Cost-effectiveness of endovascular treatment for acute ischemic stroke in China: evidence from Shandong Peninsula.

BACKGROUND: Recently, the endovascular treatment (EVT) of acute ischemic stroke has made significant progress in many aspects. Intravenous thrombolysis (IVT) is usually recommended before endovascular treatment in clinical practice, but the value of the practice is controversial. The latest meta-analysis evaluation was that the effect of EVT versus EVT plus IVT did not differ significantly. The cost-effectiveness analysis of EVT plus IVT needs further analysis. This study assesses the health benefits and economic impact of EVT plus IVT in Shandong Peninsula of China. METHOD: We followed a cross-section design using the Chinese-Shandong Peninsula public hospital database between 2013 and 2023. The real-world costs and health outcomes were collected through the Hospital Information System (HIS) and published references. We calculated incremental cost-effectiveness ratios (ICERs) from the perspective of Chinese healthcare using the complex decision model to compare the costs and effectiveness between EVT versus EVT + IVT. One-way and Monte Carlo probabilistic sensitivity analyses were performed to assess the robustness of the economic evaluation model. RESULTS: EVT alone had a lower cost compared with EVT + IVT whether short-term or long-term. Until 99% dead of AIS patients, the ICER per additional QALY was RMB696399.30 over the willingness-to-pay (WTP) threshold of 3× gross domestic product (GDP) per capita in Shandong. The probabilistic sensitivity analysis of 3 months, 1 year and long-term horizons had a 97.90%, 97.43% and 96.89% probability of cost-effective treatment under the WTP threshold (1×GDP). The results of the one-way sensitivity analysis showed that direct treatment costs for EVT alone and EVT + IVT were all sensitive to ICER. CONCLUSIONS: EVT alone was more cost-effective treatment compared to EVT + IVT in the Northeast Coastal Area of China. The data of this study could be used as a reference in China, and the use of the evaluation in other regions should be carefully considered.

Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling.

OBJECTIVE: Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs; however, concerns regarding complexities and side effects persist, driving research for more effective, low-risk strategies. The promotion of white adipose tissue (WAT) browning has emerged as a promising approach. Moreover, alisol B 23-acetate (AB23A) has demonstrated efficacy in addressing metabolic disorders, suggesting its potential as a therapeutic agent in obesity management. Therefore, in this study, we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet (HFD). METHODS: An obesity mouse model was established by administration of an HFD. Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests. Adipocyte size was determined using hematoxylin and eosin staining. The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction. Metabolic cage monitoring involved the assessment of various parameters, including food and water intake, energy metabolism, respiratory exchange rates, and physical activity. Moreover, oil red O staining was used to evaluate intracellular lipid accumulation. A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways. RESULTS: AB23A administration significantly reduced the weight of obese mice, decreased the mass of inguinal WAT, epididymal WAT, and perirenal adipose tissue, improved glucose and insulin metabolism, and reduced adipocyte size. Moreover, treatment with AB23A promoted the expression of browning markers in WAT, enhanced overall energy metabolism in mice, and had no discernible effect on food intake, water consumption, or physical activity. In 3T3-L1 cells, AB23A inhibited lipid accumulation, and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1 (mTOR-SREBP1) signaling pathway. Furthermore, 3-isobutyl-1-methylxanthine, dexamethasone and insulin, at concentrations of 0.25 mmol/L, 0.25 µmol/L and 1 µg/mL, respectively, induced activation of the mTOR-SREBP1 signaling pathway, which was further strengthened by an mTOR activator MHY1485. Notably, MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells. CONCLUSION: AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway, offering a potential strategy to prevent obesity. Please cite this article as: Han LL, Zhang X, Zhang H, Li T, Zhao YC, Tian MH, Sun FL, Feng B. Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling. J Integr Med. 2024; 22(1): 83-92.

Exposure risk assessment of representative phthalate acid esters and associated plastic debris under the agricultural land use in typical Chinese regions.

Phthalate acid esters (PAEs) are frequently detected in the global environment and can cause potential health hazards. In this study, quantitative exposure risk assessment was undertaken to derive soil generic assessment criteria (GAC) for six representative PAEs under the agricultural land use in the evaluated Chinese regions, which coupled multi-media transport and human exposure models based on multiple exposure pathways including vegetables consumption, dermal absorption, ingestion of soil and dust, and the exposure from non-soil sources. It is identified that the PAEs in agricultural soil are dominated by DEHP and DnBP representing 72-96% of the total PAEs. The GAC for BBP and DEHP, calculated on the basis of region-specific exposure parameters and soil properties in various locations, are stringent, signifying greater potential health risks from exposure to them, warranting more rigorous contamination management. The proposed soil GAC for plastic debris are 100, 107, 73 and 88 mg kg-1 for Heilongjiang Province, Beijing City, Jiangsu and Guangdong Provinces respectively. Additionally, the potential risks of 1.68 × 10-6 and 7 × 10-6 are identified for BBP and DEHP in Guangdong Province as indicated by the exceedance of target risk level of 1 × 10-6, with the consumption of vegetables being the dominant contributor to the total estimated PAEs exposure. Overall, this methodology based on the coupled contaminant transport and exposure models incorporating region-specific data provides a technical framework to derive science-based soil GAC for representative PAEs for maintaining and assessing soil quality and food safety under the agricultural land use.

The impact of transportation mode, socioeconomic deprivation and rurality on travel times to radiotherapy and surgical services for patients with prostate cancer: A national population-based evaluation.

BACKGROUND: The distances that patients have to travel can influence their access to cancer treatment. We investigated the determinants of travel time, separately for journeys by car and public transport, to centres providing radical surgery or radiotherapy for prostate cancer. METHODS: Using national cancer registry records linked to administrative hospital data, we identified patients who had radical surgery or radiotherapy for prostate cancer between January 2017 and December 2018 in the English National Health Service. Estimated travel times from the patients' residential area to the nearest specialist surgical or radiotherapy centre were estimated for journeys by car and by public transport. RESULTS: We included 13,186 men who had surgery and 26,581 who had radiotherapy. Estimated travel times by public transport (74.4 mins for surgery and 69.4 mins for radiotherapy) were more than twice as long as by car (33.4 mins and 29.1mins, respectively). Patients living in more socially deprived neighbourhoods in rural areas had the longest travel times to the nearest cancer treatment centres by car (62.0 mins for surgery and 52.1 mins for radiotherapy). Conversely patients living in more affluent neighbourhoods in urban conurbations had the shortest (18.7 mins for surgery and 17.9 mins for radiotherapy). CONCLUSION: Travel times to cancer centres vary widely according to mode of transport, socioeconomic deprivation, and rurality. Policies changing the geographical configuration of cancer services should consider the impact on the expected travel times both by car and by public transport to avoid enhancing existing inequalities in access to treatment and patient outcomes.

Assessment of the Anti-Breast Cancer Effects of Urolithin with Molecular Docking Studies in the In Vitro Condition: Introducing a Novel Chemotherapeutic Drug.

A lot of research has been done on using natural items as diabetes treatment. The molecular docking study was conducted to evaluate the inhibitory activities of urolithin A against α-amylase, α-glucosidase, and aldose reductase. The molecular docking calculations indicated the probable interactions and the characteristics of these contacts at an atomic level. The results of the docking calculations showed the docking score of urolithin A against α-amylase was -5.169 kcal/mol. This value for α-glucosidase and aldose reductase was -3.657 kcal/mol and -7.635 kcal/mol, respectively. In general, the outcomes of the docking calculations revealed that urolithin A can construct several hydrogen bonds and hydrophobic contacts with the assessed enzymes and reduces their activities considerably. The properties of urolithin against common human breast cancer cell lines, i.e., SkBr3, MDA-MB-231, MCF-7, Hs578T, Evsa-T, BT-549, AU565 and 600MPE were evaluated. The IC50 of the urolithin was 400, 443, 392, 418, 397, 530, 566 and 551 against SkBr3, MDA-MB-231, MCF-7, Hs578T, Evsa-T, BT-549, AU565 and 600MPE, respectively. After doing the clinical trial studies, the recent molecule may be used as an anti-breast cancer supplement in humans. IC50 values of urolithin A on α-amylase, α-glucosidase, and aldose reductase enzymes were obtained at 16.14, 1.06 and 98.73 µM, respectively.

Association of Neighborhood-Level Marginalization With Health Care Use and Clinical Outcomes Following Hospital Discharge in Patients Who Underwent Coronary Catheterization for Acute Myocardial Infarction in a Single-Payer Health Care System.

BACKGROUND: Canadian data suggest that patients of lower socioeconomic status with acute myocardial infarction receive less beneficial therapy and have worse clinical outcomes, raising questions regarding care disparities even in universal health care systems. We assessed the contemporary association of marginalization with clinical outcomes and health services use. METHODS: Using clinical and administrative databases in Ontario, Canada, we conducted a population-based study of patients aged ≥65 years hospitalized for their first acute myocardial infarction between April 1, 2010 and March 1, 2019. Patients receiving cardiac catheterization and surviving 7 days postdischarge were included. Our primary exposure was neighborhood-level marginalization, a multidimensional socioeconomic status metric. Neighborhoods were categorized by quintile from Q1 (least marginalized) to Q5 (most marginalized). Our primary outcome was all-cause mortality. A proportional hazards regression model with a robust variance estimator was used to quantify the association of marginalization with outcomes, adjusting for risk factors, comorbidities, disease severity, and regional cardiologist supply. RESULTS: Among 53 841 patients (median age, 75 years; 39.1% female) from 20 640 neighborhoods, crude 1- and 3-year mortality rates were 7.7% and 17.2%, respectively. Patients in Q5 had no significant difference in 1-year mortality (hazard ratio [HR], 1.08 [95% CI, 0.95-1.22]), but greater mortality over 3 years (HR, 1.13 [95% CI, 1.03-1.22]) compared with Q1. Over 1 year, we observed differences between Q1 and Q5 in visits to primary care physicians (Q1, 96.7%; Q5, 93.7%) and cardiologists (Q1, 82.6%; Q5, 72.6%), as well as diagnostic testing. There were no differences in secondary prevention medications dispensed or medication adherence at 1 year. CONCLUSIONS: In older patients with acute myocardial infarction who survived to hospital discharge, those residing in the most marginalized neighborhoods had a greater long-term risk of mortality, less specialist care, and fewer diagnostic tests. Yet, there were no differences across socioeconomic status in prescription medication use and adherence.

Characteristics and risk assessment of chilling injury on Morchella esculenta in Western Sichuan Plateau, China.

The development of precise climate risk zoning for chilling injury of Morchella esculenta can provide scientific basis for agricultural cultivation planning, dynamic assessment of chilling injury, and disaster prevention strategies. Based on meteorological data from 17 counties (cities) that located below the altitude of 3000 m in the Western Sichuan Plateau from 2011 to 2020, we analyzed the critical meteorological conditions for M. esculenta disasters in typical years. With the average yearly cold accumulation and cold injury frequency during the first day when the temperature remained stable between 5 ℃ and 10 ℃ during mushroom emergence as zoning indicators, we established a geographical spatial distribution model of the cold injury index, and then divided the risk level of M. esculenta cold injury in the Western Sichuan Plateau, evaluated the risk of cold injury. The results showed that the temperature index for chilling injury risk of M. esculenta in the study area was the daily minimum temperature ≤2.0 ℃. The daily average temperature <6.0 ℃ would cause slow growth or the cessation of growth, which was set as a warning indicator for chilling injury risk. Along the Dadu River and Minjiang River basins, the frequency of chilling injury on M. esculenta increased from south to north. Wenchuan, Maoxian, and Lixian had the fewest overall chilling injuries during the study period, whereas Jiulong, Yajiang, and Batang had the most. The duration for cold injury was mainly 1-3 d, followed by 4-5 d, and rarely for >5 d. The frequency of chilling injury lasting for more than 5 d in Xiangcheng, Batang, Jiulong, Yajiang, and Xiaojin was more than that lasting for 4-5 d. The annual average days of chilling injury of was 3.0-27.4 d, the daily average minimum temperature was -0.84-1.36 ℃, the extreme lowest temperature was -5.8-0.1 ℃, and the average accumulated cold was 0.16-9.64 ℃·d during the period of chilling injury. With the increases of elevation and latitude, the average days of chilling injury and the average accumulated cold increased. The largest duration of chilling injury was 3-20 d, the maximum accumulated cold was 0.44-13.34 ℃·d. The risk of chilling injury to M. esculenta increased from south to north and from low elevation to high elevation. The suitable planting areas were distributed in strips and branches along the direction of mountains and rivers, mainly in the flat areas of low mountains and valleys below the altitude of 2200 m, including Kangding, Luding, Danba, Wenchuan, Lixian, Maoxian, Jiuzhaigou, and Songpan.

Human health risk-based soil generic assessment criteria of representative perfluoroalkyl acids (PFAAs) under the agricultural land use in typical Chinese regions.

Perfluoroalkyl acid substances (PFAAs), such as perfluorobutanoic acid (PFBA), perfluorobutanoic sulfonic acid (PFBS), perfluorooctane acid (PFOA) and perfluoroooctane sulfonic acid (PFOS) are frequently detected in the global environment and can cause potential health hazards even at low levels. In this study, quantitative human health risk assessment was undertaken to derive soil generic assessment criteria (GAC) for four PFAAs under the agricultural land scenario in the evaluated Chinese regions, which considered multiple exposure pathways including vegetables consumption, dermal absorption, ingestion of soil and dust, and exposure from non-soil sources. It is showed that the calculated GAC for four PFAAs in Guangdong and Shandong Provinces were less stringent than those in Zhejiang and Jiangsu Provinces, and Shanghai City, owing to the low exposure from non-soil sources in former two provinces. In addition, GAC of PFOS were the most stringent in the range of 0.28-0.50 µg kg-1 in the studied regions, followed by PFOA (1.36-2.20 µg kg-1), PFBA (42.59-68.03 µg kg-1) and PFBS (474.59-749.60 µg kg-1), mainly attributable to significantly more stringent toxicological values of PFOA and PFOS. Correspondingly, the potential health hazards exist for PFOA in the studied regions except Guangdong Province, and PFOS only in Zhejiang and Jiangsu Provinces as indicated by the hazard quotients ranging from 1.04 to 19.49, but no health hazards are identified for PFBA and PFBS. The dominant exposure pathway was found to be consumption of vegetables and attached soil for PFBA and PFBS, contributing to more than 93% of the total exposure, compared to 49.91-76.69% for PFOA and PFOS due to significant exposure from non-soil sources levels. Overall, this study provides a technical reference on how to derive scientifically justifiable soil GAC for representative PFAAs for maintaining and assessing soil quality and food safety internationally under the agricultural land use.

The derivation of soil generic assessment criteria for polychlorinated biphenyls under the agricultural land scenario in Pearl and Yangtze River Delta regions, China.

The agricultural soils in China are suffered from serious polychlorinated biphenyls (PCBs) contamination, however, the valid management standards for farmland are absent to efficiently control the health risks of PCBs exposure. This study analyzed the contamination characteristics and main composition of PCBs in agricultural soils of the southeastern China from the published literature over the past 20 years, and derived the regional generic assessment criteria (GAC) using an exposure modelling approach for individual and total PCBs (∑PCBs) via multiple exposure pathways such as ingestion of soil and dust, consumption of vegetables, dermal contact with soil and dust, ingestion of soil attached to vegetables, and inhalation of soil vapour and soil-derived dust outdoors under the agricultural land scenario. It is identified that the averaged ∑PCBs concentration of 80.03 ng g-1 under the 95 % lower confidence limit with an unacceptable health risk of 4.8 × 10-6 has significantly exceeded the integrated generic assessment criteria (expressed as GACint) of 16.5 ng g-1. Accordingly, the exposure pathways from the consumption of agricultural produces and indirect ingestion of soil attached to vegetables contributed up to 62 %-88 % of the total exposure, followed by 11 %-33 % of the soil ingestion and 2 %-6 % of dermal contact. The derived GACint for ∑PCBs is extremely valuable to effectively assess and manage the PCBs contamination in agricultural soils of China.

Malnutrition and infection lead to poor prognosis and heavy financial burden of patients with chronic heart failure.

Background: Chronic heart failure (CHF) is a major public health concern, as it is associated with poor prognosis and heavy financial burden. In recent years, there has been increasing interest in medications for CHF in China, but few studies pay attention to the effects of nutrition and infection. Methods and results: This was a retrospective study collected patients with CHF admitted to the Department of Cardiology of Qilu Hospital of Shandong University from January 2017 to May 2018. Patients were classified according to the prognosis and the financial burden. Through comparison and regression analysis, we found that the factor associated with worse prognosis were decreased heart rate, albumin and prealbumin; ß-blockers and mineralocorticoid receptor antagonism (MRA) were the factor improved the prognosis of patients with CHF; the factor overburdening financial condition were infection, decreased prealbumin, high Alanine aminotransferase (ALT), usage of recombinant human brain natriuretic peptide (rhBNP) and Levosimendan; aspirin and Sacubitril/Valsartan were the factor releasing financial burden of patients with CHF. Then, we grouped by Controlling Nutritional Status (CONUT) score, which enabled evaluation of the patient's protein reserve and immune defenses. Patients in the malnutrition group had higher infection ratios, longer hospital stays, and greater hospital expenses than the normal group. The improvement ratios of therapeutic outcomes in the moderate or severe malnutrition group were lower than in the normal and mild malnutrition group. Conclusion: Malnutrition and infection caused poor prognosis and increased financial burden of patients with CHF. The high CONUT score indicated the CHF patient's unfavorable prognosis and heavy financial burden.

Life Cycle Assessment on Agricultural Production: A Mini Review on Methodology, Application, and Challenges.

Agricultural Life Cycle Assessment (LCA) is an effective tool for the quantitative evaluation and analysis of agricultural materials production and operation activities in various stages of the agricultural system. Based on the concept of life cycle, it comprehensively summarizes the impact of agriculture on the environment, which is an effective tool to promote the sustainability and green development of agriculture. In recent years, agricultural LCA has been widely used in the agroecosystem for resource and environmental impacts analysis. However, some challenges still exist in agricultural LCA, i.e., the environmental impact assessment index system needs to be improved; its application in different production mode is limited; and combination research with other models needs more attention. This paper discusses the above-mentioned challenges and recommends research priorities for both scientific development and improvements in practical implementation. In summary, further research is needed to construct a regional heterogeneity database and develop innovated methodologies to develop more meaningful functional units for agricultural products to complement LCA by other models. These efforts will make agricultural LCA more robust and effective in environmental impacts assessment to support decision making from individual farm to regional or (inter)national for the sustainable future of agriculture.

Health service planning to assess the expected impact of centralising specialist cancer services on travel times, equity, and outcomes: a national population-based modelling study.

BACKGROUND: Centralisation of specialist cancer services is occurring in many countries, often without evaluating the potential impact before implementation. We developed a health service planning model that can estimate the expected impacts of different centralisation scenarios on travel time, equity in access to services, patient outcomes, and hospital workload, using rectal cancer surgery as an example. METHODS: For this population-based modelling study, we used routinely collected individual patient-level data from the National Cancer Registration and Analysis Service (NCRAS) and linked to the NHS Hospital Episode Statistics (HES) database for 11 888 patients who had been diagnosed with rectal cancer between April 1, 2016, and Dec 31, 2018, and who subsequently underwent a major rectal cancer resection in 163 National Health Service (NHS) hospitals providing rectal cancer surgery in England. Five centralisation scenarios were considered: closure of lower-volume centres (scenario A); closure of non-comprehensive cancer centres (scenario B); closure of centres with a net loss of patients to other centres (scenario C); closure of centres meeting all three criteria in scenarios A, B, and C (scenario D); and closure of centres with high readmission rates (scenario E). We used conditional logistic regression to predict probabilities of affected patients moving to each of the remaining centres and the expected changes in travel time, multilevel logistic regression to predict 30-day emergency readmission rates, and linear regression to analyse associations between the expected extra travel time for patients whose centre is closed and five patient characteristics, including age, sex, socioeconomic deprivation, comorbidity, and rurality of the patients' residential areas (rural, urban [non-London], or London). We also quantified additional workload, defined as the number of extra patients reallocated to remaining centres. FINDINGS: Of the 11 888 patients, 4130 (34·7%) were women, 5249 (44·2%) were aged 70 years and older, and 5005 (42·1%) had at least one comorbidity. Scenario A resulted in closures of 43 (26%) of the 163 rectal cancer surgery centres, affecting 1599 (13·5%) patients; scenario B resulted in closures of 112 (69%) centres, affecting 7029 (59·1%) patients; scenario C resulted in closures of 56 (34%) centres, affecting 3142 (26·4%) patients; scenario D resulted in closures of 24 (15%) centres, affecting 874 (7·4%) patients; and scenario E resulted in closures of 16 (10%) centres, affecting 1000 (8·4%) patients. For each scenario, there was at least a two-times increase in predicted travel time for re-allocated patients with a mean increase in travel time of 23 min; however, the extra travel time did not disproportionately affect vulnerable patient groups. All scenarios resulted in significant reductions in 30-day readmission rates (range 4-48%). Three hospitals in scenario A, 41 hospitals in in scenario B, 13 hospitals in scenario C, no hospitals in scenario D, and two hospitals in scenario E had to manage at least 20 extra patients annually. INTERPRETATION: This health service planning model can be used to to guide complex decisions about the closure of centres and inform mitigation strategies. The approach could be applied across different country or regional health-care systems for patients with cancer and other complex health conditons. FUNDING: National Institute for Health Research.

Healthcare resource use and costs for people with type 2 diabetes mellitus with and without severe mental illness in England: longitudinal matched-cohort study using the Clinical Practice Research Datalink.

BACKGROUND: Approximately 60 000 people in England have coexisting type 2 diabetes mellitus (T2DM) and severe mental illness (SMI). They are more likely to have poorer health outcomes and require more complex care pathways compared with those with T2DM alone. Despite increasing prevalence, little is known about the healthcare resource use and costs for people with both conditions. AIMS: To assess the impact of SMI on healthcare resource use and service costs for adults with T2DM, and explore the predictors of healthcare costs and lifetime costs for people with both conditions. METHOD: This was a matched-cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics for 1620 people with comorbid SMI and T2DM and 4763 people with T2DM alone. Generalised linear models and the Bang and Tsiatis method were used to explore cost predictors and mean lifetime costs respectively. RESULTS: There were higher average annual costs for people with T2DM and SMI (£1930 higher) than people with T2DM alone, driven primarily by mental health and non-mental health-related hospital admissions. Key predictors of higher total costs were older age, comorbid hypertension, use of antidepressants, use of first-generation antipsychotics, and increased duration of living with both conditions. Expected lifetime costs were approximately £35 000 per person with both SMI and T2DM. Extrapolating nationally, this would generate total annual costs to the National Health Service of around £250 m per year. CONCLUSIONS: Our estimates of resource use and costs for people with both T2DM and SMI will aid policymakers and commissioners in service planning and resource allocation.

Diagnostic value of high-risk human papillomavirus viral load on cervical lesion assessment and ASCUS triage.

This study aims to evaluate HR-HPV viral load in the cervical lesion assessment and its diagnostic value on the triage of ASCUS. The three-step protocol for cervical cancer screening was carried out in 5171 patients from June 2017 to August 2019, and 1620 histopathological results were obtained. The positive rate of HR-HPV and TCT increased with the aggravation of pathological grades of cervical lesions. The sensitivity and specificity of HR-HPV (DH3) to detect CIN II+ were 91.91% and 84.46%, respectively. In comparison, the corresponding results of the cytology test were 80.51% and 83.12%. HPV16/18 viral load was positively correlated with the grade of cervical lesions (p < 0.001, r = 0.321). The diagnostic efficiency of AUC by applying HPV16/18 viral load was 0.682 for the diagnosis of CIN II+. The optimal HPV16/18 viral load for predicting CIN II+ was 6.80 RLU/CO (relative light units/cut-off), with corresponding sensitivity of 48.6%, specificity of 79.7%, and Youden index of 0.283. In the ASCUS population, viral loads were statistically different in HPV16/18 and the other 12 HR-HPV when compared cervicitis group with CIN I group and CIN II+ group (all p < 0.05). Statistical differences were detected concerning HPV16/18 viral load, contact bleeding status, and smoking status when compared cervicitis group with CIN I group and CIN II+ group (p < 0.05), with a corresponding odds ratio of 1.004, 1.533, and 5.513, respectively. Our findings suggest that HR-HPV viral load can be regarded as a useful tool to predict the grade of cervical lesions for ASCUS triage. ClinicalTrials.gov ID: NCT03178136.

Population pharmacokinetic and optimization of polymyxin B dosing in adult patients with various renal functions.

AIMS: Current FDA-approved label recommends that the dosage of polymyxin B should be adjusted according to renal function. However, the correlation between polymyxin B pharmacokinetics (PK) and creatinine clearance (CrCL) is poor. This study aimed to develop a population PK model of polymyxin B in adult patients with various renal functions and to identify a dosing strategy. METHODS: A retrospective PK study was performed in 32 adult patients with various renal function. Nonlinear mixed effects modelling was applied to build a population PK model of polymyxin B followed by Monte Carlo simulations which designed polymyxin B dosing regimens across various renal function. RESULTS: Polymyxin B PK analyses included 112 polymyxin B concentrations at steady state from 32 adult patients, in which 71.9% of them were critically ill. In the final PK model, CrCL was the significant covariate on CL (typical value 1.59 L/h; between-subject variability 13%). The mean (SD) individual empirical Bayesian estimate of CL was 1.75 (0.43) L/h. In addition, a new dosing strategy combining the PK/pharmacodynamic (PD) targets and Monte Carlo simulation indicated that the reduction of polymyxin B dose in patients with renal insufficiency improved the probability of achieving optimal exposure. For severe infections caused by organisms with minimum inhibitory concentration (MIC) ≥ 2 mg/L, a high daily dose of polymyxin B might be possible for bacterial eradication, but the risk of nephrotoxicity is increased. CONCLUSIONS: Renal function plays a significant role in polymyxin B PK, and the dose of polymyxin B should be adjusted according to CrCL in patients with renal insufficiency.

A systematic review of the budget impact analyses for antitumor drugs of lung cancer.

BACKGROUND: Budget impact analyses (BIAs) are used for reimbursement decisions and drug access medical insurance, as a supplement to cost-effectiveness analyses (CEAs). OBJECTIVES: We systematically reviewed BIAs for antitumor drugs of lung cancer to provide reference for high-value drug budget impact analyses and decision making. METHODS: We conducted a literature search on PubMed, EMbase, The Cochrane Library, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform from 2010 to 2019. The methodological indicators and result information of the budget impact analyses were extracted and evaluated for quality. RESULTS: A total of 14 studies on the budget impact for antitumor drugs of lung cancer were included, and the overall quality was good. Half of studies were from developed countries. Nine of the studies were designed using the BIA cost calculation model, and two were simulated using the Markov model Monte Carlo model. From all studies, only 14.3% reported model validation. The budget impact results of the same drug in different countries were inconsistent. CONCLUSIONS: Included studies evaluating budget impact analyses for anti-tumor drugs of lung cancer showed variability in the methodological framework for BIAs. The budget impact analyses of high-value drugs need to be more stringent to ensure the accuracy of the parameters, and should provide reliable results based on real data to decision-making departments, which should carefully consider access to lung cancer drugs.

Assessment of ethanol blended fuels for gasoline vehicles in China: Fuel economy, regulated gaseous pollutants and particulate matter.

The government of China has announced an ambitious plan to expand the mandatory use of ethanol blended gasoline fuels by 2020. Given the dissimilarity in fuel properties between China and other countries with ethanol blending practices, it is necessary to assess the energy and environmental impacts of ethanol blending. In this study, we prepared two types of ethanol blended fuels (E10, with ethanol contents of approximately 10%) with lower contents of aromatics (ELA) and olefins (ELO), respectively, compared with the market China 5 gasoline. Nine in-use gasoline vehicles varying by manufacturer, engine technology, model year, and emission standard level were analyzed using a chassis dynamometer, which followed the Worldwide Harmonized Light Vehicles Test Cycle (WLTC). Two major positive effects from using E10 fuels could be observed in this study. First, tested turbocharged gasoline direct injection (GDI) vehicles could gain reductions in CO2 emission, fuel consumption and energy consumption by switching to the higher-octane-number ELO. This finding, along with the engine development trends in the automotive industry (e.g., downsizing and higher compression ratio), may have a synergistic effect to deliver greater energy efficiency in the future. Second, the two ethanol blended fuels could be more effective in reducing the particle mass (PM) and particle number (PN) emissions than the levels of using China 5 gasoline. Notably, the benefit of using ELO was more significant, with average emission reductions of 35% for the PM and of 44% for the PN. However, ELA and ELO possibly increased emissions of gaseous pollutants for certain vehicles in the study, but the intra-vehicle differences between the various fuel groups were not statistically significant (not significant, p > 0.05, t-test). We suggest that more measurements under various environmental conditions and comprehensive air quality simulations should be conducted to better understand the environmental impacts of ethanol blending in China.

The impact of frailty on healthcare resource use: a longitudinal analysis using the Clinical Practice Research Datalink in England.

BACKGROUND: routine frailty identification and management is national policy in England, but there remains a lack of evidence on the impact of frailty on healthcare resource use. We evaluated the impact of frailty on the use and costs of general practice and hospital care. METHODS: retrospective longitudinal analysis using linked routine primary care records for 95,863 patients aged 65-95 years registered with 125 UK general practices between 2003 and 2014. Baseline frailty was measured using the electronic Frailty Index (eFI) and classified in four categories (non, mild, moderate, severe). Negative binomial regressions and ordinary least squares regressions with multilevel mixed effects were applied on the use and costs of general practice and hospital care. RESULTS: compared with non-frail status, annual general practitioner consultation incidence rate ratios (IRRs) were 1.24 (95% CI: 1.21-1.27) for mild, 1.41 (95% CI: 1.35-1.47) for moderate, and 1.52 (95% CI: 1.42-1.62) for severe frailty. For emergency hospital admissions, the respective IRRs were 1.64 (95% CI 1.60-1.68), 2.45 (95% CI 2.37-2.53) and 3.16 (95% CI: 3.00-3.33). Compared with non-frail people the IRR for inpatient days was 7.26 (95% CI 6.61-7.97) for severe frailty. Using 2013/14 reference costs, extra annual cost to the healthcare system per person was £561.05 for mild, £1,208.60 for moderate and £2,108.20 for severe frailty. This equates to a total additional cost of £5.8 billion per year across the UK. CONCLUSIONS: increasing frailty is associated with substantial increases in healthcare costs, driven by increased hospital admissions, longer inpatient stay, and increased general practice consultations.

Diagnostic performance of machine-learning-based computed fractional flow reserve (FFR) derived from coronary computed tomography angiography for the assessment of myocardial ischemia verified by invasive FFR.

To explore the diagnostic performance of a machine-learning-based (ML-based) computed fractional flow reserve (cFFR) derived from coronary computed tomography angiography (CCTA) in identifying ischemia-causing lesions verified by invasive FFR in catheter coronary angiography (ICA). We retrospectively studied 117 intermediate coronary artery lesions [40-80% diameter stenosis (DS)] from 105 patients (mean age 62 years, 32 female) who had undergone invasive FFR. CCTA images were used to compute cFFR values on the workstation. DS and the myocardium jeopardy index (MJI) of coronary stenosis were also assessed with CCTA. The diagnostic performance of cFFR was evaluated, including its correlation with invasive FFR and its diagnostic accuracy. Then, its performance was compared to that of combined DS and MJI. Of the 117 lesions, 36 (30.8%) had invasive FFR ≤ 0.80; 22 cFFR were measured as true positives and 74 cFFR as true negatives. The average time of cFFR assessment was 18 ± 7 min. The cFFR correlated strongly to invasive FFR (Spearman's coefficient 0.665, p < 0.01). When diagnosing invasive FFR ≤ 0.80, the accuracy of cFFR was 82% with an AUC of 0.864, which was significantly higher than that of DS (accuracy 75%, AUC 0.777, p = 0.013). The AUC of cFFR was not significantly different from that of combined DS and MJI (0.846, p = 0.743). cFFR ≤ 0.80 based on CCTA showed good diagnostic performance for detecting ischemia-producing lesions verified by invasive FFR. The short calculation time required renders cFFR promising for clinical use.

Examining the effect of hydroxyl groups on the thermal properties of polybenzoxazines: using molecular design and Monte Carlo simulation.

The influence of methylol and phenolic hydroxyl on the thermal properties of polybenzoxazines has been studied using two monofunctional benzoxazine monomers synthesized from para methylol-/ethyl- phenol, aniline and paraformaldehyde. The chemical structures of the synthesized monomers are confirmed by 1H nuclear magnetic resonance (NMR), 13C NMR and Fourier transform infrared spectroscopy (FT-IR). Polymerizations are monitored by differential scanning calorimetry (DSC). The glass transition temperature (T g) of each polybenzoxazine is measured by DSC as well as dynamic mechanical analysis (DMA), indicating the greatly increased T g via incorporation of methylol functionality into benzoxazine moiety. Monte Carlo simulations are also applied to further investigate the underlying structure-property relationship between intermolecular hydrogen-bonding network originating from different types of hydroxyl groups and thermal properties of polybenzoxazines. The agreement between the experimental and simulation results provide us with a fundamental understanding of the designing roles in highly thermally stable polybenzoxazines.