Using a Clinical Triggers System to Improve Early Recognition of Clinical Changes.

PURPOSE: A medical-surgical telemetry unit implemented a clinical triggers system for early recognition of clinical deterioration and bedside management between nurses and providers. The goal was to decrease cardiopulmonary arrest events. DESCRIPTION OF THE PROJECT: A clinical triggers system was developed to help nurses to identify clinical markers early and advocate for prompt bedside assessment and interventions. When clinical triggers were identified, the nurse notified the provider, who performed a bedside assessment within 15 minutes. If the provider did not respond promptly, the rapid response team was activated. OUTCOMES: Before intervention, the unit experienced 14 cardiopulmonary arrest events (rate of 1.37 per 1000 patient days). Incidences decreased annually to 5, 4, and 3 events (rates of 0.49, 0.39, and 0.3 per 1000 patient days) during the 3-year implementation period. CONCLUSIONS: The clinical triggers system was successful in achieving the project objective of decreasing unit cardiopulmonary arrest events through early recognition and response to patient deterioration during the implementation period. The clinical nurse specialist helped nurses to use the clinical triggers system to detect and respond to clinical changes. Nurses were empowered to address concerns and promote patient safety.

Anticancer Ru and Os complexes of N-(4-chlorophenyl)pyridine-2-carbothioamide: Substitution of the labile chlorido ligand with phosphines.

Half-sandwich MII(cym)Cl (cym = Î·6-p-cymene; M = Ru, Os) complexes of pyridinecarbothioamide (PCA) ligands have demonstrated potential as orally active anticancer agents. In order to investigate the impact of the substitution of the labile chlorido ligand with phosphorous donor ligands on the antiproliferative properties, the triphenylphosphine (PPh3) and 1,3,5-triaza-7-phophaadamantane (pta) analogues were prepared and characterized by spectroscopic techniques and the molecular structures of several complexes were determined by X-diffraction analysis. Interestingly, the molecular structures contained the PCA ligand deprotonated, presumably driven by the reduction in overall charge of the complex. Density Functional Theory (DFT) calculations suggested minor energy differences between the protonated and deprotonated forms. The aqueous stability and the reactivity with the amino acids l-histidine and l-cysteine were investigated by 1H NMR spectroscopy of representative examples. The most potent anticancer agents featured Ru or Os centers and a PPh3 ligand and showed IC50 values in the submicromolar range against four cancer cell lines. This suggests that the antiproliferative activity was mainly dependent on the lipophilic properties of the phosphine ligand with PPh3 having a significantly higher clog P value than pta.

Triazolyl- vs Pyridyl-Functionalized N-Heterocyclic Carbene Complexes: Impact of the Pendant N-Donor Ligand on Intramolecular C-C Bond Formation.

Organometallic Rh(Cp*) (Cp* = η5-pentamethylcyclopentadienyl) complexes with monodentate N-heterocyclic carbene (NHC) ligands bearing a pendant anthracenyl substituent have been shown to undergo intramolecular C-C coupling reactions. Herein, two bidentate NHC ligands substituted with pyridyl or triazolyl donor groups were prepared along with the corresponding MII/III (M = RuII, OsII, RhIII, IrIII) complexes. While the Rh(Cp*) complex featuring an NHC-triazole bidentate ligand underwent the equivalent reaction as the monodentate Rh(NHC) complex, i.e., it formed a polydentate ligand, the pyridyl-pendant derivative was unequivocally shown to be unreactive. This contrasting behavior was further investigated by density functional theory (DFT) calculations that highlighted significant differences between the two types of Rh(III) complexes with pendant pyridyl or triazolyl N-coordinating groups. Modeling of the reaction pathways suggests that the initial formation of a dicationic Rh(III) species is unfavorable and that the internal ligand transformation proceeds first by dissociation of the coordinated N atom of the pendant group from the Rh center. After the formation of a neutral η4-fulvene ligand via combined proton/single electron transfer, a cycloaddition occurs between the exo-ene bond of fulvene and the 9' and 10' positions on the pendant anthracenyl group. The resulting experimental UV-visible spectrum recorded in methanol of the polydentate triazolyl-based Rh species revealed the loss of the vibronic coupling typically associated with an anthracenyl functional group. Moreover, TD-DFT modeling indicates the presence of an equilibrium process whereby the N-coordination of the pendant triazolyl group to the RhIII center appears to be highly labile. Charge decomposition analysis (CDA) of the DFT-modeled species with the dissociated triazolyl group revealed a pseudo-η3-allylic interaction between the π-type MOs of the transformed anthracenyl group and the RhIII center; thus, the singly attached chelating ligand is classified as having rare nonadenticity.

Factors That Determine the Experience of Transition to an Inpatient Palliative Care Unit for Patients and Caregivers: A Qualitative Study.

Objective: Transitions in care settings near the end of life can present challenges to patients and families, especially when there are also adjustments in level of care and illness trajectory. In this study, we explored what factors influenced how patients and family caregivers experienced a transition to an inpatient Palliative Care Unit (PCU). Methods: This qualitative study was conducted at a PCU in Toronto, Canada. Semi-structured interviews were held with 29 participants (14 patients and 15 family caregivers) during their time on the PCU. Data was analyzed through an iterative process of constant comparison to generate themes. The recruitment process continued to the point of thematic saturation. Results: Five themes were identified that represented the participants' experiences in transitioning to the PCU: Being prepared, Feeling supported, Coming to terms with end of life issues, Dealing with uncertainty, and Continuity of care. Conclusions: Our findings highlight the need for clear and iterative communication with patients and family caregivers during the transition to a PCU. Identification and consideration of the common themes involved in the experience of transfer to PCU can help guide future practice and improve the experience of patients and families during transitions at the end of life.

Clinical Nurse Specialist Expands to Crisis Management Role During COVID-19 Pandemic.

PURPOSE: Emergence of the COVID-19 crisis into the healthcare system challenged existing roles and shifted organizational priorities and staff responsibilities. Operating within the spheres of impact, clinical nurse specialists (CNSs) adapted to the needs of the organization and expanded their responsibilities to provide crisis leadership. DESCRIPTION OF PROJECT: The CNSs used advanced practice nursing skills and leadership to implement hospital rounds, identify issues, make decisions, collaborate with stakeholders, disseminate new and emerging information, and evaluate processes in an ongoing pandemic. Using the health crisis management framework, the CNSs demonstrated authentic leadership throughout the prevention, preparedness, response, recovery, and rehabilitation phases. OUTCOME: Data analysis of CNS handoff and meeting communications generated these areas of focus involving the CNSs: (1) clinical practice, (2) supplies, (3) workflows, and (4) people. CONCLUSION: The CNS played a vital role in the planning, training, and evaluation of crisis preparation. New and emerging infectious diseases may continue to confront the healthcare system. Thus, healthcare systems need to remain prepared for public health threats. In the crisis leadership role, the CNS helped the transition to learn and relearn practices. As authentic leaders, CNSs instilled calmness, confidence, trust, and resiliency to the staff during the COVID-19 pandemic.

Anthracenyl Functionalization of Half-Sandwich Carbene Complexes: In Vitro Anticancer Activity and Reactions with Biomolecules.

N-Heterocyclic carbene (NHC) ligands are widely investigated in medicinal inorganic chemistry. Here, we report the preparation and characterization of a series of half-sandwich [M(L)(NHC)Cl2] (M = Ru, Os, Rh, Ir; L = cym/Cp*) complexes with a N-flanking anthracenyl moiety attached to imidazole- and benzimidazole-derived NHC ligands. The anticancer activity of the complexes was investigated in cell culture studies where, in comparison to a Rh derivative with an all-carbon-donor-atom-based ligand (5a), they were found to be cytotoxic with IC50 values in the low micromolar range. The Ru derivative 1a was chosen as a representative for stability studies as well as for biomolecule interaction experiments. It underwent partial chlorido/aqua ligand exchange in DMSO-d6/D2O to rapidly form an equilibrium in aqueous media. The reactions of 1a with biomolecules proceeded quickly and resulted in the formation of adducts with amino acids, DNA, and protein. Hen egg white lysozyme crystals were soaked with 1a, and the crystallographic analysis revealed an interaction with an l-aspartic acid residue (Asp119), resulting in the cleavage of the p-cymene ligand but the retention of the NHC moiety. Cell morphology studies for the Rh analog 3a suggested that the cytotoxicity is exerted via mechanisms different from that of cisplatin.

Heptadentate, Octadentate, Or Even Nonadentate? Denticity in the Unexpected Formation of an All-Carbon Donor-Atom Ligand in RhIII(Cp*)(Anthracenyl-NHC) Complexes.

Investigations on incorporating an N-flanking anthracenyl moiety to [Rh(Cp*)(NHC)Cl2] complexes surprisingly led to the formation of an intramolecular C-C bond between the Cp* and anthracenyl moieties, with additional auxiliary interactions between the metal and the anthracenyl ring system. In silico modeling supports a reaction mechanism whereby Rh(η4-tetramethylfulvene) intermediates undergo metallocycloaddition and the abstraction of a chlorido ligand, affording unique cationic complexes that feature Rh centers coordinated by a nonadentate ligand with exclusively carbon donor atoms. Some Rh-C interactions were extremely weak but nevertheless exhibited covalent bonding character. These weak Rh-C interactions were readily displaced by stronger electron donors, and the nonadentate ligand reverted to the heptadentate coordination mode observed in the intermediate. As far as we are aware, this study provides the first conclusive evidence of complexes bearing a single nonadentate κ9-coordinating ligand that features only carbon donors bound to a metal center.

A Bioactive l-Phenylalanine-Derived Arene in Multitargeted Organoruthenium Compounds: Impact on the Antiproliferative Activity and Mode of Action.

RuII(η6-arene) compounds carrying bioactive flavonol ligands have shown promising anticancer activity against tumor cells via a multitargeting mode of action, i.e., through interaction with DNA and inhibition of topoisomerase IIα. By introducing a novel arene ligand based on the amino acid l-phenylalanine (Phe), we aimed to alter the pharmacological properties of the complexes. We report here a series of novel RuII(η6-arene)Cl complexes with different substituents on the phenyl ring of the flavonol which should maintain the multitargeting capability of the parent η6- p-cymene (cym) complexes. Studies with selected examples revealed stability in aqueous solution after quickly forming aqua complexes but rapid decomposition in pure DMSO. The reactions with protein and DNA models proceeded quickly and resulted in cleavage of the flavonol or adduct formation, respectively. The compounds were found to be cytotoxic with significant antiproliferative activity in cancer cells with IC50 values in the low µM range, while not following the same trends as observed for the cym analogues. Notably, the cellular accumulation of the new derivatives was significantly higher than for their respective cym complexes, and they induced DNA damage in a manner similar to that of cisplatin but to a lesser extent.

Predictors of Antimicrobial Stewardship Program Recommendation Disagreement.

OBJECTIVETo identify predictors of disagreement with antimicrobial stewardship prospective audit and feedback recommendations (PAFR) at a free-standing children's hospital.DESIGNRetrospective cohort study of audits performed during the antimicrobial stewardship program (ASP) from March 30, 2015, to April 17, 2017.METHODSThe ASP included audits of antimicrobial use and communicated PAFR to the care team, with follow-up on adherence to recommendations. The primary outcome was disagreement with PAFR. Potential predictors for disagreement, including patient-level, antimicrobial, programmatic, and provider-level factors, were assessed using bivariate and multivariate logistic regression models.RESULTSIn total, 4,727 antimicrobial audits were performed during the study period; 1,323 PAFR (28%) and 187 recommendations (15%) were not followed due to disagreement. Providers were more likely to disagree with PAFR when the patient had a gastrointestinal infection (odds ratio [OR], 5.50; 95% confidence interval [CI], 1.99-15.21), febrile neutropenia (OR, 6.14; 95% CI, 2.08-18.12), skin or soft-tissue infections (OR, 6.16; 95% CI, 1.92-19.77), or had been admitted for 31-90 days at the time of the audit (OR, 2.08; 95% CI, 1.36-3.18). The longer the duration since the attending provider had been trained (ie, the more years of experience), the more likely they were to disagree with PAFR recommendations (OR, 1.02; 95% CI, 1.01-1.04).CONCLUSIONSEvaluation of our program confirmed patient-level predictors of PAFR disagreement and identified additional programmatic and provider-level factors, including years of attending experience. Stewardship interventions focused on specific diagnoses and antimicrobials are unlikely to result in programmatic success unless these factors are also addressed.Infect Control Hosp Epidemiol 2018;806-813.

Incorporating Relationship-Based Care Into a Nurse Education Program for Managing Disruptive Patient Behaviors.

PURPOSE: In the hospitalized patient, stressors can be manifested as disruptive behaviors. Nursing staff confronted with disruptive behaviors from their patients or families may have difficulty delivering care and developing therapeutic relationships. The purpose of this project was to evaluate the effects of an education program using the concepts of relationship-based care with role-play and reflective practice on the knowledge, attitudes, and confidence of the nursing staff in managing disruptive patient behaviors. DESCRIPTION: Nursing staff (N = 68) from an adult medical unit participated in an interactive education program. We compared participants' self-responses about knowledge, attitudes, and confidence before intervention and at 3-month and 1-year postintervention. The number of disruptive incidents requiring hospital security was also measured. OUTCOME: At 3-month and 1-year postintervention, staff reported higher levels of knowledge, attitudes, and confidence in managing disruptive behaviors. The number of disruptive incidents per 1000 patient days decreased from 0.78 to 0.39. CONCLUSION: Effectively managing disruptive behaviors creates a safe, healthy environment for patients and nurses. Role-play and reflective practice are useful educational methods to teach skills to manage these encounters. Clinical nurse specialists can play a key role in developing innovative education programs through interprofessional collaboration.

Incorporating a Cognitive Strategy Approach into an Outpatient Stroke Physiotherapy Programme: Case Report.

Purpose: Cognitive Orientation to daily Occupational Performance (CO-OP) has demonstrated an effect on skill performance, compared with the usual outpatient rehabilitation, in people living with stroke when implemented by occupational therapists. This study explored refining CO-OP for delivery by both occupational therapists and physiotherapists. Client Description: Two cases were recruited and treated using the CO-OP approach, which augments task-specific training with cognitive strategies and guided discovery. Intervention: Case 1 was a 79-year-old woman, 31 days after parietal stroke, and Case 2 was a 45-year-old man, 62 days after bilateral brain stem stroke. Case 1 withdrew from the study for medical reasons. Outcome measures applied were the Canadian Occupational Performance Measure, the Stroke Impact Scale (SIS), the Self-Efficacy Gauge, the Berg Balance Scale, the Box and Block Test, and the 2-minute walk test. Measures and Outcomes: After 10 sessions, Case 2 made gains in most measures, including a 22-point gain in the SIS mobility domain. Implications: The therapists reported that the combined delivery required additional communication with the patients but was feasible. Case 2 reported physical and mobility gains larger than the mean changes seen in past CO-OP research. Although these results cannot be generalized, findings suggest that the inter-professional application of CO-OP warrants further investigation.

Objectif : appliquée par des ergothérapeutes, l'approche CO-OP (Cognitive Orientation to daily Occupational Performance) est plus efficace que la réadaptation habituelle en milieu ambulatoire pour améliorer la fonction des personnes ayant subi un accident vasculaire crébral (AVC). Cette étude porte sur l'amélioration de l'approche CO-OP exécutée en parallèle par des ergothérapeutes et des physiothérapeutes. Description du client : nous avons recruté deux personnes que nous avons traitées à l'aide de l'approche CO-OP, qui complète les exercices traditionnels par des stratégies cognitives et de découverte guidée. Intervention : le premier cas était celui d'une femme âgée de 79 ans victime d'un AVC au lobe pariétal 31 jours auparavant, et le deuxième cas, celui d'un homme âgé de 45 ans victime d'un AVC bilatéral du tronc cérébral 62 jours auparavant. Le premier cas s'est retiré de l'étude pour des raisons médicales. Nous avons mesuré les résultats à l'aide de la mesure canadienne du rendement occupationnel (COPM), de l'échelle d'évaluation de l'impact de l'AVC (SIS), de l'échelle d'évaluation du sentiment d'efficacité personnelle (Self-efficacy Scale), de l'échelle de l'équilibire de Berg, du test « Boîte et blocs ¼ et du test de marche de 2 minutes. Mesures et résultats : après 10 séances, le deuxième cas avait réalisé des gains dans la plupart des mesures, dont un gain de 22 points à l'échelle SIS pour la mobilité. Implications : les thérapeutes ont indiqué que la prestation en parallèle nécessitait davantage de communication avec le patient, mais était faisable. Les gains physiques et de mobilité chez le deuxième cas sont supérieurs aux changements moyens observés lors d'études antérieures sur l'approche CO-OP. Même si on ne peut généraliser les résultats, l'application interprofessionnelle de l'approche CO-OP mérite davantage de recherche.

Coiling and maturation of a high-performance fibre in hagfish slime gland thread cells.

The defensive slime of hagfishes contains thousands of intermediate filament protein threads that are manufactured within specialized gland thread cells. The material properties of these threads rival those of spider dragline silks, which makes them an ideal model for biomimetic efforts to produce sustainable protein materials, yet how the thread is produced and organized within the cell is not well understood. Here we show how changes in nuclear morphology, size and position can explain the three-dimensional pattern of thread coiling in gland thread cells, and how the ultrastructure of the thread changes as very young thread cells develop into large cells with fully mature coiled threads. Our model provides an explanation for the complex process of thread assembly and organization that has fascinated and perplexed biologists for over a century, and provides valuable insights for the quest to manufacture high-performance biomimetic protein materials.

Clinical nurse specialists shaping policies and procedures via an evidence-based clinical practice council.

In the practice of nursing, organizations with progressive evidence-based practice programs implement structures and processes whereby nurses are engaged in the review of existing research and in the development of clinical practice documents to better align nursing practices with the best available scientific knowledge. At our academic hospital system, clinical nurse specialists (CNSs) took the lead to help transform a traditional nursing policy and procedure committee into a hospital-wide, staff-represented Clinical Practice Council (CPC) that ensures evidence-based nursing practices are reflected in the organization's nursing practice documents for the provision of patient care. Clinical nurse specialists function as mentors and cochairs who are dedicated to ensuring that nursing practice is supported by the latest evidence and committed to guiding staff nurses to continually move their practice forward. The success of the CPC is due to the leadership and commitment of the CNSs. This article describes the structure, process, and outcomes of an effective CPC where CNSs successfully engage frontline clinicians in promoting nursing care that is evidence based. Clinical nurse specialist leadership is increasingly made visible as CNSs effectively involve staff nurses in practice reforms to improve patient outcomes.

Ultrasensitive detection of drug-resistant pandemic 2009 (H1N1) influenza A virus by rare-variant-sensitive high-resolution melting-curve analysis.

Oseltamivir (Tamiflu), an oral neuraminidase inhibitor, has been widely used to treat pandemic 2009 (H1N1) influenza A. Although a majority of 2009 (H1N1) influenza A virus remains oseltamivir susceptible, the threat of resistance due to the His275Tyr mutation is highlighted by the limitations of alternative therapies and the potential for rapid, global fixation of this mutation in the circulating influenza A virus population. In order to better understand the emergence of resistance, we developed a rare-variant-sensitive high-resolution melting-curve analysis method (RVS-HRM) that is able to detect the His275Tyr oseltamivir resistance mutation to 0.5% in a background of susceptible virus. We applied RVS-HRM to clinical specimens from patients who developed oseltamivir resistance and demonstrated the ultrasensitive detection of influenza A virus N1 neuraminidase quasispecies. Interestingly, we were unable to detect the oseltamivir resistance mutation in pretreatment samples, suggesting that resistant virus does not reach even this very low detection threshold until exposed to selective drug pressure. Thus, patients naive to oseltamivir are most likely to be susceptible when this drug is used as a first-line treatment modality.

Effect of working memory and spatial attention tasks on gait in healthy young and older adults.

Changes in gait parameters induced by the concomitant performance of one of two cognitive tasks activating working memory and spatial attention, was examined in healthy young adults (YA) and older adults (OA). There was a main effect of task condition on gait-speed (p = .02), stride-length (p < .001) and double-support time (p = .04) independent of the group. There were no significant differences between working memory and spatial attention associated gait changes. Working-memory and spatial-attention dual-tasking led to a decrease in gait-speed (p = .09 and 0.01) and stride-length (p = .04 and 0.01) and increase in double-support time (p = .01 and 0.03) in YA and decrease in stride-length (p = .04 and 0.01) alone in OA. Cognitive task associated changes in gait may be a function of limited attentional resources irrespective of the type of cognitive task.

Real-time PCR testing for mecA reduces vancomycin usage and length of hospitalization for patients infected with methicillin-sensitive staphylococci.

Nucleic acid amplification tests (NAATs) have revolutionized infectious disease diagnosis, allowing for the rapid and sensitive identification of pathogens in clinical specimens. Real-time PCR testing for the mecA gene (mecA PCR), which confers methicillin resistance in staphylococci, has the added potential to reduce antibiotic usage, improve clinical outcomes, lower health care costs, and avoid emergence of drug resistance. A retrospective study was performed to identify patients infected with methicillin-sensitive staphylococcal isolates who were receiving vancomycin treatment when susceptibility results became available. Vancomycin treatment and length of hospitalization were compared in these patients for a 6-month period before and after implementation of mecA PCR. Among 65 and 94 patients identified before and after mecA PCR, respectively, vancomycin usage (measured in days on therapy) declined from a median of 3 days (range, 1 to 44 days) in the pre-PCR period to 1 day (range, 0 to 18 days) in the post-PCR period (P < 0.0001). In total, 38.5% (25/65) of patients were switched to beta-lactam therapy in the pre-PCR period, compared to 61.7% (58/94) in the post-PCR period (P = 0.004). Patient hospitalization days also declined from a median of 8 days (range, 1 to 47 days) in the pre-PCR period to 5 days (range, 0 to 42 days) in the post-PCR period (P = 0.03). Real-time PCR testing for mecA is an effective tool for reducing vancomycin usage and length of stay of hospitalized patients infected with methicillin-sensitive staphylococci. In the face of ever-rising health care expenditures in the United States, these findings have important implications for improving outcomes and decreasing costs.

Sensitive Ewing sarcoma and neuroblastoma cell lines have increased levels of BAD expression and decreased levels of BAR expression compared to resistant cell lines.

The purpose of the study is to compare the mRNA expression of pro-apoptotic and anti-apoptotic genes by using the GeneSystem 320 (Capital Genomix Inc., Gaithersburg, MD) to examine the differential expression in Ewing sarcoma and neuroblastoma cell lines. This is an alternate method for which internal controls have been built into the system for comparing mRNA. The tumor cell lines were chosen based on their previously characterized Fas-resistance or Fas-sensitive properties in order to determine the differences in their response to apoptotic signals. Two representative pro-apoptotic genes (BAD and SMAC) and one anti-apoptotic gene (BAR) were chosen for the study. The results of mRNA expression were correlated with protein expression by Western analysis. BAD was highly expressed in the Fas-sensitive cell lines while SMAC was equally expressed in both Fas-sensitive and Fas-resistant cell lines. On the other hand, BAR was highly expressed in Fas-resistant cell lines and minimally expressed in the Fas-sensitive cell lines. Our data suggests that levels of BAD and BAR mRNA expression predict sensitivity to apoptosis.