Developing an instrument to assess empowering nurse leader communication behaviours.

AIM: The overall purpose of the study was to develop an instrument to assess empowering nurse leader communication behaviours. BACKGROUND: Effective communication by nurse leaders promotes empowerment, yet communication assessments are often broad in nature without specifying precise behaviours. METHODS: An instrument development process was used to identify empowering nurse leader communication behaviours. Nurses working in United States military health care facilities (n = 240) provided responses to 47 pilot items, along with a 12-item psychological empowerment instrument to test for concurrent criterion validity. RESULTS: After review of item performance, 12 items were deleted. An exploratory factor analysis supported either a 2- or 3-factor model, with confirmatory factor analyses conducted to validate the underlying latent variables of empowering and limiting behaviours. The final nurse leader communication assessment consists of 2 factors consisting of 20 positive items (empowering subscale) and 15 negative items (limiting subscale). CONCLUSION: The final 2-factor assessment supports the theoretical premise of the empowering and limiting behaviours. Further testing may provide further dimensional clarity. IMPLICATIONS FOR NURSING MANAGEMENT: Use of the assessment can provide a basis for the development of training for individual nurse leaders or for facility nurse leaders as a collective.

Identifying the constructs of empowering nurse leader communication through an instrument development process.

AIM: The purpose of this article was to describe the constructs of empowering front-line nurse leader communication behaviours. BACKGROUND: Leaders' communication behaviours are instrumental in establishing a positive work environment. Nurse empowerment, a characteristic of a positive work environment, is influenced by communication behaviours. However, characteristics of empowering nurse leader communication behaviours have not been well-defined. METHODS: The constructs of empowering nurse leader communication behaviours were identified and refined during the instrument development process. A priori constructs were identified through a literature search, presented to focus groups of military nurses (N = 16), and refined during the procedures of item development. RESULTS: Eight final constructs emerged as a result of the iterative methods of item development: comprehensibility, listening, openness, feedback, empathy, nonverbal, paralanguage and manner. CONCLUSION: The constructs that describe empowering nurse leader communication behaviours are based on theoretical tenets of empowering communication and leadership, as well as the perspectives of military nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers can use the findings to implement innovative leadership assessments and training that focuses on Nurse Leader communication to enhance the nursing workplace environment.

Targeted messaging to improve the adoption of clinical decision support for prescription drug monitoring program use.

Clinical decision support (CDS) can prevent medical errors and improve patient outcomes. Electronic health record (EHR)-based CDS, designed to facilitate prescription drug monitoring program (PDMP) review, has reduced inappropriate opioid prescribing. However, the pooled effectiveness of CDS has exhibited substantial heterogeneity and current literature does not adequately detail why certain CDS are more successful than others. Clinicians regularly override CDS, limiting its impact. No studies recommend how to help nonadopters recognize and recover from CDS misuse. We hypothesized that a targeted educational intervention would improve CDS adoption and effectiveness for nonadopters. Over 10 months, we identified 478 providers consistently overriding CDS (nonadopters) and sent each up to 3 educational message(s) via email or EHR-based chat. One hundred sixty-one (34%) nonadopters stopped consistently overriding CDS and started reviewing the PDMP after contact. We concluded that targeted messaging is a low-resource way to disseminate CDS education and improve CDS adoption and best practice delivery.

Cellular and in vivo activity of JNJ-28871063, a nonquinazoline pan-ErbB kinase inhibitor that crosses the blood-brain barrier and displays efficacy against intracranial tumors.

JNJ-28871063 is a potent and highly selective pan-ErbB kinase inhibitor from a novel aminopyrimidine oxime structural class that blocks the proliferation of epidermal growth factor receptor (EGFR; ErbB1)- and ErbB2-overexpressing cells but does not affect the growth of non-ErbB-overexpressing cells. Treatment of human cancer cells with JNJ-28871063 inhibited phosphorylation of functionally important tyrosine residues in both EGFR and ErbB2 and blocked downstream signal transduction pathways responsible for proliferation and survival. A single dose of compound reduced phosphorylation of ErbB2 receptors in tumor-bearing mice, demonstrating target suppression in vivo. Tissue distribution studies show that JNJ-28871063 crosses the blood-brain barrier and penetrates into tumors, where it is able to accumulate to higher levels than those found in the plasma. JNJ-28871063 showed oral antitumor activity in human tumor xenograft models that overexpress EGFR and ErbB2. In an intracranial ErbB2-overexpressing tumor model, JNJ-28871063 extended survival relative to untreated animals. The brain is a primary site of metastasis for EGFR-overexpressing lung cancers and ErbB2-overexpressing breast cancers. Therefore, the ability to penetrate into the brain could be an advantage over existing therapies such as trastuzumab (Herceptin) and cetuximab (Erbitux), which are antibodies and do not cross the blood-brain barrier. These results show that JNJ-28871063 is orally bioavailable, has activity against EGFR and ErbB2-dependent tumor xenografts, and can penetrate into the brain and inhibit ErbB2-overexpressing tumor growth.

The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases.

Modulation of aberrant cell cycle regulation is a potential therapeutic strategy applicable to a wide range of tumor types. JNJ-7706621 is a novel cell cycle inhibitor that showed potent inhibition of several cyclin-dependent kinases (CDK) and Aurora kinases and selectively blocked proliferation of tumor cells of various origins but was about 10-fold less effective at inhibiting normal human cell growth in vitro. In human cancer cells, treatment with JNJ-7706621 inhibited cell growth independent of p53, retinoblastoma, or P-glycoprotein status; activated apoptosis; and reduced colony formation. At low concentrations, JNJ-7706621 slowed the growth of cells and at higher concentrations induced cytotoxicity. Inhibition of CDK1 kinase activity, altered CDK1 phosphorylation status, and interference with downstream substrates such as retinoblastoma were also shown in human tumor cells following drug treatment. Flow cytometric analysis of DNA content showed that JNJ-7706621 delayed progression through G1 and arrested the cell cycle at the G2-M phase. Additional cellular effects due to inhibition of Aurora kinases included endoreduplication and inhibition of histone H3 phosphorylation. In a human tumor xenograft model, several intermittent dosing schedules were identified that produced significant antitumor activity. There was a direct correlation between total cumulative dose given and antitumor effect regardless of the dosing schedule. These results show the therapeutic potential of this novel cell cycle inhibitor and support clinical evaluation of JNJ-7706621.

Expression analysis of secreted and cell surface genes of five transformed human cell lines and derivative xenograft tumors.

BACKGROUND: Since the early stages of tumorigenesis involve adhesion, escape from immune surveillance, vascularization and angiogenesis, we devised a strategy to study the expression profiles of all publicly known and putative secreted and cell surface genes. We designed a custom oligonucleotide microarray containing probes for 3531 secreted and cell surface genes to study 5 diverse human transformed cell lines and their derivative xenograft tumors. The origins of these human cell lines were lung (A549), breast (MDA MB-231), colon (HCT-116), ovarian (SK-OV-3) and prostate (PC3) carcinomas. RESULTS: Three different analyses were performed: (1) A PCA-based linear discriminant analysis identified a 54 gene profile characteristic of all tumors, (2) Application of MANOVA (Pcorr < .05) to tumor data revealed a larger set of 149 differentially expressed genes. (3) After MANOVA was performed on data from individual tumors, a comparison of differential genes amongst all tumor types revealed 12 common differential genes. Seven of the 12 genes were identified by all three analytical methods. These included late angiogenic, morphogenic and extracellular matrix genes such as ANGPTL4, COL1A1, GP2, GPR57, LAMB3, PCDHB9 and PTGER3. The differential expression of ANGPTL4 and COL1A1 and other genes was confirmed by quantitative PCR. CONCLUSION: Overall, a comparison of the three analyses revealed an expression pattern indicative of late angiogenic processes. These results show that a xenograft model using multiple cell lines of diverse tissue origin can identify common tumorigenic cell surface or secreted molecules that may be important biomarker and therapeutic discoveries.

A vascular endothelial growth factor receptor-2 kinase inhibitor potentiates the activity of the conventional chemotherapeutic agents paclitaxel and doxorubicin in tumor xenograft models.

Inhibition of angiogenesis may have wide use in the treatment of cancer; however, this approach alone will not cause tumor regression but may only slow the growth of solid tumors. The clinical potential of antiangiogenic agents may be increased by combining them with conventional chemotherapeutics. 4-[4-(1-Amino-1-methylethyl)phenyl]-2-[4-(2-morpholin-4-yl-ethyl)phenylamino]pyrimidine-5-carbonitrile (JNJ-17029259) represents a novel structural class of 5-cyanopyrimidines that are orally available, selective, nanomolar inhibitors of the vascular endothelial growth factor receptor-2 (VEGF-R2) and other tyrosine kinases involved in angiogenesis, such as platelet-derived growth factor receptor, fibroblast growth factor receptor, VEGF-R1, and VEGF-R3, but have little activity on other kinase families. At nanomolar levels, JNJ-17029259 blocks VEGF-stimulated mitogen-activated protein kinase signaling, proliferation/migration, and VEGF-R2 phosphorylation in human endothelial cells; inhibits the formation of vascular sprouting in the rat aortic ring model of angiogenesis; and interferes with the development of new veins and arteries in the chorioallantoic membrane assay. At higher concentrations of 1 to 3 microM, this compound shows antiproliferative activity on cells that may contribute to its antitumor effects. JNJ-17029259 delays the growth of a wide range of human tumor xenografts in nude mice when administered orally as single-agent therapy. Histological examination revealed that the tumors have evidence of reduced vascularity after treatment. In addition, JNJ-17029259 enhances the effects of the conventional chemotherapeutic drugs doxorubicin and paclitaxel in xenograft models when administered orally in combination therapy. An orally available angiogenesis inhibitor that can be used in conjunction with standard chemotherapeutic agents to augment their activity may have therapeutic benefit in stopping the progression of cancer and preventing metastasis.