Nurse-Driven Interprofessional Rounds: Improving Care Coordination and Length of Stay.

BACKGROUND: Inpatient oncology units care for patients with some of the most complex medical conditions outside of the intensive care unit. These patients benefit from structured care coordination. Reduced ability to admit patients to oncology beds contributes to delays in specialty care. OBJECTIVES: This quality improvement initiative established nurse-driven interprofessional rounds (IPRs) to reduce length of stay (LOS), improve discharge time of day, and enhance care coordination, patient flow, and access to care in the community. METHODS: Care coordination during enhanced IPRs (eIPRs) included estimation of discharge dates, comparison of LOS to a standard geometric mean LOS, and discussion of clinical milestones and barriers to progression and discharge. Data analysis evaluated the effect of eIPRs on key outcomes. FINDINGS: Although LOS variance was reduced by 15.8% and 44.1% in all-unit and hematology-oncology discharges, respectively, the results were not significant. Discharges by 2 pm improved significantly for all-unit and hematology-oncology populations, respectively. Patient flow measured by accepted patient transfers requesting hematology-oncology services improved significantly.

Oyster hatchery breakthrough of two HABs and potential effects on larval eastern oysters (Crassostrea virginica).

Harmful algal bloom (HAB) dinoflagellate species Karlodinium veneficum and Prorocentrum cordatum (prev. P. minimum) are commonly found in Chesapeake Bay during the late spring and early summer months, coinciding with the spawning season of the eastern oyster (Crassostrea virginica). Unexplained larval oyster mortalities at regional commercial hatcheries prompted screening of oyster hatchery water samples for these HAB species. Both HAB species were found in treated hatchery water during the oyster spawning season, sometimes exceeding bloom cell concentrations (≥ 1,000 cells/mL). To investigate the potential for these HAB species, independently or in co-exposure, to affect larval oyster mortality and activity, 96-h laboratory single and dual HAB bioassays with seven-day-old oyster larvae were performed. Treatments for the single HAB bioassay included fed and unfed controls, K. veneficum at 1,000; 5,000; 10,000; and 50,000 cells/mL, P. cordatum at 100; 5,000; 10,000; and 50,000 cells/mL. Subsequently, the 1,000 cells/mL K. veneficum and 50,000 cells/mL P. cordatum treatments were combined in a co-exposure treatment for the dual HAB bioassay. At all cell concentrations tested, K. veneficum swarmed oyster larvae and caused significant larval oyster mortality by 96 h (Karlo1,000: 21 ± 5%; Karlo5,000: 93 ± 2%; Karlo10,000: 85 ± 3%; Karlo50,000: 83 ± 5%, SE). In contrast, there was no significant difference in larval oyster mortality between the control treatments and any of the P. cordatum treatments by 96 h. By 24 h, larval oysters were significantly less active (immotile) in the presence of either HAB species as compared to control treatments (e.g., Karlo1,000: 37.8 ± 4.1%; Proro100: 47.3 ± 7.4%; Fed: 10.8 ± 3.2%; Unfed: 10.1 ± 4.9%, SE). In the dual HAB bioassay, larval oyster mortality associated with 1,000 cells/mL K. veneficum (44 ± 9%, SE) was not changed by the addition of 50,000 cells/mL P. cordatum (55 ± 7%, SE), demonstrating that K. veneficum was primarily responsible for the observed mortality. This study demonstrated that even low cell concentrations of K. veneficum and P. cordatum are harmful to larval oysters, and could contribute to reductions in oyster hatchery production through impacts on this critical life stage.

Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis.

Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A novel approach to mitigate the progression of local tissue damage that could complement the antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel nanoparticle engineered to bind to and modulate the activity of a diverse array of PLA2 and 3FTX isoforms found in Elapidae snake venoms. These two families of protein toxins share features that are associated with their common (membrane) targets, allowing for nanoparticle sequestration by a mechanism that differs from immunological (epitope) selection. The nanoparticles are non-toxic in mice and inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom.

Clozapine usage increases the incidence of pneumonia compared with risperidone and the general population: a retrospective comparison of clozapine, risperidone, and the general population in a single hospital over 25 months.

The aim of this study was to determine whether the incidence of pneumonia in patients taking clozapine was more frequent compared with those taking risperidone or no atypical antipsychotics at all before admission to a tertiary care medical center. This was a retrospective, case-matched study of 465 general medicine patients over a 25 month period from 1 July 2010 to 31 July 2012. Detailed electronic medical records were analyzed to explore the association between the use of two atypical antipsychotics and incidence of pneumonia. Of the 155 patients in the clozapine group, 54 (34.8%) had documented pneumonia compared with 22 (14.2%) in the risperidone group and 18 (11.6%) in the general population group. Clozapine, when compared with the untreated general population, was associated with an increased risk of pneumonia (odds ratio=4.07; 95% confidence interval=2.25-7.36). There was, however, no significant increase in the risk of pneumonia associated with the use of risperidone (odds ratio=1.26; 95% confidence interval=0.65-2.45). Clozapine use is associated with increased risk of pneumonia that may be related to immunologic factors or side effects of sedation and drooling that make aspiration more likely, although causative mechanisms require further investigation. These findings suggest that providers should use added caution in choosing candidates for clozapine therapy.

Engineering the Protein Corona of a Synthetic Polymer Nanoparticle for Broad-Spectrum Sequestration and Neutralization of Venomous Biomacromolecules.

Biochemical diversity of venom extracts often occurs within a small number of shared protein families. Developing a sequestrant capable of broad-spectrum neutralization across various protein isoforms within these protein families is a necessary step in creating broad-spectrum antivenom. Using directed synthetic evolution to optimize a nanoparticle (NP) formulation capable of sequestering and neutralizing venomous phospholipase A2 (PLA2), we demonstrate that broad-spectrum neutralization and sequestration of venomous biomacromolecules is possible via a single optimized NP formulation. Furthermore, this optimized NP showed selectivity for venomous PLA2 over abundant serum proteins, was not cytotoxic, and showed substantially long dissociation rates from PLA2. These findings suggest that it may show efficacy as an in vivo venom sequestrant and may serve as a generalized lipid-mediated toxin sequestrant.

Tuning the Protein Corona of Hydrogel Nanoparticles: The Synthesis of Abiotic Protein and Peptide Affinity Reagents.

Nanomaterials, when introduced into a complex, protein-rich environment, rapidly acquire a protein corona. The type and amount of proteins that constitute the corona depend significantly on the synthetic identity of the nanomaterial. For example, hydrogel nanoparticles (NPs) such as poly(N-isopropylacrylamide) (NIPAm) have little affinity for plasma proteins; in contrast, carboxylated poly(styrene) NPs acquire a dense protein corona. This range of protein adsorption suggests that the protein corona might be "tuned" by controlling the chemical composition of the NP. In this Account, we demonstrate that small libraries of synthetic polymer NPs incorporating a diverse pool of functional monomers can be screened for candidates with high affinity and selectivity to targeted biomacromolecules. Through directed synthetic evolution of NP compositions, one can tailor the protein corona to create synthetic organic hydrogel polymer NPs with high affinity and specificity to peptide toxins, enzymes, and other functional proteins, as well as to specific domains of large proteins. In addition, many NIPAm NPs undergo a change in morphology as a function of temperature. This transformation often correlates with a significant change in NP-biomacromolecule affinity, resulting in a temperature-dependent protein corona. This temperature dependence has been used to develop NP hydrogels with autonomous affinity switching for the protection of proteins from thermal stress and as a method of biomacromolecule purification through a selective thermally induced catch and release. In addition to temperature, changes in pH or buffer can also alter a NP protein corona composition, a property that has been exploited for protein purification. Finally, synthetic polymer nanoparticles with low nanomolar affinity for a peptide toxin were shown to capture and neutralize the toxin in the bloodstream of living mice. While the development of synthetic polymer alternatives to protein affinity reagents is in its early stages, these recent successes using only small libraries of functional monomers are most encouraging. It is likely that by expanding the chemical diversity of functional hydrogels and other polymers, a much broader range of NP-biomacromolecule affinity pairs will result. Since these robust, nontoxic polymers are readily synthesized in the chemistry laboratory, we believe the results presented in this Account offer a promising future for the development of low cost alternatives to more traditional protein affinity reagents such as antibodies.

Polymer antidotes for toxin sequestration.

Toxins delivered by envenomation, secreted by microorganisms, or unintentionally ingested can pose an immediate threat to life. Rapid intervention coupled with the appropriate antidote is required to mitigate the threat. Many antidotes are biological products and their cost, methods of production, potential for eliciting immunogenic responses, the time needed to generate them, and stability issues contribute to their limited availability and effectiveness. These factors exacerbate a world-wide challenge for providing treatment. In this review we evaluate a number of polymer constructs that may serve as alternative antidotes. The range of toxins investigated includes those from sources such as plants, animals and bacteria. The development of polymeric heavy metal sequestrants for use as antidotes to heavy metal poisoning faces similar challenges, thus recent findings in this area have also been included. Two general strategies have emerged for the development of polymeric antidotes. In one, the polymer acts as a scaffold for the presentation of ligands with a known affinity for the toxin. A second strategy is to generate polymers with an intrinsic affinity, and in some cases selectivity, to a range of toxins. Importantly, in vivo efficacy has been demonstrated for each of these strategies, which suggests that these approaches hold promise as an alternative to biological or small molecule based treatments.

Amphiphilic graft copolymers from end-functionalized starches: synthesis, characterization, thin film preparation, and small molecule loading.

End-functionalized macromolecular starch reagents, prepared by reductive amination, were grafted onto a urethane-linked polyester-based backbone using copper-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to produce novel amphiphilic hybrid graft copolymers. These copolymers represent the first examples of materials where the pendant chains derived from starch biopolymers have been incorporated into a host polymer by a grafting-to approach. The graft copolymers were prepared in good yields (63-90%) with high grafting efficiencies (66-98%). Rigorous quantitative spectroscopic analyses of both the macromolecular building blocks and the final graft copolymers provide a comprehensive analytical toolbox for deciphering the reaction chemistry. Due to the modular nature of both the urethane-linked polyester synthesis and the postpolymerization modification, the starch content of these novel hybrid graft copolymers was easily tuned from 28-53% (w/w). The uptake of two low molecular weight guest molecules into the hybrid polymer thin films was also studied. It was found that binding of 1-naphthol and pterostilbene correlated linearly with amount of starch present in the hybrid polymer. The newly synthesized graft copolymers were highly processable and thermally stable, therefore, opening up significant opportunities in film and coating applications. These results represent a proof-of-concept system for not only the construction of starch-containing copolymers, but also the loading of these novel polymeric materials with active agents.

Effectiveness of symptom validity measures in identifying cognitive and behavioral symptom exaggeration in adult attention deficit hyperactivity disorder.

This study examines the effectiveness of symptom validity measures to detect suspect effort in cognitive testing and invalid completion of ADHD behavior rating scales in 268 adults referred for ADHD assessment. Patients were diagnosed with ADHD based on cognitive testing, behavior rating scales, and clinical interview. Suspect effort was diagnosed by at least two of the following: failure on embedded and free-standing SVT measures, a score > 2 SD below the ADD population average on tests, failure on an ADHD behavior rating scale validity scale, or a major discrepancy between reported and observed ADHD behaviors. A total of 22% of patients engaged in symptom exaggeration. The Word Memory test immediate recall and consistency score (both 64%), TOVA omission errors (63%) and reaction time variability (54%), CAT-A infrequency scale (58%), and b Test (47%) had good sensitivity as well as at least 90% specificity. Clearly, such measures should be used to help avoid making false positive diagnoses of ADHD.

Category label and response location shifts in category learning.

The category shift literature suggests that rule-based classification, an important form of explicit learning, is mediated by two separate learned associations: a stimulus-to-label association that associates stimuli and category labels, and a label-to-response association that associates category labels and responses. Three experiments investigate whether information-integration classification, an important form of implicit learning, is also mediated by two separate learned associations. Participants were trained on a rule-based or an information-integration categorization task and then the association between stimulus and category label, or between category label and response location was altered. For rule-based categories, and in line with previous research, breaking the association between stimulus and category label caused more interference than breaking the association between category label and response location. However, no differences in recovery rate emerged. For information-integration categories, breaking the association between stimulus and category label caused more interference and led to greater recovery than breaking the association between category label and response location. These results provide evidence that information-integration category learning is mediated by separate stimulus-to-label and label-to-response associations. Implications for the neurobiological basis of these two learned associations are discussed.

The Prep statistic as a measure of confidence in model fitting.

In traditional statistical methodology (e.g., the ANOVA), confidence in the observed results is often assessed by computing thep value or the power of the test. In most cases, adding more participants to a study will improve these measures more than will increasing the amount of data collected from each participant. Thus, traditional statistical methods are biased in favor of experiments with large numbers of participants. This article proposes a method for computing confidence in the results of experiments in which data are collected from a few participants over many trials. In such experiments, it is common to fit a series of mathematical models to the resulting data and to conclude that the best-fitting model is superior. The probability of replicating this result (i.e., Prep) is derived for any two nested models. Simulations and empirical applications of this new statistic confirm its utility in studies in which data are collected from a few participants over many trials.

The effects of positive versus negative feedback on information-integration category learning.

A number of studies have shown that in category learning, providing feedback about errors allows faster learning than providing feedback about correct responses. However, these previous studies used explicit, rule-based tasks in which the category structures could be separated by a simple rule that was easily verbalized. Here, the results of the first experiment known to compare the efficacy of positive versus negative feedback during information-integration category learning are reported. Information-integration tasks require participants to integrate perceptual information from incommensurable dimensions, and evidence suggests that optimal responding recruits procedural learning. The results show that although nearly all of the full-feedback control participants demonstrated information-integration learning, participants receiving either positive-only or negative-only feedback generally used explicit, rule-based strategies. It thus appears that, unlike rule-based learning, consistent information-integration learning requires full feedback. The theoretical implications of these findings for current models of information-integration learning are discussed.

Category learning and multiple memory systems.

Categorization is a vitally important skill that people use every day. Early theories of category learning assumed a single learning system, but recent evidence suggests that human category learning may depend on many of the major memory systems that have been hypothesized by memory researchers. As different memory systems flourish under different conditions, an understanding of how categorization uses available memory systems will improve our understanding of a basic human skill, lead to better insights into the cognitive changes that result from a variety of neurological disorders, and suggest improvements in training procedures for complex categorization tasks.