The application of multi-criteria decision analysis in evaluating the value of drug-oriented intervention: a literature review.

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment. Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it. Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were "comparative safety/tolerability" (58 times), "comparative effectiveness/efficacy" (56 times), "comparative patient-perceived health/patient reported outcomes" (37 times), "disease severity" (34 times), and "unmet needs" (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were "cost of intervention" (17 times), "comparative other medical costs" (16 times), and "comparative non-medical costs" (18 times). Out of the 10 criteria (18 times) for assessing innovative value, "a novel pharmacological mechanism" was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, "system capacity and appropriate use of intervention" was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, "political/historical/cultural context" was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. "Swing weighting" and "a direct rating scale" were the most frequently used techniques in included articles. Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

Self-Powered Agricultural Product Preservation and Wireless Monitoring Based on Dual-Functional Triboelectric Nanogenerator.

The global annual vegetable and fruit waste accounts for more than one-fifth of food waste, mainly due to deterioration. In addition, agricultural product spoilage can produce foodborne illnesses and threaten public health. Eco-friendly preservation technologies for extending the shelf life of agricultural products are of great significance to socio-economic development. Here, we report a dual-functional TENG (DF-TENG) that can simultaneously prolong the storage period of vegetables and realize wireless storage condition monitoring by harvesting the rotational energy. Under the illumination of the self-powered high-voltage electric field, the deterioration of vegetables can be effectively slowed down. It can not only decrease the respiration rate and weight loss of pakchoi but also increase the chlorophyll levels (∼33.1%) and superoxide dismutase activity (∼11.1%) after preservation for 4 days. Meanwhile, by harvesting the rotational energy, the DF-TENG can be used to drive wireless sensors for monitoring the storage conditions and location information of vegetables during transportation in real time. This work provides a new direction for self-powered systems in cost-effective and eco-friendly agricultural product preservation, which may have far-reaching significance to the construction of a sustainable society for reducing food waste.

Unconstrained Piezoelectric Vascular Electronics for Wireless Monitoring of Hemodynamics and Cardiovascular Health.

The patient-centered healthcare requires timely disease diagnosis and prognostic assessment, calling for individualized physiological monitoring. To assess the postoperative hemodynamic status of patients, implantable blood flow monitoring devices are highly expected to deliver real time, long-term, sensitive, and reliable hemodynamic signals, which can accurately reflect multiple physiological conditions. Herein, an implantable and unconstrained vascular electronic system based on a piezoelectric sensor immobilized is presented by a "growable" sheath around continuously growing arterial vessels for real-timely and wirelessly monitoring of hemodynamics. The piezoelectric sensor made of circumferentially aligned polyvinylidene fluoride nanofibers around pulsating artery can sensitively perceive mechanical signals, and the growable sheath bioinspired by the structure and function of leaf sheath has elasticity and conformal shape adaptive to the dynamically growing arterial vessels to avoid growth constriction. With this integrated and smart design, long-term, wireless, and sensitive monitoring of hemodynamics are achieved and demonstrated in rats and rabbits. It provides a simple and versatile strategy for designing implantable sensors in a less invasive way.

Dual-sensory fusion self-powered triboelectric taste-sensing system towards effective and low-cost liquid identification.

Infusing human taste perception into smart sensing devices to mimic the processing ability of gustatory organs to perceive liquid substances remains challenging. Here we developed a self-powered droplet-tasting sensor system based on the dynamic morphological changes of droplets and liquid-solid contact electrification. The sensor system has achieved accuracies of liquid recognition higher than 90% in five different applications by combining triboelectric fingerprint signals and deep learning. Furthermore, an image sensor is integrated to extract the visual features of liquids, and the recognition capability of the liquid-sensing system is improved to up to 96.0%. The design of this dual-sensory fusion self-powered liquid-sensing system, along with the droplet-tasting sensor that can autonomously generate triboelectric signals, provides a promising technological approach for the development of effective and low-cost liquid sensing for liquid food safety identification and management.

[Comprehensive Quality Assessment of Soil-Maize Heavy Metals in High Geological Background Area].

The aim of this study was to analyze the pollution degree and causes of soil and agricultural products in high geological background areas and to provide a basis for the safe production of agricultural products and the risk control of soil heavy metals. A total of 36 sets of soil-corn collaborative samples were collected in the farming area of Baolong Town, Wushan County, Chongqing City; the contents of heavy metals (Cd, Hg, Pb, As, and Cr) and soil pH in the soil-maize were analyzed, the pollution degree of heavy metals in the soil-maize was evaluated using the Nemerow comprehensive pollution index method (PN) and comprehensive quality impact index (IICQ). The sources of heavy metals in the soil and the influencing factors of heavy metal excess in corn were also analyzed. The results showed that the average value of soil heavy metal content in the study area was higher than the national and Chongqing soil background values, and the soil heavy metal enrichment effect was obvious. Cd was the main factor of soil-maize exceeding the standard, and the overall exceeding rates of soil and corn Cd were 91.67% and 30.55%, respectively. The evaluation results of the Nemerow comprehensive pollution index showed that the soil was dominated by heavy pollution, accounting for 63.89%. The soil-maize comprehensive quality impact index was dominated by moderate and severe pollution, accounting for 44.44% and 47.22%, respectively. From the perspective of the spatial distribution of heavy metal pollution, corn and soil pollution areas were inconsistent. Soil heavy metal pollution was mainly affected by the Permian and Triassic strata and was related to the secondary enrichment of black rock series and limestone areas. The Cd content of maize was mainly affected by soil pH, and maize was relatively safe under alkaline conditions. It is suggested that the soil in the study area should be divided into risk zones according to the stratum distribution, and the planting structure should be adjusted in the high-risk areas. For the low- and medium-risk areas, it is recommended to strengthen the monitoring of agricultural inputs and reduce the input of heavy metals in the soil. Additionally, we recommend carrying out agronomic regulation in acidic soil areas to improve soil acidification, plant corn varieties with low accumulation of heavy metals, and reduce the risk of agricultural products exceeding the standard.

[Three oral Chinese patent medicines for children with tic disorder: a rapid health technology assessment].

This study aims to comprehensively evaluate the clinical value of Shaoma Zhijing Granules(SZG), Changma Xifeng Tablets(CXT), and Jiuwei Xifeng Granules(JXG) in the treatment of children with tic disorder with the method of rapid health technology assessment(RHTA), which is expected to serve as a reference for medical and health decision-making and clinical rational use of drugs in children. To be specific, relevant articles were retrieved from eight databases and three clinical trial registry platforms. After the quality evaluation, rapid assessment was carried out from the dimensions of disease burden and unmet needs, technical characteristics, safety, efficacy and economy, and the results were analyzed and presented descriptively. A total of 22 articles(1 in English, 21 in Chinese) were screened out: 18 randomized controlled trials(RCTs) and 4 clinical controlled trials(CCTs). Among them, 5 were about the SZG(all RCTs) and 9 were on CXT(6 RCTs and 3 CCTs). The rest 8 focused on JXG(7 RCTs and 1 CCT). Moreover, the overall risk of bias for 94.40% RCTs was evaluated as "some concerns" and only one(5.60%) had high risk of bias. In terms of quality, the 4 CCTs scored 5-6 points(<7 points), suggesting low quality. SZG alone or in combination with tiapride has obvious advantages in improving traditional Chinese medicine syndromes and tic symptoms compared with tiapride alone, with the average daily cost of CNY 79.44-119.16. Compared with conventional western medicine or placebo, CXT alone or in combination with conventional western medicine can improve the total effective rate and alleviate tic symptoms, and the average daily cost is CNY 22.50-67.50. JXG alone or in combination with conventional western medicine can effectively relieve tic symptoms compared with conventio-nal western medicine or placebo, with the average daily cost of CNY 82.42-164.85. The adverse events related to the three Chinese patent medicines mainly occurred in the digestive, respiratory, and nervous systems, all of which were mild. In general, SZG, CXT, and JXG are effective for children with tic disorder. They have been approved to be used in this field, of which SZG was approved in 2019, with the most up-to-date research evidence and high-quality RCT in Q1 journals. However, the comparative analysis of the three was affected by many factors, which should be further clarified. Based on the large sample data available in multiple dimensions, a comprehensive comparative evaluation of the three Chinese patent medicines should be carried out, thereby highlighting the advantages and disadvantages of them and serving a reference for rational clinical use and drug supervision.

A PREDICTION MODEL FOR SEPSIS IN INFECTED PATIENTS: EARLY ASSESSMENT OF SEPSIS ENGAGEMENT.

ABSTRACT: Purpose: To evaluate significant risk variables for sepsis incidence and develop a predictive model for rapid screening and diagnosis of sepsis in patients from the emergency department (ED). Methods: Sepsis-related risk variables were screened based on the PIRO (Predisposition, Insult, Response, Organ dysfunction) system. Training (n = 1,272) and external validation (n = 568) datasets were collected from Peking Union Medical College Hospital (PUMCH) and Beijing Tsinghua Changgung Hospital (BTCH), respectively. Variables were collected at the time of admission. Sepsis incidences were determined within 72 h after ED admissions. A predictive model, Early Assessment of Sepsis Engagement (EASE), was developed, and an EASE-based nomogram was generated for clinical applications. The predictive ability of EASE was evaluated and compared with the National Early Warning Score (NEWS) scoring system. In addition, internal and external validations were performed. Results: A total of 48 characteristics were identified. The EASE model, which consists of alcohol consumption, lung infection, temperature, respiration rate, heart rate, serum urea nitrogen, and white blood cell count, had an excellent predictive performance. The EASE-based nomogram showed a significantly higher area under curve (AUC) value of 86.5% (95% CI, 84.2%-88.8%) compared with the AUC value of 78.2% for the NEWS scoring system. The AUC of EASE in the external validation dataset was 72.2% (95% CI, 66.6%-77.7%). Both calibration curves of EASE in training and external validation datasets were close to the ideal model and were well-calibrated. Conclusions: The EASE model can predict and screen ED-admitted patients with sepsis. It demonstrated superior diagnostic performance and clinical application promise by external validation and in-parallel comparison with the NEWS scoring system.

Attitude Disparity and Worrying Scenarios in Genetic Discrimination-Based on Questionnaires from China.

Objectives: As genetic testing is increasingly used in non-medical fields, the judgment of people's potential conditions based on predictive genetic information inevitably causes genetic discrimination (henceforth GD). This article aimed to systematically investigate the disparity in attitudes and worrying scenarios concerning GD in China. Methods: A questionnaire survey of 555 respondents was conducted. Statistical tests were used to examine disparity in attitudes between gender, age, and education. A descriptive analysis was also conducted to explore other worrying scenarios. Results: It shows that (1) men are more tolerant of GD compared to women, and (2) participants aged between 18 and 30 years old possess the highest objection to GD. However, (3) no indication can attest to the relationship between educational level and perspective on GD. In addition, (4) the acceptance of gene testing in the three most common scenarios is ranked in descending order as follows: partner choice, insurance services, and recruitment. Moreover, (5) worrying scenarios relating to GD include: education, social occasions, medical services, fertility, shopping, and so on. Conclusions: Based on the results, suggestions proposed include developing a blacklist mechanism in the field of genetic data application and strengthening the security regulations for the commercial use of genetic data.

Exploring the dynamic nexus between urbanization and industrialization with carbon emissions in sub-Saharan Africa: evidence from panel PMG-ARDL estimation.

Urbanization and economic growth in sub-Saharan Africa have undergone dramatic changes in recent decades with countries in sub-Saharan Africa seeking to industrialize their economies to boost economic growth. This study, with panel data from 37 sub-Saharan countries between the time period of 1995 and 2017, employs panel cointegration tests and pooled mean group ARDL (PMG-ARDL) techniques and the Dumitrescu-Hurlin causality test to empirically examine the impact of urbanization, economic growth, energy consumption, and industrialization on carbon emissions. Results from the PMG estimator confirm no significant impact of urbanization on carbon emissions in both the long run and short run. One percent surge in energy consumption was found to have significantly caused 1.03% and 0.15% rise in carbon emissions in both long run and short run respectively, thereby reducing the environmental quality. Further findings revealed a significantly negative relationship between economic growth and carbon emissions as well as industrialization and carbon emissions. Additionally, our causality test shows a unidirectional relationship running from energy consumption to carbon emissions. Policymakers are advised to develop rural areas and plan urban centers, pay attention to sustainable energy sources and waste recycling, and educate the populace to improve environmental quality.

Spatial and Temporal Evolution and Prediction of the Coordination Level of "Production-Living-Ecological" Function Coupling in the Yellow River Basin, China.

To clarify the evolution of "production-living-ecological" function coupling in the Yellow River Basin, coordinating the spatial allocation of resources, development management and layout optimization, is an important means for achieving ecological protection and high-quality development in the region. In this paper, we conducted an empirical analysis and ARIMA prediction of the coupled production-living-ecological function coordination level in the Yellow River Basin of China from 2008 to 2018, and found that: (1) In terms of temporal evolution, the production-living-ecological function and coupling coordination level of each province and region in the Yellow River Basin generally shows a sharp and then slow upward trend, with the living functions changing more than the production and ecological functions; (2) in terms of spatial pattern, the production and living functions of each province and region show the trend of functional level increasing from east to west over time; the ecological functions, contrary to production and living functions, show a "high-low" aggregation, midstream shows "low-low" aggregation, and downstream shows "low-high" aggregation; (3) According to the regression results of the spatial Dubin model, the environmental governance level, technological research and development level, and social security level and resource dependence degree have positive promoting and spillover effects on the coupling coordination level of the "production-living-ecological" function in the region. However, population density and carbon emission intensity will hinder the development of regional coupling coordination level; (4) from the ARIMA prediction, the coupling coordination level of "production-living-ecological" in the Yellow River Basin continues the development trend of 2008-2018 in the short term, the overall coordination level is at a high level, and the variability of coupling coordination level among provinces and regions is further reduced. Finally, corresponding development countermeasures and suggestions are given to different provinces and regions based on the spatial and temporal evolution characteristics, influencing factors and development trend of the "production-living-ecological" function in the Yellow River basin.

Spatial distribution and ecological risk assessment of heavy metals in surface sediments from the northern Bohai Strait, China.

The epicontinental seas to the east of China have become highly anthropogenically impacted due to rapid economic development in recent decades, resulting in various environmental problems, including heavy metal pollution. The Bohai Strait, as a key junction connecting the material-energy exchange between the Bohai and Yellow Seas, is extremely critical in regional pollution prevention and control. To ascertain the spatial distribution and contamination levels of heavy metals in the surface sediments of the northern Bohai Strait, a systematic investigation was conducted. Geochemical analysis revealed that the concentrations (in ppm) of heavy metal elements in surface sediments vary in the range of 4.19-77.6 for As, 0.04-0.21 for Cd, 5.1-65.7 for Pb, 0.30-39.40 for Cu, 7.77-46.50 for Ni, 1.50-86.60 for Cr, 11.70-91.80 for Zn, and 0.005-0.038 for Hg. Ecological statistics indicate that the northern Bohai Strait suffers from prominent heavy metal pollution primarily induced by As, Cd, and Pb, accompanied by relatively weak pollution of Cu and Ni. Sediments collected from the submarine depressions and the southeast region exhibit higher heavy metal concentrations, and as a consequence, more serious ecological risk. Correlation analysis indicated that the accumulations of Hg, Cr, and Zn were associated with the deposition of organic matter. Preliminary provenance discrimination suggested that the pollutants were mainly derived from the eastern parts of the North Yellow Sea, rather than the Bohai region.

Microsurgical Management of Posterior Circulation Aneurysms: A Retrospective Study on Epidemiology, Outcomes, and Surgical Approaches.

Posterior circulation aneurysms have been regarded as the most challenging for endovascular coiling and microsurgical occlusion. The role of microsurgical treatment is gradually being overlooked and diminishing in the trend of endovascular treatment. As microsurgical occlusion of posterior circulation aneurysms is decreasing, we present our relevant experience to evaluate treatment options and surgical approaches. A retrospective study was conducted in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University between 2016 and 2021. Patients with posterior circulation aneurysms treated by clipping, bypass, and trapping were enrolled and followed up for at least six months. We included 50 patients carrying 53 posterior circulation aneurysms, 43 of whom had aneurysm ruptures. The posterior cerebral artery and posterior inferior cerebellar artery were the most common aneurysm locations. Direct clipping was performed in 43 patients, while bypass and trapping was performed in six patients. The retrosigmoid, far-lateral, and midline or paramedian suboccipital approaches were performed for those aneurysms in the middle and lower thirds. Aneurysms in the upper third required the lateral supraorbital approach, pterional approach, subtemporal approach, and occipital craniotomy. The lateral supraorbital approach was utilized in seven patients for aneurysms above the posterior clinoid process. Thirty-four patients recovered well with modified Rankin score 0-3 at discharge. No patient experienced aneurysm recurrence during the mean follow-up period of 3.57 years. Microsurgery clipping and bypass should be considered in conjunction with endovascular treatment as a treatment option in posterior circulation aneurysms. The lateral supraorbital approach is a feasible, safe, and simple surgical approach for aneurysms above the posterior clinoid process.

The Impact of Transformational Leadership on Organizational Commitment and Intention to Stay: Empirical Evidence From China's Performing Arts Industry.

As part of the cultural industries, performing arts has been playing an important role in enriching people's spiritual life, leveling culture and education, creating jobs, and even making economic benefits. Hence, a significant methodology is required to tackle the complicated concepts of transformational leadership (TL) and social factors in an arts industry context. This article aims to observe the direct impacts of TL on organizational commitment (OC). Furthermore, it examined the indirect effects of TL on OC and intention to stay (ITS) via person-job fit (PJF), social capital (SC), and psychological capital (PC). According to the results of this research, TL was discovered to have a positive impact on OC and PJF while having no significant effect on ITS. Furthermore, PJF had a significant impact on SC. Moreover, SC significantly influenced PC. In addition, PC was discovered to be in a significant correlation with OC while having no significant association with ITS. Finally, OC was also in a significant relationship with ITS.

In vitro Assessment of Cardiac Reprogramming by Measuring Cardiac Specific Calcium Flux with a GCaMP3 Reporter.

Cardiac reprogramming has become a potentially promising therapy to repair a damaged heart. By introducing multiple transcription factors, including Mef2c, Gata4, Tbx5 (MGT), fibroblasts can be reprogrammed into induced cardiomyocytes (iCMs). These iCMs, when generated in situ in an infarcted heart, integrate electrically and mechanically with the surrounding myocardium, leading to a reduction in scar size and an improvement in heart function. Because of the relatively low reprogramming efficiency, purity, and quality of the iCMs, characterization of iCMs remains a challenge. The currently used methods in this field, including flow cytometry, immunocytochemistry, and qPCR, mainly focus on cardiac-specific gene and protein expression but not on the functional maturation of iCMs. Triggered by action potentials, the opening of voltage-gated calcium channels in cardiomyocytes leads to a rapid influx of calcium into the cell. Therefore, quantifying the rate of calcium influx is a promising method to evaluate cardiomyocyte function. Here, the protocol introduces a method to evaluate iCM function by calcium (Ca2+) flux. An αMHC-Cre/Rosa26A-Flox-Stop-Flox-GCaMP3 mouse strain was established by crossing Tg(Myh6-cre)1Jmk/J (referred to as Myh6-Cre below) with Gt(ROSA)26Sortm38(CAG-GCaMP3)Hze/J (referred to as Rosa26A-Flox-Stop-Flox-GCaMP3 below) mice. Neonatal cardiac fibroblasts (NCFs) from P0-P2 neonatal mice were isolated and cultured in vitro, and a polycistronic construction of MGT was introduced to NCFs, which led to their reprogramming to iCMs. Because only successfully reprogrammed iCMs will express GCaMP3 reporter, the functional maturation of iCMs can be visually assessed by Ca2+ flux with fluorescence microscopy. Compared with un-reprogrammed NCFs, NCF-iCMs showed significant calcium transient flux and spontaneous contraction, similar to CMs. This protocol describes in detail the mouse strain establishment, isolation and selection of neonatal mice hearts, NCF isolation, production of retrovirus for cardiac reprogramming, iCM induction, the evaluation of iCM Ca2+ flux using our reporter line, and related statistical analysis and data presentation. It is expected that the methods described here will provide a valuable platform to assess the functional maturation of iCMs for cardiac reprogramming studies.

Rates of, and factors associated with, switching among generic levothyroxine preparations in commercially insured American adults.

IMPORTANCE: Some practice guidelines warn against generic L-thyroxine preparation switching. OBJECTIVE: To examine the rates of generic L-thyroxine preparation switching within one year of initiating L-thyroxine, and to examine factors associated with switching. DESIGN AND SETTING: Retrospective study using national data from a large administrative claims database from January 2008 through November 2018. PATIENTS: Medicare or commercially insured adults (≥18 years) who filled a generic L-thyroxine preparation. MAIN OUTCOME MEASURES: At least one switch from one generic L-thyroxine preparation to another within 1 year of L-thyroxine initiation defined by prescription fills. RESULTS: From January 2008 to November 2018, we included 483,390 patients who initiated generic L-thyroxine: mean (SD) age was 61.4 years (15.2), 75.2% were female, 72.6% were white. Within 1 year of initiating therapy, 98,013 (20%) switched to another L-thyroxine generic preparation at least once. In a multivariate logistic regression analysis, factors associated with switching included the number of pharmacies visited to fill L-thyroxine (>2 vs 1 adjusted OR [aOR] 7.15, 95% confidence interval [CI] 6.97-7.34), age ≥75 vs. <45 years (aOR 1.29, 95% CI 1.26-1.33), history of thyroid surgery (aOR 1.22, 95% CI 1.13-1.31), and first L-thyroxine fill date in 2018 vs. 2008 (aOR 3.32, 95% CI 3.14-3.51). CONCLUSIONS AND RELEVANCE: One in five patients switched among generic L-thyroxine manufacturers within one year of treatment initiation. Generic L-thyroxine switching occurred more often when more pharmacies were used to fill L-thyroxine. Given existing guideline recommendations, additional studies should clarify the impact of generic L-thyroxine switching on thyroid hormone values.

Medication Cost-Savings and Utilization of Generic Inhaled Corticosteroid (ICS) and Long-Acting Beta-Agonist (LABA) Drug Products in the USA.

BACKGROUND: In the USA, drug costs associated with the inhaled corticosteroid (ICS) and long acting ß agonist (LABA) combination products have been increasing since 2001. In January 2019, the first generic ICS/LABA drug product was approved by the U.S. Food and Drug Administration. METHODS: We investigated retrospectively the effects of the first approved generic ICS/LABA drug from 2019 to 2020 on the wholesale cost-savings and prescription dispensing using the IQVIA data system in the USA. RESULTS: The marketing of the first generic for fluticasone propionate and salmeterol xinafoate dry powder inhaler was associated with $941 million in drug cost-savings during the first year for this class of medications. Although the brand-name drug manufacturer concurrently introduced its authorized generic, these cost-savings were driven by the averaged unit cost of the approved generic at $115, compared to $169 for the authorized generic and $334 for the branded product. Generic initiation and substitution with the first generic were, respectively, higher compared to those with authorized generics; however, overall dispensing of the first generic was lower than that of its branded product. As in the case of budesonide and formoterol fumarate dry powder inhaler, marketing of authorized generics alone was not associated with any noticeable change in sales or prescription cost-saving. CONCLUSION: We estimated that more than 20% of prescription cost-saving was achieved for the ICS/LABA dry powder inhalers in the first year following the introduction of the first approved generic, even though generic utilization remained lower than that of the branded counterpart.

Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma.

Importance: Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. Objective: To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. Design, Setting, and Participants: This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. Exposures: Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. Main Outcomes and Measures: The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. Results: A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated. Conclusions and Relevance: An RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.

Achieving synergetic treatment of sludge supernatant, waste activated sludge and secondary effluent for wastewater treatment plants (WWTPs) sustainable development.

A novel process that combines partial nitrification, fermentation and Anammox-partial denitrification (NFAD) was proposed to co-treat ammonia rich sludge supernatant (NH4+-N = 1194.1 mg/L), external WAS (MLSS = 22092.6 mg/L) and WWTP secondary effluent (NO3--N = 58.6 mg/L). Three separated reactors were used for partial nitrification (PN-SBR), integrated fermentation and denitrification (IFD-SBR) and combined Anammox-partial denitrification (AD-UASB), respectively. The process resulted in excellent nitrogen removal efficiency (NRE) of 98.7%, external sludge reduction efficiency (SRE) of 44.6% and external sludge reduction rate of 4.1 kg/m3 after 200 days of continuous operation. IFD-SBR and AD-UASB contributed towards 89.4% and 9.2% nitrogen removal, respectively. In AD-UASB, cooperation between Anammox bacteria (4.1% Candidatus Brocadia) and partial denitrifying bacteria (3.2% Thauera) resulted in significant stability of Anammox pathway, which contributed up to 84.1% nitrogen removal in the combined Anammox-partial denitrification process. NFAD saved up to 100% organic resource demand and 25% of aeration consumption compared with the traditional nitrification-denitrification process.

Low-Cost, Environmentally Friendly, and High-Performance Triboelectric Nanogenerator Based on a Common Waste Material.

With the great progress in human activities and production technologies, the waste inevitably produced causes not only environmental pollution but also resource waste; meanwhile, the mobile and portable electronic devices urgently need a distributed and sustainable energy source to ensure their stable operation. Here, the waste pollutants (milk cartons) generated from daily life, commonly associated with environmental concerns, are instead identified as an available resource for preparing an emerging energy harvester (triboelectric nanogenerator, TENG), which can convert ubiquitous mechanical energy into electric power. Consequently, based on the waste material, the initial charge density of the TENG is as low as 0.035 mC m-2, which can be tremendously improved to 1.00 mC m-2 through combining a charge excitation circuit, achieving efficient energy harvesting. In addition, compared to the common dielectric film, the waste material can reduce the cost and simplify the process of the preparation of TENG. This work provides not only an innovative approach to simultaneously realize environmental protection and energy harvesting but also more material choice for the preparation of a low-cost and high-performance TENG.

A critical review on the distribution and ecological risk assessment of steroid hormones in the environment in China.

During past two decades, steroid hormones have raised significant public concerns due to their potential adverse effects on the hormonal functions of aquatic organisms and humans. Considering China being a big producer and consumer of steroid hormones, we summarize the current contamination status of steroid hormones in different environmental compartments in China, and preliminarily assess the associated risks to ecological systems. The results show that steroid hormones are ubiquitously present in Chinese surface waters where estrogens are the most studied steroids compared with androgens, progestogens and glucocorticoids. Estrone (E1), 17ß-estradiol (17ß-E2) and estriol (E3) are generally the dominant steroid estrogens in Chinese surface waters, whereas for the other steroids, androsterone (ADR), epi-androsterone (EADR), progesterone (PGT), cortisol (CRL) and cortisone (CRN) have relatively large contributions. Meanwhile, the investigations for the other environmental media such as particles, sediments, soils and groundwater have been limited, as well as for steroid conjugates and metabolites. The median risk quotients of most steroid hormones in surface waters and sediments are lower than 1, indicating low to moderate risks to local organisms. This review provides a full picture of steroid distribution and ecological risks in China, which may be useful for future monitoring and risk assessment. More studies may focus on the analysis of steroid conjugates, metabolites, solid phase fractions, analytical method development and acute/chronic toxicities in different matrices to pursue a more precise and holistic risk assessment.