Taking stock of gene therapy for cystic fibrosis

The identification of the cystic fibrosis (CF) gene opened the way for gene therapy. In the ten years since then, proof of principle in vitro and then in animal models in vivo has been followed by numerous clinical studies using both viral and non-viral vectors to transfer normal copies of the gene to the lungs and noses of CF patients. A wealth of data have emerged from these studies, reflecting enormous progress and also helping to focus and define key difficulties that remain unresolved. Gene therapy for CF remains the most promising possibility for curative rather than symptomatic therapy

Development and validation of a risk model for prediction of hazardous alcohol consumption in general practice attendees : the PredictAL study

Background: Little is known about the risk of progression to hazardous alcohol use in people currently drinking at safe limits. We aimed to develop a prediction model (predictAL) for the development of hazardous drinking in safe drinkers. Methods: A prospective cohort study of adult general practice attendees in six European countries and Chile followed up over 6 months. We recruited 10,045 attendees between April 2003 to February 2005. 6193 European and 2462 Chilean attendees recorded AUDIT scores below 8 in men and 5 in women at recruitment and were used in modelling risk. 38 risk factors were measured to construct a risk model for the development of hazardous drinking using stepwise logistic regression. The model was corrected for over fitting and tested in an external population. The main outcome was hazardous drinking defined by an AUDIT score >= 8 in men and >= 5 in women. Results: 69.0% of attendees were recruited, of whom 89.5% participated again after six months. The risk factors in the final predictAL model were sex, age, country, baseline AUDIT score, panic syndrome and lifetime alcohol problem. The predictAL model's average c-index across all six European countries was 0.839 (95% CI 0.805, 0.873). The Hedge's g effect size for the difference in log odds of predicted probability between safe drinkers in Europe who subsequently developed hazardous alcohol use and those who did not was 1.38 (95% CI 1.25, 1.51). External validation of the algorithm in Chilean safe drinkers resulted in a c-index of 0.781 (95% CI 0.717, 0.846) and Hedge's g of 0.68 (95% CI 0.57, 0.78). Conclusions: The predictAL risk model for development of hazardous consumption in safe drinkers compares favourably with risk algorithms for disorders in other medical settings and can be a useful first step in prevention of alcohol misuse

Need-based resource allocation: different need indicators, different results?

<p>Abstract</p> <p>Background</p> <p>A key policy objective in most publicly financed health care systems is to allocate resources according to need. Many jurisdictions implement this policy objective through need-based allocation models. To date, no gold standard exists for selecting need indicators. In the absence of a gold standard, sensitivity of the choice of need indicators is of concern. The primary objective of this study was to assess the consistency and plausibility of estimates of per capita relative need for health services across Canadian provinces based on different need indicators.</p> <p>Methods</p> <p>Using the 2000/2001 Canadian Community Health Survey, we estimated relative per capita need for general practitioner, specialist, and hospital services by province using two approaches that incorporated a different set of need indicators: (1) demographics (age and sex), and (2) demographics, socioeconomic status, and health status. For both approaches, we first fitted regression models to estimate standard utilization of each of three types of health services by indicators of need. We defined the standard as average levels of utilization by needs indicators in the national sample. Subsequently, we estimated expected per capita utilization of each type of health services in each province. We compared these estimates of per capita relative need with premature mortality in each province to check their face validity.</p> <p>Results</p> <p>Both approaches suggested that expected relative per capita need for three services vary across provinces. Different approaches, however, yielded different and inconsistent results. Moreover, provincial per capita relative need for the three health services did not always indicate the same direction of need suggested by premature mortality in each province. In particular, the two approaches suggested Newfoundland had less need than the Canadian average for all three services, but it had the highest premature mortality in Canada.</p> <p>Conclusion</p> <p>Substantial differences in need for health care may exist across Canadian provinces, but the direction and magnitude of differences depend on the need indicators used. Allocations from models using survey data lacked face validity for some provinces. These results call for the need to better understand the biases that may result from the use of survey data for resource allocation.</p

Persistent frequent attenders in primary care: costs, reasons for attendance, organisation of care and potential for cognitive behavioural therapeutic intervention

<p><b>Abstract</b></p> <p>Background</p> <p>The top 3% of frequent attendance in primary care is associated with 15% of all appointments in primary care, a fivefold increase in hospital expenditure, and more mental disorder and functional somatic symptoms compared to normal attendance. Although often temporary if these rates of attendance last more than two years, they may become persistent (persistent frequent or regular attendance). However, there is no long-term study of the economic impact or clinical characteristics of regular attendance in primary care. Cognitive behaviour formulation and treatment (CBT) for regular attendance as a motivated behaviour may offer an understanding of the development, maintenance and treatment of regular attendance in the context of their health problems, cognitive processes and social context.</p> <p>Methods/design</p> <p>A case control design will compare the clinical characteristics, patterns of health care use and economic costs over the last 10 years of 100 regular attenders (≥30 appointments with general practitioner [GP] over 2 years) with 100 normal attenders (6–22 appointments with GP over 2 years), from purposefully selected primary care practices with differing organisation of care and patient demographics. Qualitative interviews with regular attending patients and practice staff will explore patient barriers, drivers and experiences of consultation, and organisation of care by practices with its challenges. Cognitive behaviour formulation analysed thematically will explore the development, maintenance and therapeutic opportunities for management in regular attenders. The feasibility, acceptability and utility of CBT for regular attendance will be examined.</p> <p>Discussion</p> <p>The health care costs, clinical needs, patient motivation for consultation and organisation of care for persistent frequent or regular attendance in primary care will be explored to develop training and policies for service providers. CBT for regular attendance will be piloted with a view to developing this approach as part of a multifaceted intervention.</p

Colorectal cancer health services research study protocol: the CCR-CARESS observational prospective cohort project

BACKGROUND: Colorectal cancers are one of the most common forms of malignancy worldwide. But two significant areas of research less studied deserve attention: health services use and development of patient stratification risk tools for these patients. METHODS:DESIGN: a prospective multicenter cohort study with a follow up period of up to 5 years after surgical intervention. Participant centers: 22 hospitals representing six autonomous communities of Spain. Participants/Study population: Patients diagnosed with colorectal cancer that have undergone surgical intervention and have consented to participate in the study between June 2010 and December 2012. Variables collected include pre-intervention background, sociodemographic parameters, hospital admission records, biological and clinical parameters, treatment information, and outcomes up to 5 years after surgical intervention. Patients completed the following questionnaires prior to surgery and in the follow up period: EuroQol-5D, EORTC QLQ-C30 (The European Organization for Research and Treatment of Cancer quality of life questionnaire) and QLQ-CR29 (module for colorectal cancer), the Duke Functional Social Support Questionnaire, the Hospital Anxiety and Depression Scale, and the Barthel Index. The main endpoints of the study are mortality, tumor recurrence, major complications, readmissions, and changes in health-related quality of life at 30 days and at 1, 2, 3 and 5 years after surgical intervention. STATISTICAL ANALYSIS: In relation to the different endpoints, predictive models will be used by means of multivariate logistic models, Cox or linear mixed-effects regression models. Simulation models for the prediction of discrete events in the long term will also be used, and an economic evaluation of different treatment strategies will be performed through the use of generalized linear models. DISCUSSION: The identification of potential risk factors for adverse events may help clinicians in the clinical decision making process. Also, the follow up by 5 years of this large cohort of patients may provide useful information to answer different health services research questions

Relationships between quality of life and family function in caregiver

<p>Abstract</p> <p>Background</p> <p>There are caregivers who see their quality of life (QoL) impaired due to the demands of their caregiving tasks, while others manage to adapt and overcome the crises successfully. The influence of the family function in the main caregiver's situation has not been the subject of much evaluation. The aim of this study is to analyse the relationship between the functionality of the family and the QoL of caregivers of dependent relatives.</p> <p>Methods</p> <p>We conducted a cross-sectional study including 153 caregivers. Setting: Two health centers in the city of Salamanca(Spain). Caregiver variables analysed: demographic characteristics, care recipient features; family functionality (Family APGAR-Q) and QoL (Ruiz-Baca-Q) perceived by the caregiver. Five multiple regressions are performed considering global QoL and each of the four QoL dimensions as dependent variables. The Canonical Correspondence Analysis (CCA) was used to study the influence of the family function questionnaire on QoL.</p> <p>Results</p> <p>Family function is the only one of the variables evaluated that presented an association both with global QoL and with each of the four individual dimensions (p < 0.05). Using the CCA, we found that the physical and mental well-being dimensions are the ones which present a closer relationship with family functionality, while social support is the quality dimension that is least influenced by the Family APGAR-Q.</p> <p>Conclusion</p> <p>We find an association between family functionality and the caregiver's QoL. This relation holds for both the global measure of QoL and each of its four individual dimensions.</p

Applying diagnosis and pharmacy-based risk models to predict pharmacy use in Aragon, Spain: The impact of a local calibration

<p>Abstract</p> <p>Background</p> <p>In the financing of a national health system, where pharmaceutical spending is one of the main cost containment targets, predicting pharmacy costs for individuals and populations is essential for budget planning and care management. Although most efforts have focused on risk adjustment applying diagnostic data, the reliability of this information source has been questioned in the primary care setting. We sought to assess the usefulness of incorporating pharmacy data into claims-based predictive models (PMs). Developed primarily for the U.S. health care setting, a secondary objective was to evaluate the benefit of a local calibration in order to adapt the PMs to the Spanish health care system.</p> <p>Methods</p> <p>The population was drawn from patients within the primary care setting of Aragon, Spain (n = 84,152). Diagnostic, medication and prior cost data were used to develop PMs based on the Johns Hopkins ACG methodology. Model performance was assessed through r-squared statistics and predictive ratios. The capacity to identify future high-cost patients was examined through c-statistic, sensitivity and specificity parameters.</p> <p>Results</p> <p>The PMs based on pharmacy data had a higher capacity to predict future pharmacy expenses and to identify potential high-cost patients than the models based on diagnostic data alone and a capacity almost as high as that of the combined diagnosis-pharmacy-based PM. PMs provided considerably better predictions when calibrated to Spanish data.</p> <p>Conclusion</p> <p>Understandably, pharmacy spending is more predictable using pharmacy-based risk markers compared with diagnosis-based risk markers. Pharmacy-based PMs can assist plan administrators and medical directors in planning the health budget and identifying high-cost-risk patients amenable to care management programs.</p

Conservation and Diversity of Seed Associated Endophytes in Zea across Boundaries of Evolution, Ethnography and Ecology

Endophytes are non-pathogenic microbes living inside plants. We asked whether endophytic species were conserved in the agriculturally important plant genus Zea as it became domesticated from its wild ancestors (teosinte) to modern maize (corn) and moved from Mexico to Canada. Kernels from populations of four different teosintes and 10 different maize varieties were screened for endophytic bacteria by culturing, cloning and DNA fingerprinting using terminal restriction fragment length polymorphism (TRFLP) of 16S rDNA. Principle component analysis of TRFLP data showed that seed endophyte community composition varied in relation to plant host phylogeny. However, there was a core microbiota of endophytes that was conserved in Zea seeds across boundaries of evolution, ethnography and ecology. The majority of seed endophytes in the wild ancestor persist today in domesticated maize, though ancient selection against the hard fruitcase surrounding seeds may have altered the abundance of endophytes. Four TRFLP signals including two predicted to represent Clostridium and Paenibacillus species were conserved across all Zea genotypes, while culturing showed that Enterobacter, Methylobacteria, Pantoea and Pseudomonas species were widespread, with γ-proteobacteria being the prevalent class. Twenty-six different genera were cultured, and these were evaluated for their ability to stimulate plant growth, grow on nitrogen-free media, solubilize phosphate, sequester iron, secrete RNAse, antagonize pathogens, catabolize the precursor of ethylene, produce auxin and acetoin/butanediol. Of these traits, phosphate solubilization and production of acetoin/butanediol were the most commonly observed. An isolate from the giant Mexican landrace Mixteco, with 100% identity to Burkholderia phytofirmans, significantly promoted shoot potato biomass. GFP tagging and maize stem injection confirmed that several seed endophytes could spread systemically through the plant. One seed isolate, Enterobacter asburiae, was able to exit the root and colonize the rhizosphere. Conservation and diversity in Zea-microbe relationships are discussed in the context of ecology, crop domestication, selection and migration

Towards a collaborative research: A case study on linking science to farmers' perceptions and knowledge on Arabica coffee pests and diseases and its management

The scientific community has recognized the importance of integrating farmer's perceptions and knowledge (FPK) for the development of sustainable pest and disease management strategies. However, the knowledge gap between indigenous and scientific knowledge still contributes to misidentification of plant health constraints and poor adoption of management solutions. This is particularly the case in the context of smallholder farming in developing countries. In this paper, we present a case study on coffee production in Uganda, a sector depending mostly on smallholder farming facing a simultaneous and increasing number of socio-ecological pressures. The objectives of this study were (i) to examine and relate FPK on Arabica Coffee Pests and Diseases (CPaD) to altitude and the vegetation structure of the production systems; (ii) to contrast results with perceptions from experts and (iii) to compare results with field observations, in order to identify constraints for improving the information flow between scientists and farmers. Data were acquired by means of interviews and workshops. One hundred and fifty farmer households managing coffee either at sun exposure, under shade trees or inter-cropped with bananas and spread across an altitudinal gradient were selected. Field sampling of the two most important CPaD was conducted on a subset of 34 plots. The study revealed the following findings: (i) Perceptions on CPaD with respect to their distribution across altitudes and perceived impact are partially concordant among farmers, experts and field observations (ii) There are discrepancies among farmers and experts regarding management practices and the development of CPaD issues of the previous years. (iii) Field observations comparing CPaD in different altitudes and production systems indicate ambiguity of the role of shade trees. According to the locality-specific variability in CPaD pressure as well as in FPK, the importance of developing spatially variable and relevant CPaD control practices is proposed. (Résumé d'auteur