Does Ownership Matter for Medical System Performance? Evidence From a Natural Experiment in Suqian, China.

There has long been a major policy debate on the role of hospital ownership (private vs public) in medical system performance. China's health care delivery system is mainly a public system. In 2000, a full privatization reform was implemented in the city of Suqian, offering a unique opportunity to assess possible effects of private delivery based on a major external shock to the existing system.

Trends in Hospitalization Expenditures for Acute Exacerbations of COPD in Beijing from 2009 to 2017.

Background: Chronic obstructive pulmonary disease (COPD) is the cause of substantial economic and social burden. We investigated trends in hospitalizations for acute exacerbation of COPD in Beijing, China, from 2009 to 2017.

Patients And Methods: Investigations were conducted using data from the discharge records of inpatients that were given a primary diagnosis of acute exacerbation of COPD.

Potential Effects Of Eliminating The Individual Mandate Penalty In California.

The tax penalty for noncompliance with the Affordable Care Act's individual mandate is to be eliminated starting in 2019. We investigated the potential impact of this change on enrollees' decisions to purchase insurance and on individual-market premiums. In a survey of enrollees in the individual market in California in 2017, 19 percent reported that they would not have purchased insurance had there been no penalty.

Modeling individual health care expenditures in China: Evidence to assist payment reform in public insurance.

Reforming the payment system of public health insurance from fee-for-service to more efficient alternative schemes has become an urgent policy issue in developing countries. Using a large sample of administrative data drawn from China, we examine a variety of econometric models for predicting the medical expenditures of individuals. We show that the standard ordinary least squares model performs relatively well compared with other models.

Adverse Selection into and within the Individual Health Insurance Market in California in 2014.

Objective: The Affordable Care Act (ACA) introduced reforms to mitigate adverse selection into and within the individual insurance market. We examined the traits and predicted medical spending of enrollees in California post-ACA.

Data Sources: Survey of 2,103 enrollees in individual market plans, on- and off-exchange, in 2014.

Matching and Imputation Methods for Risk Adjustment in the Health Insurance Marketplaces.

New state-level health insurance markets, denoted , created under the Affordable Care Act, use risk-adjusted plan payment formulas derived from a population to participate in the Marketplaces. We develop methodology to derive a sample from the target population and to assemble information to generate improved risk-adjusted payment formulas using data from the Medical Expenditure Panel Survey and Truven MarketScan databases. Our approach requires multi-stage data selection and imputation procedures because both data sources have systemic missing data on crucial variables and arise from different populations.

Peptide Targeting of an Antibiotic Prodrug toward Phagosome-Entrapped Mycobacteria.

Mycobacterial infections are difficult to treat due to the bacterium's slow growth, ability to reside in intracellular compartments within macrophages, and resistance mechanisms that limit the effectiveness of conventional antibiotics. Developing antibiotics that overcome these challenges is therefore critical to providing a pipeline of effective antimicrobial agents. Here, we describe the synthesis and testing of a unique peptide-drug conjugate that exhibits high levels of antimicrobial activity against M.

Multivalent display of pendant pro-apoptotic peptides increases cytotoxic activity.

Several cationic antimicrobial peptides have been investigated as potential anti-cancer drugs due to their demonstrated selective toxicity towards cancer cells relative to normal cells. For example, intracellular delivery of KLA, a pro-apoptotic peptide, results in toxicity against a variety of cancer cell lines; however, the relatively low activity and small size lead to rapid renal excretion when applied in vivo, limiting its therapeutic potential. In this work, apoptotic peptide-polymer hybrid materials were developed to increase apoptotic peptide activity via multivalent display.

Assessing incentives for service-level selection in private health insurance exchanges.

Even with open enrollment and mandated purchase, incentives created by adverse selection may undermine the efficiency of service offerings by plans in the new health insurance Exchanges created by the Affordable Care Act. Using data on persons likely to participate in Exchanges drawn from five waves of the Medical Expenditure Panel Survey, we measure plan incentives in two ways. First, we construct predictive ratios, improving on current methods by taking into account the role of premiums in financing plans.

Integrating risk adjustment and enrollee premiums in health plan payment.

In two important health policy contexts - private plans in Medicare and the new state-run "Exchanges" created as part of the Affordable Care Act (ACA) - plan payments come from two sources: risk-adjusted payments from a Regulator and premiums charged to individual enrollees. This paper derives principles for integrating risk-adjusted payments and premium policy in individual health insurance markets based on fitting total plan payments to health plan costs per person as closely as possible. A least squares regression including both health status and variables used in premiums reveals the weights a Regulator should put on risk adjusters when markets determine premiums.

Effect of polyplex morphology on cellular uptake, intracellular trafficking, and transgene expression.

Nanoparticle morphology has been shown to affect cellular uptake, but there are few studies investigating the impact of particle shape on biologic drug delivery. Recently, our group synthesized a series of N-(2-hydroxypropyl) methacrylamide (HPMA)-oligolysine brush polymers for nucleic acid delivery that varied in oligolysine peptide length and polymer molecular weight. Interestingly, a 50% longer peptide (K15) transfected very poorly compared to the optimized polymer comprised of K10 peptide despite similar chemical composition and molecular weight.

Engineering biodegradable and multifunctional peptide-based polymers for gene delivery.

The complex nature of in vivo gene transfer establishes the need for multifunctional delivery vectors capable of meeting these challenges. An additional consideration for clinical translation of synthetic delivery formulations is reproducibility and scale-up of materials. In this review, we summarize our work over the last five years in developing a modular approach for synthesizing peptide-based polymers.

Block copolymers containing a hydrophobic domain of membrane-lytic peptides form micellar structures and are effective gene delivery agents.

Endosomal release peptides have been incorporated in synthetic gene delivery formulations to increase transfection efficiencies. In this work, cationic copolymers containing sHGP, a membrane-lytic peptide derived from HIV gp41, were synthesized and evaluated. Diblock, with sHGP displayed on one block, and statistical, with sHGP randomly displayed, copolymers were prepared via RAFT polymerization.

Influence of histidine incorporation on buffer capacity and gene transfection efficiency of HPMA-co-oligolysine brush polymers.

One of the major intracellular barriers to nonviral gene delivery is efficient endosomal escape. The incorporation of histidine residues into polymeric constructs has been found to increase endosomal escape via the proton sponge effect. Statistical and diblock copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA), oligolysine, and oligohistidine were synthesized via reversible-addition fragmentation chain transfer (RAFT) polymerization and tested for in vitro transfection efficiency, buffering ability, and polyplex uptake mechanism via the use of chemical endocytic inhibitors.

Investigation of Polyethylenimine/DNA Polyplex Transfection to Cultured Cells Using Radiolabeling and Subcellular Fractionation Methods.

Quantitative analysis of the intracellular trafficking of nonviral vectors provides critical information that can guide the rational design of improved cationic systems for gene delivery. Subcellular fractionation methods, combined with radiolabeling, produce quantitative measurements of the intracellular trafficking of nonviral vectors and the therapeutic payload. In this work, differential and density-gradient centrifugation techniques were used to determine the intracellular distribution of radiolabeled 25 kDa branched polyethylenimine (bPEI)/plasmid DNA complexes ("polyplexes") in HeLa cells over time.

Intracellular delivery and trafficking dynamics of a lymphoma-targeting antibody-polymer conjugate.

Ratiometric fluorescence and cellular fractionation studies were employed to characterize the intracellular trafficking dynamics of antibody-poly(propylacrylic acid) (PPAA) conjugates in CD22+ RAMOS-AW cells. The HD39 monoclonal antibody (mAb) directs CD22-dependent, receptor-mediated uptake in human B-cell lymphoma cells, where it is rapidly trafficked to the lysosomal compartment. To characterize the intracellular-release dynamics of the polymer-mAb conjugates, HD39-streptavidin (HD39/SA) was dual-labeled with pH-insensitive Alexa Fluor 488 and pH-sensitive pHrodo fluorophores.

Application of living free radical polymerization for nucleic acid delivery.

Therapeutic gene delivery can alter protein function either through the replacement of nonfunctional genes to restore cellular health or through RNA interference (RNAi) to mask mutated and harmful genes. Researchers have investigated a range of nucleic acid-based therapeutics as potential treatments for hereditary, acquired, and infectious diseases. Candidate drugs include plasmids that induce gene expression and small, interfering RNAs (siRNAs) that silence target genes.

The transduction of Coxsackie and Adenovirus Receptor-negative cells and protection against neutralizing antibodies by HPMA-co-oligolysine copolymer-coated adenovirus.

Adenoviral (AdV) gene vectors offer efficient nucleic acid transfer into both dividing and non-dividing cells. However issues such as vector immunogenicity, toxicity and restricted transduction to receptor-expressing cells have prevented broad clinical translation of these constructs. To address this issue, engineered AdV have been prepared by both genetic and chemical manipulation.

Reducible HPMA-co-oligolysine copolymers for nucleic acid delivery.

Biodegradability can be incorporated into cationic polymers via use of disulfide linkages that are degraded in the reducing environment of the cell cytosol. In this work, N-(2-hydroxypropyl)methacrylamide (HPMA) and methacrylamido-functionalized oligo-l-lysine peptide monomers with either a non-reducible 6-aminohexanoic acid (AHX) linker or a reducible 3-[(2-aminoethyl)dithiol] propionic acid (AEDP) linker were copolymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Both of the copolymers and a 1:1 (w/w) mixture of copolymers with reducible and non-reducible peptides were complexed with DNA to form polyplexes.

HPMA-oligolysine copolymers for gene delivery: optimization of peptide length and polymer molecular weight.

Polycations are one of the most frequently used classes of materials for non-viral gene transfer in vivo. Several studies have demonstrated a sensitive relationship between polymer structure and delivery activity. In this work, we used reverse addition-fragmentation chain transfer (RAFT) polymerization to build a panel of N-(2-hydroxypropyl)methacrylamide (HPMA)-oligolysine copolymers with varying peptide length and polymer molecular weight.

Electrostatic ligand coatings of nanoparticles enable ligand-specific gene delivery to human primary cells.

A general method of coating polymer/DNA nanoparticles was developed. Peptide coated nanoparticles were found to have favorable biophysical characteristics including small particle size, near-neutral zeta potential, and stability in serum. At appropriate formulation conditions including near-neutral charge ratio, the coated nanoparticles enabled effective ligand-specific gene delivery to human primary endothelial cells in serum-containing media.

Biodegradable polymeric vectors for gene delivery to human endothelial cells.

Endothelial cells are an important cell type to both cardiovascular disease and cancer, as they play critical roles in vascular function and angiogenesis. However, effective and safe gene delivery to primary endothelial cells in the presence of serum proteins is known to be particularly challenging. A library of biodegradable poly(beta-amino esters) was synthesized for use as potential vectors.