[Progression on Multifunctional Nanoparticles Interfering with Cell Membrane Transporters-associated Drug Resistance].

Multi-drug resistance(MDR)refers to the loss of sensitivity of tumor cells to traditional chemotherapeutics agents under the mediation of various mechanisms,resulting in the reduction of chemotherapy efficacy.Current studies suggest that a variety of factors,including cell membrane transporter-mediated efflux of anti-tumor drugs,special microenvironment in tumor tissue,DNA self-repair and anti-apoptotic process,and epithelial-mesenchymal cell transformation,may contribute to the formation of MDR.Cell membrane transporter-mediated drug efflux refers to an increase in the amount of anti-tumor drug pumped out of the cell through the up-regulation of the ATP-binding cassette transporter on tumor cell membrane,which reduces the concentration of the drug in the cell,thus forming MDR.An effective method to inhibit the efflux pump caused by overexpression of membrane transporters plays an important role in overcoming MDR.As a promising drug delivery system,multifunctional nanoparticles have demonstrated many advantages in antitumor therapy.Meanwhile,nanoparticles with tailored design are capable of overcoming MDR when combined with a variety of strategies.This paper described in detail the studies relevant to the use of multifunctional nano-sized drug delivery system combined with different strategies,such as co-delivery of agents,external responsiveness or target modification for intervention with efflux pump in order to reverse MDR.This paper provides reference for the development of nano-sized drug delivery system and the formulation of reversal strategy in the future.

The effectiveness of E-learning in continuing medical education for tuberculosis health workers: a quasi-experiment from China.

BACKGROUND: Given the context of rapid technological change and COIVD-19 pandemics, E-learning may provide a unique opportunity for addressing the challenges in traditional face-to-face continuing medical education (CME). However, the effectiveness of E-learning in CME interventions remains unclear. This study aims to evaluate whether E-learning training program can improve TB health personnel's knowledge and behaviour in China. METHODS: This study used a convergent mixed method research design to evaluate the impact of E-learning programs for tuberculosis (TB) health workers in terms of knowledge improvement and behaviour change during the China-Gates TB Project (add the time span). Quantitative data was collected by staff surveys (baseline n = 555; final n = 757) and management information systems to measure the demographic characteristics, training participation, and TB knowledge. Difference-in-difference (DID) and multiple linear regression models were employed to capture the effectiveness of knowledge improvement. Qualitative data was collected by interviews (n = 30) and focus group discussions (n = 44) with managers, teachers, and learners to explore their learning experience. RESULTS: Synchronous E-learning improved the knowledge of TB clinicians (average treatment effect, ATE: 7.3 scores/100, P = 0.026). Asynchronous E-learning has a significant impact on knowledge among primary care workers (ATE: 10.9/100, P < 0.001), but not in clinicians or public health physicians. Traditional face-to-face training has no significant impact on all medical staff. Most of the learners (57.3%) agreed that they could apply what they learned to their practice. Qualitative data revealed that high quality content is the key facilitator of the behaviour change, while of learning content difficulty, relevancy, and hardware constraints are key barriers. CONCLUSIONS: The effectiveness of E-learning in CME varies across different types of training formats, organizational environment, and target audience. Although clinicians and primary care workers improved their knowledge by E-learning activities, public health physicians didn't benefit from the interventions.

Impacts of a comprehensive tuberculosis control model on the quality of clinical services and the financial burden of treatment for patients with drug-resistant tuberculosis in China: a mixed-methods evaluation.

BACKGROUND: The China National Health Commission-Gates TB Project Phase III implemented a comprehensive TB control model including multiple interventions to address the burden of drug-resistant TB (DRTB). This study aims to evaluate the quality of DRTB clinical services and assess the financial burden of DRTB patients during the intervention period. METHODS: A mixed-methods approach was used to evaluate the effectiveness of interventions in the three project provinces: Zhejiang, Jilin and Ningxia Hui Autonomous Region. The quantitative data included de-identified DRTB registry data during 2015-2018 in project provinces from China CDC, medical records of DRTB patients registered in 2018 (n = 106) from designated hospitals, and a structured DRTB patient survey in six sample prefectures in 2019. The quality of clinical services was evaluated using seven indicators across patient screening, diagnosis and treatment. Logistic regression was conducted to explore factors associated with the extremely high financial burden. Semi-structured in-depth interviews with policymakers and focus group discussions with physicians and DRTB patients were conducted to understand the interventions implemented and their impacts. RESULTS: The percentage of bacterially confirmed patients taking a drug susceptibility test (DST) increased significantly between 2015 and 2018: from 57.4 to 93.6% in Zhejiang, 12.5 to 86.5% in Jilin, and 29.7 to 91.4% in Ningxia. The treatment enrollment rate among diagnosed DRTB patients also increased significantly and varied from 73 to 82% in the three provinces in 2018. Over 90% of patients in Zhejiang and Jilin and 75% in Ningxia remained in treatment by the end of the first six months' treatment. Among all survey respondents 77.5% incurred extremely high financial burden of treatment. Qualitative results showed that interventions on promoting rapid DST technologies and patient referral were successfully implemented, but the new financing policies for reducing patients' financial burden were not implemented as planned. CONCLUSIONS: The quality of DRTB related clinical services has been significantly improved following the comprehensive interventions, while the financial burden of DRTB patients remains high due to the delay in implementing financing policies. Stronger political commitment and leadership are required for multi-channel financing to provide additional financial support to DRTB patients.

Process evaluation of E-learning in continuing medical education: evidence from the China-Gates Foundation Tuberculosis Control Program.

BACKGROUND: E-learning is a growing phenomenon which provides a unique opportunity to address the challenges in continuing medical education (CME). The China-Gates Foundation Tuberculosis (TB) Control Program implemented online training for TB health workers in three provinces of China. We aim to evaluate the implementation of E-learning CME programs, analyse the barriers and facilitators during the implementation process, and to provide policy recommendations. METHODS: Routine monitoring data were collected through the project office from December 2017 to June 2019. In-depth interviews, focus group discussion with project management personnel, teachers, and trainees (n = 78), and staff survey (baseline n = 555, final n = 757) were conducted in selected pilot areas at the provincial, municipal, and county/district levels in the three project provinces (Zhejiang, Jilin, and Ningxia). Descriptive analysis of quantitative data summarized the participation, registration, and certification rates for training activities. Thematic approach was used for qualitative data analysis. RESULTS: By the end of June 2019, the national and provincial remote training platforms had organized 98 synchronous learning activities, with an average of 173.2 people [standard deviation (SD) = 49.8] per online training session, 163.3 people (SD = 41.2) per online case discussion. In the pilot area, 64.5% of TB health workforce registered the asynchronous learning platform, and 50.1% obtained their professional certifications. Participants agreed that E-learning CME was more economical, has better content as well as more flexible work schedules. However, the project still faced challenges in terms of unmet learning needs, disorganized governance, insufficient hardware and software, unsupported environment, and lack of incentive mechanisms. CONCLUSIONS: Our results suggested that it's feasible to conduct large scale E-learning CME activities in the three project provinces of China. Training content and format are key facilitators of the program implementation, while the matching of training supply and demand, organizational coordination, internet technology, motivations, and sustainability are key barriers.

Multi-source financing for tuberculosis treatment in China: key issues and challenges.

BACKGROUND: The End Tuberculosis (TB) Strategy of the World Health Organization highlights the need for patient-centered care and social protection measures that alleviate the financial hardships faced by many TB patients. In China, TB treatments are paid for by earmarked government funds, social health insurance, medical assistance for the poor, and out-of-pocket payments from patients. As part of Phase III of the China-Gates TB project, this paper introduces multi-source financing of TB treatment in the three provinces of China and analyzes the challenges of moving towards universal coverage and its implications of multi-sectoral engagement for TB care. MAIN TEXT: The new financing policies for TB treatment in the three provinces include increased reimbursement for TB outpatient care, linkage of TB treatment with local poverty alleviation programs, and use of local government funds to cover some costs to reduce out-of-pocket expenses. However, there are several challenges in reducing the financial burdens faced by TB patients. First, medical costs must be contained by reducing the profit-maximizing behaviors of hospitals. Second, treatment for TB and multi-drug resistant TB (MDR-TB) is only available at county hospitals and city or provincial hospitals, respectively, and these hospitals have low reimbursement rates and high co-payments. Third, many patients with TB and MDR-TB are at the edge of poverty, and therefore ineligible for medical assistance, which targets extremely poor individuals. In addition, the local governments of less developed provinces often face fiscal difficulties, making it challenging to use of local government funds to provide financial support for TB patients. We suggest that stakeholders at multiple sectors should engage in transparent and responsive communications, coordinate policy developments, and integrate resources to improve the integration of social protection schemes. CONCLUSIONS: The Chinese government is examining the establishment of multi-source financing for TB treatment by mobilization of funds from the government and social protection schemes. These efforts require strengthening the cooperation of multiple sectors and improving the accountability of different government agencies. All key stakeholders must take concrete actions in the near future to assure significant progress toward the goal of alleviating the financial burden faced by TB and MDR-TB patients.

Implementing a new tuberculosis surveillance system in Zhejiang, Jilin and Ningxia: improvements, challenges and implications for China's National Health Information System.

BACKGROUND: China is still faced with the public health challenge of tuberculosis (TB), and a robust surveillance system is critical for developing evidence-based TB control policies. The Tuberculosis Information Management System (TBIMS), an independent system launched in 2005, has encountered several challenges in meeting the current needs of TB control. The Chinese government also planned to establish the National Health Information System (NHIS) aggregating data in different areas. The China National Health Commission-Gates TB Project Phase III launched a new TB surveillance system to address these challenges and also as a pilot for the countrywide implementation of the NHIS. This commentary highlights the improvements and challenges in implementing the new TB system and also discusses the implications for the roll-out of the NHIS. MAIN TEXT: The new TB surveillance system piloted in each prefecture of the project provinces was designed based on the local information system under the unified principle of organizing patient information under a unique ID and realizing the function of data exchange. Upon mid-2019, the data exchange successful rate reached almost 100%, and the system showed good performance in data completeness. Major improvements of the new system included achieving automatic data extraction instead of manual entry, assisting clinical service provision, and the augmented statistical functions. The major challenges in the implementation and scale-up of the new system were the licensing issue and the diversities of infrastructures that hinder the promotion of the new system at a low cost. This pilot also accumulated experiences for the roll-out of the NHIS regarding the technical solutions of reforming current information systems as well as effective training approaches for the developers and users of the new system. CONCLUSIONS: The successful implementation of the new TB surveillance system in the three TB designated medical institutions demonstrated how the diverse infrastructures of the information system could be reformed to achieve the functions of automatic data extraction and data exchange and better cater to the needs of healthcare workers. This pilot also accumulated rich experiences and lessons learnt for developing technical solutions and personnel training for the scale-up of the NHIS.

Impact of multiple policy interventions on the screening and diagnosis of drug-resistant tuberculosis patients: a cascade analysis on six prefectures in China.

BACKGROUND: The detection of drug-resistant tuberculosis (DR-TB) is a major health concern in China. We aim to summarize interventions related to the screening and detection of DR-TB in Jiangsu Province, analyse their impact, and highlight policy implications for improving the prevention and control of DR-TB. METHODS: We selected six prefectures from south, central and north Jiangsu Province. We reviewed policy documents between 2008 and 2019, and extracted routine TB patient registration data from the TB Information Management System (TBIMS) between 2013 and 2019. We used the High-quality Health System Framework to structure the analysis. We performed statistical analysis and logistic regression to assess the impact of different policy interventions on DR-TB detection. RESULTS: Three prefectures in Jiangsu introduced DR-TB related interventions between 2008 and 2010 in partnership with the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) and the Bill & Melinda Gates Foundation (Gates Foundation). By 2017, all prefectures in Jiangsu had implemented provincial level DR-TB policies, such as use of rapid molecular tests (RMT), and expanded drug susceptibility testing (DST) for populations at risk of DR-TB. The percentage of pulmonary TB cases confirmed by bacteriology increased from 30.0% in 2013 to over 50.0% in all prefectures by 2019, indicating that the implementation of new diagnostics has provided more sensitive testing results than the traditional smear microscopy. At the same time, the proportion of bacteriologically confirmed cases tested for drug resistance has increased substantially, indicating that the intervention of expanding the coverage of DST has reached more of the population at risk of DR-TB. Prefectures that implemented interventions with support from the Global Fund and the Gates Foundation had better detection performance of DR-TB patiens compared to those did not receive external support. However, the disparities in DR-TB detection across prefectures significantly narrowed after the implementation of provincial DR-TB polices. CONCLUSIONS: The introduction of new diagnostics, including RMT, have improved the detection of DR-TB. Prefectures that received support from the Global Fund and the Gates Foundation had better detection of DR-TB. Additionally, the implementation of provincial DR-TB polices led to improvements in the detection of DR-TB across all prefectures.

Is tuberculosis patients management improved in the integrated TB control model in West China? A survey in Guizhou Province, China.

BACKGROUND: Tuberculosis (TB) patient management (TPM) is crucial to improve patient compliance to treatment. The coverage of TPM delivered by TB dispensaries or Centers for Disease Control and Prevention (CDC) was not high under the previous CDC model of TB control in China. In the integrated TB control model in China, TB patient management (TPM) was mainly delivered by lay health workers (LHWs) in primary health care (PHC) sectors. This study aims to investigate TPM delivery in resource-limited western China and to identify factors affecting TPM delivery by LHWs under the integrated TB control model. METHODS: A stratified random sampling was used to select study sites. Pulmonary TB (PTB) patients ≥15 years old from selected counties/districts in Guizhou Province were surveyed from August 2015 to May 2016. Structured questionnaires were used to collect data. A χ2 test and logistic regression were used to identify factors associated with self-administered treatment (non-TPM). RESULTS: In total, 638 PTB patients were included in the final analysis. Close to 30% of patients were ethnic minorities. More than 30% of patients were from counties with high TB burden, and 24.9% of patients had poor compliance to treatment. Only 37.1% of patients received TPM delivered by LHWs under the integrated TB control model throughout the treatment period. The main reasons for unwillingness to manage reported by patients included social stigma and no perceived need. Being ethnic minorities (OR = 3.35) was a main factor associated with lower likelihood of receiving TPM, while living in areas with middle or high TB burden may increase the likelihood of receiving TPM (OR = 0.17 and 0.25, respectively). Among current management approaches, more than 85% of patients chose phone reminder as their preferred TPM by LHWs. CONCLUSIONS: TPM under the integrated model in West China is still low and need further improvement, and the impeding factors of TPM need to be addressed. Strengthening patient-centered and community-based TPM and developing more feasible approaches of TPM delivery should be explored in future research in this region.

Impact of an innovative tuberculosis financing and payment model on health service utilization by tuberculosis patients in China: do the poor fare better than the rich?

BACKGROUND: Tuberculosis (TB) prevalence is closely associated with poverty in China, and poor patients face more barriers to treatment. Using an insurance-based approach, the China-Gates TB program Phase II was implemented between 2012 and 2014 in three cities in China to improve access to TB care and reduce the financial burden on patients, particularly among the poor. This study aims to assess the program effects on service use, and its equity impact across different income groups. METHODS: Data from 788 and 775 patients at baseline and final evaluation were available for analysis respectively. Inpatient and outpatient service utilization, treatment adherence, and patient satisfaction were assessed before and after the program, across different income groups (extreme poverty, moderate poverty and non-poverty), and in various program cities, using descriptive statistics and multi-variate regression models. Key stakeholder interviews were conducted to qualitatively evaluate program implementation and impacts. RESULTS: After program implementation, the hospital admission rate increased more for the extreme poverty group (48.5 to 70.7%) and moderate poverty group (45.0 to 68.1%), compared to the non-poverty group (52.9 to 64.3%). The largest increase in the number of outpatient visits was also for the extreme poverty group (4.6 to 5.7). The proportion of patients with good medication adherence increased by 15 percentage points in the extreme poverty group and by ten percentage points in the other groups. Satisfaction rates were high in all groups. Qualitative feedback from stakeholders also suggested that increased reimbursement rates, easier reimbursement procedures, and allowance improved patients' service utilization. Implementation of case-based payment made service provision more compliant to clinical pathways. CONCLUSION: Patients in extreme or moderate poverty benefited more from the program compared to a non-poverty group, indicating improved equity in TB service access. The pro-poor design of the program provides important lessons to other TB programs in China and other countries to better address TB care for the poor.

Impact of an innovative financing and payment model on tuberculosis patients' financial burden: is tuberculosis care more affordable for the poor?

BACKGROUND: In response to the high financial burden of health services facing tuberculosis (TB) patients in China, the China-Gates TB project, Phase II, has implemented a new financing and payment model as an important component of the overall project in three cities in eastern, central and western China. The model focuses on increasing the reimbursement rate for TB patients and reforming provider payment methods by replacing fee-for-service with a case-based payment approach. This study investigated changes in out-of-pocket (OOP) health expenditure and the financial burden on TB patients before and after the interventions, with a focus on potential differential impacts on patients from different income groups. METHODS: Three sample counties in each of the three prefectures: Zhenjiang, Yichang and Hanzhong were chosen as study sites. TB patients who started and completed treatment before, and during the intervention period, were randomly sampled and surveyed at the baseline in 2013 and final evaluation in 2015 respectively. OOP health expenditure and percentage of patients incurring catastrophic health expenditure (CHE) were calculated for different income groups. OLS regression and logit regression were conducted to explore the intervention's impacts on patient OOP health expenditure and financial burden after adjusting for other covariates. Key-informant interviews and focus group discussions were conducted to understand the reasons for any observed changes. RESULTS: Data from 738 (baseline) and 735 (evaluation) patients were available for analysis. Patient mean OOP health expenditure increased from RMB 3576 to RMB 5791, and the percentage of patients incurring CHE also increased after intervention. The percentage increase in OOP health expenditure and the likelihood of incurring CHE were significantly lower for patients from the highest income group as compared to the lowest. Qualitative findings indicated that increased use of health services not covered by the standard package of the model was likely to have caused the increase in financial burden. CONCLUSIONS: The implementation of the new financing and payment model did not protect patients, especially those from the lowest income group, from financial difficulty, due partly to their increased use of health service. More financial resources should be mobilized to increase financial protection, particularly for poor patients, while cost containment strategies need to be developed and effectively implemented to improve the effective coverage of essential healthcare in China.

Large medial sphenoid wing meningiomas: long-term outcome and correlation with tumor size after microsurgical treatment in 127 consecutive cases.

AIM: We present the long-term outcomes as well as their correlation with tumor size in 127 consecutive patients harboring large MSWM after microsurgical treatment. MATERIAL AND METHODS: The retrospective analysis of clinical data and follow-up data of 127 microsurgical treated patients with MSWM was performed. The mean maximum diameter of tumors was 5.2cm (ranged 1.5-10.0cm). RESULTS: 104 cases (81.9%) achieved gross total resection. There was no operative mortality. Detailed follow-up data was available in 120 cases for a mean duration of 81.6 months (12-216 months). The permanent morbidity was 14.2%. The mean KPS score 1 year after surgery was 90.6 (ranged 60-100). Among 74 patients of preoperative visual acuity (VA) impairment, postoperative VA improved in 42 cases (56.8%), unchanged in 30 (40.5%), and deteriorated in 2 (2.7%). MR images revealed tumor recurrence after total resection in 10 cases (10.2%) and tumor progression after subtotal resection in 10 cases (45.5%). CONCLUSION: Tumor recurrence was the major risk in the long run, thus the initial surgery was extremely important and hence should be aggressive. The size of tumor affected the extent of tumor removal determining clinical outcomes including VA improvement and KPS score immediately after surgery; however, it was not correlated with long-term overall outcomes.

[Endoscopic anatomy involving the extended transsphenoidal approach].

OBJECTIVE: To provide pertinent anatomic data and details for the clinical application of the extended transsphenoidal approach; to probe the anatomic characteristic and method under endoscope; METHODS: 25 adult cadaver heads fixed in formalin were used to dissect, observe, measure and photograph the relationship between the neural and vascular structure and the important anatomic landmarks related to the extended transsphenoidal approach under endoscope. RESULTS: The posterior and lateral wall of sphenoidal sinus could be well exposed by bilateral approach under endoscope. The clinical application of endoscope could improve the illumination of the operative field, magnify the objects and provide two-dimensional images. The distortion of the images under endoscope depended upon the distance between the lens and the object as well as the angle of the lens. To establish the anatomic vertical compartment under the endoscope might be helpful to the operation. The midline vertical compartment consisted of the planum sphenoidale, tuberculum sella, sella and clival indentation. The paramedian vertical compartment was composed of the medial third of the optic canal and the carotid artery protuberance. The lateral vertical compartment contained four bony protuberances (optic, cavernous sinus apex, maxillary, and mandibular). Endoscopic surgical maneuvering was under non-midline direction. Precise surgical landmarks are essential for a successful operation. These landmarks allowed the surgeon to recognize and approach the surgical target without confusion. The nasopharynx, middle turbinate, and inferior turbinate were some of the landmarks in the nasal cavity. Once the sphenoidal sinus was entered, the anatomic structures of the sphenoidal sinus posterior wall, which were described above, were the unique landmarks that will guide the surgeon to the surgical target. CONCLUSION: The anatomic characteristics under endoscope were different from those under microscope. The application of the extended transsphenoidal approach under endoscope could provide more extensive vision and satisfied exposure to reach the area of the central skull base.

[Surgical management of chronic subdural hematoma].

OBJECTIVE: To report the experience of surgical treatment of chronic subdural hematoma (CSDH). METHODS: The clinical features, radiological findings, operative techniques and outcome of 156 patients with CSDH were analyzed retrospectively. RESULTS: All the patients (156) were initially treated by burr hole craniostomy with closed-system drainage, and 10 out of the 156 patients were reoperated by larger craniotomy. Of all the patients, 143 (91.7%) were cured, 8 (5.1%) had recurrence, 3 (1.9%) got hemiparalysis, and 2 (1.3%) died due to other diseases. CONCLUSION: Burr hole craniostomy with closed-system drainage is effective for the initial treatment of CSDH. Craniotomy should be carried out only in patients with accumulating hematomas.