Injection Drug Use Among West Virginia Medicaid Beneficiaries: An Analysis of Health Outcomes, Service Utilization, and Cost

In the United States, injection drug use is a serious public health concern associated with an array of negative health outcomes and substantial financial consequences for systems of care. The purpose of this study was to characterize a statewide sample of Medicaid insured persons who inject drugs in terms of health outcomes, service utilization and cost. A cross-sectional, retrospective analysis of West Virginia Medicaid claims data between 2014 and 2016 was conducted. Between 2014 and 2016, 5,082 West Virginia Medicaid beneficiaries amassed 14,414 service visits, among which inpatient, emergency room, and mental health and substance abuse were the most common. Drug poisonings (n=5,077), soft-tissue infections (n=4,127) and other infectious diseases (n=2,141) were the most common clinical conditions within this sample. Medicaid claims data were not a suitable proxy for state surveillance data as it pertains to new cases of Hepatitis B, Hepatitis C, HIV and heroin overdoses. Ordinal logistic regression results indicate that infectious diseases like endocarditis and soft-tissue infections are associated with increased service utilization. Similarly, multiple regression models show increased cost among individuals with HIV, endocarditis, and Hepatitis B. Preventative services, e.g. syringe exchange programs, are important tools to reducing the spread of infectious diseases, and thereby decrease frequent service utilization and cost among injection drug users

Metal Parts Generation by Three Dimensional Printing

Mechanical Engineerin

Three Dimensional Printing of Tungsten Carbide-Cobalt Using a Cobalt Oxide Precursor

Tungsten Carbide 10 wt% Cobalt parts were formed by Slurry-based Three Dimensional Printing (3DPTM). The slurry contained a mixture of Tungsten Carbide and Cobalt Oxide powders, as well as dispersing and redispersing agents. The cobalt oxide is fully reduced to cobalt metal during the early stages of the sintering process. A new binder system, polyethylenimine, is described for use with powders with acidic surfaces, such as WC. Sintered densities approach the theoretical values for WC-10% Co, and the microstructures produced are similar to those of conventionally processed (press and sinter) materials. Up to four parts were produced in a single print run using a layer thickness of 25 Pm, with good dimensional agreement between them, and within the range of target dimensions after sintering.Mechanical Engineerin

Modeling and Designing Components with Locally Controlled Composition

SFF processes have demonstrated the ability to produce parts with locally controlled composition. In the limit, processes such as 3D Printing,cancreate parts with composition control on thelength scaleiof 100 microns.ToexploitthispC)tential,~e\\ZJnethodsto rnod~l, exchange, and process parts.with local composition needtobe.deyeloped..... Anapproachtc) modeling a part's geometty,.topology, and composition will be presented.· This.approachis based on sUbdividing the solidmodel into sub-regions and associating analytic composition blending functions \\lith each region. These blending functions definethe composition throughout the model as mixtures ofthe primary materials available to·the SEF machine. Various design tools will also be presented, for example, specification of com~ositionasa function of the distance from the surface of a part. Finally,the role of design rules specifying maximum concentrations and concentration.gradients will be discussed.Mechanical Engineerin

In Vivo rapid delivery of vasopressin from an implantable drug delivery micro-electro-mechanical device

A miniaturized implantable rapid drug delivery device based on micro-electro-mechanical-systems technology was recently developed and characterized. This device is intended to address acute conditions in high-risk subjects. This work provides an in vivo proof-of-concept for the device in a rabbit model, by releasing a physiologically active dose of vasopressin, a vasoconstrictor. The devices were implanted subcutaneously and activated to rapidly release vasopressin, with monitoring of mean arterial pressure and plasma levels.Device releases showed a rapid and measurable effect on mean arterial pressure as well as a continuous diffusion of vasopressin into the bloodstream, consistent with a depot effect. Plasma levels in rabbits receiving vasopressin with the device rose monotonically to 24.4 ± 2.9 ng/mL after one hour. Bioavailability after one hour was calculated to be 6.2 ± 2.8 % (mean ± s.d.).A new modality for rapid and controlled drug delivery has been developed. The device can be used as a new implantable device controlled by medical algorithms (based on heart rate or mean arterial pressure, for example) for autonomous operation in high-risk populations that require immediate ambulatory intervention.Keywords: Subcutaneous drug delivery; vasopressin; MEMS; rabbit; bioavailability

In Vivo rapid delivery of vasopressin from an implantable drug delivery micro-electro-mechanical device

A miniaturized implantable rapid drug delivery device based on micro-electro-mechanical-systems technology was recently developed and characterized. This device is intended to address acute conditions in high-risk subjects. This work provides an in vivo proof-of-concept for the device in a rabbit model, by releasing a physiologically active dose of vasopressin, a vasoconstrictor. The devices were implanted subcutaneously and activated to rapidly release vasopressin, with monitoring of mean arterial pressure and plasma levels.Device releases showed a rapid and measurable effect on mean arterial pressure as well as a continuous diffusion of vasopressin into the bloodstream, consistent with a depot effect. Plasma levels in rabbits receiving vasopressin with the device rose monotonically to 24.4 ± 2.9 ng/mL after one hour. Bioavailability after one hour was calculated to be 6.2 ± 2.8 % (mean ± s.d.).A new modality for rapid and controlled drug delivery has been developed. The device can be used as a new implantable device controlled by medical algorithms (based on heart rate or mean arterial pressure, for example) for autonomous operation in high-risk populations that require immediate ambulatory intervention.Keywords: Subcutaneous drug delivery; vasopressin; MEMS; rabbit; bioavailability

Zero-order controlled release of ciprofloxacin-HCl from a reservoir-based, bioresorbable and elastomeric device

A reservoir-based device constructed of a completely biodegradable elastomer can enable several new implantation and insertion options for localized drug therapy, particularly in the case of urological therapies. We performed an in vitro performance evaluation of an implantable, bio-resorbable device that supplies short-term controlled release of ciprofloxacin-HCl (CIP). The proposed device functions through a combination of osmosis and diffusion mechanisms to release CIP for short-term therapies of a few weeks duration. Poly(glycerol-co-sebacic acid) (PGS) was cast in a tubular geometry with solid drug powder packed into its core and a micro-machined release orifice drilled through its wall. Drug release experiments were performed to determine the effective release rate from a single orifice and the range of orifice sizes in which controlled zero-order release was the main form of drug expulsion from the device. It is demonstrated that PGS is sufficiently permeable to water to allow the design of an elementary osmotic pump for drug delivery. Indeed, PGS's water permeability is several orders of magnitude larger than commonly used cellulose acetate for elementary osmotic pumps.Deshpande Center for Technological InnovationSamsung Scholarship Foundatio

An implantable microdevice to perform high-throughput in vivo drug sensitivity testing in tumors

Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic markers of tumor response to available drugs. A more accurate analysis of drug sensitivity would involve studying tumor response in vivo. To this end, we have developed an implantable device that can perform drug sensitivity testing of several anticancer agents simultaneously inside the living tumor. The device contained reservoirs that released microdoses of single agents or drug combinations into spatially distinct regions of the tumor. The local drug concentrations were chosen to be representative of concentrations achieved during systemic treatment. Local efficacy and drug concentration profiles were evaluated for each drug or drug combination on the device, and the local efficacy was confirmed to be a predictor of systemic efficacy in vivo for multiple drugs and tumor models. Currently, up to 16 individual drugs or combinations can be assessed independently, without systemic drug exposure, through minimally invasive biopsy of a small region of a single tumor. This assay takes into consideration physiologic effects that contribute to drug response by allowing drugs to interact with the living tumor in its native microenvironment. Because these effects are crucial to predicting drug response, we envision that these devices will help identify optimal drug therapy before systemic treatment is initiated and could improve drug response prediction beyond the biomarkers and in vitro and ex vivo studies used today. These devices may also be used in clinical drug development to safely gather efficacy data on new compounds before pharmacological optimization.National Cancer Institute (U.S.) (Innovative Molecular Analysis Technologies Program R21-CA177391)Kibur Medical, Inc

Long-term dopamine neurochemical monitoring in primates

Many debilitating neuropsychiatric and neurodegenerative disorders are characterized by dopamine neurotransmitter dysregulation. Monitoring subsecond dopamine release accurately and for extended, clinically relevant timescales is a critical unmet need. Especially valuable has been the development of electrochemical fast-scan cyclic voltammetry implementing microsized carbon fiber probe implants to record fast millisecond changes in dopamine concentrations. Nevertheless, these well-established methods have only been applied in primates with acutely (few hours) implanted sensors. Neurochemical monitoring for long timescales is necessary to improve diagnostic and therapeutic procedures for a wide range of neurological disorders. Strategies for the chronic use of such sensors have recently been established successfully in rodents, but new infrastructures are needed to enable these strategies in primates. Here we report an integrated neurochemical recording platform for monitoring dopamine release from sensors chronically implanted in deep brain structures of nonhuman primates for over 100 days, together with results for behavior-related and stimulation-induced dopamine release. From these chronically implanted probes, we measured dopamine release from multiple sites in the striatum as induced by behavioral performance and reward-related stimuli, by direct stimulation, and by drug administration. We further developed algorithms to automate detection of dopamine. These algorithms could be used to track the effects of drugs on endogenous dopamine neurotransmission, as well as to evaluate the long-term performance of the chronically implanted sensors. Our chronic measurements demonstrate the feasibility of measuring subsecond dopamine release from deep brain circuits of awake, behaving primates in a longitudinally reproducible manner. Keywords: striatum; voltammetry; neurotransmitters; chronic implantsNational Institute of Neurological Diseases and Stroke (U.S.) (Grant R01 NS025529)National Institute of Neurological Diseases and Stroke (U.S.) (Grant F32 NS093897)United States. Army Research Office (Contract W911NF-16-1-0474)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01 EB016101

Focal, remote-controlled, chronic chemical modulation of brain microstructures

Direct delivery of fluid to brain parenchyma is critical in both research and clinical settings. This is usually accomplished through acutely inserted cannulas. This technique, however, results in backflow and significant dispersion away from the infusion site, offering little spatial or temporal control in delivering fluid. We present an implantable, MRI-compatible, remotely controlled drug delivery system for minimally invasive interfacing with brain microstructures in freely moving animals. We show that infusions through acutely inserted needles target a region more than twofold larger than that of identical infusions through chronically implanted probes due to reflux and backflow. We characterize the dynamics of in vivo infusions using positron emission tomography techniques. Volumes as small as 167 nL of copper-64 and fludeoxyglucose labeled agents are quantified. We further demonstrate the importance of precise drug volume dosing to neural structures to elicit behavioral effects reliably. Selective modulation of the substantia nigra, a critical node in basal ganglia circuitry, via muscimol infusion induces behavioral changes in a volume-dependent manner, even when the total dose remains constant. Chronic device viability is confirmed up to 1-y implantation in rats. This technology could potentially enable precise investigation of neurological disease pathology in preclinical models, and more efficacious treatment in human patients. Keywords: brain; drug delivery; substantia nigra; neural implant; PETNational Institutes of Health (U.S.) (Grant R01 EB016101)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01 EB016101)National Cancer Institute (U.S.) (Grant P30-CA14051