Cost-Effectiveness Analysis of Regorafenib versus Other Third-Line Treatments for Metastatic Colorectal Cancer.

Background: Regorafenib, a novel multikinase inhibitor, has been approved by the US Food and Drug Administration as a standard treatment choice for metastatic colorectal cancer (mCRC). Nonetheless, its substantial cost places a significant burden on social health resources and patients. However, the cost-effectiveness (CE) of regorafenib compared to other third-line therapies is still undetermined. Objective: This study aims to assess the CE of regorafenib compared to other third-line therapies for the treatment of mCRC. Methods: We conducted a comprehensive literature search in PubMed, Medline, Scopus, Embase, Cochrane Library, as well as nine other databases to identify relevant studies published up to October 2023, focusing on patients with mCRC and examining the cost-effectiveness of regorafenib. Following the screening and extraction of pertinent data, the study quality was assessed using the Quality of Health Economic Studies (QHES) checklist. Results: The literature search yielded 751 records, and after applying the inclusion criteria, 13 studies from 7 different countries were included. Of these, 7 studies evaluated the cost-effectiveness of regorafenib compared to trifluridine/tipiracil (TAS-102), 3 studies compared regorafenib with best supportive care (BSC), and 3 studies compared regorafenib with fruquintinib, serplulimab, and regorafenib dose optimization (ReDo).The quality of the included studies was high with an average QHES scores of 85.62. Regorafenib standard dose proves to be less cost-effective than alternative third-line therapies. Implementing a dose optimization strategy could potentially rectify this disparity and enhance the cost-effectiveness of regorafenib. Conclusion: The use of the standard dose of regorafenib is generally regarded as not cost-effective when compared to other third-line therapies for patients with mCRC. However, implementing a dose-escalation strategy may enhance regorafenib's cost-effectiveness. Consequently, significant price reductions or optimizing the dose of regorafenib are required to achieve cost-effectiveness.

Analysis of the spatial-temporal evolution of Green and low carbon utilization efficiency of agricultural land in China and its influencing factors under the goal of carbon neutralization.

Agricultural land is the most basic input factor for agricultural production and an essential component of terrestrial ecosystems, which plays a vital role in achieving carbon neutrality. Giving full play to the carbon-neutral contribution of agricultural land is a crucial part of China's economic transformation and green development. It incorporates carbon and pollution emissions from agricultural land use into the unexpected outputs of the Green and Low-carbon Utilization Efficiency of Agricultural Land (GLUEAL) evaluation system. The study utilized several advanced analytical tools, including the super-efficient Slacks-Based Measure (SBM) model, Exploratory Spatial-Temporal Data Analysis (ESTDA) method, Geodetector, and Geographically and Temporally Weighted Regression (GTWR) model. The objective was to examine the spatial-temporal evolution of GLUEAL and identify the factors that influenced it in all 31 provinces of China from 2005 to 2020. The results show that: (1) The overall spatial-temporal evolution of GLUEAL showed an increasing trend, but the disparity between provinces and regions became wider. (2) Most provinces have not yet made significant spatial and temporal jumps. They have high spatial cohesion with specific "path-dependent" characteristics. (3) The Geodetector results reveal that the Number of Rural Labor Force with Higher Education (NRLFHE) and Technology Support for Agriculture (TSA) have insufficient explanatory power on average for GLUEAL. Agricultural Economic Development Level (AEDL), Urbanization Level (UL), Multiple Crop Index (MCI), Planting Structure (PS), Degree of Crop Damage (DCD), Financial support for agriculture (FSA), and Agricultural mechanization level (AML) had stronger explanatory power on average for GLUEAL and were important factors influencing GLUEAL levels. (4) The average influence of AEDL, UL, FSA, and AML on GLUEAL changed from negative to positive. The average influence of MCI and DCD on GLUEAL was negative, and the average influence of PS on GLUEAL changed from positive to negative. This study provides a comprehensive description of the spatial and temporal evolution of GLUEAL in China. It reveals the key factors influencing GLUEAL and analyzes their spatial variations and impact patterns. These findings offer robust evidence for government policymakers to formulate policy measures for sustainable agricultural development and optimized resource allocation, promoting the transformation of agricultural land towards green and low-carbon practices and advancing the achievement of sustainable development goals.

Gas-to-ionic liquid partition: QSPR modeling and mechanistic interpretation.

The present work was devoted to explore the quantitative structure-property relationships for gas-to-ionic liquid partition coefficients (log KILA ). A series of linear models were first established for the representative dataset (IL01). The optimal model was a four-parameter equation (1Ed) consisting of two electrostatic potential-based descriptors ( Σ V s , i n d - ${{\rm { \Sigma }}{V}_{s,ind}^{-}}$ and Vs,max ), one 2D matrix-based descriptor (J_D/Dt) and dipole moment (µ). All of the four descriptors introduced in the model can find the corresponding parameters, directly or indirectly, from Abraham's linear solvation energy relationship (LSER) or its theoretical alternatives, which endows the model good interpretability. Gaussian process was utilized to build the nonlinear model. Systematical validations, including 5-fold cross-validation for the training set, the validation for test set, as well as a more rigorous Monte Carlo cross-validation were performed to verify the reliability of the constructed models. Applicability domain of the model was evaluated, and the Williams plot revealed that the model can be used to predict the log KILA values of structurally diverse solutes. The other 13 datasets were also processed in the same way, and all of the linear models with expressions similar to equation 1Ed were obtained. These models, whether linear of nonlinear, represent satisfactory statistical results, which confirms the universality of the method adopted in this study in QSPR modeling of gas-to-IL partition.

The Spatial-Temporal Transition and Influencing Factors of Green and Low-Carbon Utilization Efficiency of Urban Land in China under the Goal of Carbon Neutralization.

Urban-land development and utilization is one of the main sources of carbon emissions. Improving the green and low-carbon utilization efficiency of urban land (GLUEUL) under the goal of carbon neutrality is crucial to the low-carbon transition and green development of China's economy. Combining the concept of green and low-carbon development in urban land use, carbon emissions and industrial-pollution emissions are incorporated into the unexpected outputs of the GLUEUL evaluation system. The super-efficient slacks-based measure (SBM) model, Exploratory Spatial-Temporal Data Analysis (ESTDA) method and Geographically and Temporally Weighted Regression (GTWR) model were used to analyze the spatial-temporal transition and the influencing factors of GLUEUL in 282 cities in China from 2005 to 2020. The result shows that: (1) From 2005 to 2020, the green and low-carbon land-utilization efficiency of Chinese cities shows an increasing temporal-evolution trend, but the gap between cities is gradually widening. (2) From the spatial-temporal dynamic characteristics of Local Indicators of Spatial Association (LISA), regions with the highest GLUEUL have strong dynamics and instability, while cities at the lowest level have a relatively stable spatial structure. On the whole, the local-spatial-transfer direction of GLUEUL of each city is stable, with certain path-dependent characteristics. (3) There are differences in the degree of influence and direction of action of different factors on GLUEUL. The economic development level, industrial-structure upgrading, financial support, wealth level, and green-technology-innovation ability have positive effects on overall GLUEUL, with industrial-structure upgrading promoting GLUEUL the most, while urban population size, foreign-investment scale, and financial-development level play a negative role. This study can provide some empirical and theoretical references for the improvement of GLUEUL.

Efficacy assessment for low-level laser therapy in the treatment of androgenetic alopecia: a real-world study on 1383 patients.

Low-level laser therapy (LLLT) has been a treatment modality by many androgenetic alopecia (AGA) patients in recent years. It remained unclear as to how long the treatment regime should be maintained, and which characteristics of patients should this be recommended. A real-world study was carried out with an FDA-cleared low-level laser helmet for 1383 patients. Ordinal logistic regression analysis with propensity score matching (PSM) was used to investigate the factors related to efficacy assessment. More than 80% of users were between 18 and 40 years old. The median use times were 133 for mild AGA patients and 142 for moderate-to-severe AGA patients, which equated to 38 weeks and 40 weeks, respectively. The overall clinical effectiveness was nearly 80%. PSM analysis revealed that gender (P = 0.002), use period (P = 0.068), scalp conditions with dandruff, rash, and itchy symptoms were associated with the grading of efficacy assessment. Male users (ordinal OR: 1.35, CI: (1.01, 1.79)); use for more than 180 times or use period for 1 year (ordinal OR: 1.40, CI: (1.11, 1.96)); and those with scalp dandruff (ordinal OR: 1.34, CI: (1.01, 1.87)), rash (ordinal OR: 1.47, CI: (1.04, 2.07)), and itchy symptoms (ordinal OR: 1.51, CI: (1.12, 2.03)) had better efficacy assessments. The recommended treatment regime with low-level laser helmet was more than 1 year or 180 use times. Male patients with dandruff, rash, and itchy symptoms in scalps tended to have a better efficacy assessment.

Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage.

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

Statistical Assessment of Depth Normalization for Small RNA Sequencing.

PURPOSE: Methods for depth normalization have been assessed primarily with simulated data or cell-line-mixture data. There is a pressing need for benchmark data enabling a more realistic and objective assessment, especially in the context of small RNA sequencing. METHODS: We collected a unique pair of microRNA sequencing data sets for the same set of tumor samples; one data set was collected with and the other without uniform handling and balanced design. The former provided a benchmark for evaluating evidence of differential expression and the latter served as a test bed for normalization. Next, we developed a data perturbation algorithm to simulate additional data set pairs. Last, we assembled a set of computational tools to visualize and quantify the assessment. RESULTS: We validated the quality of the benchmark data and showed the need for normalization of the test data. For illustration, we applied the data and tools to assess the performance of 9 existing normalization methods. Among them, trimmed mean of M-values was a better scaling method, whereas the median and the upper quartiles were consistently the worst performers; one variation of remove unwanted variation had the best chance of capturing true positives but at the cost of increased false positives. In general, these methods were, at best, moderately helpful when the level of differential expression was extensive and asymmetric. CONCLUSION: Our study (1) provides the much-needed benchmark data and computational tools for assessing depth normalization, (2) shows the dependence of normalization performance on the underlying pattern of differential expression, and (3) calls for continued research efforts to develop more effective normalization methods.

Bayesian Hidden Markov Models for Dependent Large-Scale Multiple Testing.

An optimal and flexible multiple hypotheses testing procedure is constructed for dependent data based on Bayesian techniques, aiming at handling two challenges, namely dependence structure and non-null distribution specification. Ignoring dependence among hypotheses tests may lead to loss of efficiency and bias in decision. Misspecification in the non-null distribution, on the other hand, can result in both false positive and false negative errors. Hidden Markov models are used to accommodate the dependence structure among the tests. Dirichlet mixture process prior is applied on the non-null distribution to overcome the potential pitfalls in distribution misspecification. The testing algorithm based on Bayesian techniques optimizes the false negative rate (FNR) while controlling the false discovery rate (FDR). The procedure is applied to pointwise and clusterwise analysis. Its performance is compared with existing approaches using both simulated and real data examples.

Quantitative assessment of skin swelling using optical coherence tomography.

BACKGROUND: Preclinical and clinical studies suggest that optical coherence tomography (OCT) is a useful tool to visualize inflammatory conditions. OBJECTIVE: The objective of this study was to evaluate the usefulness of combining OCT and various image processing techniques for quantitative assessment of histamine-induced tissue swelling. METHODS: Both time-domain and frequency-domain OCT were used on a mouse ear model. The ear thickness and volume before and after histamine challenge were determined from pixel locations in 2D scans and voxel number counting in 3D scans. Swelling kinetics was analyzed on 3D contour mapping. Microvessel network was visualized using speckle decorrelation analysis. RESULTS: OCT images showed that the thickness and volume changes were histamine dose and contact time dependent. The 3D mapping showed that the histamine-induced swelling spread slowly and directionally. OCT data indicated that microvessel opening and vessel dilation occurred prior to tissue swelling. CONCLUSION: OCT is a robust and quantitative non-invasive imaging tool for assessing skin swelling.

A hybrid hierarchical Bayesian model for spatiotemporal surveillance data.

Due to the low signal-to-noise ratio and high-dimensional structure, spatiotemporal data analysis is challenging. In outbreak detection, the assumptions for control charts, including independence, normality, and stationarity, are often violated in syndromic surveillance data. We develop a novel hybrid hierarchical Bayesian model through the combination of the Dirichlet process and particle filters to resolve these issues. We use a modified adjacency matrix as the observation matrix in the Markovian state-space model. This methodology achieves dimension reduction and computational efficiency and enjoys a superior detection performance with the ability to incorporate online updating for data streaming applications. Our data set is derived from the Indiana Public Health Emergency Surveillance System. It consists of surveillance data on emergency room visits for influenza-like and respiratory illness from 2008 to 2010. We are able to detect the 2009 H1N1 outbreak as well as the seasonal influenza outbreaks. Numerical results show that our Dirichlet process/particle filter models improve the outbreak detection performance in both simulation and real data analysis.

Electronic Health Record (EHR)-Based Community Health Measures: An Exploratory Assessment of Perceived Usefulness by Local Health Departments.

BACKGROUND: Given the widespread adoption of electronic health record (EHR) systems in health care organizations, public health agencies are interested in accessing EHR data to improve health assessment and surveillance. Yet there exist few examples in the U.S. of governmental health agencies using EHR data routinely to examine disease prevalence and other measures of community health. The objective of this study was to explore local health department (LHD) professionals' perceptions of the usefulness of EHR-based community health measures, and to examine these perceptions in the context of LHDs' current access and use of sub-county data, data aggregated at geographic levels smaller than county. METHODS: To explore perceived usefulness, we conducted an online survey of LHD professionals in Indiana. One hundred and thirty-three (133) individuals from thirty-one (31) LHDs participated. The survey asked about usefulness of specific community health measures as well as current access to and uses of sub-county population health data. Descriptive statistics were calculated to examine respondents' perceptions, access, and use. A one-way ANOVA (with pairwise comparisons) test was used to compare average scores by LHD size. RESULTS: Respondents overall indicated moderate agreement on which community health measures might be useful. Perceived usefulness of specific EHR-based community health measures varied by size of respondent's LHD [F(3, 88) = 3.56, p = 0.017]. Over 70% of survey respondents reported using community health data, but of those < 30% indicated they had access to sub-county level data. CONCLUSION: Respondents generally preferred familiar community health measures versus novel, EHR-based measures that are not in widespread use within health departments. Access to sub-county data is limited but strongly desired. Future research and development is needed as LHD staff gain access to EHR data and apply these data to support the core function of health assessment.

The impact of the 2006 Massachusetts health care reform law on spine surgery patient payer-mix status and age.

OBJECTIVE Several similarities exist between the Massachusetts health care reform law of 2006 and the Affordable Care Act (ACA). The authors' prior neurosurgical research showed a decrease in uninsured surgeries without a significant change in surgical volume after the Massachusetts reform. An analysis of the payer-mix status and the age of spine surgery patients, before and after the policy, should provide insight into the future impact of the ACA on spine surgery in the US. METHODS Using the Massachusetts State Inpatient Database and spine ICD-9-CM procedure codes, the authors obtained demographic information on patients undergoing spine surgery between 2001 and 2012. Payer-mix status was assigned as Medicare, Medicaid, private insurance, uninsured, or other, which included government-funded programs and workers' compensation. A comparison of the payer-mix status and patient age, both before and after the policy, was performed. The New York State data were used as a control. RESULTS The authors analyzed 81,821 spine surgeries performed in Massachusetts and 248,757 in New York. After 2008, there was a decrease in uninsured and private insurance spine surgeries, with a subsequent increase in the Medicare and "other" categories for Massachusetts. Medicaid case numbers did not change. This correlated to an increase in surgeries performed in the age group of patients 65-84 years old, with a decrease in surgeries for those 18-44 years old. New York showed an increase in all insurance categories and all adult age groups. CONCLUSIONS After the Massachusetts reform, spine surgery decreased in private insurance and uninsured categories, with the majority of these surgeries transitioning to Medicare. Moreover, individuals who were younger than 65 years did not show an increase in spine surgeries, despite having greater access to health insurance. In a health care system that requires insurance, the decrease in private insurance is primarily due to an increasing elderly population. The Massachusetts model continues to show that this type of policy is not causing extreme shifts in the payer mix, and suggests that spine surgery will continue to thrive in the current US health care system.

Impact of the 2006 Massachusetts health care insurance reform on neurosurgical procedures and patient insurance status.

OBJECTIVE The Massachusetts health care insurance reform law passed in 2006 has many similarities to the federal Affordable Care Act (ACA). To address concerns that the ACA might negatively impact case volume and reimbursement for physicians, the authors analyzed trends in the number of neurosurgical procedures by type and patient insurance status in Massachusetts before and after the implementation of the state's health care insurance reform. The results can provide insight into the future of neurosurgery in the American health care system. METHODS The authors analyzed data from the Massachusetts State Inpatient Database on patients who underwent neurosurgical procedures in Massachusetts from 2001 through 2012. These data included patients' insurance status (insured or uninsured) and the numbers of procedures performed classified by neurosurgical procedural codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Each neurosurgical procedure was grouped into 1 of 4 categories based on ICD-9-CM codes: 1) tumor, 2) other cranial/vascular, 3) shunts, and 4) spine. Comparisons were performed of the numbers of procedures performed and uninsured patients, before and after the implementation of the reform law. Data from the state of New York were used as a control. All data were controlled for population differences. RESULTS After 2008, there were declines in the numbers of uninsured patients who underwent neurosurgical procedures in Massachusetts in all 4 categories. The number of procedures performed for tumor and spine were unchanged, whereas other cranial/vascular procedures increased. Shunt procedures decreased after implementation of the reform law but exhibited a similar trend to the control group. In New York, the number of spine surgeries increased, as did the percentage of procedures performed on uninsured patients. Other cranial/vascular procedures decreased. CONCLUSIONS After the Massachusetts health care insurance reform, the number of uninsured individuals undergoing neurosurgical procedures significantly decreased for all categories, but more importantly, the total number of surgeries performed did not change dramatically. To the extent that trends in Massachusetts can predict the overall US experience, we can expect that some aspects of reimbursement may be positively impacted by the ACA. Neurosurgeons, who often treat patients with urgent conditions, may be affected differently than other specialists.

Epidemiology and Management of Acute Kidney Injury in Hepatocellular Carcinoma Patients Undergoing Transcatheter Arterial Chemoembolization.

Transcatheter arterial chemoembolization (TACE) is an effective therapy for hepatocellular carcinoma (HCC). However, acute kidney injury (AKI) may occur after TACE due to the contrast agent and cytotoxic anticancer drugs used in this procedure. Post-TACE AKI is not an unusual event, and may adversely affect patient outcome. Coexisting situations including cirrhosis, renal insufficiency, diabetes and hypertension play a role in the development of HCC, and may predispose patients to AKI after TACE. Most post-TACE are transient and reversible, while prolonged AKI may predict a decreased survival. The best strategy to manage post-TACE AKI is prevention. Patients, before undergoing TACE, should be carefully assessed. In this study, we reviewed the current literature published in English about the incidence rate, risk factors, management and prognosis of AKI in patients with HCC undergoing TACE for a better understanding of this complication.

Quantitative structure-hydrophobicity relationships of molecular fragments and beyond.

Quantitative structure-property relationship (QSPR) models were firstly established for the hydrophobic substituent constant (πX) using the theoretical descriptors derived solely from electrostatic potentials (EPSs) at the substituent atoms. The descriptors introduced are found to be related to hydrogen-bond basicity, hydrogen-bond acidity, cavity, or dipolarity/polarizability terms in linear solvation energy relationship, which endows the models good interpretability. The predictive capabilities of the models constructed were also verified by rigorous Monte Carlo cross-validation. Then, eight groups of meta- or para-disubstituted benzenes and one group of substituted pyridines were investigated. QSPR models for individual systems were achieved with the ESP-derived descriptors. Additionally, two QSPR models were also established for Rekker's fragment constants (foct), which is a secondary-treatment quantity and reflects average contribution of the fragment to logP. It has been demonstrated that the descriptors derived from ESPs at the fragments, can be well used to quantitatively express the relationship between fragment structures and their hydrophobic properties, regardless of the attached parent structure or the valence state. Finally, the relations of Hammett σ constant and ESP quantities were explored. It implies that σ and π, which are essential in classic QSAR and represent different type of contributions to biological activities, are also complementary in interaction site.

A Bayesian spatio-temporal approach for real-time detection of disease outbreaks: a case study.

BACKGROUND: For researchers and public health agencies, the complexity of high-dimensional spatio-temporal data in surveillance for large reporting networks presents numerous challenges, which include low signal-to-noise ratios, spatial and temporal dependencies, and the need to characterize uncertainties. Central to the problem in the context of disease outbreaks is a decision structure that requires trading off false positives for delayed detections. METHODS: In this paper we apply a previously developed Bayesian hierarchical model to a data set from the Indiana Public Health Emergency Surveillance System (PHESS) containing three years of emergency department visits for influenza-like illness and respiratory illness. Among issues requiring attention were selection of the underlying network (Too few nodes attenuate important structure, while too many nodes impose barriers to both modeling and computation.); ensuring that confidentiality protections in the data do not impede important modeling day of week effects; and evaluating the performance of the model. RESULTS: Our results show that the model captures salient spatio-temporal dynamics that are present in public health surveillance data sets, and that it appears to detect both "annual" and "atypical" outbreaks in a timely, accurate manner. We present maps that help make model output accessible and comprehensible to public health authorities. We use an illustrative family of decision rules to show how output from the model can be used to inform false positive-delayed detection tradeoffs. CONCLUSIONS: The advantages of our methodology for addressing the complicated issues of real world surveillance data applications are three-fold. We can easily incorporate additional covariate information and spatio-temporal dynamics in the data. Second, we furnish a unified framework to provide uncertainties associated with each parameter. Third, we are able to handle multiplicity issues by using a Bayesian approach. The urgent need to quickly and effectively monitor the health of the public makes our methodology a potentially plausible and useful surveillance approach for health professionals.

A spatio-temporal absorbing state model for disease and syndromic surveillance.

Reliable surveillance models are an important tool in public health because they aid in mitigating disease outbreaks, identify where and when disease outbreaks occur, and predict future occurrences. Although many statistical models have been devised for surveillance purposes, none are able to simultaneously achieve the important practical goals of good sensitivity and specificity, proper use of covariate information, inclusion of spatio-temporal dynamics, and transparent support to decision-makers. In an effort to achieve these goals, this paper proposes a spatio-temporal conditional autoregressive hidden Markov model with an absorbing state. The model performs well in both a large simulation study and in an application to influenza/pneumonia fatality data.

[Investigation of occupational health status of female workers in pharmaceutical industry of Shandong and Gansu provinces].

OBJECTIVE: To investigate occupational health status of female workers in pharmaceutical industries and to propose the protective measures for the occupational health. METHOD: A total of 2816 female workers from 19 pharmaceutical industries in Shandong and Gansu provinces were investigated by a questionnaire. RESULTS: 73.1% of female workers exposed to occupational hazards, mainly to toxic chemicals. 63.2% of them suffered from dysmenorrhea; 38.5% of them have reproductive system diseases, i.e. mammary gland hyperplasia (44.1%), cervical erosion (26.5%), uterine annex inflammation (24.2%); 17.1% of them suffered from accidental work injuries; 34.7% of them complained about low back pain, and 29.7% of them perceived hearing loss. 94.9% of female workers hoped to get the occupational health and labor protection knowledge and skills. CONCLUSION: Strengthening the supervision of labor protection for female workers, including technical measures occupational hazards control and health-related knowledge, and improving the occupational health status of female workers should be conducted.

A simple and sensitive HPLC-ESI-MS/MS method for the determination of andrographolide in human plasma.

A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination of andrographolide in human plasma was established. Dehydroandrographolide was used as the internal standard (I.S.). The plasma samples were deproteinized with methanol and separated on a Hanbon C(18) column with a mobile phase of methanol-water (70:30, v/v). HPLC-ESI-MS/MS was performed in the selected ion monitoring (SIM) mode using target ions at [M-H(2)O-H](-), m/z 331.1 for andrographolide and [M-H](-), m/z 331.1 for the I.S. Calibration curve was linear over the range of 1.0-150.0ng/mL. The chromatographic separation was achieved in less than 6.5min. The lower limits of quantification (LLOQ) was 1.0ng/mL. The intra and inter-run precisions were less than 6.95 and 7.22%, respectively. The method was successfully applied to determine the plasma concentrations of andrographolide in Chinese volunteers.