Medicaid care management: Description of high-cost addictions treatment clients

High utilizers of alcohol and other drug treatment (AODTx) services are a priority for healthcare cost control. We examine characteristics of Medicaid-funded AODTx clients, comparing three groups: individuals < 90th percentile of AODTx expenditures (n = 41,054); high-cost clients in the top decile of AODTx expenditures (HC; n = 5,718); and 1760 enrollees in a chronic care management (CM) program for HC clients implemented in 22 counties in New York State. Medicaid and state AODTx registry databases were combined to draw demographic, clinical, social needs and treatment history data. HC clients accounted for 49% of AODTx costs funded by Medicaid. As expected, HC clients had significant social welfare needs, comorbid medical and psychiatric conditions, and use of inpatient services. The CM program was successful in enrolling some high-needs, high-cost clients but faced barriers to reaching the most costly and disengaged individuals.     

Utility of clinical comprehensive genomic characterization for diagnostic categorization in patients presenting with hypocellular bone marrow failure syndromes

Bone marrow failure (BMF) related to hypoplasia of hematopoietic elements in the bone marrow is a heterogeneous clinical entity with a broad differential diagnosis including both inherited and acquired causes. Accurate diagnostic categorization is critical to optimal patient care and detection of genomic variants in these patients may provide this important diagnostic and prognostic information. We performed real-time, accredited (ISO15189) comprehensive genomic characterization including targeted sequencing and whole exome sequencing in 115 patients with BMF syndromes (median age 24 years, range: 3 months - 81 years). In patients with clinical diagnoses of inherited BMF syndromes, acquired BMF syndromes or clinically unclassifiable BMF we detected variants in 52% (12 of 23), 53% (25 of 47) and 56% (25 of 45) respectively. Genomic characterization resulted in a change of diagnosis in 30 of 115 (26%) including the identification of germline causes for 3 of 47 and 16 of 45 cases with pre-test diagnoses of acquired and clinically unclassifiable BMF respectively. The observed clinical impact of accurate diagnostic categorization included choice to perform allogeneic stem cell transplantation, disease-specific targeted treatments, identification of at-risk family members and influence of sibling allogeneic stem cell donor choice. Multiple novel pathogenic variants and copy number changes were identified in our cohort including in TERT, FANCA, RPS7 and SAMD9. Whole exome sequence analysis facilitated the identification of variants in two genes not typically associated with a primary clinical manifestation of BMF but also demonstrated reduced sensitivity for detecting low level acquired variants. In conclusion, genomic characterization can improve diagnostic categorization of patients presenting with hypoplastic BMF syndromes and should be routinely performed in this group of patients.     

Trichotillomania: a review and case report

Although patients with trichotillomania typically present to dermatologists, the diagnosis and treatment lie in the field of psychiatry. We report an unusual case of a 33-year-old woman with severe trichotillomania. We review common clinical and pathologic findings of this often chronic and socially debilitating disorder. In addition, we discuss treatment options for dermatologists and how collaboration with psychiatrists is the most effective management for these difficult-to-treat patients.     

Health Behaviors of Older Chinese Adults Living in New York City

The dramatic increase in the number of older immigrants living in the U.S. presents new challenges to policy makers concerned with promoting healthy aging. To date, however, strikingly little is known regarding the health and health trajectories of older immigrants. This paper examines the prevalence and predictors of important health behaviors associated with chronic disease prevention, including current smoking status, physical activity, alcohol use, and body mass index (BMI). We analyzed data from the 2003 New York City Chinese Health Survey (NYC CHS), the largest probability-based sample of Chinese immigrants residing in two distinct communities. In-person interviews were conducted with 517 representative men and women aged 55-75. Logistic regression modeling was used to test the influence of demographic, socioeconomic status, acculturation, and health characteristics on selected health behaviors. Results revealed that having more education and better physical health status were associated with greater participation in physical activity. Gender-specific analyses indicated that the effect of selected predictors varied between the sexes. For example, among older Chinese women, acculturation was negatively associated with alcohol use. This study provides some of the first evidence on health behaviors of one of the fastest growing older immigrant groups in the U.S. Study results add to the emerging literature on the complex nature of immigrant health trajectories, and demonstrate that contrary to prior research, living a greater proportion of time in the U.S. can be associated with selected positive health behaviors. Further longitudinal studies are needed to help inform policy initiatives to encourage healthy aging among diverse older immigrant groups.     

Effectiveness of a mycoplasma elimination reagent on a mycoplasma-contaminated hybridoma cell line

Mycoplasma contamination in cell culture is a frequently occurring serious limitation to biomedical research, particularly when it affects the irreplaceable cell lines. Although there are few reports of its successful elimination through rigorous protocols, it is the usual practice to destroy the infected cultures. Lately, a physical method using a mycoplasma-eliminating surfactin was described to effectively eliminate mycoplasma contamination from infected cell lines upon single use. We made an attempt using surfactin, an anti-mycoplasma biosurfactant, to eliminate mycoplasma from an extensively infected irreplaceable hybridoma cell line. There were apparent indications of limited elimination, suggesting the possible usefulness of surfactin in achieving total decontamination. However, it was observed that surfactin was toxic to the infected hybridoma cells plated at various cell densities and exposure times. It is suggested that preliminary tests should be performed to determine the cytotoxicity of surfactin with sufficient back-ups of the contaminated cell culture before decontamination is attempted. Additionally, possible ways to enhance its effectiveness are discussed.     

Engineering exosome polymer hybrids by atom transfer radical polymerization

Exosomes are emerging as ideal drug delivery vehicles due to their biological origin and ability to transfer cargo between cells. However, rapid clearance of exogenous exosomes from the circulation as well as aggregation of exosomes and shedding of surface proteins during storage limit their clinical translation. Here, we demonstrate highly controlled and reversible functionalization of exosome surfaces with well-defined polymers that modulate the exosome’s physiochemical and pharmacokinetic properties. Using cholesterol-modified DNA tethers and complementary DNA block copolymers, exosome surfaces were engineered with different biocompatible polymers. Additionally, polymers were directly grafted from the exosome surface using biocompatible photo-mediated atom transfer radical polymerization (ATRP). These exosome polymer hybrids (EPHs) exhibited enhanced stability under various storage conditions and in the presence of proteolytic enzymes. Tuning of the polymer length and surface loading allowed precise control over exosome surface interactions, cellular uptake, and preserved bioactivity. EPHs show fourfold higher blood circulation time without altering tissue distribution profiles. Our results highlight the potential of precise nanoengineering of exosomes toward developing advanced drug and therapeutic delivery systems using modern ATRP methods.

Exosomes are a subclass of lipid bilayer-enclosed extracellular vesicles (EVs) that play a crucial role in intercellular communication (1–3). They are secreted by most cell types in the body and are known to interact with recipient cells in several ways, including surface receptor interactions, membrane fusion, receptor-mediated endocytosis, phagocytosis and/or micropinocytosis (4, 5). Their nanoscopic size (30 to 150 nm), high biocompatibility, low immunogenicity (depending on the cell source), and ability to cross biological barriers, including the blood–brain barrier, make them an ideal vehicle for exogenous drug delivery (6–9). Over the last decade, multiple studies have shown effective utility of exosomes for the delivery of small molecule drugs, proteins, nucleic acids and nanoparticles for the treatment of several diseases (10–12). Although initial progress toward their clinical translation has been made, the need for a more robust platform persists. The therapeutic potential of exosomes is largely restricted due to their low exogenous drug-loading efficiency and limited ex vivo stability (13, 14). Moreover, systemically administered exosomes suffer from rapid clearance from blood in 2 to 20 min postinjection that is poorly suited for longer therapeutic action (15, 16).Engineering exosomes to incorporate nonnative moieties or materials can augment their therapeutic capabilities (17–19). While bioengineering methods by genetically modifying the exosome-secreting cells have been explored, such approaches require careful design and expensive reagents, yet suffer from low incorporation efficiency and limited scalability. Alternatively, ex vivo engineering of exosome surfaces with synthetic macromolecules is a powerful approach to easily modulate their surface interactions and consequently alter or enhance their biochemical and physicochemical properties.Here, we create a polymer-based platform that expands the structural repertoire of engineered exosomes and addresses the shortcomings of the ex vivo and in vivo stability of exosome-based therapeutics. We combine our previously reported method for rapid and on-demand functionalization of exosomes through DNA tethers (20) with atom transfer radical polymerization (ATRP) techniques (21–23) to engineer exosome polymer hybrids (EPHs). These EPHs display significantly enhanced stability and pharmacokinetics. We explore the preparation methods for EPHs by either tethering preformed DNA block copolymers (DNABCPs) onto the exosome membrane (“grafting-to”) or by grafting polymers directly from the exosomal surface (“grafting-from”) (Fig. 1) using DNA initiators. These membrane-tethering approaches allow precise control over the polymer length, composition, and loading on the exosome surface and thereby show minimal effect on the accessibility of surface proteins or other membrane-tethered agents that may be used for targeted delivery. We show that the cellular uptake and bioactivity of native and drug-loaded exosomes are preserved following polymer functionalization. Tethered polymers enhance the stability of exosomes under different storage conditions, including in the presence of proteolytic enzymes. The blood circulation half-lives of EPHs are significantly increased using different polymers, while maintaining their intrinsic tissue-targeting properties.Open in a separate windowFig. 1.Preparation of EPHs using DNA tethers. Chol-DNA embeds into the exosome membrane to form Exo-ssDNA (single-stranded DNA) species with DNA strands orienting outward. Hybridization of complementary DNA block copolymer (DNA′-Polymer) to the DNA tethers on Ex-ssDNA species generates Exo-dsDNA-Polymer (Exo-Polymer) by the “grafting-to” strategy. Alternatively, for the “grafting-from” strategy, a complementary DNA initiator (DNA′-Initiator) functionalized with the α-bromoisobutyrate group is hybridized with the DNA tethers, followed by surface-initiated ATRP to prepare Exo-Polymer species.     

Ferumoxytol Can Be Used for Quantitative Magnetic Particle Imaging of Transplanted Stem Cells

Molecular Imaging and Biology - To evaluate, if clinically translatable ferumoxytol nanoparticles can be used for in vivo detection and quantification of stem cell transplants with magnetic...     

The Relative Effect of Household and Workplace Smoking Restriction on Health Status Among Chinese Americans Living in New York City

Households and workplaces are the predominant location for exposure to secondhand smoke. The purpose of this study is to examine the association between health status and smoking restrictions at home and work and to compare the relative effect of household and workplace smoking restrictions on health status. This study uses data from a cross sectional representative probability sample of 2,537 Chinese American adults aged 18–74 living in New York City. The analysis was limited to 1,472 respondents who work indoors for wages. Forty-three percent of respondents reported a total smoking ban at home and the workplace, 20% at work only, 22% home only, and 15% reported no smoking restriction at home or work. Smokers who live under a total household smoking ban only or both a total household and total workplace ban were respectively 1.90 and 2.61 times more likely to report better health status compared with those who reported no smoking ban at work or home. Before the NYC Clean Indoor Air Act second-hand smoke (SHS) exposure among this immigrant Chinese population at home and work was high. This study finds that household smoking restrictions are more strongly associated with better health status than workplace smoking restrictions. However, better health status was most strongly associated with both a ban at work and home. Public health efforts should include a focus on promoting total household smoking bans to reduce the well-documented health risks of SHS exposure. Shelley and Hung are with the Department of Sociomedical Sciences, Columbia University Mailman School of Public Health, New York, NY, USA; Yerneni and Fahs are with the Brookdale Center on Aging, Hunter College, City University of New York, New York, NY, USA. Fahs and Das are with the Economics Program Graduate Center, City University of New York, New York, USA. An erratum to this article can be found at     

A computational model for stress reduction at the skin-implant interface of osseointegrated prostheses

Osseointegrated implants (OI)s for transfemoral prosthetic attachment offer amputees an alternative to the traditional socket attachment. Potential benefits include a natural transfer of loads directly to the skeleton via the percutaneous abutment, relief of pain and discomfort of residual limb soft tissues by eliminating sockets, increased sensory feedback, and improved function. Despite the benefits, the skin-implant interface remains a critical limitation, as it is highly prone to bacterial infection. One approach to improve clinical outcomes is to minimize stress concentrations at the skin-implant interface due to shear loading, reducing soft tissue breakdown and subsequent risk of infection. We hypothesized that broadening the bone base at the distal end of the femur would provide added surface area for skin adhesion and reduce stresses at the skin-implant interface. We tested this hypothesis using finite element models of an OI in a residual limb. Results showed a dramatic decrease in stress reduction, with up to ~90% decrease in stresses at the skin-implant interface as cortical bone thickness increased from 2 to 8 mm. The findings in this study suggests that surgical techniques could stabilize the skin-implant interface, thus enhancing a skin-to-bone seal around the percutaneous device and minimizing infection.