Preoperative assessment of fistula-in-ano using SonoVue enhancement during three-dimensional transperineal ultrasound.

Background: Accurate preoperative evaluation of fistula-in-ano can guide the choice of surgical procedure and may improve healing rates. This prospective study aimed to evaluate the accuracy of conventional 3D transperineal ultrasound (3D-TPUS) compared with SonoVue (SVE)-enhanced 3D-TPUS for the detection and classification of anal fistula. Methods: In this prospective study, 3D-TPUS reconstructions were performed before and after SVE enhancement in 60 patients with fistula-in-ano who intended to undergo surgery at the Department of Anorectal Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University (P. R. China) between January 2021 and October 2021. Accuracies of anal fistula classification, complexity classification, detection of anal fistula branches, and detection of internal opening between 3D-TPUS and SVE 3D-TPUS were compared based on a reference standard-intraoperative findings. Results: This study enrolled 60 patients (mean age, 37.1 ± 11.4 years; mean follow-up, 9 ± 3 months). Intraoperative findings showed that the fistula type was intersphincteric in 23 patients (38.3%), trans-sphincteric in 35 (58.3%; 12 high and 23 low), and suprasphincteric in 2 (3.3%). Moreover, 68 internal openings were found. Compared with the accuracy of 3D-TPUS, that of SVE 3D-TPUS was similar in fistula classification [95.0% (57/60) vs 96.7% (58/60), P = 0.392], but significantly higher in internal opening evaluation [80.9% (55/68) vs 97.1% (66/68), P = 0.001], complexity classification [85.0% (51/60) vs 98.3% (59/60), P = 0.018], and detection of fistula branches [70.4% (19/27) vs 92.6% (25/27), P = 0.031]. Conclusions: SVE 3D-TPUS may be a useful examination for patients with perianal fistulae because of its high accuracy and consistency with intraoperative findings, especially in complex fistula-in-ano and difficult cases.

Cost-effectiveness of camrelizumab plus chemotherapy versus chemotherapy alone as first-line therapy in advanced or metastatic esophageal squamous cell carcinoma.

OBJECTIVE: Camrelizumab combination therapy for advanced or metastatic esophageal squamous cell carcinoma (ESCC) has considerable survival benefits. This study investigated the cost-effectiveness of camrelizumab combination therapy versus chemotherapy alone as a first-line treatment for patients with ESCC from the perspective of the Chinese healthcare system. METHODS: A three-state partitioned survival model was developed to estimate total costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) over a 20-year time horizon. Sensitivity and scenario analyses were also performed. RESULTS: Camrelizumab plus chemotherapy increased QALYs by 0.30 (0.43 LYs), with an incremental cost of $9,272. The ICERs for camrelizumab plus chemotherapy vs chemotherapy alone was $31,062/QALY ($21,599/LY), and the INHB was 0.05 QALY at the cost-effective threshold of $37,653/QALY (3 times China's GDP per capita). One-way sensitivity analyses showed that the ICER was the most sensitive to utility values in the PFS state. Probabilistic sensitivity analyses suggested that camrelizumab combination therapy had a probability of 74.04% cost-effectiveness at a threshold of $37,653/QALY. Scenario analyses confirmed that the findings were robust. CONCLUSIONS: Camrelizumab combination therapy is likely to have a cost-effectiveness advantage over chemotherapy alone for previously untreated advanced or metastatic ESCC in China.

Risk Assessment of (Herbal) Teas Containing Pyrrolizidine Alkaloids (PAs) Based on Margin of Exposure Approach and Relative Potency (REP) Factors.

Pyrrolizidine alkaloids (PAs) present distinct toxicity potencies depending on their metabolites and in vivo toxicokinetics. To represent the potency differences of various PAs, the interim relative potency (REP) factors have been derived. However, little is known about the risk assessment for (herbal) teas when taking REP factors into account. In this study, a set of 68 individual 1,2-unsaturated PA in 21 types of (herbal) teas was analyzed using LC-MS/MS. The REP factors for these PAs were applied on the PA levels. The margin of exposure (MOE) approach was employed to assess the risks of the exposure to PAs due to consumption of (herbal) teas. The results show that the total PA levels ranged from 13.4 to 286,682.2 µg/kg d.m., which were decreased by REP correction in most of the teas. The MOE values for tephroseris, borage and lemon balm (melissa) tea based on REP-corrected PA levels were below 10,000, assuming daily consumption of one cup of tea during a lifetime, indicating that consuming these teas may raise a concern. Our study also indicates a priority for risk management for tephroseris tea, as having nephrosis tea for more than 11.2 weeks during a 75-year lifetime would result in an MOE of 10,000.

High-throughput FastCloning technology: A low-cost method for parallel cloning.

FastCloning, a reliable cloning technique for plasmid construction, is a widely used protocol in biomedical research laboratories. Only two-step molecular manipulations are required to add a gene (cDNA) of interest into the desired vector. However, parallel cloning of the gene into multiple vectors is still a labor-intensive operation, which requires a range of primers for different vectors in high-throughput cloning projects. The situation could even be worse if multiple fragments of DNA are required to be added into one plasmid. Here, we describe a high-throughput FastCloning (HTFC) method, a protocol for parallel cloning by adding an adaptor sequence into all vectors. The target gene and vectors were PCR amplified separately to obtain the insert product and linear vectors with 18-base overlapping at each end of the DNAs required for FastCloning. Furthermore, a method for generating polycistronic bacterial constructs based on the same strategy as that used for HTFC was developed. Thus, the HTFC technique is a simple, effective, reliable, and low-cost tool for parallel cloning.

Cost-Effectiveness of Tislelizumab Versus Docetaxel for Previously Treated Advanced Non-Small-Cell Lung Cancer in China.

Background: Tislelizumab, a new high-affinity programmed cell death protein-1 (PD-1) inhibitor, significantly prolonged the overall survival in pretreated non-small-cell lung cancer (NSCLC). This study aimed to assess the cost-effectiveness of tislelizumab versus docetaxel for this population in China. Methods: A three-state partitioned survival model was developed to simulate advanced NSCLC. Efficacy and safety data were based on a global phase 3 clinical trial (RATIONALE 303). Utilities were mainly extracted from previously published resources. Costs were calculated from the Chinese healthcare system's perspective, and only direct medical costs were covered. The main outcomes included total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were carried to test the uncertainty of the modeling results. In addition, several scenarios including tislelizumab price before negotiation, different docetaxel price calculation, 50-year time horizon, and alternative utility values were assessed. Results: The model predicted an average gain of 0.62 LYs and 0.51 QALY for tislelizumab vs. docetaxel, at the additional cost of $9,219. The resulting ICER was $15,033.92/LY and $18,122.04/QALY, both below the cost-effective threshold (CET) of three times gross domestic product (GDP) per capita in China. Sensitivity analyses showed that the results are robust over a plausible range for majority of inputs. Utility of progression-free survival (PFS), followed by the price of tislelizumab, had the greatest impact on the ICER. The probability of being cost-effective for tislelizumab was 96.79% at the CET we set. Conclusion: Tislelizumab improves survival, increases QALYs, and can be considered a cost-effective option at current price compared with docetaxel for pretreated advanced NSCLC in China.

Trends of Antibiotic Use and Expenditure After an Intensified Antimicrobial Stewardship Policy at a 2,200-Bed Teaching Hospital in China.

Objective: This study aimed to evaluate the effects of intensified Chinese special rectification activity on clinical antibiotic use (CSRA) policy on a tertiary-care teaching hospital. Methods: A 48-month longitudinal dataset involving inpatients, outpatients, and emergency patients were collected. Study period included pre-intervention stage (adopting soft measures like systemic training) and post-intervention stage (applying antibiotic control system to intensify CSRA policy). Antibiotic use was evaluated by antibiotic use rate (AUR) or antibiotic use density (AUD). Economic indicator was evaluated by antibiotic cost in prescription or antibiotic expenditure in hospitalization. Data was analyzed by interrupted time series (ITS) analysis. Results: The medical quality indicators remained stable or improved during the study period. AUR of inpatients (AURI) declined 0.553% per month (P = 0.025) before the intervention and declined 0.354% per month (P = 0.471) after the intensified CSRA policy was implemented. AUD, expressed as defined daily doses per 100 patients per day (DDDs/100PD), decreased by 1.102 DDDs/100PD per month (P = 0.021) before and decreased by 0.597 DDDs/100PD per month (P = 0.323) thereafter. The ratio of antibiotic expenditure to medication expenditure (AE/ME) decreased by 0.510% per month (P = 0.000) before and fell by 0.096% (P = 0.000) per month thereafter. AE per patient decreased by 25.309 yuan per month (P = 0.002) before and decreased by 7.987 yuan per month (P = 0.053) thereafter. AUR of outpatient (AURO) decreased by 0.065% per month before (P = 0.550) and decreased by 0.066% per month (P = 0.994) thereafter. The ratio of antibiotic cost to prescription cost in outpatient (ACO/PCO) decreased by 0.182% per month (P = 0.506) before and decreased by 0.216% per month (P = 0.906) thereafter. AUR of emergency patient (AURE) decreased by 0.400% per month (P = 0.044) before and decreased by 0.092% per month (P = 0.164) thereafter. The ratio of antibiotic cost to prescription cost in emergency patient (ACE/PCE) decreased by 0.616% per month (P < 0.001) before and decreased by 0.151% per month (P < 0.001) thereafter. Conclusions: Implementation of CSRA policy was associated with declining antibiotic use and antibiotic expenditure in inpatients, outpatients, and emergency patients. However, it is also important to note that the declining trend of antibiotic consumption slowed due to the limited capacity for decline in the later stages of CSRA intervention.

Collaborative Assessment and Health Risk of Heavy Metals in Soils and Tea Leaves in the Southwest Region of China.

The collaborative assessment and health risk evaluation of heavy metals (HMs) enrichment in soils and tea leaves are crucial to guarantee consumer safety. However, in high soil HM geochemical background areas superimposed by human activities, the health risk associated with HMs in soil-tea systems is not clear. This study assessed the HMs concentration (i.e., chromium (Cr), cadmium (Cd), arsenic (As), and lead (Pb)) in tea leaves and their relationship with soil amounts in the southwest region of China to evaluate the associated health risk in adults. The results revealed that the average soil concentration of Cr was the highest (79.06 mg kg-1), followed by Pb (29.27 mg kg-1), As (14.87 mg kg-1), and Cd (0.18 mg kg-1). Approximately 0.71, 4.99, 7.36, and 10.21% of soil samples exceeded the threshold values (NY/T 853-2004) for Pb, Cr, As, and Cd, respectively. Furthermore, the average concentration of Pb, As, and Cd in tea leaves was below the corresponding residue limits, but Cr was above the allowed limits. Correlation analysis revealed that the Pb, Cr, As, and Cd amounts in tea leaves were positively correlated to their soil amounts (p < 0.01) with an R2 of 0.203 **, 0.074 **, 0.036 **, and 0.090 **, respectively. Additionally, approximately 40.38% of the samples were found to be contaminated. Furthermore, spatial distribution statistical analysis revealed that Lancang was moderately contaminated, while Yingjiang, Zhenkang, Yongde, Zhenyuan, Lüchun, Jingdong, Ximeng, and Menglian were slightly contaminated areas. The target hazard quotients (THQ; health risk assessment) of Pb, Cr, As, and Cd and the hazard index (HI) of all the counties were below unity, suggesting unlikely health risks from tea consumption.

Cost-Effectiveness Analysis of Anlotinib as Third- or Further-Line Treatment for Relapsed Small Cell Lung Cancer (SCLC) in China.

INTRODUCTION: The survival of patients with relapsed small cell lung cancer (SCLC) has achieved little progress in the last several decades. ALTER1202 confirmed the efficacy and safety of anlotinib as a third- or further-line option for relapsed SCLC. This study aimed to assess the cost-effectiveness of anlotinib compared with placebo as third- or further-line treatment for advanced SCLC in China. METHODS: A Markov model was developed to simulate the process of advanced SCLC and estimate the incremental cost-effectiveness ratio (ICER) of anlotinib versus placebo. The health outcomes and utilities were derived from the ALTER1202 (NCT03059797) and published sources, respectively. Total costs were calculated from the perspective of Chinese society. One-way and probabilistic sensitivity analyses (PSA) were conducted to explore the model uncertainties. RESULTS: Anlotinib was estimated to result in an additional 0.12 quality-adjusted life-years (QALYs) at an incremental cost of $2131.32, resulting in an ICER of $17,741.94/QALY. The ICER did not exceed the willingness-to-pay (WTP) threshold of $30,833 per QALY, which was three times the gross domestic product (GDP) per capita of China in 2019. One-way sensitivity analysis showed that the cost of anlotinib exerted the maximum influence on the result of the model, followed by the utility of progression-free survival (PFS) state in the anlotinib group and median overall survival (mOS) in the anlotinib group. In PSA, the probability of anlotinib being cost-effective was 26.6% and 78.5% when the WTP threshold was one and three times the GDP per capita, respectively. CONCLUSION: Anlotinib is likely to be a cost-effective option compared with placebo for patients with relapsed SCLC who experience failure of at least two lines of chemotherapy in China.

Secondary overtriage of isolated facial trauma.

DESIGN: Retrospective chart review. SETTING: Academic, tertiary care, level I trauma center in a rural state. BACKGROUND: Unnecessary transfer of certain facial trauma patients results in a burden of time, money, and other resources on both the patient and healthcare system; identification and development of outpatient treatment pathways for these patients is a significant opportunity for cost savings. OBJECTIVES: To investigate the treatment and disposition of un-complicated, stable, isolated facial trauma injuries transferred from outside hospitals and determine the significance of secondary overtriage. METHODS: Retrospective chart review utilizing our institutional trauma database, including patients transferred to our emergency department between January 2012 and December 2017. Patients were identified by ICD9 or ICD10 codes and only those with isolated facial trauma were included. RESULTS: We identified 538 isolated facial trauma patients who were transferred to our institution during the study period. The majority of those patients were transferred via ground ambulance for an average of 76 miles. Overall, 82% of patients (N = 440) were discharged directly from our institution's emergency department. Almost 30% of patients did not require any formal treatment for their injuries; the potential savings associated with elimination of these unnecessary transfers was estimated to be between $388,605 and $771,372. CONCLUSIONS: We identified a high rate of patients with stable, isolated facial trauma that could potentially be evaluated and treated without emergent transfer. The minimization of these unnecessary transfers represents a significant opportunity for cost and resource utilization savings. LEVEL OF EVIDENCE: 2b- Economic and Cost Analysis.

Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma.

Importance: Treatment with atezolizumab plus bevacizumab may prolong overall survival among patients with unresectable hepatocellular carcinoma. However, to our knowledge, the cost-effectiveness of using this high-priced therapy for this indication is currently unknown. Objective: To evaluate the cost-effectiveness of atezolizumab plus bevacizumab to treat unresectable hepatocellular carcinoma from the US payer perspective. Design, Setting, and Participants: This economic evaluation used a partitioned survival model consisting of 3 discrete health states to assess the cost-effectiveness of treatment of hepatocellular carcinoma with atezolizumab plus bevacizumab vs sorafenib. The characteristics of patients in the model were similar to patients in a phase 3, open-label randomized clinical trial (IMbrave150) who had unresectable hepatocellular carcinoma and had not previously received systemic treatment. Key clinical data were generated from the IMbrave150 trial conducted between March 15, 2018, and January 30, 2019, and cost and health preference data were collected from the literature. Main Outcomes and Measures: Costs, quality-adjusted life-years (QALYs), incremental cost-utility ratios, incremental net health benefits, and incremental net monetary benefits were calculated for the 2 treatment strategies. Subgroup, 1-way sensitivity, and probabilistic sensitivity analyses were performed. Results: Treatment of hepatocellular carcinoma with atezolizumab plus bevacizumab added 0.530 QALYs and resulted in an incremental cost of $89 807 compared with sorafenib therapy, which had an incremental cost-utility ratio of $169 223 per QALY gained. The incremental net health benefit was -0.068 QALYs, and the incremental net monetary benefit was -$10 202 at a willingness-to-pay threshold of $150 000/QALY. The probabilistic sensitivity analysis indicated that treatment with atezolizumab plus bevacizumab achieved a 35% probability of cost-effectiveness at a threshold of $150 000/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the hazard ratio of overall survival. The subgroup analysis found that treatment with atezolizumab plus bevacizumab was associated with preferred incremental net health benefits in several subgroups, including patients with hepatitis B and C. Conclusions and Relevance: Atezolizumab plus bevacizumab treatment is unlikely to be a cost-effective option compared with sorafenib for patients with unresectable hepatocellular carcinoma. Reducing the prices of atezolizumab and bevacizumab may improve cost-effectiveness. The economic outcomes also may be improved by tailoring treatments based on individual patient factors.

Cost-Effectiveness of Genomic Test-Directed Olaparib for Metastatic Castration-Resistant Prostate Cancer.

Purpose: The effectiveness of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib for metastatic castration-resistant prostate cancer (MCRPC) with multiple loss-of-function alterations in genes that are involved in DNA repair has been demonstrated. We aimed to evaluate the cost-effectiveness of genomic test-directed olaparib on MCRPC from the US payer perspective. Methods: A partitioned survival model was adopted to project the disease course of MCRPC had at least one gene alteration in BRCA1, BRCA2 and ATM (Scenario A) and has alterations in any of all 15 prespecified genes (Scenario B) after next-generation sequencing test. The efficacy and toxicity data were gathered from the PROfound trial. Clinical probabilities related to survival were estimated from the reported survival probabilities in each PROfound group. Cost and health preference data were derived from the literature. The incremental cost-effectiveness ratio (ICER) was measured. Subgroup analysis and sensitivity analysis were performed for exploring the model uncertainties. Results: Olaparib yielded an additional 0.063 and 0.068 of quality-adjusted life year (QALY) with the augmented cost of $7,382 and saved the cost of $ 1,980 compared to standard care in scenario A and B, respectively, which yielded an ICER of $116,903/QALY and a cost-saving option. The lower weekly cost related to olaparib treatment led to the dominant findings in scenario B. The varied results between scenario A and B could be partly explained by different the number need to screen for identifying eligible patients who could be administered with olaparib, which sharply augmented the costs of the olaparib arm in scenario A. Subgroup analysis and sensitivity analysis revealed the results were generally robust in both of two scenarios. Conclusion: The genomic test-directed olaparib is a preferred option compared with standard care strategy for men with MCRPC who had any of all 15 prespecified genes.

Depression and social support between China' rural and urban empty-nest elderly.

This study compared levels of depression and social support among empty-nest elderly who living in the rural and urban area of Hunan province, China. This cross-sectional study enrolled 809 empty-nest elderly living throughout the province as the study respondents. The general information, depression conditions and social supports were investigated by using the self-made General Information Questionnaire, Geriatric Depression Scale (GDS) and Social Support Rating Scale (SSRS). Variables are presented as mean ± standard deviation (SD) or frequency. Independent t-test and χ(2)-tests were used to compare the socio-demographic factors, depression score and social support scores of the rural empty-nest elderly to the urban empty-nest ones; multilevel modeling was used to analyze the socio-demographic factors and social support predicted the level of depression among the empty-nest old subjects. The differences in gender, education level, marital status, economic status, self-perceived income, insurance, children visit frequency and religious beliefs factors between rural and urban empty-nester old people were statistically significant (p<0.05). The average GDS score of rural group was (14.57 ± 5.43), which was higher than the average GDS score (13.18 ± 6.51) of urban group (p<0.01). Objective support scores showed statistical significance between the rural and urban empty-nest elderly (p<0.05). There are differences between rural and urban empty-nest elderly in the aspects of general data, depression status, social support and so on, we should intervene them effectively according to their different characteristics.

Emerging governance approaches for tourism in the protected areas of china.

This paper examines the recent evolution in the governance of protected area tourism in China. China now sees cooperation in the form of public-private partnerships occurring between authorized private tourism enterprises in various organizational forms and the public managers from specific portfolio departments of governments at different levels. Three types of governance models are visible: the Leasing Model, the Non-listed Share-holding Model, and the Public-listed Share-holding Model. Theories of corporate governance were applied to these models to analyze the internal and external mechanisms of supervision and incentives for both the government agencies and the authorized tourism enterprises for nature-based tourism operations. The Principal-Agent problem and the supervision mechanism are the focus of the analysis. The emerging governance approaches for tourism in protected areas of China are all theoretically viable, as explained by the theory of property rights and corporate governance, and practically viable as elaborated in the cases of the three types of governance models summarized in this paper.