Effects of Ending the Use of Seclusion and Mechanical Restraint in the Pennsylvania State Hospital System, 2011-2020.

The Pennsylvania State Hospital System's use of containment procedures has been studied for >30 years. This prospective study assessed the effects of ending the use of seclusion and mechanical restraint in the system's six civil hospitals and two forensic centers from 2011 to 2020. The study examined the effect of this change on key safety measures: physical restraint, assaults, aggression, and self-injurious behavior. In total, 68,153 incidents, including 9,518 episodes of physical restraint involving 1,811 individuals, were entered into a database along with patients' demographic and diagnostic information. All data were calculated per 1,000 days to control for census changes. During the study, mechanical restraint was used 128 times and seclusion four times. Physical restraint use decreased from a high of 2.62 uses per 1,000 days in 2013 to 2.02 in 2020. The average length of time a person was held in physical restraint was reduced by 64%, from 6.6 minutes in 2011 to 2.4 minutes in 2020 (p<0.001). All safety measures improved or were unchanged. Use of unscheduled medication did not change. The hospital system safely ended the use of mechanical restraint and seclusion by using a recovery approach and by following the six core strategies for seclusion and restraint reduction.

Internal circulation and mixing within tight-squeezing deformable droplets.

The internal flow and mixing properties inside deformable droplets, after reaching the steady state within two types of passive droplet traps, are visualized and analyzed as dynamical systems. The first droplet trap (constriction) is formed by three spheres arranged in an equilateral triangle, while the second consists of two parallel spherocylinders (capsules). The systems are assumed to be embedded in a uniform far-field flow at low Reynolds number, and the steady shapes and interfacial velocities on the drops are generated using the boundary-integral method. The internal velocity field is recovered by solving the internal Dirichlet problem, also via a desingularized boundary-integral method. Calculation of 2D streamlines within planes of symmetry reveals the internal equilibria of the flow. The type of each equilibrium is classified in 3D and their interactions probed using passive tracers and their Poincaré maps. For the two-capsule droplet, saddle points located on orthogonal symmetry planes influence the regular flow within the drop. For the three-sphere droplet, large regions of chaos are observed, embedded with simple periodic orbits. Flow is visualized via passive dyes, using material lines and surfaces. In 2D, solely the interface between two passive interior fluids is advected using an adaptive number of linked tracer particles. The reduction in dimension decreases the number of required tracer points, and also resolves arbitrarily thin filaments, in contrast to backward cell-mapping methods. In 3D, the advection of a material surface, bounded by the droplet interface, is enabled using an adaptive mesh scheme. Off-lattice 3D contour advection allows for highly resolved visualizations of the internal flow and quantification of the associated degree of mixing. Analysis of the time-dependent growth of material surfaces and 3D mixing numbers suggests the three-sphere droplet exhibits superior mixing properties compared to the two-capsule droplet.

The psychoactive cathinone derivative pyrovalerone alters locomotor activity and decreases dopamine receptor expression in zebrafish (Danio rerio).

INTRODUCTION: Pyrovalerone (4-methyl-ß-keto-prolintane) is a synthetic cathinone (beta-keto-amphetamine) derivative. Cathinones are a concern as drugs of abuse, as related street drugs such as methylenedioxypyrovalerone have garnered significant attention. The primary mechanism of action of cathinones is to inhibit reuptake transporters (dopamine and norepinephrine) in reward centers of the central nervous system. METHODS: We measured bioenergetic, behavioral, and molecular responses to pyrovalerone (nM-µM) in zebrafish to evaluate its potential for neurotoxicity and neurological impairment. RESULTS: Pyrovalerone did not induce any mortality in zebrafish larvae over a 3- and 24-hr period; however, seizures were prevalent at the highest dose tested (100 µM). Oxidative phosphorylation was not affected in the embryos, and there was no change in superoxide dismutase 1 expression. Following a 3-hr treatment to pyrovalerone (1-100 µM), larval zebrafish (6d) showed a dose-dependent decrease (70%-90%) in total distance moved in a visual motor response (VMR) test. We interrogated potential mechanisms related to the hypoactivity, focusing on the expression of dopamine-related transcripts as cathinones can modulate the dopamine system. Pyrovalerone decreased the expression levels of dopamine receptor D1 (~60%) in larval zebrafish but did not affect the expression of tyrosine hydroxylase, dopamine active transporter, or any other dopamine receptor subunit examined, suggesting that pyrovalerone may regulate the expression of dopamine receptors in a specific manner. DISCUSSION: Further studies using zebrafish are expected to reveal new insight into molecular mechanisms and behavioral responses to cathinone derivates, and zebrafish may be a useful model for understanding the relationship between the dopamine system and bath salts.

Psychiatric use of unscheduled medications in the Pennsylvania state hospital system: effects of discontinuing the use of P.R.N. orders.

The objective of this prospective study was to assess patient exposure to the psychiatric use of unscheduled medications at all nine Pennsylvania state hospitals and to unify practice guidelines in this regard. In August 2004, a decision was made to discontinue the use of p.r.n. orders for psychiatric indications. All unscheduled medications, (p.r.n. and STAT physician's order) administered for psychiatric indications were entered into a uniform database. A total of 46,913 unscheduled medications were administered to people served in the hospital system throughout this 15 month study. During March 2004, 87.7 unscheduled medications per 1,000 days-of-care were administered in the hospital system. During the last month of this study, May 2005, this rate had decreased to 17 per 1,000 days-of-care. Many hospital safety measures significantly improved as a result of this change. Cessation of p.r.n. medication use for psychiatric indications has significantly decreased patient exposure to unnecessary psychotropic medications and has resulted in a safer hospital system.

A water-activated pump for portable microfluidic applications.

An on-chip micropump for portable microfluidic applications was investigated using mathematical modeling and experimental testing. This micropump is activated by the addition of water, via a dropper, to ionic polymer particles that swell due to osmotic effects when wetted. The resulting particle volume increase deflects a membrane, forcing a separate fluid from an adjacent reservoir. The micropump components, along with the microfluidic components, are fabricated using the contact liquid photolithographic polymerization (CLiPP) method. The maximum flow rate achieved with this pump is 17 microL per minute per mg of dry polymer particles of 355-425 microm in diameter. The pump flow rate may be controlled by adjusting the particle size and amount, the membrane properties, and the channel dimensions. The experimental results demonstrate good agreement with an analytical model describing the particle swelling and its coupling with resistive forces from the bending membrane, viscous flow in the microchannel, and interfacial effects. Key features of this micropump are that it can be placed directly on a microdevice, and that it requires only a small amount of water and no external power supply to function. Therefore, this pumping system is useful for applications in which a highly portable device is required.

An effervescent reaction micropump for portable microfluidic systems.

A water-activated, effervescent reaction was used to transport fluid in a controllable manner on a portable microfluidic device. The reaction between sodium bicarbonate and an organic acid, tartaric acid and/or benzoic acid, was modeled to analyze methods of controlling the generation of carbon-dioxide gas for the purposes of pumping fluids. Integration and testing of the effervescent reaction pump in a microfluidic device was made possible by using elastomeric polymers as both photopolymerizable septa and removable lids. These materials combined to enable facile access to otherwise gas-tight devices. Based on theoretical predictions for 0.33 mg of sodium bicarbonate and a stoichiometric amount of organic acid, the pumping flow rate could be varied from 0.01 microL s(-1) to 70 microL s(-1). The flow rate is controlled by adjusting any or all of the particle size of the least soluble reactant, the amount of reactants used, and the type of organic acid selected. The tartaric acid systems rapidly produce carbon dioxide; however, the gas generation rates dramatically decrease over the course of the reaction. In contrast, carbon dioxide production rate in the benzoic acid systems is lower and nearly constant for several minutes. Water activation and direct placement on a microfluidic device are key features of this micropump, which is therefore useful for portable microfluidic applications.

In situ fabrication of macroporous polymer networks within microfluidic devices by living radical photopolymerization and leaching.

Novel fabrication techniques and polymer systems are being explored to enable mass production of low cost microfluidic devices. In this contribution we discuss a new fabrication scheme for making microfluidic devices containing porous polymer components in situ. Contact lithography, a living radical photopolymer (LRPP) system and salt leaching were used to fabricate multilayer microfluidic devices rapidly with various channel geometries and covalently attached porous polymer plugs made of various photopolymerizable substrates. LRPP systems offer the advantages of covalent attachment of microfluidic device layers and facile surface modification via grafting. Several applications of the porous plugs are also explored, including a static mixer, a high surface area-to-volume reactor and a rapidly responding hydrogel valve. Quantitative and qualitative data show an increase in mixing of a fluorescein and a water stream for channels containing porous plugs relative to channels with no porous plugs. Confocal laser scanning microscopy images demonstrate the ability to graft a functional material onto porous plug surfaces. A reaction was carried out on the grafted pore surfaces, which resulted in fluorescent labelling of the grafted material throughout the pores of the plug. Homogenous fluorescence throughout the depth of the porous plug and along pore surfaces indicated that the porous plugs were surface modified by grafting and that reactions can be carried out on the pore surfaces. Finally, porous hydrogel valves were fabricated which swelled in response to contact with various pH solutions. Results indicate that a porous hydrogel valve will swell and close more rapidly than other valve geometries made with the same polymer formulation. The LRPP-salt leaching method provides a means for rapidly incorporating porous polymer components into microfluidic devices, which can be utilized for a variety of pertinent applications upon appropriate selection of porous plug materials and surface treatments.

Pennsylvania State Hospital system's seclusion and restraint reduction program.

OBJECTIVES: This study examined the use of seclusion and mechanical restraint from 1990 to 2000 and the rate of staff injuries from patient assaults from 1998 to 2000 in a state hospital system. METHODS: Records of patients older than 18 years who were civilly committed to one of the nine state hospitals in Pennsylvania were included in the analyses. Two databases were used in each of the nine hospitals: one identified date, time, duration, and justification for each episode of seclusion or restraint and the other identified when a patient was hospitalized and the demographic characteristics and the diagnosis of the patient. Rate and duration of seclusion and restraint were calculated. Reports from compensation claims were used to determine staff injuries from patient assaults. RESULTS: The rate and duration of seclusion and mechanical restraint decreased dramatically during this period. From 1990 to 2000, the rate of seclusion decreased from 4.2 to .3 episodes per 1,000 patient-days. The average duration of seclusion decreased from 10.8 to 1.3 hours. The rate of restraint decreased from 3.5 to 1.2 episodes per 1,000 patient-days. The average duration of restraint decreased from 11.9 to 1.9 hours. Patients from racial or ethnic minority groups had a higher rate and longer duration of seclusion than whites. Seclusion tended to be less likely, but longer, during the night shift. Patients were restrained less often during the night shift, but for a longer duration. The rate of restraint was higher during the week than during weekends and holidays. Younger patients were more likely to be secluded and restrained, but older patients remained secluded and restrained longer. No significant changes were seen in rates of staff injuries from 1998 to 2000. CONCLUSIONS: Many factors contributed to the success of this effort, including advocacy efforts, state policy change, improved patient-staff ratios, response teams, and second-generation antipsychotics.

Correlation between reduction of seclusion and restraint and assaults by patients in Pennsylvania's state hospitals.

OBJECTIVE: This prospective study assessed the use of seclusion and restraint in the Pennsylvania state hospital system from 2001 through 2010. It also examined the correlation between declining use of containment procedures and assaults by patients on other patients and staff. METHODS: The 12,900 anonymized records involving the 1,801 unique, civilly committed individuals who were physically or mechanically restrained and secluded in the nine civil hospitals during this study period were entered into a database. The data set included demographic and diagnostic information about the patients and the cause and effect of the procedures. These data were compared with rates of patient-to-patient and patient-to-staff assaults to determine any correlation between changes in use of containment and assaults. RESULTS: From 2001 to 2010, the use of mechanical restraint significantly declined from .37 to .08 episodes per 1,000 days (p<.018), and the use of seclusion significantly declined from .21 to .01 episodes per 1,000 days (p<.001). Persons with an axis I diagnosis of psychotic disorder accounted for 44% of containment procedures used during this study. Patient-to-patient assaults declined slightly, and patient-to-staff assaults were unaffected. CONCLUSIONS: Decreasing the use of containment procedures did not increase assaults. Better leadership, data transparency, use of clinical alerts, workforce development, policy changes, enhanced use of response teams, implementation of dialectical behavior therapy, and discontinuation of the psychiatric use of PRN orders contributed to the change in use of containment procedures. A philosophical change to a recovery model of psychiatric care and services was the driving force behind this transformation.

Relationship Between Seclusion and Restraint Reduction and Assaults in Pennsylvania's Forensic Services Centers: 2001-2010.

OBJECTIVE: This prospective study assessed the use of seclusion and restraint in Pennsylvania forensic centers from 2001 through 2010. It also examined the correlation between declining use of containment procedures and patient-to-patient and patient-to-staff assaults. METHODS: The 2,741 episodes of restraint or seclusion involving 801 unique individuals served in state forensic centers during the study period were entered into a uniform database. Included in this data set were demographic and diagnostic data as well as the causes and injuries associated with each use of these procedures. These data were correlated with rates of patient-to-patient and patient-to-staff assaults with any injury for each month of this study. RESULTS: From 2001 to 2010, the rate of use of mechanical restraint significantly declined from 1.63 to .04 episodes per 1,000 days (p<.001), and the rate of use of seclusion significantly declined from .89 to .04 episodes per 1,000 days (p<.001). There was a nonsignificant decline in the use of physical restraint during this span. During this decade, the rate of patient-to-staff assaults declined, and the rate of patient-to-patient assaults was unaffected. CONCLUSIONS: Decreasing the use of containment procedures had a positive effect on reducing assaults. Leadership, data transparency, use of clinical alerts, workforce development, policy changes, and discontinuation of psychiatric use of PRN orders were all contributing factors. A philosophical change toward a recovery model of psychiatric care and services was the driving force behind this transformation.

Buoyancy-driven coalescence of spherical drops covered with incompressible surfactant at arbitrary Péclet number.

Collision efficiencies are determined for two surfactant-covered spherical drops in the limits of nearly uniform surface coverage and bulk insolubility for Brownian and/or gravitational motion as a function of drop-size ratio, drop-to-medium viscosity ratio, and retardation parameter. For two equal-sized drops in Brownian motion in the limit of small viscosity ratio, the calculated collision efficiencies agree well with earlier results for bubbles. While the two-sphere relative mobility functions for motion parallel to the drops' line of centers tend to the same values in the limits of infinite viscosity ratio and infinite retardation parameter, the asymmetric mobility functions do not, because the coefficients for the rotational term in Lamb's singular solution are independent of the presence of surfactant. The complex dependence of the transverse mobility functions on the viscosity ratio and retardation parameter makes it possible for the gravitational collision efficiency to increase slightly with viscosity ratio at fixed size ratio and retardation parameter of O(10(3)) or larger. Typical hydrosols are also studied in gravitational motion at arbitrary Péclet number, showing the combined influence of Brownian and gravitational motion.

Electroosmotic flow in channels with step changes in zeta potential and cross section.

We consider the effects that step changes in zeta potential and cross section have on electroosmosis in long-and-narrow channels with arbitrary cross-sectional shapes. The Stokes equation of flow is solved analytically utilizing the thin Debye layer approximation to provide effective slip velocities on the channel walls. The effects of channel dimensions, surface potentials, applied pressure drop, and applied voltage are discussed. One anecdotal case, a two-region rectangular channel, is presented to illustrate the solution. The flow in each region is a combination of a uniform electroosmotic flow and a nonuniform pressure-driven flow. The electroosmotic pumping causes the pressure gradient in each region to adjust so that the flow rate is the same in each region and the overall applied pressure drop is met, resulting in convex velocity profiles in some regions and concave velocity profiles in other regions. By appropriate choice of the applied pressure drop, flat velocity profiles may be achieved in one or more regions.

A three-dimensional boundary-integral algorithm for thermocapillary motion of deformable drops.

A three-dimensional boundary-integral algorithm has been developed to handle the tangential Marangoni stresses in thermocapillary motion of drops. Depending on whether the integration and observation points are on the same or different drops, singularity or near-singularity subtraction is used in the inhomogeneous term of the boundary-integral formulation. Integration is then performed analytically over flat triangles in the subtracted region. Relative trajectories for two deformable drops are calculated for different values of the drop size ratio, drop-to-medium thermal conductivity ratio, and viscosity ratio and compared to those for spherical and slightly deformable drops. Results indicate that deformation increases the minimum separation and inhibits coalescence but is not important enough for appropriate physical parameters to induce the capture or breakup behaviors observed in buoyancy. Interaction times calculated by artificially continuing spherical drop trajectories yield results accurate to within about 10%.

Secondary membranes for flux optimization in membrane filtration of biologic suspensions.

We employ in situ deposited secondary membranes of yeast (SMYs) to optimize permeate flux during microfiltration and ultrafiltration of protein solutions. The deposited secondary membrane was periodically removed by backflushing, and a new cake layer was deposited at the start of the next cycle. The effects of backflushing time, backflushing strength, wall shear rate, and amount of secondary membrane deposited on the permeate flux were examined. Secondary membranes were found to increase the permeate flux in microfiltration by severalfold. Protein transmission was also enhanced owing to the presence of the secondary membrane, and the amount of protein recovered was more than twice that obtained during filtration of protein-only solutions under otherwise identical conditions. In ultrafiltration, the flux enhancement owing to the secondary membrane was only 50% or less. In addition, the flux for ultrafiltration was relatively insensitive to changes in the concentration of yeast used during deposition of SMY and to the backflushing strength used to periodically remove the secondary membrane.

Cellulase retention and sugar removal by membrane ultrafiltration during lignocellulosic biomass hydrolysis.

Technologies suitable for the separation and reuse of cellulase enzymes during the enzymatic saccharification of pretreated corn stover are investigated to examine the economic and technical viability of processes that promote cellulase reuse while removing inhibitory reaction products such as glucose and cellobiose. The simplest and most suitable separation is a filter with relatively large pores on the order of 20-25 mm that retains residual corn stover solids while passing reaction products such as glucose and cellobiose to form a sugar stream for a variety of end uses. Such a simple separation is effective because cellulase remains bound to the residual solids. Ultrafiltration using 50-kDa polyethersulfone membranes to recover cellulase enzymes in solution was shown not to enhance further the saccharification rate or overall conversion. Instead, it appears that the necessary cellulase enzymes, including beta-glucosidase, are tightly bound to the substrate; when fresh corn stover is contacted with highly washed residual solids, without the addition of fresh enzymes, glucose is generated at a high rate. When filtration was applied multiple times, the concentration of inhibitory reaction products such as glucose and cellobiose was reduced from 70 to 10 g/L. However, an enhanced saccharification performance was not observed, most likely because the concentration of the inhibitory products remained too high. Further reduction in the product concentration was not investigated, because it would make the reaction unnecessarily complex and result in a product stream that is much too dilute to be useful. Finally, an economic analysis shows that reuse of cellulase can reduce glucose production costs, especially when the enzyme price is high. The most economic performance is shown to occur when the cellulase enzyme is reused and a small amount of fresh enzyme is added after each separation step to replace lost or deactivated enzyme.

Combined sedimentation and filtration process for cellulase recovery during hydrolysis of lignocellulosic biomass.

A combined sedimentation and ultrafiltration process was investigated for recovering cellulase enzymes during the hydrolysis of lignocellulosic biomass. Lignocellulosic particles larger than approx 50 microm in length were first removed via sedimentation using an inclined settler. Ultrafiltration was then used to retain the remaining lignocellulosic particles and the cellulose enzymes, while transmitting fermentable sugars and other small molecules. The permeate flux from the ultrafiltration step for a feed consisting of 0.22 w/v% cellulase is 64+/-5 L/m2-h, while that for a feed consisting of the settler overflow from a mixture 0.22 w/v% cellulase and 10 wt% lignocellulose fed to the settler is 130+/-20 L/m2-h. The higher permeate flux in the latter case is presumably due to binding of a portion of the cellulase enzymes to the lignocellulosic particles during hydrolysis and filtration, preventing the enzymes from fouling the membrane. A filter paper activity assay shows little loss in enzymatic activity throughout the combined sedimentation/ultrafiltration separation process.

Simulations of gravity-induced trapping of a deformable drop in a three-dimensional constriction.

An efficient algorithm is developed to determine the three-dimensional shape of a deformable drop trapped under gravity in a constriction, employing an artificial evolution to a steady state. During the simulation, the drop surface is advanced using a rationally-devised normal "velocity", based on local deviation from the Young-Laplace equation and the adjacent solid shape, to approach the trapped drop shape. The artificial "time-dependent" evolution of the drop to the static, trapped shape requires that the free portions of the drop interface eventually satisfy the Young-Laplace equation, and the drop-solid contact portions of the drop interface conform to the solid surface. The significant advantage of this solution method is that a simple, numerically-efficient "velocity" is used to construct the evolution to the steady state; the coated areas where the drop is in near contact with solid boundaries of the constriction do not have to be specified a priori, but are found in the course of the solution. Alternative methods (e.g., boundary integral) based on realistic time-marching would be much more costly for determining the trapped state. Trapping conditions and drop shapes are studied for gravity-induced settling of a deformable drop into a three-dimensional constriction. For conditions near critical, where the trapped-drop steady state ceases to exist, severe surface-mesh distortions are treated by a combination of 'passive mesh stabilization', mesh relaxation and topological mesh transformations through node reconnections. For Bond numbers above a critical value, the drop is deformable enough to pass through the hole of the constriction, with no trapping. Critical Bond numbers are determined by linearly fitting minima of the root-mean-squared (rms) surface velocities versus corresponding Bond numbers greater than critical, and then extrapolating the Bond number to where the minimum rms velocity is zero (i.e., the drop becomes trapped). For ring and hyperbolic-tube constrictions, with axes parallel to the gravity vector, the results for trapped drops and critical Bond numbers are in close agreement with those obtained by the previous, highly-accurate axisymmetric method [1]. Also, the three-dimensional Young-Laplace and boundary-integral methods show good agreement for the static shape of a drop trapped in a tilted three-sphere constriction. For all constriction types studied, including circular rings, hyperbolic tubes and agglomerates of three and four spheres, the critical Bond number increases nearly linearly with an increase in the drop-to-hole size ratio. In contrast, the constriction type and tilt angle, which is the angle between the gravity vector and the normal to the plane of the constriction hole, have generally a weaker effect on the critical Bond number.

Mechanisms for agglomeration and deagglomeration following oblique collisions of wet particles.

Previous studies on wetted, particle-particle collisions have been limited to head-on collisions, but in many-particle flows, collisions are inherently oblique. In this work, we explore such oblique collisions experimentally and theoretically. Whereas in normal collisions particles rebound only due to solid deformation, we observe in oblique collisions a new outcome where the particles initially form a rotating doublet and then deagglomerate at a later time due to so-called centrifugal forces. Surprisingly, we discover the essential role of capillary forces in oblique collisions even when the capillary number (viscous over capillary forces) is high. This recognition leads to the introduction of a dimensionless number, the centrifugal number (centrifugal over capillary forces), which together with the previously established Stokes number characterizes the regime map of outcomes. Unexpectedly, we observe a normal restitution coefficient greater than unity at large impact angles, the mechanism for which may also be observed in other agglomerating systems.

Soft-lithography fabrication of microfluidic features using thiol-ene formulations.

In this work, a novel thiol-ene based photopolymerizable resin formulation was shown to exhibit highly desirable characteristics, such as low cure time and the ability to overcome oxygen inhibition, for the photolithographic fabrication of microfluidic devices. The feature fidelity, as well as various aspects of the feature shape and quality, were assessed as functions of various resin attributes, particularly the exposure conditions, initiator concentration and inhibitor to initiator ratio. An optical technique was utilized to evaluate the feature fidelity as well as the feature shape and quality. These results were used to optimize the thiol-ene resin formulation to produce high fidelity, high aspect ratio features without significant reductions in feature quality. For structures with aspect ratios below 2, little difference (<3%) in feature quality was observed between thiol-ene and acrylate based formulations. However, at higher aspect ratios, the thiol-ene resin exhibited significantly improved feature quality. At an aspect ratio of 8, raised feature quality for the thiol-ene resin was dramatically better than that achieved by using the acrylate resin. The use of the thiol-ene based resin enabled fabrication of a pinched-flow microfluidic device that has complex channel geometry, small (50 µm) channel dimensions, and high aspect ratio (14) features.