Analyzing the occupational exposure risks of dental healthcare workers from the perspective of repeated occupational exposure.

Background: Healthcare workers in dental hospitals frequently experience repeated occupational exposures (ROEs). In our study, we aim to analyze these repeated exposures among dental healthcare workers (DHWs), assess the risk levels of different risk factors, and explore the significance of ROE data for infection control in dental hospitals.

Methods: Based on hospital statistical data, we categorized the occupational exposure incidents at West China Hospital of Stomatology over the past seven years into initial and repeated exposures.

A systematic review and meta-analysis of the morbidity of efficacy endpoints and bleeding events in elderly and young patients treated with the same dose rivaroxaban.

Rivaroxaban is a new direct oral anticoagulant, and the same dose is recommended for older and young patients. However, recent real-world studies show that older patients may need dose adjustment to prevent major bleeding. At present, the evidence for dose adjustment in older patients is extremely limited with only a few reports on older atrial fibrillation patients.

High temperature shock threatens methane production via disturbing microbial interactions in anaerobic digestion.

Operational strategies shape microbial interactions determining anaerobic digesting process, but it is unclear whether and how the microbial network properties impact gas generation, especially in the transitional stage after operations. This research examined how the high temperature shock affected microbial diversity and network traits connected with the biogas production in a swine manure-fed anaerobic digester. Rising temperature (from 35 °C to 50 °C) significantly reduced biogas and methane production (p < 0.

Innovative Design and Analysis for PK/PD Biosimilar Bridging Studies with Multiple References.

When there are multiple reference products, (e.g., EU-approved product and US-licensed product), a pharmacokinetic/pharmacodynamic (PK/PD) bridging study is often conducted in order to bridge the clinical data from the original region (e.

Chitosan-based multifunctional flexible hemostatic bio-hydrogel.

Realizing the potential application of chitosan as an effective biomedical hemostatic agent has become an emerging research hotspot. However, fabricating a flexible chitosan-based hemostatic bio-hydrogel with self-adhesion feature in humid conditions and rapid hemostasis capability remains a challenge. Herein, we reported the development of chitosan-based hydrogels (DCS-PEGSH gels) with typical multilevel pore structures, which were cross-linked by 3-(3,4-dihydroxyphenyl) propionic acid-modified chitosan (DCS) and sebacic acid-terminated polyethylene glycol modified by p-hydroxybenzaldehyde (PEGSH).

A mussel-inspired flexible chitosan-based bio-hydrogel as a tailored medical adhesive.

The significant progress in efforts to design hydrogel adhesive mimicking mussels' functions has been witnessed in recent years. However, it is still an arduous challenge to fabricate self-adhesive hydrogel adhesive that tradeoff of exalting features containing scalability, self-healing, degradability, biocompatibility, and antibacterial properties. Herein, we manufactured a multi-functional physical hydrogel adhesive by integrating catechol groups modified chitosan and polyvinyl alcohol (PVA).

The use of real-world data/evidence in regulatory submissions.

The 21st Century Cures Act passed by the United States (US) Congress in December 2016 requires the US Food and Drug Administration (FDA) shall establish a program to evaluate the potential use of real-world evidence (RWE) which is generated from real-world data (RWD) to (i) support approval of new indication for a drug approved under section 505 (c) and (ii) satisfy post-approval study requirements. RWE offers the opportunities to develop robust evidence using high-quality data and sophisticated methods for producing causal-effect estimates regardless randomization is feasible. In this article, we have demonstrated that the assessment of treatment effect (RWE) based on RWD could be biased due to the potential selection and information biases of RWD.

A robust regenerated cellulose-based dual stimuli-responsive hydrogel as an intelligent switch for controlled drug delivery.

Constructing robust hydrogels with biodegradability and dual stimuli-responsive by utilizing natural polymer as raw materials remains a sustaining challenge. Herein, we proposed an interpenetrating strategy in which N-isopropyl acrylamide (NIPAM) and acrylamide (AM) block copolymers were introduced as the second network into the carboxymethyl cellulose single network gel (CMC gel) to construct a dual-network robust hydrogel (CMC/PNIPAM-co-PAM). The dual-network design strategy effectively improves the mechanical strength of CMC gel.

Composited Gels from Nature Growing Scaffold: Synthesis, Properties, and Application.

As a nature ultralight, well-aligned porous and anisotropy feedstock, cornstalk pith (CSP) has not been exploited for material design. Herein, we use CSP as substrate to prepare multifunctional elastic composite gels. First, CSP is pretreated by ferric chloride then immersed in an unsaturated monomer solution, following by a polymerization to form enhanced networks.

Practical Issues in Clinical Inspection Process.

Regulatory inspection of clinical trial is necessary in order for (1) assessing compliance with statutory requirements and regulatory requirement governing the conduct of clinical trials and (2) verifying the accuracy and reliability of clinical trial data submitted to regulatory agencies such as the United States Food and Drug Administration (FDA) in support of research or marketing applications. This article provides an overview of clinical inspection process and issues that are commonly encountered during the conduct of clinical trials. In addition, a couple of sampling plans for clinical inspection of relatively large trials are proposed.

On evaluation of consistency in multi-regional clinical trials.

In recent years, multi-regional clinical trials (MRCT) that conduct clinical trials simultaneously in Asian Pacific region, Europe, and the United States have become very popular for global pharmaceutical development. The main purpose of multi-regional clinical trials is to shorten the time for pharmaceutical development and regulatory submission, and approval around the world. In practice, however, clinical results observed from some regions (sub-population) may not be consistent with the results from other regions and/or all regions combined (entire population).

On hybrid parallel-crossover designs for assessing drug interchangeability of biosimilar products.

In recent years, a specific hybrid parallel-crossover design that consists of two sequences of treatments, namely R-R-R-R and R-T-R-T, where T and R is a proposed biosimilar product and an innovative biological product, respectively, have been proposed and received much attention for assessing drug interchangeability between T and R, where R could be either a US-licensed product or an EU-reference product. In practice, there are three types of hybrid parallel-crossover designs that are commonly employed in assessing drug interchangeability of biosimilar products. These three types of parallel-crossover hybrid designs include (1) a parallel + 2 × 2 crossover design, (2) a parallel + 2 × 3 crossover design, and (3) a parallel + 2 × 4 crossover design.

Sample size requirement in analytical studies for similarity assessment.

For the assessment of biosimilar products, the FDA recommends a stepwise approach for obtaining the totality-of-the-evidence for assessing biosimilarity between a proposed biosimilar product and its corresponding innovative biologic product. The stepwise approach starts with analytical studies for assessing similarity in critical quality attributes (CQAs), which are relevant to clinical outcomes at various stages of the manufacturing process. For CQAs that are the most relevant to clinical outcomes, the FDA requires an equivalence test be performed for similarity assessment based on an equivalence acceptance criterion (EAC) that is obtained using a single test value of some selected reference lots.

On safety margin for drug interchangeability.

As more and more generic (or biosimilar) drug products become available in the market place, it is a concern whether the approved generic (or biosimilar) drug products are safe and efficacious and hence can be used interchangeably. According to current regulation, most regulatory agencies such as the United States Food and Drug Administration (FDA) indicate an approved generic (or biosimilar) drug product can serve as a substitute for the innovative drug product. Bioequivalence (biosimilarity) assessment for regulatory approval among generic copies (or biosimilars) of the innovative drug product are not required.

On the evaluation of reliability, repeatability, and reproducibility of instrumental evaluation methods and measurement systems.

Validation of instrumental evaluation methods or measurement systems plays an important role in both pharmaceutical and cosmetic research and development. In practice, it is suggested that validation should be performed according to performance characteristics as described in the United States Pharmacopedia and National Formulary (USP/NF, 2000) for analytical methods validation. A validated method or measurement system is expected to achieve a certain degree of accuracy and reliability.

Analytical Similarity Assessment in Biosimilar Studies.

For assessment of biosimilarity, the US Food and Drug Administration (FDA) recommends a stepwise approach for obtaining the totality-of-the-evidence for demonstrating biosimilarity between a proposed biosimilar product and an innovative (reference) biological product. The stepwise approach starts with analytical studies for functional and structural characterization at various stages of manufacturing process of the proposed biosimilar product. Analytical similarity assessment involves identification of critical quality attributes (CQAs) that are relevant to clinical outcomes.

Some thoughts on drug interchangeability.

Current regulation for generic approval is based on the assessment of average bioequivalence. As indicated by the United States Food and Drug Administration (FDA), an approved generic drug can be used as a substitute for the innovative drug. FDA does not indicate that two generic copies of the same innovative drug can be used interchangeably even though they are bioequivalent to the same brand-name drug.