Impact of a trauma recovery center on emergency department utilization for victims of violence.

BACKGROUND: Victims of violence are at high risk for unmet mental and physical health care needs which can translate into increased Emergency Department (ED) visits. We investigated the effectiveness of participation in a psychosocial, case management-based trauma recovery program on ED utilization. METHODS: A retrospective cohort study of ED utilization before and after referral to a Trauma Recovery Center (TRC). Charts of TRC participants from 6/2017-5/2019 who consented in clinic to their medical records being used for research were reviewed. The primary outcome was the change in ED utilization 6 months pre- and post-referral to a TRC. The secondary outcomes were factors associated with ED visits after TRC referral, including victimization or mental health issues. RESULTS: The study group contained 143 patients, of which 82% identified as female and 62% identified as white. Many (39%, n = 56) were part of one or more vulnerable populations and type of victimization varied extensively. Intervention uptake was high as almost all (92%, n = 132) had at least one TRC encounter [median of 6 encounters (IQR 2-13)] and an average of 2.7 services used. Most participants (67.1%, n = 96) had no change in ED use. Forty (28.0%) had at least 1 ED visit 6 months before, 38 (26.8%) had at least 1 ED visit 6 months afterwards, and 81 (56.6%) had no ED visits during either timeframe. ED visits per person in the 6 months prior to referral were not different from visits per person in the 6 months after referral (0.52 vs 0.49, p = 0.76, paired t-test). Negative binomial regression indicated number of ED visits before referral (IRR 1.5, 95% confidence interval [1.27-1.79]) and pre-existing mental health conditions (IRR 2.2, 95% confidence interval [0.98-5.02]) were most associated with an increase in the incidence rate ratio of ED visits in the 6 months after referral. CONCLUSION: Despite high engagement, a multidisciplinary Trauma Recovery Center did not reduce ED utilization. ED utilization prior to TRC was the most predictive factor of ED utilization afterwards.

Manual Palpation versus Ultrasound to Identify the Intervertebral Space for Spinal Anesthesia in Infants.

Purpose: Awake spinal anesthesia continues as an alternative to general anesthesia for infants. Standard clinical practice includes the manual palpation of surface landmarks to identify the desired intervertebral space for lumbar puncture (LP). The current study investigates the accuracy of manual palpation for identifying the intended intervertebral site for LP, using ultrasonography for confirmation and to determine the interspace where the conus medullaris ends. Patients and Methods: After informed parental consent, patients less than one year of age undergoing spinal anesthesia for lower abdominal, urologic, or lower extremity surgical procedures were included. Patients were held in the seated position and an attending pediatric anesthesiologist or pediatric anesthesiology fellow declared the vertebral interspace intended for needle insertion, palpated surface landmarks, and placed a mark at the site. A research anesthesiologist then determined the actual vertebral interspace of the marked site and the location of the conus medullaris using ultrasonography. The time to complete both techniques (manual palpation and ultrasonography) was recorded. Results: The study cohort included 50 infants (median age of 7 months). Sixteen vertebral interspaces (32%) were inaccurately marked. One was marked two spaces higher than intended, ten were marked one space higher than intended, and five were marked one space lower than intended. In one patient, the intended vertebral interspace for the lumbar puncture overlaid the conus medullaris. The median time required was 25 seconds (IQR 14.3, 32) for palpation and 39 seconds (IQR 29, 63.8) for ultrasonography. Conclusion: Manual palpation of surface landmarks to determine the correct interspace for LP for spinal anesthesia in infants is inaccurate. The time required to perform spinal ultrasonography in infants for determination of the optimal site for LP is brief and may be useful in ensuring accurate identification of the correct interspace and the location of the conus medullaris.

Magnetically-stimulated transformations in the nanostructure of PEGylated phytantriol-based nanoparticles for on-demand drug release.

Lipid-based liquid crystalline (LLC) systems are formed by the self-assembly of lipid materials in aqueous environments. The internal nanostructures of LLC systems can be manipulated using remote stimuli and have the potential to serve as 'on-demand' drug delivery systems. In this study, a magnetically-responsive system that displayed a transition in nanostructure from liposomes to cubosomes/hexasomes under external alternating magnetic field (AMF) was established by the incorporation of iron oxide nanoparticles (IONPs) into a PEGylated phytantriol (PHYT)-based LLC system. Small angle X-ray scattering (SAXS) was utilized to assess the equilibrium phase behaviour of the systems with different compositions of the lipids to find the optimized formulation. Time-resolved SAXS was then used to determine the dynamic transformation of nanostructures of the IONP-containing systems with the activation of AMF. The formulation containing PHYT and DSPE-PEG2000 at a 95 to 5 molar percent ratio produced a transition from lamellar phase to bicontinuous cubic phase, showing a slow-to-fast drug release profile. Inclusion of either 5 nm or 15 nm IONPs imparted magnetic-responsiveness to the system. The magnetically-responsive system produced an 'on-demand' drug delivery system from which the drug release was able to be triggered externally by AMF-stimulation.

Self-Assembled Nanostructured Lipid Systems: Is There a Link between Structure and Cytotoxicity?

Self-assembly of lipid-based liquid crystalline (LLC) nanoparticles is a formulation art arising from the hydrophilic-lipophilic qualities and the geometric packing of amphiphilic lipid molecules in an aqueous environment. The diversity of commercialized amphiphilic lipids and an increased understanding of the physicochemical factors dictating their membrane curvature has enabled versatile architectural design and engineering of LLC nanoparticles. While these exotic nanostructured materials are hypothesized to form the next generation of smart therapeutics for a broad field of biomedical applications, biological knowledge particularly on the systemic biocompatibility or cytotoxicity of LLC materials remains unclear. Here, an overview on the interactions between LLCs of different internal nanostructures and biological components (including soluble plasma constituents, blood cells, and isolated tissue cell lines) is provided. Factors affecting cell-nanoparticle tolerability such as the type of lipids, type of steric stabilizers, nanoparticle surface charges, and internal nanostructures (or lipid phase behaviors) are elucidated. The mechanisms of cellular uptake and lipid transfer between neighboring membrane domains are also reviewed. A critical analysis of these studies sheds light on future strategies to transform LLC materials into a viable therapeutic entity ideal for internal applications.

Naphthalocyanine as a New Photothermal Actuator for Lipid-Based Drug Delivery Systems.

One approach to address the substantial global burden of ocular diseases such as aged related macular degeneration is using light-activated drug delivery to obviate the need for highly invasive and frequent, costly intravitreal injections. To enable such systems, new light responsive materials are required. This communication reports the use of silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (SiNC), a small molecule photosensitizer, as a new actuator for triggering light responsive lipid-based drug delivery systems. Small-angle X-ray scattering was used to confirm that the addition of SiNC imparted light sensitivity to the lipid systems, resulting in a complete phase transition within 20 s of near-infrared irradiation. The phase transition was also reversible, suggesting the potential for on-demand drug delivery. When compared to the phase transitions induced using alternative light responsive actuators, gold nanorods and graphene, there were some differences in phase behavior. Namely, the phytantriol with SiNC system transitioned directly to the inverse micellar phase, skipping the intermediate inverse hexagonal structure. The photodynamic properties and efficiency in controlling the release of drug suggest that SiNC-actuated lipid systems have the potential to reduce the burden of repeated intravitreal injections.

Investigation of Donor-Acceptor Stenhouse Adducts as New Visible Wavelength-Responsive Switching Elements for Lipid-Based Liquid Crystalline Systems.

The ability of donor-acceptor Stenhouse adducts (DASAs) to function as a green light responsive switch for lipid-based liquid crystalline drug delivery systems was investigated. The host matrix comprising phytantriol cubic phase was selected due to its high sensitivity toward changes in lipid packing. Small-angle X-ray scattering demonstrated that the matrix undergoes rapid and fully reversible order-order phase transitions upon irradiation with 532 nm light, converting between the bicontinuous cubic phase and reversed hexagonal phases. This approach shows promise for use as an actuator for the development of visible wavelength light-activated, "on-demand" drug delivery systems.

Graphene as a photothermal actuator for control of lipid mesophase structure.

The optical density of pristine graphene is high and broad in the near infrared region of the electromagnetic spectrum positioning this material as a highly efficient photothermal agent for in vivo applications. In this study, surfactant assisted exfoliated graphene was incorporated within bulk lipid samples of varying lipid types: glyceryl monoether, glyceryl monooleate and phytantriol. The pristine graphene sheets did not disrupt the packing of the liquid crystals while being in sufficiently intimate contact to provide localized heating and induce phase transitions. The phase progressions induced through heating using NIR irradiation of the entrained graphene particles within the bulk liquid crystal were studied using SAXS and confirmed using polarized optical microscopy. Increases in apparent temperature experienced by the matrix of up to 50 °C were observed by establishing a SAXS versus bulk temperature calibration curve allowing in situ measurements. The studies demonstrate the potential for use of graphene as a photothermal actuator across a range of lipid based systems of interest in controlled drug delivery.

Lipid-based drug delivery systems in the treatment of wet age-related macular degeneration.

Recent advances in drug delivery technology have amplified potential opportunities to treat the debilitating diseases that affect the posterior segment of the eye in a less invasive and more efficient manner. Current methods for effective drug delivery to the back of the eye are hindered by many barriers and limitations. As a consequence, considerable efforts have been directed towards developing new materials to selectively deliver drug directly to the target site. This review focuses on lipid-based delivery systems which show promise in improving treatment for the most common disease of the posterior segment of the eye in the developed world, age-related macular degeneration, with an emphasis upon on-demand delivery systems as they have greater potential to overcome the current limitations.

Lipid Liquid-Crystal Phase Change Induced through near-Infrared Irradiation of Entrained Graphene Particles.

Lipid packing is intimately related to the geometry of the lipids and the forces that drive self-assembly. Here, the photothermal response of a cubic liquid-crystalline phase formed using phytantriol in the presence of low concentrations of pristine graphene was evaluated. Small-angle X-ray scattering showed the reversible phase changes from cubic to hexagonal to micellar due to localized heating through irradiation with near-infrared (NIR) light and back to cubic after cooling.

Phospholipid-based self-assembled mesophase systems for light-activated drug delivery.

The manipulation of the structure of phospholipid-based mesophases to induce a slow to fast drug release profile has potential for use in therapeutic situations where continuous absorption of drug is not desirable and reduce the frequency of injection for short acting or rapidly cleared drugs in treatments for diseases such as macular degeneration. This study had two aims; firstly to confirm the phase behaviour of 20 mol% cholesterol in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), which was previously reported to transition from lamellar (slow release) to bicontinuous cubic (fast release) phase with increasing temperature. Contrary to the literature, no bicontinuous cubic phase was observed but a transition to the inverse hexagonal phase occurred at all POPE : cholesterol ratios investigated. The second aim was to render these mesophases responsive to near-infrared laser (NIR) irradiation by incorporation of gold nanorods (GNR) incorporated into the POPE system to induce photothermal heating. The inclusion of 3 nM GNR in POPE systems induced reversible disruption of lipid packing equivalent to increasing the temperature to 55 °C when irradiated for 30 s. This study confirmed that although the previously published phase behavior was not correct, GNR and NIR can be used to manipulate the self-assembled mesophases in phospholipid-based systems and highlights the potential for a phospholipid-based light-activated drug delivery system.

A novel approach to enhance the mucoadhesion of lipid drug nanocarriers for improved drug delivery to the buccal mucosa.

Targeted drug delivery to the buccal mucosa offers distinct advantages over oral delivery to the gastrointestinal tract including by-passing hepatic first-pass metabolism. However, the buccal route is often limited by low bioavailability, low drug loading and reduced residence time due to salivary excretion and clearance. To overcome these limitations, a novel mucoadhesive formulation based on liquid crystalline nanoparticles was designed. Utilising a pH induced in situ transition from a stable vesicle formulation to dispersed inverse hexagonal phase nanoparticles (hexosomes) enhanced adsorption onto the mucosal surface was enabled. Firstly, the phase behaviour of the amphiphilic lipid phytantriol (PHY) and oleic acid (OA) was assessed from pH 2-9 using small-angle X-ray scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) to determine the appropriate composition for the vesicle to hexosome transition. The colloidal stability of the formulation was determined using turbidity studies. Dispersions comprising 30% w/w OA in PHY were able to form stable vesicles at pH 8 and transition to hexosomes when exposed to pH<7 (as encountered on the buccal mucosal surface). Subsequent ex vivo studies utilising excised porcine buccal tissue indicated significant retention of the in situ-formed PHY/OA hexosomes when compared to control DOPC vesicles (p<0.005), confirmed independently using confocal fluorescence microscopy, radioactive scintillation counting and HPLC analysis for incorporated drug. Thus, a novel approach providing a stable vesicle formulation, with in situ transformation to mucoadhesive hexosomes has been identified with the potential to enhance drug delivery to mucosal surfaces.