Zebrafish as a genetic model in pre-clinical drug testing and screening

The traditional drug discovery pipeline for the identification and development of compounds that selectively target specific molecules to ameliorate disease remains a major focus for medical research. However, the zebrafish is increasingly providing alternative strategies for various components of this pipeline. Zebrafish and their embryos are small, easily accessible and relatively low cost, making them applicable to high-throughput, small molecule screening. Zebrafish can also be manipulated by a range of forward and reverse genetics techniques to facilitate gene discovery and functional studies. Moreover, their physiological and developmental complexity provides accurate models of human disease to underpin mechanism of action and in vivo validation studies. Finally, several of these biological characteristics make zebrafish eminently suitable for toxicity testing, including eco-toxicology. Here we review the application of zebrafish to preclinical drug development and toxicity testing, including recent advances in mutant generation, drug screening and toxicology that serve to further enhance the capabilities of this valuable model organism in drug discovery.

Development and validation of the influenza intensity and impact questionnaire (FluiiQ™)

Objective
Clinical trials of new agents to reduce the severity and impact of influenza require accurate assessment of the effect of influenza infection. Because there are limited high-quality adult influenza Patient Reported Outcomes (PRO) measures, the aim was to develop and validate a simple but comprehensive questionnaire for epidemiological research and clinical trials.

Methods
Construct and item generation was guided by the literature, concept mapping, focus groups, and interviews with individuals with laboratory-confirmed influenza and expert physicians. Items were administered to 311 people with influenza-like illness (ILI) across 25 US sites. Analyses included classic psychometrics, structural equation modeling (SEM), and Rasch analyses.

Results
Concept mapping generated 149 concepts covering the influenza experience and clustered into symptoms and impact on daily activities, emotions, and others. Items were drafted using simplicity and brevity criteria. Eleven symptoms from the literature underwent review by physicians and patients, and two were removed and one added. The symptoms domain factored into systemic and respiratory symptoms, whereas the impact domains were unidimensional. All domains displayed good internal consistency (Cronbach α ≥ 0.8) except the three-item respiratory domain (α = 0.48). A five-factor SEM indicated excellent fit where systemic, respiratory, and daily activities domains differentiated patients with ILI or confirmed influenza. All scales were responsive over time.

Conclusions
Patient and clinician consultations resulted in an influenza PRO measure with high validity and good overall evidence of reliability and responsiveness. The Influenza Intensity and Impact Questionnaire (FluiiQ™) will improve the evaluation of existing and future agents designed to prevent or control influenza infection by increasing the breadth and depth of measurement in this field.

Transcultural adaption and validation of the Spanish version of the Bipolar Depression Rating Scale (BDRS-S)

The Bipolar Depression Rating Scale (BDRS) arguably better captures symptoms in bipolar depression especially depressive mixed states than traditional unipolar depression rating scales. The psychometric properties of the Spanish adapted version, BDRS-S, are reported.

Validation of DNA methylation biomarkers for diagnosis of acute lymphoblastic leukemia

DNA methylation biomarkers capable of diagnosis and subtyping have been found for many cancers. Fifteen such markers have previously been identified for pediatric acute lymphoblastic leukemia (ALL). Validation of these markers is necessary to assess their clinical utility for molecular diagnostics. Substantial efficiencies could be achieved with these DNA methylation markers for disease tracking with potential to replace patient-specific genetic testing.

Cancer Treatment Survey (CaTS): development and validation of a new instrument to measure patients' preparation for chemotherapy and radiotherapy

Objective: Cancer patients experience high levels of pre-treatment anxiety. Chemotherapy and radiotherapy are threatening medical procedures. Preparation for these procedures should include the provision of sensory and procedural information, and addressing fears. The aim of this study was to develop a cancer treatment survey (CaTS) to assess the preparation for chemotherapy and radiotherapy in cancer patients.

Methods: Drawing on evidence for how to prepare patients for threatening procedures, items were generated by psychosocial/clinical experts and pilot tested with cancer patients. The 36-item draft CaTS was administered to 192 cancer patients commencing chemotherapy for lymphoma, breast or colon cancer. Participants also completed the Hospital Anxiety and Depression Scale (HADS) and basic medical and demographic information was recorded.

Results: A systematic process of item selection removed 11 items. Factor analysis indicated a two-factor solution, with 11 items representing sensory/psychological concerns and 14 items representing procedural concerns. The two subscales demonstrated excellent internal reliability with Cronbach's alpha both over 0.90 and the average inter-item correlation for each scale exceeded 0.30. Divergent validity was established for both CaTS subscales with the HADS-A and-T (all r<0.30). Younger participants (under 65 years of age) had significantly greater procedural concerns (p = 0.001; medium effect).

Conclusions: The CaTS is a two factor, 25-item measure that assesses sensory/psychological concerns and procedural concerns relating to cancer treatment. The instrument provides a reliable and valid outcome measure for interventions to prepare cancer patients for chemotherapy and radiotherapy.

The internal consistency and construct validity of the partners in health scale : validation of a patient rated chronic condition self-management measure

PURPOSE: The purpose of this study was to test the internal consistency and construct validity of the revised 12-item self-rated Partners in Health (PIH) scale used to assess patients' chronic condition self-management knowledge and behaviours. METHODS: Baseline PIH data were collected for a total of 294 patients with a range of co-morbid chronic conditions including diabetes, cardiovascular disease and arthritis. Scale data for the initial sample of 176 patients were analysed for internal consistency and construct validity using Reliability Analysis and Factor Analysis. Construct validity was tested in a separate sample of 118 patients using confirmatory factor analysis and a structural equation model. RESULTS: Good internal consistency was indicated with a Cronbach's alpha coefficient of 0.82 in the initial sample. Factor analysis for this sample revealed four key factors (knowledge, coping, management of condition and adherence to treatment) across the twelve items of the scale. These four key factors were then confirmed by applying the exploratory structural equation model to the separate sample. CONCLUSION: The PIH scale exhibits construct validity and internal consistency. It therefore is both a generic self-rated clinical tool for assessing self-management in a range of chronic conditions as well as an outcome measure to compare populations and change in patient self-management knowledge and behaviour over time. The four domains of self-management provide a valid measure of patient competency in relation to the self-management of their chronic condition(s).

Adaptation and validation of a survey instrument measuring perceived preparedness of nursing graduates

BACKGROUND: In Australia, a significant percentage of bachelor of nursing students are employed in the aged care sector, or in aged care settings, as assistants in nursing (AINs) or personal care assistants. However the value of aged care in nursing education is often overlooked. AIM: To outline the adaptation and validation of a survey, originally developed for medical graduates, for use with nursing graduates. DISCUSSION: Adaptation of the instrument was undertaken as part of a doctoral study that aimed to explore whether employment as an undergraduate assistant in nursing (AIN) in aged care prepares new graduates for clinical work. CONCLUSION: Outlining each step of the modification process can help nurse researchers who want to adapt existing instruments to meet their research objectives. IMPLICATIONS FOR PRACTICE: Undergraduate AIN employment has the potential to supplement clinical learning without the restrictions inherent in the student role. Furthermore, it has the potential to enhance recruitment and retention in the aged care sector.