Potentially inappropriate medications among older patients with Parkinson's disease: a cross-sectional analysis of a national health insurance database in China.

BACKGROUND: With the rapid aging trend of China's population, the issue of drug rational use in older adults has become more and more prominent. Parkinson's disease (PD) is the one of the most common age-related neurodegenerative disorders. Pharmaceutical treatment plays a cardinal role in alleviating motor and non-motor symptoms to improve the quality of life of patients with PD. Patients with PD have complex medical needs yet little is known about the use of potentially inappropriate medications (PIM) among them in China. We quantify the prevalence of PIM use and identify its predictors among older persons with PD in China. METHODS: We conducted a cross-sectional analysis using a national representative database of all medical insurance beneficiaries across China, extracting records of ambulatory visits of older adults with PD between 2015 and 2017. Beneficiaries aged 65 and above were eligible for inclusion. The prevalence of patients exposed to overall PIMs and PIMs related to motor and cognitive impairment was calculated based on Beers Criteria 2015 version. Potential predictors of PIM concerning patients' characteristics were estimated using multivariate logistic regression. RESULTS: A total of 14,452 older adults with PD were included. In total, 8,356 (57.8%) patients received at least one PIM; 2,464 (17.1%) patients received at least one motor-impairing PIM and 6,201 (42.9%) patients received at least one cognition-impairing PIM. The prevalence of overall PIM use was higher in patients of older age group (54.7% [65-74] vs. 59.5% [75-84; OR, 1.22; 95% CI, 1.14-1.31] vs.65.5% [≥ 85; OR, 1.58; 95% CI, 1.38-1.80) and females (61.4% [female] vs. 55.0% [males; OR, 0.77; 95% CI, 0.72-0.82). CONCLUSIONS: Prescribing PIMs for older adults with PD was common in China, especially for females and older age groups, yet younger patients were more inclined to be prescribed with motor or cognition-impaired PIMs. Our findings represent a clear target awaiting multidimensional efforts to promote the rational prescribing of medications for this vulnerable population.

Appropriate use of antibiotics for acute respiratory infections at primary healthcare facilities in China: a nationwide cross-sectional study from 2017 to 2019.

Background: The appropriateness of antibiotic use for acute respiratory infections (ARIs) in Chinese primary healthcare facilities (PHFs) remained uncertain. We aimed to evaluate to what degree antibiotic prescribing for ARIs were aligned with guideline recommendations in primary settings across China. Methods: We collected outpatient prescriptions from 262 Chinese PHFs in 27 cities of six provinces between 2017 and 2019. The appropriate antibiotic prescribing was defined as prescribing antibiotic classes that were recommended by Chinese clinical guidelines, if patients were prescribed antibiotics. We evaluated the magnitude of antibiotics prescribed for acute upper respiratory infections (AURIs), acute bronchitis, and community-acquired pneumonia (CAP) and their appropriateness. Findings: Overall, 55.1% (87,684/159,150), 66.8% (30,836/46,153), and 68.5% (4615/6733) of outpatients with AURIs, acute bronchitis, and CAP treated at PHFs in China were prescribed with antibiotics. Of all antibiotic prescriptions, only 20.0% (17,542/87,684), 18.6% (5724/30,836) and 69.6% (3211/4615) used antibiotic classes that were recommended by the guidelines for AURIs, acute bronchitis, and CAP, respectively. Patients residing in the Chinese central region (17.0%, 15.4%, 69.3% for AURIs, acute bronchitis, and CAP, respectively) were less likely to be prescribed with antibiotics that were appropriately selected. Interpretation: Unnecessary antibiotics were widely prescribed for patients with AURIs or acute bronchitis and most patients with ARIs did not receive guideline-recommended antibiotic classes in Chinese PHFs. Interventions to promote evidence-based treatment and the appropriate use of antibiotics are urgently needed at the primary level across China. Funding: This work was supported by the National Natural Science Foundation of China [grant number 72074007, 81973294].

Correlation between clinical trial endpoints of marketed cancer drugs and reimbursement decisions in China.

Objective: This study aimed to assess whether different clinical trial endpoints in pivotal trials of cancer drugs were associated with reimbursement decisions in China. Materials and methods: Cancer drugs marketed before June 30th, 2021 with publicly available technical review reports for application of drug registration on Center for Drug Evaluation (CDE) website were reviewed. The trial design characteristics and relevant clinical outcomes [e.g., overall survival (OS), progression-free survival (PFS) and objective response rate (ORR)] were extracted from the technical review reports, while the reimbursement decisions were reviewed from National Healthcare Security Administration (NHSA) website. The differences in trial characteristics and clinical outcomes between drugs with positive reimbursement decisions and negative ones were compared by hypothesis test (Pearson's chi-squared test, Fisher's exact test, independent samples t-test and Mann-Whitney U test). The correlation between different clinical trial endpoints and reimbursement decisions was analyzed by multivariate logistic regression. Results: There were 112 cancer drug indications included in this study. Among these indications, 76 received a positive reimbursement decision, and the most common primary endpoints of them were PFS (42.1%) and ORR (30.3%). Taking PFS (OR = 7.333) and ORR (OR = 5.271) as the primary endpoints were more likely to receive a positive reimbursement decision compared with OS (P = 0.003). The proportion of drugs marketed with phase I (75.0%) and phase II (85.7%) clinical trials receiving positive reimbursement decisions are significantly higher than those marketed with phase III clinical trials (61.3%, P = 0.043). The magnitude of clinical benefit only had subtle influences (Prisk benefit - OS = 0.627, Prisk benefit - PFS = 0.087, Psurvival benefit - OS = 0.545, Psurvival benefit - PFS = 0.189) on the drug reimbursement decisions, however, the drug prices and clinical needs also made a difference on that. Conclusion: This study found that, in Chinese drug price negotiations from 2017 to 2021, policymakers have focused more on meeting clinical needs and filling therapeutical gaps in National Reimbursement Drug List (NRDL), while requirements for the selection of primary endpoints, clinical trial phases, and clinical benefits have been reduced. In the future, emphasis should be put on the use of surrogate endpoints and clinical benefits.

Turbostratic Boron-Carbon-Nitrogen and Boron Nitride by Flash Joule Heating.

Turbostratic layers in 2D materials have an interlayer misalignment. The lack of alignment expands the intrinsic interlayer distances and weakens the optical and electronic interactions between adjacent layers. This introduces properties distinct from those structures with well-aligned lattices and strong coupling interactions. However, direct and rapid synthesis of turbostratic materials remains a challenge owing to their thermodynamically metastable properties. Here, a flash Joule heating (FJH) method to achieve bulk synthesis of boron-carbon-nitrogen ternary compounds with turbostratic structures by a kinetically controlled ultrafast cooling process that takes place within milliseconds (103  to 104 K s-1 ) is reported. Theoretical calculations support the existence of turbostratic structures and provide estimates of the energy barriers with respect to conversion into the corresponding well-aligned counterparts. When using non-carbon conductive additives, a direct synthesis of boron nitride is possible. The turbostratic nature facilitates mechanical exfoliation and more stable dispersions. Accordingly, the addition of flash products to a poly(vinyl alcohol) nanocomposite film coating a copper surface greatly improves the copper's resistance to corrosion in 0.5 m sulfuric acid or 3.5 wt% saline solution. FJH allows the use of bulk materials as reactants and provides a rapid approach to large quantities of the hitherto hard-to-access turbostratic materials.

Porphyrin-based donor-acceptor COFs as efficient and reusable photocatalysts for PET-RAFT polymerization under broad spectrum excitation.

Covalent organic frameworks (COFs) are crystalline and porous organic materials attractive for photocatalysis applications due to their structural versatility and tunable optical and electronic properties. The use of photocatalysts (PCs) for polymerizations enables the preparation of well-defined polymeric materials under mild reaction conditions. Herein, we report two porphyrin-based donor-acceptor COFs that are effective heterogeneous PCs for photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT). Using density functional theory (DFT) calculations, we designed porphyrin COFs with strong donor-acceptor characteristics and delocalized conduction bands. The COFs were effective PCs for PET-RAFT, successfully polymerizing a variety of monomers in both organic and aqueous media using visible light (λ max from 460 to 635 nm) to produce polymers with tunable molecular weights (MWs), low molecular weight dispersity, and good chain-end fidelity. The heterogeneous COF PCs could also be reused for PET-RAFT polymerization at least 5 times without losing photocatalytic performance. This work demonstrates porphyrin-based COFs that are effective catalysts for photo-RDRP and establishes design principles for the development of highly active COF PCs for a variety of applications.