The impact of drug shortages on drug prices: evidence from China.

Introduction: Drug shortages pose a serious global public health challenge, affecting China and other countries. Evidence from USA shows that short-supplied drugs demonstrated a very high price growth during and after a shortage. However, the effect of shortages on drug prices in China remains unknown. This paper aims to understand the impact of drug shortages on prices and explore implications for shortage prevention policy. Methods: We collected the purchase prices and delivery rates of 120 drugs from April 2019 to December 2021 across whole China. We examined price progression of affected drugs using linear mixed-effects models and performed subgroup analyses based on the number of manufacturers and the severity of shortage. Results: Non-shortage cohort had an annual price growth of 11.62% (95% confidence interval [CI] 8.34 to 14.98). Shortage cohort demonstrated an annual price growth of 8.08% (95%CI 0.12 to 16.77) in the period preceding a shortage, 27.57% (95%CI 6.17 to 52.87) during a shortage, and 9.38% (95%CI -12.64 to 36.39) in the post-shortage period. Drug shortages' impact on prices varied across subgroups. Compared with that of drug markets supplied by a single manufacturer, the price growth rate of markets supplied by more than one manufacture declined more after the shortage resolution. Conclusion: Shortages resulted in significant price increases of study markets, especially the low-priced markets, while the shortage resolution slowed the growth. The primary shortage driver has shifted from the low price to others drivers, such as unavailability of active pharmaceutical ingredients. For currently sole-supplied drugs, the expedited review of applications from other manufacturers should be considered.

Comprehensive assessment of river ecological environment in nature reserve based on TOPSIS combined with grey correlation method.

The main driving factors of river ecological environment were analyzed to reveal the response mechanism of river ecosystem to ecological environmental factors. The results showed that the driving factors of river water quality were resistivity, COD and reoxidation potential, the driving factors of soil environment along river banks were total phosphorus, total nitrogen and pH, and the driving factors of plant nutrition along river banks were total potassium and total nitrogen. The contribution rates of water quality, soil and plant to river ecological environment health were 43, 51 and 70%, respectively. The comprehensive ecological environment of Menghuo River, Gongyihai, Arulendi River, Yiniu River, Dahonggou River and Nanya River is superior to each other, with the comprehensive proximity index of 0.6258, 0.5908, 0.5524, 0.5265, 0.5195 and 0.3889, respectively. Each detection index can accurately and truly invert the ecological environment health status of rivers in the protected areas.

How does digital finance affect green technology innovation in the polluting industry? Based on the serial two-mediator model of financing constraints and research and development (R&D) investments.

This paper evaluates the importance of combining digital finance with conventional finance and information technology (IT) to bring new opportunities for green technology innovation and transformation within polluting industries. This study builds a theoretical framework "digital finance → financing constraints → R&D investment → green technology innovation" to demonstrate the causal mechanism between digital finance and firms' green innovation by using the serial two-mediator model. The study shows that digital finance could reduce financial constraints and increase R&D investments, thereby improving enterprises' green technology innovation in the long run. Moreover, based on the moderating effect model, we find that digital transformation in a polluting firm tends to strengthen the linkage between digital finance and green technology innovation through supervising the use of loans, reviewing green technology innovation projects, and reducing managers' short-sighted behaviors to avoid agency problems. Furthermore, the heterogeneity analysis shows that the effects of digital finance on green innovation are more apparent in state-owned enterprises and the regions with lower financial development and with higher financial supervision.

Non-Invasive Skin Imaging Assessment of Human Stress During Head-Down Bed Rest Using a Portable Handheld Two-Photon Microscope.

Spaceflight presents a series of physiological and pathological challenges to astronauts resulting from ionizing radiation, microgravity, isolation, and other spaceflight hazards. These risks cause a series of aging-related diseases associated with increased oxidative stress and mitochondria dysfunction. The skin contains many autofluorescent substances, such as nicotinamide adenine dinucleotide phosphate (NAD(P)H), keratin, melanin, elastin, and collagen, which reflect physiological and pathological changes in vivo. In this study, we used a portable handheld two-photon microscope to conduct high-resolution in vivo skin imaging on volunteers during 15 days of head-down bed rest. The two-photon microscope, equipped with a flexible handheld scanning head, was used to measure two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) images of the left forearm, left front chest, and forehead of volunteers. Changes in TPEF, SHG, and the extended SHG-to-AF(TPEF) aging index of the dermis (SAAID) were measured. It was found that TPEF intensity increased during bed rest and was restored to normal levels after recovery. Meanwhile, SHG increased slightly during bed rest, and the skin aging index increased. Moreover, we found the skin TPEF signals of the left forearm were significantly negatively associated with the oxidative stress marker malondialdehyde (MDA) and DNA damage marker 8-hydroxy-2'-desoxyguanosine (8-OHdG) values of subjects during head-down bed rest. Meanwhile, the SHG signals were also significantly negatively correlated with MDA and 8-OHDG. A significant negative correlation between the extended SAAID of the left chest and serum antioxidant superoxide dismutase (SOD) levels was also found. These results demonstrate that skin autofluorescence signals can reflect changes in human oxidant status. This study provides evidence for in-orbit monitoring of changes in human stress using a portable handheld two-photon microscope for skin imaging.

Comparison of yield and relative costs of different screening algorithms for tuberculosis in active case-finding: a cross-section study.

BACKGROUND: Part of tuberculosis (TB) patients were missed if symptomatic screening was based on the main TB likely symptoms. This study conducted to compare the yield and relative costs of different TB screening algorithms in active case-finding in the whole population in China. METHODS: The study population was screened based on the TB likely symptoms through a face-to-face interview in selected 27 communities from 10 counties of 10 provinces in China. If the individuals had any of the enhanced TB likely symptoms, both chest X-ray and sputum tests were carried out for them furtherly. We used the McNemar test to analyze the difference in TB detection among four algorithms in active case-finding. Of four algorithms, two were from WHO recommendations including 1a/1c, one from China National Tuberculosis Program, and one from this study with the enhanced TB likely symptoms. Furthermore, a two-way ANOVA analysis was performed to analyze the cost difference in the performance of active case-finding adjusted by different demographic and health characteristics among different algorithms. RESULTS: Algorithm with the enhanced TB likely symptoms defined in this study could increase the yield of TB detection in active case-finding, compared with algorithms recommended by WHO (p < 0.01, Kappa 95% CI: 0. 93-0.99) and China NTP (p = 0.03, Kappa 95% CI: 0.96-1.00). There was a significant difference in the total costs among different three algorithms WHO 1c/2/3 (F = 59.13, p < 0.01). No significant difference in the average costs for one active TB case screened and diagnosed through the process among Algorithms 1c/2/3 was evident (F = 2.78, p = 0.07). The average costs for one bacteriological positive case through algorithm WHO 1a was about two times as much as the costs for one active TB case through algorithms WHO 1c/2/3. CONCLUSIONS: Active case-finding based on the enhanced symptom screening is meaningful for TB case-finding and it could identify more active TB cases in time. The findings indicated that this enhanced screening approach cost more compared to algorithms recommend by WHO and China NTP, but the increased yield resulted in comparative costs per patient. And it cost much more that only smear/bacteriological-positive TB cases are screened in active case-finding.

Adverse events in Chinese human immunodeficiency virus (HIV) patients receiving first line antiretroviral therapy.

BACKGROUND: Although the global human immunodeficiency virus (HIV) epidemic has improved significantly due to antiretroviral treatment (ART), ART-related adverse events (AEs) remain an issue. Therefore, investigating the factors associated with ART-related AEs may provide vital information for monitoring risks. METHODS: A prospective cohort study was conducted among adult patients (aged 18 years or older) with HIV who received Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV) as first-line ART regimens. All AEs during the first 12 months of therapy were recorded. Logistic regression analysis was used to identify variables associated with AEs. RESULTS: Four hundred seventy-four patients receiving TDF+ 3TC+ EFV ART regimens between March 2017 and October 2017 were included in the study analysis. Among them, 472 (99.6%) experienced at least one AE, 436 (92.0%) patients experienced at least one AE within 1 month of treatment, 33 (7.0%) between one and 3 months of treatment, and three (0.6%) patients after 3 months of treatment. The most commonly reported AE was nervous system (95.6%) related, followed by dyslipidemia (79.3%), and impaired liver function (48.1%). Patients with baseline body mass index (BMI) greater than 24 kg/m2 (adjusted OR 1.77, 95%CI 1.03-3.02), pre-existing multiple AEs (adjusted OR 2.72, 95%CI 1.59-4.64), and pre-existing severe AEs (adjusted OR 5.58, 95%CI 2.65-11.73) were at increased odds of developing a severe AE. Patients with baseline BMI greater than 24 kg/m2 (adjusted OR 2.72, 95%CI 1.25-5.89) were more likely to develop multiple AEs. CONCLUSION: The incidence of ART-related adverse events over a 12-month period in China was high. Baseline BMI greater than 24 kg/m2, pre-existing multiple AEs, and pre-existing severe AEs were shown to be independent risk factors for developing a severe AE.

Estimation of stress distribution in ferromagnetic tensile specimens using low cost eddy current stress measurement system and BP neural network.

Estimation of the stress distribution in ferromagnetic components is very important for evaluating the working status of mechanical equipment and implementing preventive maintenance. Eddy current testing technology is a promising method in this field because of its advantages of safety, no need of coupling agent, etc. In order to reduce the cost of eddy current stress measurement system, and obtain the stress distribution in ferromagnetic materials without scanning, a low cost eddy current stress measurement system based on Archimedes spiral planar coil was established, and a method based on BP neural network to obtain the stress distribution using the stress of several discrete test points was proposed. To verify the performance of the developed test system and the validity of the proposed method, experiment was implemented using structural steel (Q235) specimens. Standard curves of sensors at each test point were achieved, the calibrated data were used to establish the BP neural network model for approximating the stress variation on the specimen surface, and the stress distribution curve of the specimen was obtained by interpolating with the established model. The results show that there is a good linear relationship between the change of signal modulus and the stress in most elastic range of the specimen, and the established system can detect the change in stress with a theoretical average sensitivity of -0.4228 mV/MPa. The obtained stress distribution curve is well consonant with the theoretical analysis result. At last, possible causes and improving methods of problems appeared in the results were discussed. This research has important significance for reducing the cost of eddy current stress measurement system, and advancing the engineering application of eddy current stress testing.

[Staged retrograde flexible ureteroscopic lithotripsy versus miniaturized percutaneous nephrolithotomy for renal stones of 2-4 cm in diameter: a randomized controlled trial].

OBJECTIVE: To compare the efficacy and safety of staged retrograde flexible ureteroscopic lithotripsy (FURS) and miniaturized percutaneous nephrolithotomy (m-PCNL) for treatment of renal stones of 2-4 cm in diameter. METHODS: This randomized controlled trial was conducted in 70 patients with renal stones of 2-4 cm in diameter admitted in our hospital between January 2013 and December 2015. The patients were randomized to receive staged FURS (35 cases) or m-PCNL (35 cases), and the total treatment time, total hospital stay after procedure, total medical cost, treatment success, decrease in hemoglobin level and complications were compared between the two groups. RESULTS: The treatment success rate was 100% in both groups, but the complete stone-free rate was significantly lowered in FURS group than m-PCNL group (65.71% vs 94.29%, P<0.01). The average decrease in hemoglobin level was 3.37∓1.56 g/L in FURS group and 11.93∓2.24 g/L in m-PCNL group (P<0.01). The overall complication rates in the two groups were 6.25% and 9.37%, respectively (P>0.05). Minor complications (grade I by Clavien-Dindo classification) occurred in one case in FURS group (fever) and two cases in m-PCNL group (self-limiting hematuria); major complications (grade II) occurred in one case in FURS group (steinstrase) and one case in m-PCNL group (blood transfusion). In staged FURS and m-PCNL groups, the mean total treatment time was 4.06∓1.11 vs 1.26∓0.47 weeks (P<0.01), the mean hospital stay after procedure was 3.66∓1.29 vs 5.13∓0.43 days (P<0.01), and the mean total medical cost was 54 291.00 RMB ∓6149.00 vs 23 482.00 RMB ∓2317.00 (P<0.01), respectively. CONCLUSION: FURS is safe and effective for treatment of renal stones of 2-4 cm in diameter, and a staged procedure is necessary to achieve a stone-free status for large calculi. Both sophisticated equipment and rich surgical experience are essential to ensure treatment success.

Local recurrence following mastectomy and autologous breast reconstruction: incidence, risk factors, and management.

BACKGROUND: Breast reconstruction (BR), including autologous breast reconstruction (ABR) after mastectomy (MST), has been gaining popularity all around the world, especially in the People's Republic of China during the past decade. However, there is a small proportion, but a significant number, of patients who develop local recurrence (LR) of breast cancer postoperatively. The purpose of this study is to examine the incidence of LR, discuss risk factors associated with LR, and management of LR following MST and ABR. METHODS: A total of 397 patients who underwent MST and ABR after diagnosis of breast cancer were included in this retrospective study. Data were analyzed by the Kaplan-Meier method, the log-rank statistical test, and Cox proportional hazards model. RESULTS: From January 1999 to December 2011, 400 ABRs were performed in 397 patients in Fudan University Shanghai Cancer Center. The median follow-up time in the study was 3.6 years. LR occurred in 11 of 397 patients, with a median time to LR of 2.9 years. In univariate and multivariate analyses, tumor stage, hormonal therapy (yes or no), and tumor type (multifocal or nonmultifocal) were significantly associated with LR after ABR following MST. CONCLUSION: ABR is an oncologically safe surgical procedure with an acceptable LR rate of 2.8%. Risk factors associated with high rate of LR were higher tumor stage, absence of hormonal therapy, and multifocal tumor type.

Validation of the laparoscopically stapled approach as a standard technique for left lateral segment liver resection.

BACKGROUND: Left lateral sectionectomy (LLS) is the most common type of anatomic laparoscopic liver resection performed, accounting for 20 % of all laparoscopic hepatectomies. Because there has been no standardized surgical technique for laparoscopic left lateral sectionectomy (LLLS), we offer an established operation: laparoscopically stapled left lateral sectionectomy (LSLLS). Our aim was to perform a case-controlled study of LSLLS with traditional (without vascular staplers) laparoscopic left lateral sectionectomy (TLLLS), validating the standardization and reproducibility of LSLLS. METHODS: From February 2009 to December 2011, a total of 49 LSLLSs were performed. The results were compared with 33 cohort-matched TLLLSs from an earlier time period. Ordered sample cluster analysis was used to determine the learning curve of LSLLS based on the operating time and blood loss. RESULTS: All LSLLS were performed successfully. There were no conversions to laparotomy or hand-assisted laparoscopic resection. Two endoscopic linear staplers were used in each case. Despite a higher hospital cost ($10,892 ± $944 vs. $8,962 ± $943, p < 0.05), LSLLS compared favorably with TLLLS regarding operating time (103 ± 21 vs. 151 ± 32 min, p < 0.05) and blood loss (70.8 ± 41.6 vs. 173.3 ± 131.1 ml, p < 0.05). No specific complications related to laparoscopy were observed. Ordered sample cluster analysis demonstrated a learning curve of 18 cases for LSLLS. CONCLUSIONS: This study demonstrates the standardization and reproducibility of LSLLS. We therefore propose LSLLS as the standard technique for lesions located in the left lateral section of the liver.