Health-related quality of life of Chinese AIDS patients: a multi-region study.

OBJECTIVE: To assess the health-related quality of life (HRQOL) of Chinese AIDS patients in three regions (Shanghai, Zhejiang, and Henan) and to examine the relationship between region and the HRQOL. METHOD: A cross-sectional study was conducted from 2017 to 2018. Multistage stratified sampling was employed to recruit 1,273 AIDS patients from local Centers for Disease Control and Prevention. Data were collected by means of face-to-face interview using a structured questionnaire including the SF-12 and various rating scales. The multivariate linear and logistic regression models were performed to analyze the relationship of region and a variety of factors with the HRQOL and health utility. RESULTS: The three most affected dimensions were mental health, general health, and vitality as 18.2%, 18.0%, and 16.4% of the patients reported problems respectively. The mean (SD) scores of physical component summary (PCS) and mental component summary (MCS), were 48.19 (8.02) and 46.74 (10.71) respectively. The mean (SD) health utility score was 0.75 (0.13) assessed by the SF-6D derived from the SF-12. Region, age, employment status, individual income, government assistance and stigma significantly affected the patients' HRQOL (P < 0.01). BMI, opportunistic infection, treatment compliance and time of treatment were also found to be significant factors of the HRQOL. CONCLUSION: This study comprehensively estimated the HRQOL and health utility for the AIDS population in China, their HRQOL was mainly deteriorated in psychological dimensions, and geographical area may be closely related. Hence, close attention needs to be paid on the regional differences in HRQOL and the psychological problems of the patients.

Psychometric performance of EQ-5D-5L and SF-6DV2 in measuring health status of populations in Chinese university staff and students.

AIMS: To compare measurement properties of EQ-5D-5L and SF-6DV2 in university staff and students in China. METHODS: A total of 291 staff and 183 undergraduates or postgraduates completed the two instruments assigned in a random order. The health utility scores (HUS) of EQ-5D-5L and SF-6DV2 were calculated using the respective value sets for Chinese populations. The agreement of HUSs was examined using intraclass correlation coefficients (ICC) and Bland-Altman plot. Convergent validity of their HUSs and similar dimensions were assessed using Spearman's correlation coefficient. Known-group validity of the HUSs and EQ-VAS score was assessed by comparing the scores of participants with and without three conditions (i.e., disease, symptom or discomfort, and injury), as well as number of any of the three conditions; their sensitivity was also compared. RESULTS: The ICCs between the two HUSs were 0.567 (staff) and 0.553 (students). Bland-Altman plot found that EQ-5D-5L HUSs were generally higher. Strong correlation was detected for two similar dimensions (pain/discomfort of EQ-5D-5L and pain of SF-6DV2; anxiety/depression of EQ-5D-5L and mental health of SF-6DV2) in both samples. The correlation between the two HUSs were strong (0.692 for staff and 0.703 for students), and were stronger than their correlations with EQ-VAS score. All the three scores could discriminate the difference in three known-groups (disease, symptom or discomfort, number of any of the three conditions). The two HUSs were more sensitive than EQ-VAS score; and either of them was not superior than the other. CONCLUSIONS: Both EQ-5D-5L and SF-6DV2 HUSs have acceptable measurement properties (convergent validity, known-groups validity, sensitivity) in Chinese university staff and students. Nevetheless, only EQ-5D-5L (PD and AD) and SF-6DV2 (PN and MH) showed indicated good convergent validity as expected. Two types of HUSs cannot be used interchangeably, and each has its own advantages in sensitivity.

A head-to-head comparison of the EQ-5D-3L index scores derived from the two EQ-5D-3L value sets for China.

OBJECTIVE: Two EQ-5D-3L (3L) value sets (developed in 2014 and 2018) co-exist in China. The study examined the level of agreement between index scores for all the 243 health states derived from them at both absolute and relative levels and compared the responsiveness of the two indices. METHODS: Intraclass correlations coefficient (ICC) and Bland-Altman plot were adopted to assess the degree of agreement between the two indices at the absolute level. Health gains for 29,403 possible transitions between pairs of 3L health states were calculated to assess the agreement at the relative level. Their responsiveness for the transitions was assessed using Cohen effect size. RESULTS: The mean (SD) value was 0.427 (0.206) and 0.649 (0.189) for the 3L2014 and 3L2018 index scores, respectively. Although the ICC value showed good agreement (i.e., 0.896), 88.9% (216/243) of the points were beyond the minimum important difference limit according to the Bland-Altman plot. The mean health gains for the 29,403 health transitions was 0.234 (3L2014 index score) and 0.216 (3L2018 index score). The two indices predicted consistent transitions in 23,720 (80.7%) of 29,403 pairs. For the consistent pairs, Cohen effective size value was 1.05 (3L2014 index score) or 1.06 (3L2018 index score); and the 3L2014 index score only yielded 0.007 more utility gains. However, the results based on the two measures varied substantially according to the direction and magnitude of health change. CONCLUSION: The 3L2014 and 3L2018 index scores are not interchangeable. The choice between them is likely to influence QALYs estimations.

Cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders in Singapore.

BACKGROUND: The study evaluated the cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders (MSDs) in Singapore. METHODS: A decision-analytic model was constructed to compare the cost-effectiveness of hydrotherapy to land-based therapy over 3 months from societal perspective. Target population comprised patients with low back pain (LBP), osteoarthritis (OA), rheumatoid arthritis (RA), total hip replacement (THR) and total knee replacement (TKR). Subgroup analyses were carried out to determine the cost-effectiveness of hydrotherapy in individual MSDs. Relative treatment effects were obtained through a systematic review of published data. RESULTS: Compared to land-based therapy, hydrotherapy was associated with an incremental cost-effectiveness ratio (ICER) of SGD 27 471 per quality-adjusted life-year (QALY) gained, which was below the willingness-to-pay threshold of SGD 70 000 per QALY (one gross domestic product per capita in Singapore in 2015). For the respective MSDs, hydrotherapy were dominant (more effective and less costly) in THR and TKR, cost-effective for LBP and RA, and not cost-effective for OA. Treatment adherence and cost of hydrotherapy were key drivers to the ICER values. CONCLUSIONS: Hydrotherapy was a cost-effective rehabilitation compared to land-based therapy for a population with MSDs in Singapore. However, the benefit of hydrotherapy was not observed in patients with OA.

Health-Related Quality of Life and Its Factors of Hemodialysis Patients in Suzhou, China.

BACKGROUND: To identify factors of health-related quality of life (HRQOL) of Chinese end-stage renal disease patients undergoing hemodialysis (HD). METHODS: In all, 315 HD patients were recruited from a tertiary hospital in Suzhou, -China. Each patient completed the Kidney Disease Quality of Life Short Form. It generated 4 types of HRQOL scores: PCS score, MCS score, kidney disease component summary (KDCS) score, and SF-6D index score. Multiple linear regressions were conducted to identify the factors associated with each of the scores. RESULTS: Factors associated with poorer HRQOL were determined including: middle age and above (≥45 years), without partner, presence of complication, long dialysis vintage (≥4.5 years) with physical component summary; low education level, presence of comorbidity, long dialysis vintage, low hemoglobin level with mental component summary; without partner, presence of comorbidity, long dialysis vintage with KDCS; middle age and above, without partner, low education level; long dialysis vintage, more frequent dialysis (≥2 times/week) with SF-6D. CONCLUSION: The study evaluated the HRQOL of HD patients in mainland China.

[Cellular Uptake and Localization of Novel NSCLC Penetrating Peptide with Neuropilin-1 Binding Motif].

OBJECTIVE: To synthesize and study the specific binding affinity of tumor-penetrating peptide YCCS to non-small cell lung carcinoma (NSCLC) cells in vitro. METHODS: YCCS peptide was designed by fusing the neuropilin-1 (NRP-1) binding sequence and NSCLC binding peptide CS. YCCS peptide was synthesized and fluorescent labeled with N-terminal FITC. NRP-1 positive human NSCLC cell A549, NRP-1 positive human breast cancer cell MDA-MB-231, normal human bronchial epithelium HBE135-E6E7 and human liver cell HL-7702 were incubated respectively, then we observed the specific binding affinity of tumor-penetrating peptide YCCS to NSCLC cells. RESULTS: After treated with 5 µmol/L peptide, significant fluorescent signals of FITC-YCCS peptide were demonstrated only in NSCLC A549 cells but marginal captured signal in MDA-MB-231, normal human HBE135-E6E7 or HL-7702 cells, which revealed specific NSCLC cells binding affinity. In 20 µmol/L treated group, non-specific binding were found in MDA-MB-231 and HL-7702 cells. CONCLUSION: The results of this novel designed YCCS peptide indicated a promising strategy for improving tumor penetrating with delivery capability of drugs to NSCLC A549 cells when treated with 5 µmol/L peptide.

Efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil monotherapy for refractory metastatic colorectal cancer: a retrospective cohort study.

Background: Several studies demonstrated trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) had better efficacy than the monotherapy of TAS-102 in refractory metastatic colorectal cancer (mCRC). However, it remains unclear whether Chinese population can benefit from this combination or not. Hence, we conducted this retrospective cohort study to compare the efficacy and safety between TAS-102 plus BEV with TAS-102 monotherapy in refractory mCRC. Methods: This retrospective cohort study enrolled patients (any age) with refractory mCRC from Hunan Cancer Hospital. The main inclusion criteria were histopathologically and/or radiographically confirmed refractory mCRC, World Health Organization (WHO) performance status of 0 to 2, adequate organ function, and initial treatment of TAS-102 with or without BEV between November 2020 and October 2022. Previous therapy with fruquintinib or regorafenib was allowed but not mandatory. Baseline demographic and clinical characteristics were collected appropriately. Every 2 or 3 treatment cycles, the patients were assessed by computed tomography (CT) scans and clinical assessments until disease progression or loss to follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI-CTCAE 5.0) were presented as n (%). The primary endpoint was investigator-evaluated overall survival (OS). As this is a retrospective cohort study, sample size calculation was not performed. Eligible patients would be enrolled as many as possible. Results: A total of 90 patients were enrolled, including 58 patients who received TAS-102 plus BEV and another 32 patients who received TAS-102 monotherapy. The known baseline characteristics were comparable (P<0.05). With a median follow-up of 4.60 months (range, 0.20-22.80), the median OS (mOS) time in the TAS-102 plus BEV group was longer than that in the TAS-102 monotherapy group (10.83 vs. 7.43 months), but the difference was not significant (P=0.79). The median progression-free survival (mPFS) time was comparable between the two groups (4.67 vs. 4.30 months, P=0.96). Multivariate Cox regression analysis demonstrated that undergoing therapy after TAS-102 either with or without BEV was an independent risk factor for OS [hazard ratio (HR) =0.25; 95% confidence interval (CI): 0.09-0.71, P<0.01], and previous treatment with cetuximab was an independent protective factor for PFS (HR =0.17; 95% CI: 0.03-0.91, P=0.04). Of the 70 patients who were evaluated, those receiving TAS-102 plus BEV showed trend of a higher objective response rate (ORR) and disease control rate (DCR) than those who received TAS-102 monotherapy (P=0.16 and P=0.29, respectively). Adverse events (AEs) were similar between the two groups, except that the incidence of platelet count decrease (grade ≥3) was significantly higher in the TAS-102 plus BEV group. Conclusions: There was a trend in favor of the combination of BEV plus TAS-102 regarding OS and DCR, without reaching statistical significance, and it means that there was no clear advantage of one over the other in terms of efficacy. Further prospective studies are still necessary to draw a definite conclusion.

DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma.

Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has been shown to exhibit anti-angiogenic and anti-tumor effects apart from its antimalarial activity. In this study, we demonstrate that the combined treatment of cisplatin (CDDP) and DHA exerts a strong, synergistic anti-proliferative effect in human lung carcinoma cells, including A549 and A549/DDP cells, with an average combination index below 0.7. Moreover, the in vivo anti-tumor efficacy of CDDP treatment was increased by DHA. The enhanced anti-cancer activities were also accompanied by reduced tumor microvessel density, increased CDDP concentration within A549 and A549/DDP xenograft BALB/c athymic mice models and suppressed expression of the vascularization-related proteins HIF-1α and VEGF both in vivo and in vitro. Furthermore, the level of apoptosis in the tumor cells increased with the combined treatment of DHA and CDDP. Taken together, our results indicate that a combination of DHA and CDDP treatments synergistically affects tumor angiogenesis, and these results provide a clear rationale for the investigation of these drugs in future clinical trials.

Laparoscopic drainage of cryptogenic liver abscess.

BACKGROUND: To retrospectively compare the outcomes of percutaneously drained and laparoscopically drained liver abscesses. METHODS: Eight-five consecutive patients with radiological evidence of liver abscess were treated at National University Hospital of Singapore from 2005 to 2011. Multivariable logistic regression was used to identify failures of intervention. This was defined as persistent objective signs of sepsis. Complications, length of antibiotic therapy, and hospital stay were recorded but not used as indicators for failure of intervention. A propensity score analysis was used to adjust for possible confounders. RESULTS: Twenty-seven (40.3%) patients in the percutaneous group did not respond to primary intervention compared to 2 patients (11.1%) in the laparoscopic group (p = 0.020). Two patients within the percutaneous group died from progression of sepsis despite intervention. In the multivariate model with propensity score, laparoscopic drainage had a protective effect against failure compared to percutaneous drainage of liver abscess (odds ratio [OR], 0.03; 95% confidence interval [CI], [0-0.4]; p = 0.008). There were no differences in complications related to the intervention (p = 0.108). Mean duration of antibiotics (p = 0.437) and hospital stay (p = 0.175) between the groups was similar. CONCLUSIONS: Laparoscopic drainage of cryptogenic liver abscesses should be considered as an option for drainage of liver abscess.

Empirical evidence of the continuing improvement in cost efficiency of an endoscopic surveillance programme for gastric cancer in Singapore from 2004 to 2010.

BACKGROUND: Endoscopic surveillance has been proven effective in prolonging the survival of gastric cancer (GC) patients. However, there is limited evidence on the cost efficiency of delivering this intervention, especially on a national level in spite of cost efficiency being a major determinant of the actual cost-effectiveness of a cancer prevention programme. The Singapore Gastric Cancer Epidemiology Clinical and Genetic Programme (GCEP) is a demonstration project offering scheduled endoscopy to the Chinese population aged 50 years or older in Singapore. By assessing the cost efficiency of the GCEP, this study aimed to provide empirical evidence on the cost structure and mechanisms underlying cost generation in conducting GC surveillance, thus informing resource allocation and programme budgeting for the Singapore government. METHODS: From a societal perspective, we reported on the direct cost (resource consumption) of conducting endoscopic surveillance through the GCEP network. We retrospectively collected individual-level data of 216 subjects recruited at the National University Hospital, Singapore from 01/04/2004 to 31/10/2010. The Overall Cost, Clinical Cost, GCEP Cost and Personal Cost incurred in serving one subject was computed and discounted as 2004 US dollar (US$) per capita for every year. The Generalized Estimation Equation (GEE) was used to model the data. RESULTS: All cost indices continuously declined over the 6.5-year costing period. For the total sample, Overall Cost, Clinical Cost, GCEP Cost and Personal Cost declined by 42.3%, 54.1%, 30% and 25.7% respectively. This downward trend existed for age and gender subgroups and the high risk group only with cost reductions varying between 3.5% and 58.4%. The GEE models confirmed statistical significance of the downward trend and of its association with risk profile, where the moderate risk group had cost indices at most 77% of the high risk group. CONCLUSIONS: Our study offered empirical evidence of improved cost efficiency of a surveillance programme for GC in the early phase of programme implementation. Mechanisms such as economies of scale and self-learning were found to be involved in the cost reduction. Our findings highlighted the importance of assessing the cost efficiency and offered valuable insights for future programme budgeting and policy making.

Validation of the functional assessment of cancer therapy-gastric module for the Chinese population.

BACKGROUND: Quality of life (QoL) assessment has become an important aspect of the clinical management of gastric cancer (GC), which poses a greater health threat in Chinese populations around the world. Functional Assessment of Cancer Therapy-Gastric Module (FACT-Ga), a questionnaire developed specifically to measure QoL of patients with GC, has never been validated in Chinese subjects. The current study was designed to examine the psychometric properties of FACT-Ga as a GC specific QoL instrument for its future use in Chinese populations. METHODS: A sample of 67 Chinese patients with GC in the National University Hospital, Singapore was investigated cross-sectionally. The participants independently completed either English or Chinese versions of the FACT-Ga and the European Quality of Life-5 Dimensions (EQ-5D). Reliability was measured as the Cronbach's α for EQ-5D, and five subscale scores and two total scores of FACT-Ga. The sensitivity to patients' clinical status was evaluated by comparing EQ-5D and FACT-Ga scores between clinical subgroups classified by Clinical Stage and Treatment Intent. The construct validity of FACT-Ga was assessed internally by examining the item-to-scale correlations and externally by contrasting the FACT-Ga subscales with the EQ-5D domains. RESULTS: For both FACT-Ga and EQ-5D, patients treated with curative intent rated their QoL higher than those treated for palliation, and early stage patients scored higher than those in the late stage. The sensitivity to clinical status of FACT-Ga scores were differential as four of seven FACT-Ga scores were significant for Treatment Intent while only one subscale score was significant for Clinical Stage. Six FACT-Ga scores had Cronbach's α of 0.8 or above indicating excellent reliability. For construct validity, 45 of 46 items converged about their respective subscales. The monotrait-multimethod correlations between QoL constructs of FACT-Ga and EQ-5D were stronger than the multitrait-multimethod correlations as theoretically hypothesized, suggesting good convergent and discriminant validities. CONCLUSIONS: Given the excellent reliability and good construct validity, FACT-Ga scores are able to distinguish patient groups with different clinical characteristics in the expected direction. Therefore FACT-Ga can be used as a discriminative instrument for measuring QoL of Chinese patients with GC.

A cross-sectional study evaluating health-related quality of life of Chinese pediatric patients with hematological malignancies using EQ-5D-Y.

Background: The study aimed to assess health-related quality of life (HRQoL) and to estimate the health utility of pediatric patients with hematological malignancies (HMs) in China. Method: A cross-sectional study recruited a series of pediatric inpatients diagnosed with HM from November 2018 to May 2019 in the Shanghai Children's Medical Center. Subjects were interviewed to collect sociodemographic information about themselves and their guardians. The EQ-5D-Y was completed by each patient to rate their own HRQoL, which later derived the health utility. The health status was also assessed by clinicians following the Eastern Cooperative Oncology Group (ECOG) system. Upon the descriptive analysis and univariate analysis, multivariate generalized linear models were built to explore the associations of risk factors with HRQoL measures of utility, Visual Analog Scale (VAS) score, and the five EQ-5D-Y domains. Results: The 96 subjects had a mean age of 10.5 years and included 62 (64.4%) boys. There were 46 (47.9%) and 25 (26.0%) children diagnosed with acute lymphoblastic leukemia and non-Hodgkin's lymphoma, respectively. The means (SD) of utility and EQ-VAS scores were 0.88 (0.10) and 85.8 (15.1), respectively. Twenty-six (27.1%) patients were graded poor health by the ECOG standard (score 2/3). Both univariate and multivariate analyses found strong correlations between ECOG and HRQoL. After adjusting for covariates, poor ECOG score was significantly associated with an impaired utility and VAS of -0.103 and -8.65, respectively. With regard to individual HRQoL domains, worse ECOG was more likely to report health problems with an increased risk of 2.94 to 12.50; residence, income, guardians' education, and disease duration were also found to be significantly related to either the utility or certain health domains. Conclusion: The HRQoL of Chinese pediatric patients with HM is considered relatively poor and of great concern to healthcare. With the strong correlations between EQ-5D-Y-related HRQoL measures and the traditional clinical index ECOG, the EQ-5D-Y is able to provide valuable evidence for clinical decision-making at the individual level. At the same time, its health utility can inform resource allocation at a macro level.

Willingness to pay for and willingness to vaccinate with the COVID-19 vaccine booster dose in China.

Objective: The present study aims to assess the willingness to pay (WTP) for and willingness to vaccinate (WTV) with the Coronavirus (COVID-19) vaccine booster dose in China when the pandemic is under adequate control and the majority of the population is vaccinated. This study is also to identify significant factors associated with the WTP. Methods: This was a cross-sectional study on adults with no past or present COVID-19 infection. An online questionnaire was distributed to collect data on vaccination status, quarantine experience, and factors related to health beliefs on vaccination. The WTV was assessed through the vaccination preference. The WTP was examined by payment scale (PS) and iterative bidding game (IBG) administered in random order. Three IBG algorithms with different starting-price were presented randomly. The average WTP of PS and IBG were analyzed as primary outcomes using univariate and multivariate analyses. Multivariate ordered logistic regression was performed to identify significant factors for the WTP. Results: The survey recruited 543 participants with a mean age of 32 years and 57.80% being female. The WTV rate was 86.74%, while 94.66% of participants completed full-schedule or enhanced vaccination. The mean WTP was CNY 149 (±CNY 197) and the median WTP was CNY 80. Regarding significant factors for the WTP, urban residents were 57% more likely (95% CI: 1.11-2.22) to pay for a high-priced vaccine than rural residents. Respondents who completed full-schedule vaccination were 46% more likely (95% CI: 1.03-2.07) to pay for a high-priced vaccine than those who completed enhanced vaccination. Respondents with a low household income of CNY 40k or lower were 62% less likely (95% CI: 0.21-0.66) to pay for a high-priced vaccine than those with a middle household income of CNY 110k-210k. Other significant factors associated with the WTP included the perceived benefit of vaccination and peer environmental pressure in the health belief model. Conclusion: The WTV with the COVID-19 vaccine booster dose was high in China. The WTP was influenced by the place of residence, vaccination status, household income, perceived benefit of vaccination, and environmental peer pressure. Study findings can inform policymakers to better design vaccination programs and financial schemes involving out-of-pocket payments.

Cost-effectiveness analysis of glecaprevir/pibrentasvir regimen for treating Chinese patients with chronic hepatitis C genotype 1 and genotype 2 infection.

BACKGROUND: Hepatitis C virus (HCV) infection is an important health threat in China to which direct acting antivirals (DAAs) are very effective. In 2019, another novel DAA glecaprevir/pibrentasvir (GLE/PIB) was officially approved. Knowledge of its cost-effectiveness would be informative for clinical decision-making but has not been evaluated. This study aims to evaluate the cost-effectiveness of GLE/PIB to inform policy-making on drug reimbursement and HCV eradication. METHODS: Markov models were developed from the payers' perspective and simulated the lifetime experience of adult patients chronically infected with HCV genotype 1 or genotype 2. Two regimens, GLE/PIB and pegylated interferon (pegIFN) plus ribavirin (RBV), were compared in cost and quality adjusted life years (QALY) with both outcomes being discounted to 2020 values. The incremental cost-effectiveness ratio (ICER) was computed to reflect the incremental benefit of GLE/PIB versus pegIFN + RBV. The robustness of the model outcomes was examined using deterministic and probabilistic sensitivity analysis (PSA) to identify influential parameters and to assess the probability of GLE/PIB being cost-effective. The GDP per capita in China in 2019 ($10,275) was used as the threshold for cost-effectiveness. RESULTS: For the entire target population, GLE/PIB was the dominant regimen attaining a cost-saving of $255 and 1.17 more QALYs relative to pegIFN + RBV. The finding was more pronounced for HCV genotype 1 infection by saving $1,656 and creating 1.37 more QALYs. At the $10,275 threshold, the probability of GLE/PIB being cost-effective was 99.32% overall and 99.85% for HCV genotype 1 infection. The age of starting DAA treatment, price of pegIFN + RBV, cost of cirrhosis treatment and duration of the GLE/PIB regimen were the five most influential factors. For the patients with HCV genotype 2 infection, the ICER of GLE/PIB was $12,914/QALY with 95% confidence interval of $4,047/QALY to $37,640/QALY. The GLE/PIB regimen statistically cannot be ruled out as a cost-effective option for HCV genotype 2 infection. CONCLUSIONS: GLE/PIB is a cost-effective strategy to treat chronic HCV genotype 1 and HCV genotype 2 infection in China. This regimen should be initiated at a younger age to maximize its value. To achieve national eradication, it may be timely to consider replacing pegIFN + RBV with DAAs, such as GLE/PIB, as the first-line treatment.

Cost-Effectiveness Analysis of Pan-Genotypic Sofosbuvir-Based Regimens for Treatment of Chronic Hepatitis C Genotype 1 Infection in China.

Background: Hepatitis C virus (HCV) genotype 1 is the most prevalent HCV infection in China. Sofosbuvir-based direct antiviral agent (DAA) regimens are the current mainstays of treatment. Sofosbuvir/velpatasvir (SOF/VEL) and sofosbuvir/ledipasvir (SOF/LDV) regimens became reimbursable in China in 2020. Thus, this study aimed to identify the optimal SOF-based regimen and to inform efficient use of healthcare resources by optimizing DAA use in treating HCV genotype 1. Methods and Models: A modeling-based cost-utility analysis was conducted from the payer's perspective targeting adult Chinese patients with chronic HCV genotype 1 infection. Direct medical costs and health utilities were inputted into a Markov model to simulate lifetime experiences of chronically infected HCV patients after receiving SOF/LDV, SOF/VEL or the traditional strategy of pegylated interferon (pegIFN) + ribavirin (RBV). Discounted lifetime cost and quality adjusted life years (QALYs) were computed and compared to generate the incremental cost utility ratio (ICUR). An ICUR below the threshold of 31,500 $/QALY suggests cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model findings. Results: Both SOF/LDV and SOF/VEL regimens were dominant to the pegIFN + RBV regimen by creating more QALYs and incurring less cost. SOF/LDV produced 0.542 more QALYs but cost $10,390 less than pegIFN + RBV. Relative to SOF/LDV, SOF/VEL had an ICUR of 168,239 $/QALY which did not meet the cost-effectiveness standard. Therefore SOF/LDV was the optimal strategy. These findings were robust to linear and random variations of model parameters. However, reducing the SOF/VEL price by 40% would make this regimen the most cost-effective option. Conclusions: SOF/LDV was found to be the most cost-effective treatment, and SOF/VEL was also economically dominant to pegIFN + RBV. These findings indicated that replacing pegIFN + RBV with DAA regimens could be a promising strategy.

Clinical utility of flexion-extension ratio measured by surface electromyography for patients with nonspecific chronic low-back pain.

BACKGROUND: Patients with chronic nonspecific low-back pain (CNSLBP) lack the flexion-relaxation phenomenon in full-trunk bending. This can be quantified by surface electromyography (SEMG) measurement of lumbar erector muscle. The study objective is to explore the clinical utility of the SEMG flexion-extension ratio (FER) in distinguishing patients with CNSLBP from painfree persons. METHODS: This was a comparative cross-sectional study. We adopted a balanced study design by recruiting 130 participants each for the CNSLBP and control arms. Each participant underwent dynamic SEMG measurement in full-trunk bending, which consisted of standing, flexion, relaxation, and extension. The FER ratio was the ratio of the maximum SEMG in flexion to the maximum SEMG during extension. Receiver-operating characteristic (ROC) analysis was conducted to identify optimal values of the FER and associated sensitivity, specificity, and diagnostic accuracy. RESULTS: The CNSLBP group and control group were generally comparable in terms of demographics and clinical profile. The CNSLBP group had higher SEMG amplitudes during flexion but lower SEMG during extension. The mean (SD) FER of the CNSLBP group was 0.90 (0.26), which was almost double that of controls 0.47 (0.14). The ROC curve identified an optimal FER cutoff of ≥ 0.692, for which sensitivity and specificity were 76.15% (95%confidence interval [CI], 68.14-82.66) and 98.46% (95%CI, 94.56-99.58). The diagnostic accuracy was 92.1% (95%CI, 88.70-95.54). CONCLUSION: The FER derived by lumbar muscle SEMG is able to distinguish patients with CNSLBP from pain-free people with excellent accuracy. This provides good evidence that a customized FER can be used in various clinical scenarios.

[Dihydroartemisinin down-regulates the expression of transferrin receptor in myeloid leukemia cells].

This article reports the effect of dihydroartemisinin (DHA) on transferrin receptor (TfR) in myeloid leukemia cells by establishing the model of normal iron HL60 and K562 cells and iron overload K562 cells in vitro. The TfR content of myeloid leukemia cells was determined by flow cytometry, and the effect of DHA on iron content in K562 cells was determined by atomic absorption spectrophotometric analysis. Furthermore, the inhibitory effect of DHA on the anti-proliferation and expression of TfR protein and mRNA in myeloid leukemia cells was studied. As a result, DHA effectively decreased the TfR content and down-regulated TfR protein expression in normal iron HL60 and K562 cells in a dose- and time-dependent manner and inhibited the cell proliferation. The IC50 were 1.74 and 11.33 micromol x L(-1), respectively. DHA exerted more pronounced inhibitory action on expression of TfR protein and mRNA in iron overload K562 cells. Compared to normal iron K562 cells, the TfR protein and mRNA levels were lowered by 28.1% (P < 0.01) and 26. 2% (P < 0. 05) , respectively, after DHA treatment for 48 h in iron overload K562 cells. Moreover, DHA decreased the iron content of iron overload K562 cells and inhibited the proliferation of iron overload K562 cells more potently. DHA effectively down-regulated the TfR content as well as expression of TfR protein and mRNA in normal iron myeloid leukemia cells. DHA also inhibited the proliferation of HL60 and K562 cells. The anti-proliferation effect of DHA on iron overload K562 cells was more striking.

Bioinspired Block Copolymer for Mineralized Nanoporous Membrane.

Homoporous membranes fabricated by self-assembled block copolymers (BCPs) have gained growing attention for their easy availability of well-ordered nanostructures for precise separation. However, it remains a challenges to improve the mechanical integrity, hydrophilic properties, and pore functionalities of the existing systems. To this end, we report an organic-mineral composite hybrid nanoporous BCP membrane with attractive superhydrophilicity, mechanical stability, and fouling-resistance derived from a bioinspired block copolymer, poly(propylene carbonate)- block-poly(4-vinylcatechol acetonide) (PPC- b-PVCA). The key advances include the following. (1) The PPC minor block is qualified as sacrificial domain because of its alkali sensitivity for generating monodisperse nanopores. (2) The PVCA matrix block contains the catechol groups, which enables the formation of inorganic layer  via a biomineralization process, thus producing an organic-mineral composite nanoporous BCP membrane with attractive superhydrophilicity, mechanical stability, and fouling resistance. A ∼200 nm thickness BCP film with monodisperse through-pores of 12 nm diameter cylinders oriented perpendicularly to a supporting microfiltration membrane is fabricated by sequential blade-casting, solvent annealing, hydrolysis sacrificial block, and biomineralization process. The mechanical stability, high water flow (114 L m-2 h-1 bar-1), size fractionation of nanoparticles, as well as protein antiadsorption performance make the strategy provided here hold the promise of affording an advance platform for filtration, catalysis, and drug delivery.

Evaluating health-related quality of life impact of chronic conditions among older adults from a rural town in Suzhou, China.

This study aimed to estimate the loss of health-related quality of life (HRQOL) associated with common chronic conditions in older Chinese population.Weitang Geriatric Diseases Study is a community-based health survey on 5557 Chinese aged 60 years or older. The study population was measured with EQ-5D-3L for HRQOL assessment. We also assessed the coexisting chronic conditions of depression, cognitive dysfunction, stroke, heart disease, diabetes, hypertension, obesity, hyperlipidemia and visual impairment based on self-completed questionnaires, biomarkers and medical records. Ordinary Least Square regression was performed to model the relationship between the conditions and the EQ-5D-3L index scores. The robust standard error (RSE) estimator was adopted to calculate 95% confidence interval (CI) for coefficients. The mean EQ-5D-3L representing overall HRQOL was 0.954 (standard deviation: 0.081) with 70% of participants reporting full health. After controlling for socio-demographic characteristics and comorbidities, depression, stroke, heart disease and cognitive dysfunction had significantly adverse impact on the EQ-5D index score. The respective coefficients (95% CI) of each condition were -0.191 (-0.233, -0.150), -0.052 (-0.086, -0.019), -0.019 (-0.029, -0.010), and -0.016 (-0.024, -0.008). Chronic conditions were found to contribute to HRQOL loss in older Chinese population. The utility and utility decrement estimated can be used for quality-adjusted life-year calculation.

Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells.

Artesunate (ART), a semi-synthetic derivative of artemisinin extracted from the Chinese herb Artemisia annua, is a safe and effective antimalarial drug. In the present investigation, we analyzed the inhibitory effects of ART on angiogenesis and on VEGF production in chronic myeloid leukemia (CML) K562 cells in vitro and in vivo. In order to analyze the effect of ART on VEGF secretion in K562 cells, we examined the level of VEGF secreted in conditioned media (CM) by ELISA assay. The result showed that ART could decrease the VEGF level in CM of K562 cells, even at a lower concentration (2 micromol/l, P<0.01). The inhibitory effect of in vitro angiogenesis was tested on aortic sprouting in fibrin gel. ART could effectively suppress the stimulating angiogenic ability of CM by pretreated with K562 cells for 48 h in a time-dependent manner (days 3-14). The antiangiogenic effect of ART was further evaluated in vivo in chicken chorioallantoic membrane (CAM) neovascularization model. The result indicated that the stimulating angiogenic activity was decreased in response to the K562 cells treated with ART or the CM from K562 cells pretreated with ART in a dose-dependent manner (3-12 micromol/l). Furthermore, we analyzed the level of VEGF expression by western blot and detected the form of VEGF mRNA by RT-PCR in K562 cells. The experiments showed that ART could inhibit the VEGF expression, correlated well with the level of VEGF secreted in CM. These findings suggest that ART might present potential antileukemia effect as a treatment for CML therapy, or as an adjunct to standard chemotherapeutic regimens.