Economic evaluations in the treatment and evaluation of patients with periodontal disease: A critical review.

AIM: To evaluate the types and quality of reporting of economic evaluations carried out in the clinical management of periodontal disease over 32 years from 1987 to 2019. MATERIAL AND METHODS: A systematic search of articles from 1987 to 2019 was conducted using PubMed, Web of Science, The Cochrane Central Register of Controlled Trials, Health Technology Assessment Database and Embase. The quality of the economic evaluations was assessed based on the Consolidated Health Economic Evaluation Reporting Standard checklist. Due to considerable between-study heterogeneity, a meta-analysis was not performed. RESULTS: Twenty one publications were included. 11 studies used cost-effectiveness analysis, five used cost-minimization analysis, four used cost-utility analysis and two used cost-benefit analysis. Comparators, choice of health outcomes, estimating resources and costs were fully reported in all studies. Many studies had inadequate reporting in terms of estimating resources and costs, choice of health outcomes, characterizing heterogeneity and study perspective. CONCLUSIONS: There has been an increase in health economics studies in the field of clinical periodontology over the past decade. Several studies did not report study perspective, and the health outcomes chosen were not relevant for some studies. Future studies should follow an economic evaluation checklist for high-quality reporting and consistency.

Nonviral Gene Delivery with Cationic Glycopolymers.

The field of gene therapy, which aims to treat patients by modulating gene expression, has come to fruition and has landed several landmark FDA approvals. Most gene therapies currently rely on viral vectors to deliver nucleic acid cargo into cells, but there is significant interest in moving toward chemical-based methods, such as polymer-based vectors, due to their low cost, immunocompatibility, and tunability. The full potential of polymer-based delivery systems has yet to be realized, however, because most polymeric transfection reagents are either too inefficient or too toxic for use in the clinic. In this Account, we describe developments in carbohydrate-based cationic polymers, termed glycopolymers, for enhanced nonviral gene delivery. As ubiquitous components of biological systems, carbohydrates are a rich class of compounds that can be harnessed to improve the biocompatibility of non-native polymers, such as linear polyamines used for promoting transfection. Reineke et al. developed a new class of carbohydrate-based polymers called poly(glycoamidoamine)s (PGAAs) by step-growth polymerization of linear monosaccharides with linear ethyleneamines. These glycopolymers were shown to be both efficient and biocompatible transfection reagents. Systematic modifications of the structural components of the PGAA system revealed structure-activity relationships important to its function, including its ability to degrade in situ. Expanding upon the development of step-growth glycopolymers, monosaccharides, such as glucose, were functionalized as vinyl-based monomers for the formation of diblock copolymers via radical addition-fragmentation chain-transfer (RAFT) polymerization. Upon complexation with plasmid DNA, the glucose-containing block creates a hydrophilic shell that promotes colloidal stability as effectively as PEG functionalization. An N-acetyl-d-galactosamine variant of this diblock polymer yields colloidally stable particles that show increased receptor-mediated uptake by liver hepatocytes in vitro and promotes liver targeting in mice. Finally, the disaccharide trehalose was incorporated into polycationic structures using both step-growth and RAFT techniques. It was shown that these trehalose-based copolymers imparted increased colloidal stability and yielded plasmid and siRNA polyplexes that resist aggregation upon lyophilization and reconstitution in water. The aforementioned series of glycopolymers use carbohydrates to promote effective and safe delivery of nucleic acid cargo into a variety of human cells types by promoting vehicle degradation, tissue-targeting, colloidal stabilization, and stability toward lyophilization to extend shelf life. Work is currently underway to translate the use of glycopolymers for safe and efficient delivery of nucleic acid cargo for gene therapy and gene editing applications.

Polycation Architecture and Assembly Direct Successful Gene Delivery: Micelleplexes Outperform Polyplexes via Optimal DNA Packaging.

Cellular delivery of biomacromolecules is vital to medical research and therapeutic development. Cationic polymers are promising and affordable candidate vehicles for these precious payloads. However, the impact of polycation architecture and solution assembly on the biological mechanisms and efficacy of these vehicles has not been clearly defined. In this study, four polymers containing the same cationic poly(2-(dimethylamino)ethyl methacrylate) (D) block but placed in different architectures have been synthesized, characterized, and compared for cargo binding and biological performance. The D homopolymer and its diblock copolymer poly(ethylene glycol)-block-poly(2-(dimethylamino) ethyl methacrylate) (OD) readily encapsulate pDNA to form polyplexes. Two amphiphilic block polymer variants, poly(2-(dimethylamino)ethyl methacrylate)-block-poly(n-butyl methacrylate) (DB) and poly(ethylene glycol)-block-poly(2-(dimethylamino)ethyl methacrylate)-block-poly(n-butyl methacrylate) (ODB), self-assemble into micelles, which template pDNA winding around the cationic corona to form micelleplexes. Micelleplexes were found to have superior delivery efficiency compared to polyplexes and detailed physicochemical and biological characterizations were performed to pinpoint the mechanisms by testing hypotheses related to cellular internalization, intracellular trafficking, and pDNA unpackaging. For the first time, we find that the higher concentration of amines housed in micelleplexes stimulates both cellular internalization and potential endosomal escape, and the physical motif of pDNA winding into micelleplexes, reminiscent of DNA compaction by histones in chromatin, preserves the pDNA secondary structure in its native B form. This likely allows greater payload accessibility for protein expression with micelleplexes compared to polyplexes, which tightly condense pDNA and significantly distort its helicity. This work provides important guidance for the design of successful biomolecular delivery systems via optimizing the physicochemical properties.

Cell Penetrating Polymers Containing Guanidinium Trigger Apoptosis in Human Hepatocellular Carcinoma Cells unless Conjugated to a Targeting N-Acetyl-Galactosamine Block.

A series of 3-guanidinopropyl methacrylamide (GPMA)-based polymeric gene delivery vehicles were developed via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers have been evaluated for their cellular internalization ability, transfection efficiency, and cytotoxicity. Two homopolymers: P(GPMA20), P(GPMA34), were synthesized to study the effect of guanidium polymer length on delivery efficiency and toxicity. In addition, an N-acetyl-d-galactosamine (GalNAc)-based hydrophilic block was incorporated to produce diblock polymers, which provides a neutral hydrophilic block that sterically protects plasmid-polymer complexes (polyplexes) from colloidal aggregation and aids polyplex targeting to hepatocytes via binding to asialoglycoprotein receptors (ASGPRs). Polyplexes formed with P(GPMAx) (x = 20, 34) homopolymers were shown to be internalized via both energy-dependent and independent pathways, whereas polyplexes formed with block polymers were internalized through endocytosis. Notably, P(GPMAx) polyplexes enter cells very efficiently but are also very toxic to human hepatocellular carcinoma (HepG2) cells and triggered cell apoptosis. In comparison, the presence of a carbohydrate block in the polymer structures reduced the cytotoxicity of the polyplex formulations and increased gene delivery efficiency with HepG2 cells. Transfection efficiency and toxicity studies were also carried out with HEK 293T (human embryonic kidney) cells for comparison. Results showed that polyplexes formed with the P(GPMAx) homopolymers exhibit much higher transfection efficiency and lower toxicity with HEK 293T cells. The presence of the carbohydrate block did not further increase transfection efficiency in comparison to the homopolymers with HEK 293T cells, likely due to the lack of ASGPRs on the HEK 293T cell line. This study revealed that although guanidinium-based polymers have high membrane permeability, their application as plasmid delivery vehicles may be limited by their high cytotoxicity to certain cell types. Thus, the use of cell penetrating structures in polyplex formulations should be used with caution and carefully tailored toward individual cell/tissue types.

High-viscosity versus low-viscosity cement for the treatment of vertebral compression fractures: A meta-analysis of randomized controlled trials.

BACKGROUND: High viscosity cement (HVC) and low viscosity cement (LVC) have been used to treat osteoporotic vertebral compression fractures (OVCFs). Our study was to assess the safety and efficacy of HVC and LVC in treating OVCFs. METHODS: We searched the electronic database for randomized controlled trials of HVC and LVC to treat OVCFs. Random-effects model was performed to pool the outcomes about operation time, visual analogue scale (VAS), bone cement injection volume, oswestry disability index (ODI), bone cement leakage and adjacent vertebral fractures. RESULTS: Twelve randomized trials were included in the meta-analysis. The 2 groups had similar changes in terms of bone cement injection volume, ODI and adjacent vertebral fractures. The HVC group showed shorter operation time and better VAS score improvement. The bone cement leakage rate of the HVC group was significantly better than LVC group (P < .00001).According to the location of bone cement leakage, in the leakages of the veins (P < .00001), the intervertebral disc (P < .00001), the paravertebral area (P = .003) and the intraspinal space (P = .03), the HVC group were significantly better than the LVC group. CONCLUSIONS: In terms of bone cement injection volume, ODI and adjacent vertebral fractures, the 2 group are equivalent. HVC had a shorter operation time, lower bone cement leakage rate and better VAS score improvement, compared with LVC.

Polyamide membranes with nanoscale Turing structures for water purification.

The emergence of Turing structures is of fundamental importance, and designing these structures and developing their applications have practical effects in chemistry and biology. We use a facile route based on interfacial polymerization to generate Turing-type polyamide membranes for water purification. Manipulation of shapes by control of reaction conditions enabled the creation of membranes with bubble or tube structures. These membranes exhibit excellent water-salt separation performance that surpasses the upper-bound line of traditional desalination membranes. Furthermore, we show the existence of high water permeability sites in the Turing structures, where water transport through the membranes is enhanced.