Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial.

BACKGROUND Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, physical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment.Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN A phase II randomized, double-blind pilot clinical trial. SCOPE male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. INSTRUMENTATION clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011).

Predicting response and survival in chemotherapy-treated triple-negative breast cancer.

BACKGROUND In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

"Adolescent-onset Still's disease": characteristics and outcome in comparison with adult-onset Still's disease.

OBJECTIVES: To determine if adolescent onset systemic juvenile idiopathic arthritis (JIA) and adult onset Still's disease (AOSD) represent the same clinical continuum of disease. METHODS: Retrospective review of available clinical data on all pediatric and adult patients diagnosed with Still's disease within the last 10 years at a university hospital. Assessment of functional outcomes at last visit by clinical evaluation and HAQ or c-HAQ. RESULTS: Nine patients were identified as adolescent onset systemic JIA and were compared with 10 patients with AOSD (onset > 18 years old). No statistically significant differences were found between the two groups in terms of clinical presentation at onset and outcome at follow up. CONCLUSION: Adolescent patients presenting with systemic JIA have a disease onset and course undistinguishable from that of AOSD patients, suggesting that they represent a continuum of a single disease entity.

Determination and Evaluation of Alternative Methods for Managing and Controlling Highway-Related Dust Phase II—Demonstration Project, June 2005

The State of Iowa currently has approximately 69,000 miles of unpaved secondary roads. Due to the low traffic count on these unpaved o nts as ng e two dust ed d roads, paving with asphalt or Portland cement concrete is not economical. Therefore to reduce dust production, the use of dust suppressants has been utilized for decades. This study was conducted to evaluate the effectiveness of several widely used dust suppressants through quantitative field testing on two of Iowa’s most widely used secondary road surface treatments: crushed limestone rock and alluvial sand/gravel. These commercially available dust suppressants included: lignin sulfonate, calcium chloride, and soybean oil soapstock. These suppressants were applied to 1000 ft test sections on four unpaved roads in Story County, Iowa. Tduplicate field conditions, the suppressants were applied as a surface spray once in early June and again in late August or early September. The four unpaved roads included two with crushed limestone rock and two with alluvial sand/gravel surface treatmewell as high and low traffic counts. The effectiveness of the dust suppressants was evaluated by comparing the dust produced on treated and untreated test sections. Dust collection was scheduled for 1, 2, 4, 6, and 8 weeks after each application, for a total testiperiod of 16 weeks. Results of a cost analysis between annual dust suppressant application and biennial aggregate replacement indicated that the cost of the dust suppressant, its transportation, and application were relatively high when compared to that of thaggregate types. Therefore, the biennial aggregate replacement is considered more economical than annual dust suppressant application, although the application of annual dust suppressant reduced the cost of road maintenance by 75 %. Results of thecollection indicated that the lignin sulfonate suppressant outperformed calcium chloride and soybean oil soapstock on all four unpavroads, the effect of the suppressants on the alluvial sand/gravel surface treatment was less than that on the crushed limestone rock, the residual effects of all the products seem reasonably well after blading, and the combination of alluvial sand/gravel surface treatment anhigh traffic count caused dust reduction to decrease dramatically.

Cooperatives and Contracting in Agriculture: The Case of West Liberty Foods, October 2005

The West Liberty Foods turkey cooperative was formed in 1996 to purchase the assets and assume operations of Louis Rich Foods (an investor-owned processing rm), which, at the time, announced the imminent shutdown of its West Liberty, Iowa, processing facility. We study the creation and performance of this �new generation� cooperative using eld interviews with grower members and company management. We describe changes, before and after the buyout, in the contractual apparatus used for procuring live turkeys, and in the communication requirements, work expectations, and nancial positions of growers. During the private ownership period, most of the inputs (except labor and facilities) were provided by the rm; there was substantial supervision of the growers' actions; growers faced little price and production risk; and growers' equity was due largely to ownership of land and other farm assets. Our interviews reveal that, after cooperative formation, growers were exposed to considerable additional risk; monitoring of growers by the rm was less intensive; grower time and effort commitments to turkey production increased substantially; and a signicant fraction of rm (cooperative) equity came from growers' willingness to leverage their farm and personal assets (and hence indirectly their existing relationships with local lenders). We argue that some of these changes are consistent with a nancial contract where asset pledging and its corollary risk generate higher work effort by growers and a reduction in agency rents. These economies likely compensate for an organizational deadweight loss traditionally associated with cooperative governance.

Work capacity evaluation among nursing aides

Work force aging generates the need to develop studied with the purpose to evaluate work capacity. The objective of this study was to analyze the work capacity of the nursing aides of a public health institute. A cross-sectional study was developed on the work capacity of these professionals regarding their demographic, work and lifestyle characteristics (n=241). A univariate logistic regression analysis was performed with inadequate work capacity (score below 37) as the dependent variable. There was an association with age (the eldest), work time at the institution (the oldest), body mass index (obesity) and item 1 of the work capacities index: present work capacity. This information can be used to create preventive measures and restore work capacity.

Business Organization and Coordination in Marketing Specialty Hogs: A Comparative Analysis of Two Firms from Iowa, November 2005

We study business organization and coordination of specialty-market hog production using a comparative analysis of two Iowa pork niche-marketing firms. We describe and analyze each firms management of five key organizational challenges: planning and logistics, quality assurance, process verication and management of �credence attributes,� business structure, and profit sharing. Although each firm is engaged in essentially the same activity, there are substantial differences across the two firms in the way production and marketing are coordinated. These differences are partly explained by the relative size and age of each firm, thus highlighting the importance of organizational evolution in agricultural markets, but are also partly the result of a formal organizational separation between marketing and production activities in one of the firm.

Confronting a victim of intimate partner violence in nursing care : a literature review

Intimate partner violence is a growing problem in health care. The purpose of this thesis was to find ways of confronting a victim of intimate partner violence in nursing care and methods how nurses can encourage the victim to disclose the abuse. The aim of this thesis was to help the health care professionals to understand the issue and the need of the victims better, and that way provide a better care. This thesis is a literature review of previously made research articles about intimate partner violence. The research material consisted of 10 published articles, which were collected from different databases. The articles were published within 10 years. A content analysis method was used to examine the articles by making descriptive summary tables according to each questions. The results of this study showed multiple factors which the health care providers should take into consideration when caring the patients. Asking with a non-judgemental attitude, in a safe, confidential setting without the partner present and prioritizing the abuse was mentioned to be important for the victims. Routinely screening and different kind of brochures was considered as good methods to encourage the victims to disclose the abuse. The need for better training and counselling of the health care providers was also discovered. The results of this thesis, did answer to the chosen study questions and that way the purpose of the thesis was filled. Hopefully, in the future this problem can be minimized and prevented in advanced. Further studies are needed to examine whether these caring methods are actually being used in clinical settings and do they have any effect.

Political-ethical skill development in nursing undergraduates

This research aimed to identify political-ethical skills developed in a training process compatible with the expected profile set by the National Curriculum Guidelines for the Undergraduate Nursing Degree. A case study was conducted with units represented by 32 former students from a particular religious teaching institution who already were in the job market. The content of the interviews was analyzed using the thematic analysis technique, which resulted in the following categories: "Political-ethical skills in the formative process" and "Political-ethical skills as a product of the educational process." From the former students’ perspective, these categories reinforced the social role of the nurse and the need for students to be reflective, understanding and participative in the transformation of society.

The use of the quality model of Parasuraman, Zeithaml and Berry in health services

This is an article about the theoretical model for assessing quality in health services proposed by Parasuraman, Zheitaml and Berry, in order to measure the degree of satisfaction of users. This model is based on the analysis of expectations and perceptions of users of health services, by means of five dimensions: tangibility, reliability, responsiveness, assurance and empathy. From the difference between what is expected by the user and the service offered, gaps or shortcomings are derived that may be the main obstacle for users to perceive the provision of such services with quality. It was observed that the use of the psychometric scale called Service Quality (SERVQUAL) in some studies about satisfaction, obtained very favorable results in the institutions in which it was employed. The analysis revealed the need to improve the existing models of evaluation, as well as the importance of measuring user satisfaction in health institutions.

An easy functional capacity evaluation in chronic low back pain

Lifting is said to be on of the major risk factors for the onset of low back pain, several different measures has been developed to study this. Several programs are available in order to measure these components, or to determine the ability of an individual to perform a certain job or to discover if the job creates dangerous positions for the worker. In these different fields reliable and valid instruments exist but they are costly and time spending. We present a simplified functional capacity measuring that we use daily in practise. Method: 280 patients have been evaluated on this base. The majority was referred to multidisciplinary rehabilitation treatment. The patients had recurrent back problems for months or years. Inclusion criteria were between 18 and 64 years, currently of work, no work compensation. Exclusion criteria were chronic low back pain with a specific cause. They followed a one-hour evaluation test as a functional capacity evaluation at the end of the multidisciplinary treatment period, it was compared to the PILE-test done at the beginning and at the end. Results: We included 280 subjects: 160 men and 120 women. Mean age 43.6 by the women and 44 years by the men. We studied the caring foot-hip, hip-shoulder, 5 m carrying, pushing and tiring and the global weight carried during the test. We found this global value to be 696 kg by men and 422 kg by women suffering from chronic lumbar pain. The increase in this value had a clear incidence on a greater work ability, as had a decrease. Conclusions: We were able to develop a lifting capacity program that is easy to reproduce and not expensive, giving us the possibility to have an idea on how to reorient the patients according to their work place and their capacities. We could also have an information of work performance and power consumption. It should be more tested and compared to standard capacity in the healthy population.

Occupational low back pain in nursing workers: massage versus pain

Objective: To assess the efficacy of massage for decreasing occupational low back pain in workers of a Nursing team in an Emergency Room. Method: A randomized controlled trial, using a socio-demographic/morbidity questionnaire and a Pain Numeric Scale. Forty-five subjects were randomly allocated for intervention (G1 – Massage by acupressure), placebo group (G2 – application of Garlium Arseneid Laser 904nm turned off) and control (G3 – no intervention). Results: The main triggering factor, as well as the worsening of pain, was the patient manipulation, both with a prevalence of 34.9%. The main treatment for low back pain before this research was the use of medication, with a prevalence of 44.2%. In accordance with a variance analysis, only G1 presented a significant statistical difference, with a better result after 12 sessions. Massage presented an enormous effect (d = 4.59), corresponding to 86% of reduction in the pain level. Conclusion: Massage was effective to decrease occupational low back pain of those Nursing workers.


The view of teachers on bullying and implications for nursing

Objective: To understand school bullying from the perspective of teachers and reflect about the possible actions of the health area when coping with it. The guidelines of the School Health Program of the Ministries of Health and Education were used to reach that purpose. Method: A qualitative study carried out with teachers of a public school in Minas Gerais. Focus groups were used to collect data and the empirical material was decoded from thematic analysis of content, resulting in an analytical category: conceptions and experiences of teachers on bullying. Results: Specific perceptions about the phenomenon and the use of ineffective intervention resources were identified. In the interpretive plan were problematized the health and nursing contributions with resizing the interventions and the continuing training process of teachers. Conclusion: The results point to the construction of intersectoral practices for coping with bullying.


Stress, coping and presenteeism in nurses assisting critical and potentially critical patients

Objective to verify the associations between stress, Coping and Presenteeism in nurses operating on direct assistance to critical and potentially critical patients. Method this is a descriptive, cross-sectional and quantitative study, conducted between March and April 2010 with 129 hospital nurses. The Inventory of stress in nurses, Occupational and Coping Questionnaire Range of Limitations at Work were used. For the analysis, the Kolmogorov-Smirnov test, correlation coefficient of Pearson and Spearman, Chi-square and T-test were applied. Results it was observed that 66.7% of the nurses showed low stress, 87.6% use control strategies for coping stress and 4.84% had decrease in productivity. Direct and meaningful relationships between stress and lost productivity were found. Conclusion stress interferes with the daily life of nurses and impacts on productivity. Although the inability to test associations, the control strategy can minimize the stress, which consequently contributes to better productivity of nurses in the care of critical patients and potentially critical.