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OBJECTIVES: To discuss professional cancer navigation roles, models, implementation process and outcomes of patients and families dealing with head and neck cancers. One specific research is presented as an illustration. DATA SOURCES: Published scientific papers, research review articles, implementations studies. CONCLUSION: Two independent cohorts of patients with head and neck cancers were compared according to the presence of the professional navigator (Exposed cohort n=83) or not (Historical cohort n=75). The Exposed cohort showed a better profile on several indicators of outcomes. The results clearly indicate an association between the presence of the professional navigator with continuity of care (higher satisfaction and shorter duration of hospitalization), and empowerment (fewer cancer-related problems, including body images concerns, and better emotional quality of life). IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can not only play an important role in continuity of care but also in supportive care by helping patients to cope better with cancer treatments, recovery or cancer progression and death issues. Copyright © 2009 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Objective: Implementation of routine Screening for Distress constitutes a major change in cancer care, with the aim of achieving person-centered care., Method: Using a cross-sectional descriptive design within a University Tertiary Care Hospital setting, 911 patients from all cancer sites were screened at the time of their first meeting with a nurse navigator who administered a paper questionnaire that included: the Distress Thermometer (DT), the Canadian Problem Checklist (CPC), and the Edmonton Symptom Assessment System (ESAS)., Results: Results showed a mean score of 3.9 on the DT. Fears/worries, coping with the disease, and sleep were the most common problems reported on the CPC. Tiredness was the most prevalent symptom on the ESAS. A final regression model that included anxiety, the total number of problems on the CPC, well-being, and tiredness accounted for almost 50% of the variance of distress. A cutoff score of 5 on the DT together with a cutoff of 5 on the ESAS items represents the best combination of specificity and sensitivity to orient patients on the basis of their reported distress., Significance of Results: These descriptive data will provide valuable feedback to answer practical questions for the purpose of effectively implementing and managing routine screening in cancer care.

Unlabelled: Fillion et al. (2012) recently designed a conceptual framework for professional cancer navigators describing key functions of professional cancer navigation., Purpose: Building on this framework, this study defines the core areas of practice and associated competencies for professional cancer navigators., Methods: The methods used in this study included: literature review, mapping of navigation functions against practice standards and competencies, and validation of this mapping process with professional navigators, their managers and nursing experts and comparison of roles in similar navigation programs., Findings: Associated competencies were linked to the three identified core areas of practice, which are: 1) providing information and education, 2) providing emotional and supportive care, and 3) facilitating coordination and continuity of care., Conclusion: Cancer navigators are in a key position to improve patient and family empowerment and continuity of care., Implications: This is an important step for advancing the role of oncology nurses in navigator positions and identifying areas for further research.

The CNS disposition and metabolism of Fosdevirine (FDV), an HIV non-nucleoside reverse transcriptase inhibitor, was investigated in four patients who unexpectedly experienced seizures after at least 4 weeks of treatment in a Phase IIb, HIV-1 treatment experienced study. In addition, the CNS disposition and metabolism of FDV was examined in samples from rabbit, minipig, and monkey studies. LC-MS was used to characterize and estimate the concentrations of FDV and its metabolites in cerebral spinal fluid (seizure patients, rabbit, and monkey) and brain homogenate (rabbit, minipig, and monkey). The application of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) provided the spatial distribution of FDV and its metabolites in brain tissue (rabbit, minipig, and monkey). A cysteine conjugate metabolite resulting from an initial glutathione (GSH) Michael addition to the trans-phenyl acrylonitrile moiety of FDV was the predominant drug-related component in the samples from seizure patients, rabbits, and minipigs. This metabolite persisted in the CNS for an extended period of time after the last dose in both seizure patients and minipigs. Furthermore, the localization of this metabolite was found to be highly associated with the white matter in rabbit and minipig brain sections by MALDI IMS. In contrast, the predominant component in monkey CNS was FDV, which was shown to be highly associated with the gray matter. On the basis of these data, several hypothesizes are considered, which might provide insights into species differences in CNS toxicity/seizures observed after FDV dosing.

For many cancer control programs, cancer navigation has emerged as a specific strategy to improve access to supportive care and the patients' experience of cancer care. This study contributes to a better understanding of professional navigation by comparing two Canadian models: Quebec's Pivot Nurse in Oncology (PNO) and Nova Scotia's Cancer Patient Navigator (CPN). Qualitative interviews were conducted with professional navigators, patients and family members, front-line staff, physicians and health administrators (interviews: n = 49; focus groups: n = 10). The two models were analyzed using the professional navigation framework (Fillion et al., 2012). Although the models are different, results show that professional navigators in both programs perform similar functions and face similar challenges. This study highlights the complexity and the value of cancer navigation and recommends relevant actions to optimize its management within the health care system.

Aim: To evaluate potential drug interactions with antiretroviral therapies or supportive therapies for use in conjunction with the once daily, next generation non-nucleoside reverse transcriptase inhibitor GSK2248761 in patients with HIV-1 infection., Methods: A series of phase I drug interaction studies was conducted., Results: GSK2248761 was shown to be a weak CYP3A4 and CYP2D6 inhibitor in a clinical study with a probe cocktail. Mean plasma concentration-time profiles for atazanavir, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), darunavir (DRV, administered with ritonavir [RTV]), and drospirenone/ethinylestradiol were similar following co-administration of GSK2248761. Plasma raltegravir AUC(0,τ) and C(max) increased by 18% with no change in Cτ when raltegravir was co-administered with GSK2248761. Lopinavir (LPV) plasma AUC(0,τ), C(max) and Cτ decreased by 23%, 14% and 40%, respectively, following administration of lopinavir/ritonavir with GSK2248761. Atorvastatin, rosuvastatin and simvastatin AUC(0,∞) and C(max) increased following co-administration with GSK2248761, with the largest changes observed for simvastatin (3.7-fold and 4.3-fold). Changes in maximum and extent of GSK2248761 exposure were marginal after co-administration with atazanavir, TDF/FTC and raltegravir compared with GSK2248761 administered alone. Co-administration of GSK2248761 with DRV/RTV and LPV/RTV increased plasma GSK2248761 exposures by 1.25- to ≤2-fold compared with GSK2248761 administered alone, and increases in GSK2248761 exposure were higher following single dose co-administration of DRV/RTV or LPV/RTV compared with multiple doses. There were few drug-related AEs, and no treatment-related trends in blood chemistry, haematology, urinalysis, vital signs or ECG findings., Conclusions: These studies indicate that GSK2248761 was safe and well tolerated in healthy adults treated in these studies at the doses and duration of therapy evaluated., (© 2012 ViiV Healthcare. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

Purpose/objectives: To elaborate, refine, and validate the professional navigation framework in a Canadian context., Research Approach: A two-step approach consisting of a qualitative evaluative design and formal consultations., Setting: Two applications of professional navigators in Quebec and Nova Scotia, Canada., Participants: Patient navigators, medical oncology specialists, nurses and oncology staff, administrators, family physicians, patients with cancer, and patients' families and significant others., Methods: Individual interviews (n = 49) and focus groups (n = 10) were conducted with professional navigators, patients and family members, front-line staff, family physicians, and health administrators. Formal consultations (n = 13) occurred with clinical experts, managers, and researchers from across Canada., Main Research Variables: The interview guide was based on an evaluative conceptual framework integrating questions related to the implementation process of the role of professional navigators and their organizational and clinical functions., Findings: Results support a bi-dimensional framework and define key role functions. The first dimension, health system-oriented, refers to continuity of care. The second dimension, patient-centered, corresponds to empowerment. For each dimension, related concepts were illustrated from data. Examples of outcomes also were suggested., Conclusions: The framework brings clarity to the role and functions of professional navigators and suggests relevant outcomes for program evaluations., Interpretation: With a clear definition of their role, professional navigators may be more efficient and less challenged in terms of setting priorities and making decisions while having to face demands from the health system and patients. The integrative framework could improve the effectiveness of cancer navigation programs.

A model that predicts human metabolism and disposition of drug candidates would be of value in early drug development. In this study, a chimeric (uPA+/+)/SCID mouse model was evaluated with three structurally distinct compounds (GW695634, a benzophenone, SB-406725, a tetrahydroisoquinoline and GW823093, a fluoropyrrolidine) for which human metabolism and disposition was characterized. Human metabolite profiles in plasma and/or urine were compared to those of chimeric (uPA+/+)/SCID and control CD-1 or (uPA+/+)/SCID) mice. GW695634 and SB-406725 exhibited primarily hepatic metabolism and were chosen as probes to assess which human metabolites would likely circulate systemically. GW823093 exhibited a combination of hepatic and extrahepatic metabolism such that renal excretion of drug-related material was ~2-fold greater in humans than in mice, and thus chosen as a probe to assess if the chimeric (uPA+/+)/SCID mouse would predict the urinary excretion of human metabolites. We observed that human metabolism and disposition was well represented for GW695634, somewhat represented for GW823093 and minimally represented for SB-406725. Collectively, the results of this and other studies suggest that while limitations for prediction of human metabolism and disposition exist, humanized chimeric mouse models can potentially represent informative new tools in drug discovery and development.

Implementing oncology nurse navigators or IPOs (which stands for "infirmière pivot en oncologie") is a key element of the Québec Cancer Control Program in order to improve the continuity of care. This qualitative study describes the process of implementing IPOs in teams working both in hospitals and in the community. Several groups of stakeholders (IPOs, physicians, nurses, various health workers, administrators, people with cancer and their families) described how they perceive the functions and effects related to this implementation. After putting results into perspective, we recommend developing measures promoting the dissemination of the role and integration of IPOs in formally defined health teams. We strongly advocate for the continuation of joint efforts in order to define and clarify this complex role.

Morphological evaluation of humanized chimeric mouse livers from the PhoenixBio (uPA(+/+)/SCID) mouse model show robust replacement and expansion with human hepatocytes, however areas of human hepatocytes had prominent steatosis and a variable lack of sinusoids which was consistent with decreased hepatocellular perfusion and lacked bile canalicular formation between human and mouse hepatocytes.

GW695634 is the prodrug of GW678248, a novel non-nucleoside reverse transcriptase inhibitor with potent antiviral activity against HIV/AIDS efavirenz- and nevirapine-resistant viruses. In mice, rats, and monkeys following oral administration of [(14)C]GW695634, the primary pathway of metabolic clearance was by amide hydrolysis and the main route of elimination (46%-75% of the dose) was in the feces. The primary metabolic pathway of clearance for GW695634 and GW678248 in the preclinical species was by amide hydrolysis. At least six metabolites were observed that were the products of GW695634 and GW678248 amide hydrolysis.

Fresh hepatocytes have been the choice for interspecies comparative drug metabolism studies. Cryopreserved hepatocytes represent a readily available alternative when combined with acceptance limits based on the metabolic turnover of 7-ethoxycoumarin. Results for the ten NCEs examined show that the metabolites formed were strongly correlated in fresh and cryopreserved hepatocytes.

A profile of the role and functions of an oncology patient-navigator nurse (OPN) and the preliminary phases to implementing this role within a team specializing in oncology are first presented. This is followed by a qualitative study that provides a descriptive assessment for implementing an initial OPN in the head and neck oncology area of a university hospital centre (UHC) with a supraregional model for oncology. Three groups of stakeholders (individuals with cancer and families, caregivers, network partners) were interviewed on three occasions: before, during and after implementation. The results show that this new role can be integrated within a team specializing in oncology. The beneficial effects of this role on the process of adaptation to illness, interdisciplinary work and continuity of care are described. Several recommendations are formulated, one being the importance of situating the implementation process from an organizational change perspective.

GW395058, a PEGylated peptide agonist of the thrombopoietin receptor, stimulates megakaryocytopoiesis and has previously been shown to increase platelet counts in vivo. The pharmacokinetics and pharmacodynamics of GW395058 were characterized using a randomized, crossover study in a large-animal model (dog) of chemotherapy-induced thrombocytopenia. Nine beagle dogs received i.v. carboplatin (350 mg/m(2)) on day 0 and day 28. GW395058 (1.31 mg/kg) (n = 6) or vehicle control (n = 3) was administered on day 1 and day 29 either as an i.v. bolus or s.c. injection. After i.v. administration, peak concentrations of GW395058 occurred rapidly, while the half-life averaged approximately 56 h. Bioavailability (+/- standard deviation) of GW395058 given s.c. was 78.2% (20.9%). GW395058 (i.v. and s.c.) ameliorated the platelet nadir (p = 0.0086) and resulted in a shorter time to recovery compared to the control group. The mean nadir platelet counts following carboplatin administration were 197,000 cells/microl (80,000) for the i.v. GW395058-dose group, 183,000 cells/microl (72,000) for the s.c.-dose group and 71,000 cells/microl (38,000) for the vehicle-alone group. GW395058 reduced the thrombocytopenic effects of carboplatin in dogs. No GW395058-related adverse side effects were observed.

GW395058, a potent PEGylated peptide human thrombopoietin receptor (HuTPOr) agonist in vitro, is being evaluated for the treatment of thrombocytopenia. GW395058 shares no sequence homology with TPO. In this report the pharmacokinetics and hematological effects of GW395058 in rats and monkeys are described. Doses eliciting thrombocytosis in rodents (2 or 10 microg/kg s.c.) produced insufficient plasma concentration data for pharmacokinetic parameter estimate calculations. At higher i.v. doses in rats (500, 1,000 or 2,000 microg/kg) serum t1/2 (half-life) values were >20 h, and the area under the concentration time curve increased proportionally with dose. In cynomolgus monkeys GW395058 plasma t1/2 values ranged from 37 to 68 h after s.c. or i.v. dosing, and similar values were observed in rhesus monkeys following s.c. dosing. Rat platelet counts increased following 2 (1.6-fold) or 10 microg/kg (fourfold) s.c. doses. Cynomolgus and rhesus monkey platelet counts did not change significantly at comparable s.c. doses, but did increase slightly (

Administration of exogenous proteins and peptides as therapeutics carries with it the potential for immune system recognition and the development of neutralizing antibodies to endogenous regulatory proteins. PEGylation of proteins typically reduces their immunogenicity in vivo. GW395058 is a PEGylated peptide thrombopoietin receptor (TPOr) agonist being evaluated for the treatment of chemotherapy-induced thrombocytopenia. Although GW395058 shares no homology with TPO, it does compete with TPO for binding to a common receptor, and a similarity in local structure could result in shared epitopes. Thus GW395058 could elicit TPO-neutralizing antibodies. In this study, we evaluated the immunogenicity of GW395058 in mice, the potential of rabbit antibodies elicited by immunizations with the non-PEGylated parent peptide AF15705 to cross-react with recombinant human (rHu) TPO, and the potential of mouse anti-rHuTPO antibodies elicited by repeated dosing with rHuTPO to cross-react with AF15705. GW395058-dosed mice failed to produce antibodies to AF15705 or rHuTPO. Mouse anti-rHuTPO did not cross-react with AF15705 and rabbit anti-AF15705 antibodies failed to cross-react with rHuTPO. GW395058 caused no immune-mediated lesions in mice, but rHuTPO suppressed megakaryocytopoiesis and caused B-lymphocyte hyperplasia in lymphoid tissues consistent with antigenic stimulation. These data suggest that the potential for an immune response to GW395058 in man would be low.

A novel scintillation proximity competitive hybridization assay was developed for determining plasma concentrations of compound 4003W94, a 15-base phosphorothioate antisense deoxyribonucleotide that is currently under preclinical evaluation for the treatment of restenosis following coronary artery angioplasty. The principle of the assay involves the hybridization binding of antisense (4003W94) to a biotinylated sense oligonucleotide to form a double-stranded nucleic acid complex on the surface of scintillation proximity beads derivatized with streptavidin. As in a competitive radioimmunoassay, there is an inverse relationship between the amount of radioactivity in the final binding complex and the amount of 4003W94 present in the sample being analyzed. Because this is a homogenous assay, no physical separation of bound from free radioligand is necessary. Conventional cross-reactivity studies with either 3'- or 5'-deletion oligomers of 4003W94 indicated that cross-reactivity generally decreased with each base deletion. The assay was used to determine plasma concentrations of 4003W94 equivalents in rhesus monkeys during an exploratory 14-day toxicity study. This method conceivably could be adapted for use as an effective in vitro screening tool for the identification of potential antisense oligonucleotide drug candidates or as a diagnostic tool for the detection of pathological disorders.

A technique for the detection of von Willebrand factor multimers separated by discontinuous SDS agarose electrophoresis has been developed using non-radioactive compounds. The multimeric patterns were visualized by monospecific anti-human vWF:Ag followed by incubation with biotinylated antibody. After addition of avidin-biotin-peroxidase complex, the peroxidase activity was detected by 4-chloro-1-naphthol, giving sharp bands with a clear background. By this method, the differences of vWF:Ag multimers could be easily observed between normal plasma and the plasmas from variant type vWD (IIA, IIB, platelet-type). Large and intermediate multimers were absent in the plasma with vWD type IIA, while only large multimers were absent in the plasma with vWD IIB and platelet-type. The absence of large multimers was also observed in two commercial FVIII preparations having the ratio of vWF/vWF:Ag 0.18 and 0.63. The preparation with the ratio of 0.63 showed the presence of larger intermediate multimers. Electrophoresis in SDS 1.5% agarose gel revealed triplet structure of each small multimer, and a relative increase of the smallest subband was observed in vWD IIA plasma, platelet-type vWD plasma and commercial FVIII preparations. The procedures described are easy and safe to perform and are useful for screening or classifying cases with vWD in general laboratories.