Mutation analysis of the ATP7B gene in a new group of Wilson's disease patients: contribution to diagnosis.

Wilson's disease (WD), an autosomal recessive disorder of copper transport with a broad range of genotypic and phenotypic characteristics, results from mutations in the ATP7B gene. Herein we report the results of mutation analysis of the ATP7B gene in a group of 118 Wilson disease families (236 chromosomes) prevalently of Italian origin. Using DNA sequencing we identified 83 disease-causing mutations. Eleven were novel, while twenty one already described mutations were identified in new populations in this study. In particular, mutation analysis of 13 families of Romanian origin showed a high prevalence of the p.H1069Q mutation (50%). Detection of new mutations in the ATP7B gene in new populations increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.

Review of therapeutic drug monitoring of anticancer drugs part two - Targeted therapies.

Most of oral targeted therapies are tyrosine kinase inhibitors (TKIs). Oral administration generates a complex step in the pharmacokinetics (PK) of these drugs. Inter-individual PK variability is often large and variability observed in response is influenced not only by the genetic heterogeneity of drug targets, but also by the pharmacogenetic background of the patient (e.g. cytochome P450 and ABC transporter polymorphisms), patient characteristics such as adherence to treatment and environmental factors (drug-drug interactions). Retrospective studies have shown that targeted drug exposure, reflected in the area under the plasma concentration-time curve (AUC) correlates with treatment response (efficacy/toxicity) in various cancers. Nevertheless levels of evidence for therapeutic drug monitoring (TDM) are however heterogeneous among these agents and TDM is still uncommon for the majority of them. Evidence for imatinib currently exists, others are emerging for compounds including nilotinib, dasatinib, erlotinib, sunitinib, sorafenib and mammalian target of rapamycin (mTOR) inhibitors. Applications for TDM during oral targeted therapies may best be reserved for particular situations including lack of therapeutic response, severe or unexpected toxicities, anticipated drug-drug interactions and/or concerns over adherence treatment. Interpatient PK variability observed with monoclonal antibodies (mAbs) is comparable or slightly lower to that observed with TKIs. There are still few data with these agents in favour of TDM approaches, even if data showed encouraging results with rituximab, cetuximab and bevacizumab. At this time, TDM of mAbs is not yet supported by scientific evidence. Considerable effort should be made for targeted therapies to better define concentration-effect relationships and to perform comparative randomised trials of classic dosing versus pharmacokinetically-guided adaptive dosing.

Changes in patterns of practice for prostate cancer radiotherapy in Italy 1995-2003. A survey of the Prostate Cancer Study Group of the Italian Radiation Oncology Society.

Aims and background. In 2002, a survey including 1759 patients treated from 1980 to 1998 established a "benchmark" Italian data source for prostate cancer radiotherapy. This report updates the previous one. Methods. Data on clinical management and outcomes of 3001 patients treated in 15 centers from 1999 through 2003 were analyzed and compared with those of the previous survey. Results. Significant differences in clinical management (-10% had abdominal ma-gnetic resonance imaging; +26% received ≥70 Gy, +48% conformal radiotherapy, -20% pelvic radiotherapy) and in G3-4 toxicity rates (-3.8%) were recorded. Actuarial 5-year overall, disease-specific, clinical relapse-free, and biochemical relapse-free survival rates were 88%, 96%, 96% and 88%, respectively. At multivariate analysis, D'Amico risk categories significantly impacted on all the outcomes; higher radiotherapy doses were significantly related with better overall survival rates, and a similar trend was evident for disease-specific and biochemical relapse-free survival; cumulative probability of 5-year late G1-4 toxicity was 24.8% and was significantly related to higher radiotherapy doses (P <0.001). Conclusions. The changing patterns of practice described seem related to an improvement in efficacy and safety of radiotherapy for prostate cancer. However, the impact of the new radiotherapy techniques should be prospectively evaluated.

Internal test sets studies in a group of antimalarials

Topological indices have been applied to build QSAR models for a set of 20 antimalarial cyclic peroxy cetals. In order to evaluate the reliability of the proposed linear models leave-n-out and Internal Test Sets (ITS) approaches have been considered. The proposed procedure resulted in a robust and consensued prediction equation and here it is shown why it is superior to the employed standard cross-validation algorithms involving multilinear regression models

The organizational culture of a Brazilian public hospital

The objective of this research was to analyze the organizational culture of a Brazilian public hospital. It is a descriptive study with quantitative approach of data, developed in a public hospital of São Paulo State, Brazil. The sample was composed by 52 nurses and 146 nursing technicians and auxiliaries. Data were collected from January to June 2011 using the Brazilian Instrument for Assessing Organizational Culture – IBACO. The analysis of the organizational values showed the existence of hierarchical rigidity and centralization of power within the institution, as well as individualism and competition, which hinders teamwork. The values concerning workers’ well-being, satisfaction and motivation were not highly valued. In regard to organizational practices, the promotion of interpersonal relationship, continuous education, and rewarding practices were not valued either. It becomes apparent that traditional models of work organization support work practices and determine the organizational culture of the hospital.


Validation of the potentially avoidable hospital readmission rate as a routine indicator of the quality of hospital care

BACKGROUND: The hospital readmission rate has been proposed as an important outcome indicator computable from routine statistics. However, most commonly used measures raise conceptual issues. OBJECTIVES: We sought to evaluate the usefulness of the computerized algorithm for identifying avoidable readmissions on the basis of minimum bias, criterion validity, and measurement precision. RESEARCH DESIGN AND SUBJECTS: A total of 131,809 hospitalizations of patients discharged alive from 49 hospitals were used to compare the predictive performance of risk adjustment methods. A subset of a random sample of 570 medical records of discharge/readmission pairs in 12 hospitals were reviewed to estimate the predictive value of the screening of potentially avoidable readmissions. MEASURES: Potentially avoidable readmissions, defined as readmissions related to a condition of the previous hospitalization and not expected as part of a program of care and occurring within 30 days after the previous discharge, were identified by a computerized algorithm. Unavoidable readmissions were considered as censored events. RESULTS: A total of 5.2% of hospitalizations were followed by a potentially avoidable readmission, 17% of them in a different hospital. The predictive value of the screen was 78%; 27% of screened readmissions were judged clearly avoidable. The correlation between the hospital rate of clearly avoidable readmission and all readmissions rate, potentially avoidable readmissions rate or the ratio of observed to expected readmissions were respectively 0.42, 0.56 and 0.66. Adjustment models using clinical information performed better. CONCLUSION: Adjusted rates of potentially avoidable readmissions are scientifically sound enough to warrant their inclusion in hospital quality surveillance.

Empowering a group of seniors in a rural community

OBJECTIVE To describe the stages of the empowerment process of a group of seniors in a rural community. METHOD Convergent care research whose foundation is to use the scope of practice. Conducted with the proposal to change the practice of 21 seniors and nine health professionals, with the aim of health promotion empowerment. Data were collected during 22 meetings, and group interviews at the end of the intervention. RESULTS Showed that despite the initial impact of the change, the group was able to welcome the new change, taking advantage of the space to express anxieties, share joys, and build new knowledge, which led to the incorporation of changes that reflected in the development of healthy habits and improvements in interpersonal relationships. CONCLUSION The convergent care research consisted of strategy that changed the group's lives, empowering them with health promoting actions.

Instrument for assessing the quality of mobile emergency pre-hospital care: content validation

OBJECTIVES To validate an instrument to assess quality of mobile emergency pre-hospital care. METHOD A methodological study where 20 professionals gave their opinions on the items of the proposed instrument. The analysis was performed using Kappa test (K) and Content Validity Index (CVI), considering K> 0.80 and CVI ≥ 0.80. RESULTS Three items were excluded from the instrument: Professional Compensation; Job Satisfaction and Services Performed. Items that obtained adequate K and CVI indexes and remained in the instrument were: ambulance conservation status; physical structure; comfort in the ambulance; availability of material resources; user/staff safety; continuous learning; safety demonstrated by the team; access; welcoming; humanization; response time; costumer privacy; guidelines on care; relationship between professionals and costumers; opportunity for costumers to make complaints and multiprofessional conjunction/actuation. CONCLUSION The instrument to assess quality of care has been validated and may contribute to the evaluation of pre-hospital care in mobile emergency services.

Burnout and associated factors in employees of a Swiss teaching hospital

Background Working in a teaching hospital is a highly stressful occupation, which can lead to burnout. The consequences of burnout in health professionals can be very serious, both for themselves and patients. The aim of this cross-sectional study was to assess the extent of burnout and associated factors in hospital employees. Methods In the Fall of 2007, all employees of a Swiss teaching hospital were invited to complete a job satisfaction survey. It included the work-related burnout scale (scored 0-100) of the Copenhagen Burnout Inventory (CBI-French version), measuring the degree of physical and psychological fatigue and exhaustion perceived as related to the person's work; a high degree of burnout was defined as a score _50. Logistic regression analyses were used to determine factors associated with a high degree of burnout. Results A total of 4575 individuals returned the questionnaire (response rate 54%). Of them, 1503 (33%) had a high degree of burnout. The rate of burnout was higher among women (34.3% versus 30.5%, P = 0.012) and respondents younger than 40 years (37.7% versus 28.6%, P < 0.001). Executives were less prone to burnout than employees (27.1% versus 33.9%, P < 0.0019). Rates of burnout differed by profession: nurses and physicians had higher rates than administrative and logistic staff (42.8% and 37.4% versus 25.6% and 20.9%, respectively P < 0.001). Burnout was inversely associated with job satisfaction. In multivariate analysis, factors associated with burnout were overall dissatisfaction (OR 3.23; 95% CI 2.66-3.91), dissatisfaction with workload (OR 2.09; 95% CI 1.74-2.51) and work-life balance (OR 2.25; 95% CI 1.83-2.77), being a woman (OR 1.56; 95% CI 1.28-1.90), working fulltime (OR 1.41; 95% CI 1.08-1.85) and working as a nurse, a physician or in the psychosocial sector. Conclusions One-third of respondents, mostly nurses and physicians, experienced burnout and had lower levels of job satisfaction. The factors associated with burnout may help to tailor programmes aiming at reducing burnout at both the individual and organizational level within the hospital.

Phylogenetic relationships among four species of the guarani group of Drosophila (Diptera, Drosophilidae) as inferred by molecular and morphological analyses

Traditionally, the Drosophila guarani species group has been divided into two subgroups: the guarani and the guaramunu subgroups. Two, out of the four species included in this research, are members of the guarani subgroup (D. ornatifrons Duda, 1927 and D. subbadia Paterson & Mainland, 1943) and two are included in the guaramunu subgroup (D. maculifrons Duda, 1927 and D. griseolineata Duda, 1927). However, some authors have suggested that D. maculifrons and D. griseolineata are much closer to some species of the Drosophila tripunctata group than to some of the species of the guarani group. To add new data to the matter under dispute, Polyacrylamide Gel Eletrophoresis (PAGE-SDS) was used for the analysis and comparison of protein composition and Random Amplified Polymorphic DNA (RAPD) analysis to find differences in genomic DNA, in addition to the analysis of quantitative morphological characters previously described. Analysis of PAGE-SDS results in a dendrogram that pointed out D. subbadia as being the most distant within the Drosophila guarani group. However, these results were not supported either by RAPD analysis or by the analysis of continuous morphological characters, which supplied the clustering of D. subbadia with D. ornatifrons. Although our data give strong support to the clustering of D. subbadia and D. ornatifrons, none of the dendrograms provided a clade comprising D. maculifrons and D. griseolineata. Thus, this research does not support the traditional subdivision of the D. guarani group into those two subgroups.

Revision of the Leucosphyrus group of Anopheles (Cellia) (Diptera, Culicidae)

Revision of the Leucosphyrus Group of Anopheles (Cellia) (Diptera, Culicidae). This is a comprehensive revision of 20 species of the Leucosphyrus Group of the Neomyzomyia Series of Anopheles (Cellia). Morphological description of the adults, male and female, male genitalia, pupa and fourth-instar larva are provided for each taxon in addition to bionomics, distribution data and systematic discussion for each species, including diagnostic characters. Identification keys for females and fourth-instar larvae are provided. When possible medical importance of each species is included. Illustrations of of the adults, fourth-instar larvae and pupae are provided. Distribution maps for each species are mainly based on the material examined; however, when possible published data were also used. Tables on adult character variations, fourth-instar larval and pupal setal branching are included as appendices. A neotype for An. takasagoensis Morishita and An. sulawesi Koesoemawinangoen, and a lectotype for An. balabacensis Baisas, are designated. The authorship of An. sulawesi previously cited as Waktoedi is corrected to Koesoemawinangoen.

La chaîne des secours: le modèle vaudois [An efficient example of a Swiss pre-hospital chain of survival: the state of Vaud model].

The state of Vaud model of the pre-hospital chain of survival is an example of an efficient way to deal with pre-hospital emergencies. It revolves around a centrally located dispatch center managing emergencies according to specific key words, allowing dispatchers to send out resources among which we find general practitioners, ambulances, physician staffed fast response cars or physician staffed helicopters and specific equipment. The Vaud pre-hospital chain of survival has been tailored according to geographical, demographical and political necessities. It undergoes constant reassessment and needs continuous adaptations to the ever changing demographics and epidemiology of pre-hospital medicine.