Global, Regional, and National Burdens of Stroke in Children and Adolescents From 1990 to 2019: A Population-Based Study.

BACKGROUND: Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels. METHODS: The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019. RESULTS: The global age-standardized incidence of stroke increased (average annual percentage change, 0.15% [95% uncertainty interval, 0.09%-0.21%]), while YLLs decreased substantially (average annual percentage change, -3.33% [95% uncertainty interval, -3.38% to -3.28%]) among children and adolescents between 1990 and 2019. Ischemic stroke accounted for 70% of incident cases, and intracerebral hemorrhage accounted for 63% of YLLs. Children under 5 years of age had the highest incidence of ischemic stroke, while adolescents aged 15 to 19 years had the highest incidence of hemorrhagic stroke. In 2019, low-income and middle-income countries were responsible for 84% of incident cases and 93% of YLLs due to childhood stroke. High-sociodemographic index countries had a reduction in YLLs due to stroke that was more than twice as fast as that of low-income and middle-income. CONCLUSIONS: Globally, the burden of childhood stroke continues to increase, especially among females, children aged <5 years, and low-sociodemographic index countries, such as sub-Saharan Africa. The burden of childhood stroke is likely undergoing a significant transition from being fatal to causing disability. Global public health policies and the deployment of health resources need to respond rapidly and actively to this shift.

Organophosphate Esters in Building Materials from China: Levels, Sources, Emissions, and Preliminary Assessment of Human Exposure.

Source characteristics and health risks of indoor organophosphate esters (OPEs) are limited by the lack of knowledge on emission processes. This study attempted to integrate the contents and emissions of OPEs from indoor building materials to assess human health effects. Thirteen OPEs were investigated in 80 pieces of six categories of building materials. OPEs are ubiquitous in the building materials and ∑13OPE contents varied significantly (p < 0.05) from 72.8 ng/g (seam agent) to 109,900 ng/g (wallpaper). Emission characteristics of OPEs from the building materials were examined based on a microchamber method. Depending on the sample category, the observed initial area-specific emission rates of ∑13OPEs varied from 154 ng/m2/h (carpet) to 2760 ng/m2/h (wooden floorboard). Moreover, the emission rate model was developed to predict the release levels of individual OPEs, quantify source contributions, and assess associated exposure risks. Source apportionments of indoor OPEs exhibited heterogeneities in multiple environmental media. The joint OPE contribution of wallpaper and wooden floorboard to indoor dust was up to 94.8%, while latex paint and wooden floorboard were the main OPE contributors to indoor air (54.2%) and surface (76.1%), respectively. Risk assessment showed that the carcinogenic risks of tris(2-chloroethyl) phosphate (3.35 × 10-7) were close to the acceptable level (1 × 10-6) and deserved special attention.

[Water Environment Characteristics and Water Quality Assessment of Typical Lakes in Inner Mongolia].

Lakes on the Inner Mongolia Plateau, located in the ecologically fragile area of the northern border of China, play a very important role in regulating the regional climate and ecological environment and maintaining biodiversity. Owing to the dual influence of natural factors and human factors, the lake water environment in Inner Mongolia is facing challenges. To clarify the overall water quality of lakes in Inner Mongolia, based on the water quality data of typical lakes in Inner Mongolia in autumn 2019(October-November) and summer 2021(July-August), the temporal and spatial variation in water quality was discussed, and the influence of different indexes on lake water quality was analyzed, and the key factors affecting lake water quality were identified. The results showed as follows:① the spatiotemporal distribution of multiple physicochemical indices of typical lakes in Inner Mongolia were different in the two seasons. On the time scale, the concentration of ammonia nitrogen(NH4+-N) and nitrite nitrogen(NO2--N) were lower in autumn than that in summer, whereas dissolved oxygen(DO) was higher in autumn than that in summer. On the spatial scale, the concentrations of total phosphorus(TP), total nitrogen(TN), chemical oxygen demand(COD), and salinity(Sal) and other indicators in the southwest lakes of Inner Mongolia were higher than those of lakes in the northeast, but the DO index showed the opposite trend. ② Dissolved total solids(TDS) was the main characteristic factor of water quality of typical lakes in Inner Mongolia. ③ The spatiotemporal distribution of lake water quality index(WQI) was significantly different. The lake water quality level decreased with the increase in TDS, and the lake water quality was better in autumn than that in summer.

Correlates of residents' enrolment intention toward inclusive commercial health insurance in China: involvement, perceived benefit, perceived sacrifice, and government participation.

Background: As an application of inclusive finance in health insurance, inclusive commercial health insurance (ICHI) is a new public-private partnership-based health insurance scheme and has been vigorously promoted by the Chinese government in recent years to develop China Multi-level Health Insurance System, a system that aims to seek a mix of public and private sources to provide more affordable financial protection to all levels of society in line with their needs. However, the overall enrolment of ICHI scheme is still at a low level, and little is known about what influences residents' enrolment intentions. The aim of this study was to examine the multidimensional factors influencing residents' behavioral intentions and to develop a multivariate conceptual model to explore the psychographic process in the formation of enrolment intention. Methods: The empirical data used for model validation were obtained from a cross-sectional study conducted in Nanjing, China, a representative pilot city of ICHI scheme in 2022. Exploratory factor analysis, ANOVA, standard multiple regression, and hierarchical multiple regression were mainly employed for hypothesis testing. Results: The findings revealed that involvement, perceived benefit, and perceived sacrifice are all crucial psychographic process factors in the formation of residents' enrolment intentions. Government participation positively moderates the influence path of "perceived benefit-enrolment intention" but negatively moderates the path of "perceived sacrifice-enrolment intention". Moreover, it was discovered that perceived benefit mediates the effect of involvement on enrolment intention, while perceived sacrifice does not. Conclusions: Improving residents' perceived benefit and involvement degree of the product, as well as reducing their perceived sacrifice, are both key to increasing their enrolment intentions. This study also points out that one of the main dilemmas in the current development of ICHI scheme is the low level of involvement among residents, and that optimizing the product design to make it more relevant to residents' lives is a more beneficial strategy to increase overall involvement.

Assessment of disaster preparedness and related impact factors among emergency nurses in tertiary hospitals: descriptive cross-sectional study from Henan Province of China.

Background: The aim of this study was to investigate the current state of disaster preparedness and to determine associated factors among emergency nurses from tertiary hospitals in Henan Province of China. Methods: This multicenter descriptive cross-sectional study was conducted with emergency nurses from 48 tertiary hospitals in Henan Province of China between September 7, 2022-September 27, 2022. Data were collected through a self-designeds online questionnaire using the mainland China version of the Disaster Preparedness Evaluation Tool (DPET-MC). Descriptive analysis and multiple linear regression analysis were used to evaluate disaster preparedness and to determine factors affecting disaster preparedness, respectively. Results: A total of 265 emergency nurses in this study displayed a moderate level of disaster preparedness with a mean item score of 4.24 out 6.0 on the DPET-MC questionnaire. Among the five dimensions of the DPET-MC, the mean item score for pre-disaster awareness was highest (5.17 ± 0.77), while that for disaster management (3.68 ± 1.36) was the lowest. Female gender (B = -9.638, p = 0.046) and married status (B = -8.618, p = 0.038) were negatively correlated with the levels of disaster preparedness. Five factors positively correlated with the levels of disaster preparedness included having attended in the theoretical knowledge training of disaster nursing since work (B = 8.937, p = 0.043), having experienced the disaster response (B = 8.280, p = 0.036), having participated in the disaster rescue simulation exercise (B = 8.929, p = 0.039), having participated in the disaster relief training (B = 11.515, p = 0.025), as well as having participated in the training of disaster nursing specialist nurse (B = 16.101, p = 0.002). The explanatory power of these factors was 26.5%. Conclusion: Emergency nurses in Henan Province of China need more education in all areas of disaster preparedness, especially disaster management, which needs to be incorporated into nursing education, including formal and ongoing education. Besides, blended learning approach with simulation-based training and disaster nursing specialist nurse training should be considered as novel ways to improve disaster preparedness for emergency nurses in mainland China.

Levels, distribution, childhood exposure assessment, and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust from nine cities in China.

Household dust is an important source of premature exposure to polybrominated diphenyl ethers (PBDEs), especially for children. In this onsite study, 246 dust samples were collected from 224 households in nine Chinese cities during 2018-2019. Questionnaires were administered to explore the association between household-related information and PBDEs in household dust. The median concentration of Σ12PBDEs in household dust from 9 cities was 138 ng/g (94-227 ng/g), with the arithmetic mean of 240 ± 401 ng/g. Among the nine cities, the highest median concentration of Σ12PBDEs in household dust was found in Mianyang (295.57 ng/g), while the lowest was found in Wuxi (23.15 ng/g). BDE-71 was the most dominant congener, ranging from 42.08 % to 98.15 % of the 12 PBDE congeners among 9 cities. Three potential sources for the indoor environment were Penta-BDE, Octa-BDE commercial products, and photolytic bromine from Deca-BDEs based on the largest contribution (81.24 %). Under the moderate exposure scenario, the exposure levels through ingestion and dermal absorption for children were 7.30 × 10-1 ng/kg BW/day and 3.26 × 10-2 ng/kg BW/day, respectively. Temperature, CO2, years of residence, income, family size, household size, use of computers, heating, use of insecticide, and use of humidifiers were influential factors for PBDE concentrations in household dust. Based on the evidence of the correlation between PBDEs and these household parameters, it can be applied to reduce PBDE concentrations in household dust, which is a basis for controlling PBDEs pollution in Chinese households and protecting population health.

The influence of price value on purchase intention among patients with chronic diseases in medical e-commerce during the COVID-19 pandemic in China.

Background: During the COVID-19 pandemic, medical e-commerce (MEC) has provided a way for patients with chronic diseases to purchase drugs online to maintain social distancing, decrease the risk of infection and community transmission, and relieve the burden on medical resources. Therefore, research which seeks to elucidate the drivers of purchase intention (PI) among patients with chronic diseases in MEC is vital. This study extended the theory of planned behavior (TPB) by integrating the price value (PV) variable into the original TPB framework and explored the effect of PV on patients' PI in MEC during the coronavirus pandemic. Methods: Empirical data was gathered from 414 Chinese participants. Structural equation modeling was applied to explore the mechanism of chronic patients' PI in MEC. In addition, this study also estimated the moderating effect of gender, income, and region and the mediating role of attitude (ATT), subjective norm (SN), and perceived behavioral control (PBC) between PV and PI. Results: Patients' PI in MEC is significantly affected by ATT, SN, and PBC. PV delivers significant influence on ATT, SN, PBC, and PI, with PV having the strongest effect on ATT. Gender, income, and region can significantly moderate the relationship between PV and ATT. Conclusion: These findings can contribute to design targeted interventions to increase the adoption of MEC for patients with chronic diseases, decrease infection rates, and alleviate the strain on medical resources in the COVID-19 era.

Improved cryopreservation media formulation reduces costs of maintenance while preserving function of genetically modified insect cells.

Insect cell lines are an invaluable resource that facilitate various fundamental and applied research programs. Genetically engineered insect cell lines, in particular, serve as a platform through which the function of heterologously expressed proteins can be studied. However, a barrier to more widespread utilization and distribution of insect cell lines, genetically modified or not, is the technical and operational challenge associated with traditional cryopreservation methods, including their dependence on the use of liquid nitrogen facilities, animal or human serum products, and relatively high concentrations of permeating cryoprotectants (e.g., DMSO). Recent innovations in cryopreservation technologies have produced reagents with improved abilities to effectively preserve mammalian cell lines for long periods in regular laboratory deep freezers without using serum products, but their effectiveness in preserving genetically engineered insect cell lines has not yet been evaluated. In this study, we engineered Sf9 cells to express a dopamine receptor and used them as a model for evaluating the efficacy of a novel cryopreservation medium product, C80EZ®-INSECT, in not only preserving cell viability and proliferation efficiency but also maintaining the insect cell line's "functionality" after storage at -80°C. We found that the engineered Sf9 cells frozen using C80EZ®-INSECT with 5% DMSO alone and stored at -80°C for 6 mo displayed higher viability and growth rates than cells frozen using traditional fetal bovine serum (FBS)-based cryopreservation media with 10% DMSO that were stored at -80°C or in liquid nitrogen for the same period of time. We also found that after 6 mo of storage at -80°C or in liquid nitrogen the cells retained a responsiveness to dopamine comparable to that of the initial cell line, regardless of the cryopreservation reagent used. These results suggest that, due to the unique characteristics of C80EZ®-INSECT in preventing ice recrystallization and reducing ice crystal size and cellular apoptosis during cryostorage procedures, it is an effective cryopreservation reagent for genetically engineered Sf9 cells, and it practically eliminates the need for liquid nitrogen-based storage facilities and FBS-based cryopreservation formulations, as well as reduces the use of permeating cryoprotectants.

[Water Environmental Characteristics and Water Quality Assessment of Lakes in Tibetan Plateau].

Lakes are an important water resource and biological habitat in the Tibetan Plateau. Owing to the combined influence of climate, topography, and other natural factors as well as human factors, the water environment of the lakes on the Tibetan Plateau is facing more and more severe problems and challenges. To clarify the present status, distribution pattern, main characteristic factors of water quality, and important factors affecting the water quality of lakes on the Tibetan Plateau, the water environment of 12 typical lakes on the Tibet Plateau was investigated in summer (July-August) and autumn (October-November) in 2020. The field sampling and laboratory test data comprehensive analysis showed that:① several physical and chemical parameters of typical lakes on the Tibetan Plateau differed in spatiotemporal distribution. ② Salinity was the main characteristic of water quality in the typical lakes on the Tibetan Plateau. ③ The spatiotemporal distribution of lake eutrophication index showed little diversity and basically ranged from poor nutrition to moderate nutrition. The spatial and temporal distributions in the lake water quality index (WQI) were significantly different. The lake WQI grade decreased from "Moderate" to "Very poor" with the increase in salinity area, and the lake water quality in autumn was better than that in summer. ④ The spatiotemporal differences in lake water quality on the Tibetan Plateau were mainly controlled by precipitation, evapoconcentration, and human activities. This study will provide scientific basis for water environment protection and improvement of water ecosystems on the Tibetan Plateau.

Global, regional, and national burdens of HIV and other sexually transmitted infections in adolescents and young adults aged 10-24 years from 1990 to 2019: a trend analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: Sexually transmitted infections (STIs), including HIV, are major sexual health issues among adolescents and young adults globally, but data on the burden and trends of these diseases are sparse. We aimed to assess the trends in the burden of HIV and other STIs among adolescents and young adults aged 10-24 years from 1990 to 2019 on the global, regional, and national level. METHODS: In this trend analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we reported on the number, rates per 100 000 population, and average annual percentage changes (AAPCs) of incidence and disability-adjusted life-years (DALYs) of HIV and other STIs (syphilis, chlamydia, gonorrhoea, trichomonas, and genital herpes) at the global, regional, and national level among individuals aged 10-24 years. We further analysed these global trends by age, sex, and social development index (SDI). We also used joinpoint regression analysis to identify the year with the most substantial changes in global trends. FINDINGS: Globally, the incidence of HIV among adolescents and young adults decreased from 34·5 per 100 000 population (95% uncertainty interval [UI] 29·3 to 39·7) in 1990 to 22·7 per 100 000 population (20·3 to 25·8) in 2019, AAPC -2·6 [95% CI -3·1 to -2·0]); specific years in which HIV incidence decreased significantly were 1998, 2005, and 2014. Incidence of other STIs increased from 6986·3 per 100 000 population (95% UI 5504·8-8645·0) in 1990 to 7088·7 100 000 population (5620·1-8697) in 2019 (AAPC 0·2 [95% CI 0·1-0·3]); we found a substantial decrease in the incidence of other STIs in 2011 only. The rate of decrease in the incidence of other global STIs between 2009 and 2019 was approximately one-fifth the rate of the decrease in the global incidence of HIV for the same time period (AAPC -0·7 [95% CI -0·8 to -0·7] vs AAPC -3·4 [-3·8 to -3·1]). Regionally, sub-Saharan Africa had the highest incidence and highest DALYs from HIV and other STIs, and Oceania and Eastern Europe had the largest increase in the incidence and DALYs from HIV and other STIs between 1990 and 2019. By SDI quintile, the middle-SDI countries had the largest increase in HIV incidence between 1990 and 2019 and the DALYs from other STIs in the same period decreased in all SDI quintiles. Globally, females accounted for 278 076 (65·8%) of the 0·42 million incident HIV cases in 2019 and 68 115 077 (51·6%) of the 132·0 million incident cases of other STIs. Of all age groups, adolescents aged 10-14 years had the largest increase in the incidence of other STIs between 1990 and 2019 (from 1158·9 per 100 000 population [95% UI 857·8-1556·5] in 1990 to 1215·4 per 100 000 population [893·5-1616·1] in 2019; AAPC 0·1 [95% CI 0·1-0·2]). The individual STIs with the highest incident rates varied between age groups and sex. INTERPRETATION: Global HIV incidence among adolescents and young adults decreased between 1990 and 2019, with significant decreases coinciding with the implementation of antiretroviral therapy and pre-exposure prophylaxis. The incidence of other STIs in this population increased over the same period and only started decreasing in 2011, at a rate of only one-fifth of the rate of decrease of HIV. Earlier sexual health education and targeted STI screening are urgently required for adolescents and young adults. FUNDING: National Natural Science Foundation of China and the China Postdoctoral Science Foundation.

Characteristics, distribution, and children exposure assessment of 13 metals in household dust in China: A big data pilot study.

To explore the pollution characteristics of metals in household dust in China and their exposure to children, this study searched peer-reviewed papers published during 1980-2020 and analyzed 30 eligible papers screened under the per-decided strategy. We evaluated the sample-weighted concentration (SWC) of each metal, explored the sources of metals, and presented the quantitative description of spatial-temporary characteristics and children exposure to 13 metals with multi-route under a general living scenario. The results showed the concentrations of 13 metals with a range of 0.89-29 090.19 mg/kg. The SWC of Cd in household dust from rural areas was 3.29 times of that from urban areas, while the SWC of Ni from urban areas was 3.71 times of that from rural areas. The results showed that four principal components were extracted, and the cumulative contribution rate reached 79.127%. The exposure dose of 13 metals to children aged 2-3 years was presented with the highest by ingestion. Metals such as Fe, Zn, and Mn posed inevitable health risk to children with high exposure. Countermeasures should be carried out to minimize the children exposure to metals in household dust urgently, such as the establishment of environmental health standard for household dust.

Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database.

OBJECTIVES: Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. METHODS: A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. RESULTS: Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6-9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833-$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314-$34,995]; p<0.0001). CONCLUSIONS: Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

Source, Characterization of Indoor Dust PAHs and the Health Risk on Chinese Children.

Polycyclic aromatic hydrocarbons (PAHs) in indoor dust are one of the common exposure sources for children worldwide. The aim of this study is to explore PAHs pollution status in indoor dust and estimate health risk on Chinese children with big data. Weighted average concentration was used to analyze source and characterization of PAHs in indoor dust based on peer-reviewed literature. According to specific inclusion criteria, 17 studies were included finally to analyze weighted average concentration. The national average concentration of Σ16PAHs was approximately 25.696 µg/g. The highest concentration of Σ16PAHs was in Shanxi (2111.667 µg/g), and the lowest was in Hong Kong (1.505 µg/g). The concentrations in Shanxi and Guangdong were higher than national level and the over standard rate was 18.18%. The concentrations of individual PAHs varied greatly across the country, and Flu in Shanxi was the highest (189.400 µg/g). The sources of PAHs varied in different regions and combustion processes played a leading role. PAHs exposure through ingestion and dermal contact was more carcinogenic than inhalation. The incremental lifetime cancer risk model indicated that children lived in Shanxi were found in the highest health risk coupled with the highest BaPE concentration (54.074 µg/g). Although PAHs concentrations of indoor dust showed a downward trend from 2005 to 2018, indoor environmental sanitation should be improved with multidisciplinary efforts. Health standard should be possibly established to minimize children exposure to PAHs in indoor dust in China.

A Semi-Quantitative Risk Assessment and Management Strategies on COVID-19 Infection to Outpatient Health Care Workers in the Post-Pandemic Period.

BACKGROUND: In the pandemic of COVID-19, due to asymptomatic patients and high personnel fluidity in outpatient clinics, health care workers (HCWs) in outpatients were facing severe threat from infection. There is an urgent need for a risk assessment to recognize and prevent infection risks. PURPOSE: To establish a semi-quantitative risk assessment model on COVID-19 infections for HCWs in outpatient departments, and apply it to practices. Further to provide infection risk management strategies to reduce infection threats in the post-pandemic of COVID-19. METHODS: We used the method of Brainstorm, Literature study and Analytic Hierarchy Process (AHP) for risk factors selection and model construction, we also created corresponding indicators for each risk factors, in order to collect data in assessment practice. RESULTS: Eighteen risk factors were recognized and selected for model construction, by scatter plot, these risk factors had been classified into four parts, spanned the scopes of diagnosis and treatment, environment, personal protection and emergency handling, with specific management suggestions provided. In the practice, outpatient clinics were divided into three risk levels, 5 clinics in high risk level, 9 in medium risk level and 11 in low risk level. CONCLUSION: A proper comprehensive risk assessment model for COVID-19 infections has been successfully established. With the model, the ability to COVID-19 prevention in outpatients can be easily evaluated. The strategies on disinfection, surveillance and personal protection were also valuable references in the post-pandemic of COVID-19.

Lipase-catalyzed Synthesis of Feruloylated Lysophospholipid in Toluene-Ionic Liquids and Its Antioxidant Activity.

In this study, Novozym 435-catalyzed interesterification of ethyl ferulate (EF) with phosphatidylcholine (PC) in a two-phase system consisting of an ionic liquid (IL) and toluene was optimized to prepare feruloylated lysophospholipids (FLPs). Optimum conditions for the interesterification process were found to be [Bmim][Tf2N]/toluene ratio of 1:1 (v/v), solvent volume of 4 mL, molecular sieves (4 Å) concentration of 80 mg/mL, reaction temperature of 55°C, substrate molar ratio of 5:1 (PC/EF), Novozym 435 concentration of 50 mg/mL. Under these conditions, two FLPs products (1-FLP and 2-FLP) with total conversion rate of 50.79% were obtained. Because the formation of 1-FLP was significantly higher than 2-FLP, 1-FLP was purified and characterized by LC-MS and NMR. In addition, 1-FLP showed DPPH scavenging activity comparable with those of EF and BHT. Therefore, this study provides a good method for transformation of ferulic acid to improve its solubility and promote its application as functional ingredient in the food and pharmaceutical industries.

Sulfonylureas and Metformin Were Not Associated With an Increased Rate of Serious Bleeding in Warfarin Users: A Self-Controlled Case Series Study.

Drug interactions between warfarin and sulfonylureas are suggested by pharmacokinetic information and prior studies. However, clinical evidence on the association of such interactions and the risk of bleeding is lacking. Using healthcare claims data from 5 US Medicaid programs from 1999-2011 and a self-controlled case series design with warfarin as an object drug, we calculated confounder-adjusted rate ratios (RRs) for concomitant use of sulfonylureas and metformin for 3 outcomes separately: (i) serious bleeding as a composite outcome of gastrointestinal bleeding (GIB) and nontraumatic intracranial hemorrhage (ICH); (ii) GIB; and (iii) ICH. In 6,463 warfarin users experiencing serious bleeding, an increased rate of serious bleeding was not associated with concomitant use of glimepiride (RR: 0.93; 95% confidence interval (CI) 0.75-1.15), glipizide (RR: 0.97; 95% CI 0.84-1.13), glyburide (RR: 0.89; 95% CI 0.76-1.06), or metformin (RR: 0.85; 95% CI 0.76-0.96), nor was the occurrence of the component outcomes of GIB or ICH. These results suggest that use of sulfonylureas or metformin was not associated with an increased rate of serious bleeding in warfarin users.

Brominated flame retardants in atmospheric fine particles in the Beijing-Tianjin-Hebei region, China: Spatial and temporal distribution and human exposure assessment.

Atmospheric fine particle (PM2.5) samples were collected over a whole year (April 2016 - March 2017) across five sampling locations in the Beijing-Tianjin-Hebei (BTH) region, to investigate the occurrence of novel brominated flame retardants (NBFRs) and polybrominated diphenyl ethers (PBDEs). The concentrations of ∑9NBFRs were in the range of 0.63-104 pg/m3 (15.6 ±â€¯16.8 pg/m3) in atmospheric PM2.5, while the levels of ∑9PBDEs (excluding BDE-209) ranged from 0.05 to 19.1 pg/m3 (2.9 ±â€¯3.8 pg/m3) and BDE-209 concentrations ranged from 0.88 to 138 pg/m3 (22 ±â€¯28 pg/m3). Relatively higher levels of NBFRs and PBDEs were found at urban sampling sites in Beijing City and Shijiazhuang City. Decabromodiphenylethane (DBDPE) and BDE-209 were the dominant compounds with the relative abundances of 72% in ∑9NBFRs and 90% in ∑10PBDEs, respectively. Generally, the levels of most target BFRs in summer were lower than those in other seasons. However, there were no notable seasonal differences in levels of DBDPE and BDE-209 in atmospheric PM2.5 samples across the BTH region. Significant and positive correlations were found between the concentrations of BFRs and PM2.5. Daily human exposure via inhalation revealed that children have a higher probability of suffering from the adverse effects of BFRs than that of adults. In addition, residents living near sampling locations across the BTH region may suffer high exposure risks to BDE-209 and NBFRs.

Serious Hypoglycemia and Use of Warfarin in Combination With Sulfonylureas or Metformin.

Prior research suggests that warfarin, when given concomitantly with some sulfonylureas, may increase the risk of serious hypoglycemia. However, the clinical significance remains unclear. We examined rate ratios (RRs) for the association between serious hypoglycemia and concomitant use of warfarin with either sulfonylureas or metformin using a self-controlled case series design and US Medicaid claims (supplemented with Medicare claims) from 1999 to 2011. Across all risk windows combined, warfarin was associated with an elevated rate of serious hypoglycemia when given concomitantly with glimepiride (RR, 1.47; 95% confidence interval (CI), 1.07-2.02) and metformin (RR, 1.73; 95% CI, 1.38-2.16). Particularly in the late risk window (>120 days since beginning concomitancy), most of the RRs for warfarin were elevated: glipizide (RR, 1.72; 95% CI, 1.29-2.29), glyburide (RR, 1.57; 95% CI, 1.15-2.15), metformin (RR, 2.26; 95% CI, 1.67-3.05), and glimepiride (RR, 1.56; 95% CI, 0.97-2.50). These results are consistent with a previously hypothesized hypoglycemic effect of warfarin in patients with type 2 diabetes through inhibition of the carboxylation of osteocalcin.

Comparative risk of serious hypoglycemia with oral antidiabetic monotherapy: A retrospective cohort study.

PURPOSE: To examine and compare risks of serious hypoglycemia among antidiabetic monotherapy-treated adults receiving metformin, a sulfonylurea, a meglitinide, or a thiazolidinedione. METHODS: We performed a retrospective cohort study of apparently new users of monotherapy with metformin, glimepiride, glipizide, glyburide, pioglitazone, rosiglitazone, nateglinide, or repaglinide within a dataset of Medicaid beneficiaries from California, Florida, New York, Ohio, and Pennsylvania. We did not include users of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, or sodium-glucose co-transporter 2 inhibitors. We identified serious hypoglycemia outcomes within 180 days following new use using a validated, diagnosis-based algorithm. We calculated age- and sex-standardized outcome occurrence rates for each drug and generated propensity score-adjusted hazard ratios vs metformin using Cox proportional hazards regression. RESULTS: The ranking of standardized occurrence rates of serious hypoglycemia was glyburide > glimepiride > glipizide > repaglinide > nateglinide > rosiglitazone > pioglitazone > metformin. Rates were increased for all study drugs at higher average daily doses. Adjusted hazard ratios (95% confidence intervals) vs metformin were 3.95 (3.66-4.26) for glyburide, 3.28 (2.98-3.62) for glimepiride, 2.57 (2.38-2.78) for glipizide, 2.03 (1.64-2.52) for repaglinide, 1.21 (0.89-1.66) for nateglinide, 0.90 (0.75-1.07) for rosiglitazone, and 0.80 (0.68-0.93) for pioglitazone. CONCLUSIONS: Sulfonylureas were associated with the highest rates of serious hypoglycemia. Among all study drugs, the highest rate was seen with glyburide. Pioglitazone was associated with a lower adjusted hazard for serious hypoglycemia vs metformin, while rosiglitazone and nateglinide had hazards similar to that of metformin.

Resistance risk assessment for fludioxonil in Bipolaris maydis.

Bipolaris maydis (anamorph: Cochliobolus heterostrophus) is the causal agent of Southern Corn Leaf Blight (SCLB), leading to huge annually losses worldwide. Although fludioxonil, a phenylpyrrole fungicide with a broad spectrum of activity, was introduced in the 1990s, no baseline sensitivity has been established for B. maydis. One hundred field isolates were used to establish a baseline sensitivity of B. maydis against fludioxonil during 2015-2016. The results showed that the baseline sensitivity was distributed as a unimodal curve with a mean EC50 value of 0.044±0.022µgmL-1. With repeated exposure to fludioxonil, a total of five fludioxonil-resistant mutants (RF>100, RF=Resistance factor) were obtained in the laboratory. Compared with the parental isolates, the five fludioxonil-resistant mutants showed decreased fitness in sporulation and virulence, and exhibited different features of sensitivity to various stresses (oxidation and osmotic pressure, cell membrane and cell wall inhibitors), but not in mycelial growth on PDA without stress amendation. The five fludioxonil-resistant mutants showed a positive cross-resistance between fludioxonil and the dicarboximide fungicide procymidone, but not between fludioxonil and boscalid or fluazinam. All mutants exhibited stable resistance to fludioxonil after 10 transfers, as indicated by resistance factor values that ranged from 116.82 to 445.59. When treated with 1.0 M NaCl, all the fludioxonil-resistant mutants showed greater mycelial glycerol content than corresponding parental isolates. Sequencing alignment results of Bmos1 indicated that mutant R27-5 had a single point mutation (Z1125K), while the mutant R104 had a 34-bp deletion fragment between the codons of amino acid residues 1125 to 1236 and encodes a putative attenuated 1133-AA protein. The 34-bp deletion fragment led to not only a 11-AA deletion(DNAVNQKLAVR), but also the resulting frameshift mutation and early stop. The mutations of R27-5 and R104 were located in the Rec domain of the Bmos1 gene. No mutations at the Bmos1 were detected in the other three resistant mutants R27-1, R27-2 and R32.