs. METHODS: We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model. RESULTS: Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE. CONCLUSIONS: The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

Hospitalization costs of treating colorectal cancer in China: A retrospective analysis.

BACKGROUND: The objective of this study was to explore the influence factors of hospitalization costs of treating colorectal cancer in China. And the study provides new estimates on hospitalization costs and length of hospital stay for patients with colorectal cancer in China. METHODS: Data for inpatient hospitalization associated with colorectal cancer were obtained from a 3-tier hospital in Guangdong Province and were analyzed post hoc. We conducted descriptive statistical methods, Wilcoxon rank-sum tests (for 2 groups) and the Kruskal-Wallis test (for more than 2 groups) to analyze the hospitalization costs of treating colorectal cancer. RESULTS: The analysis included 8021 patients (female: 40.54%; mean age; 61.80 ±â€Š13.28 years; male: 59.46%; mean age: 61.80 ±â€Š13.28 years). The overall mean length of hospital stay was 11.35 days. Over the 5 years, the mean length of hospital stay showed a small decrease from 12.22 days in 2012 to 10.69 days in 2016, while per-day costs showed a trend of increase between 2012 and 2015 (increase from < 1190.94 to < 1382.50). The mean length of hospital stay was statistically significant difference was found for sexes (P = .039) and insurance status (P < .001). The mean hospitalization costs were < 16,279.58. Mean hospitalization costs were different among the UEBMI, the URBMI and the Unspecified (< 17,114.58, < 15,555.05, and < 17,735.30, respectively; P < .001). CONCLUSION: The study showed that hospitalization costs increase were associated with a small decreasing length of hospital stay and increasing per-day hospitalization costs. Moreover, the proportion of the hospitalization costs reimbursed by insurances increased. For inpatients with UEBMI, it possibly lead to over treatment and the medical expense rise which result in medical resources waste and significant society costs. The rising hospitalization costs may lead to a remarkably increased financial burden in the future in China.

A Low-Cost Palmtop High-Speed Capillary Electrophoresis Bioanalyzer with Laser Induced Fluorescence Detection.

In this work, we developed a miniaturized palmtop high-speed capillary electrophoresis (CE) system integrating whole modules, including picoliter-scale sample injection, short capillary-based fast CE, high-voltage power supply, orthogonal laser induced fluorescence (LIF) detection, battery, system control, on-line data acquisition, processing, storage, and display modules. A strategy of minimalist miniaturization combining minimal system design and low-cost system construction was adopted to achieve the instrument miniaturization with extremely low cost, which is differing from the current microfabrication strategy used in most reported miniaturized CE systems. With such a strategy, the total size of the bioanalyzer was minimized to 90 × 75 × 77 mm (length × width × height) and the instrument cost was reduced to ca. $500, which demonstrated the smallest and lowest-cost CE instrument with LIF detection in so far reported systems. The present bioanalyzer also exhibited comparable analytical performances to previously-reported high-speed CE systems. A limit of detection of 1.02 nM sodium fluorescein was obtained. Fast separations were achieved for multiple types of samples as amino acids, amino acid enantiomers, DNA fragments, and proteins with high efficiency. We applied this instrument in colorectal cancer diagnosis for detecting KRAS mutation status by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Nickel electrodes as a cheap and versatile platform for studying structure and function of immobilized redox proteins.

Practical use of many bioelectronic and bioanalytical devices is limited by the need of expensive materials and time consuming fabrication. Here we demonstrate the use of nickel electrodes as a simple and cheap solid support material for bioelectronic applications. The naturally nanostructured electrodes showed a surprisingly high electromagnetic surface enhancement upon light illumination such that immobilization and electron transfer reactions of the model redox proteins cytochrome b5 (Cyt b5) and cytochrome c (Cyt c) could be followed via surface enhanced resonance Raman spectroscopy. It could be shown that the nickel surface, when used as received, promotes a very efficient binding of the proteins upon preservation of their native structure. The immobilized redox proteins could efficiently exchange electrons with the electrode and could even act as an electron relay between the electrode and solubilized myoglobin. Our results open up new possibility for nickel electrodes as an exceptional good support for bioelectronic devices and biosensors on the one hand and for surface enhanced spectroscopic investigations on the other hand.

Twelve-week ribavirin-free direct-acting antivirals for treatment-experienced Chinese with HCV genotype 1b infection including cirrhotic patients.

BACKGROUND: Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis. METHODS: One hundred forty treatment-experienced GT1b CHC Chinese with and without cirrhosis were included in this study. Ninety-four patients were treated with either daclatasvir (DCV, 60 mg)-sofosbuvir (SOF, 400 mg) (group 1, n = 46) or ledipasvir (LDV, 90 mg)-SOF (400 mg) (group 2, n = 48) for 12 weeks. Forty-six patients treated with pegylated interferon and RBV therapy for 72 weeks were enrolled as the control group (group 3). Patients were followed at 4-weekly intervals till 24 weeks after the end of treatment. RESULTS: All patients in group 1 (46/46, 100 %) and 2 (48/48, 100 %) had achieved sustained virologic response at 24 weeks after the end of treatment (SVR 24), which was significantly higher than that of group 3 (13/46, 28.3 %) (p < 0.001). The SVR 24 rates of cirrhotic patients in group 1 (27/27, 100 %) and 2 (27/27, 100 %) were also significantly higher than that of group 3 (3/25, 12 %) (p < 0.001). Twelve weeks of RBV-free LDV-SOF and DCV-SOF was either cost-saving or cost-effective. Adverse events were significantly lower in group 1 and 2 compared with group 3 (p < 0.001). CONCLUSION: Compared with standard therapies, 12 weeks of RBV-free DAA therapies is highly effective, well tolerated and cost-effective in treatment-experienced Chinese with GT1b CHC including patients with cirrhosis.