Ana Fernández

OXA-235, a Novel Class D β-Lactamase Involved in Resistance to Carbapenems in Acinetobacter baumannii

ABSTRACT We investigated the mechanism of carbapenem resistance in 10 Acinetobacter baumannii strains isolated from the United States and Mexico between 2005 and 2009. The detection of known metallo-β-lactamase or carbapenem-hydrolyzing oxacillinase (OXA) genes by PCR was negative. The presence of plasmid-encoded carbapenem resistance genes was investigated by transformation of A. baumannii ATCC 17978. Shotgun cloning experiments and sequencing were performed, followed by the expression of a novel β-lactamase in A. baumannii. Three novel OXA enzymes were identified, OXA-235 in 8 isolates and the amino acid variants OXA-236 (Glu173-Val) and OXA-237 (Asp208-Gly) in 1 isolate each. The deduced amino acid sequences shared 85% identity with OXA-134, 54% to 57% identities with the acquired OXA-23, OXA-24, OXA-58, and OXA-143, and 56% identity with the intrinsic OXA-51 and, thus, represent a novel subclass of OXA. The expression of OXA-235 in A. baumannii led to reduced carbapenem susceptibility, while cephalosporin MICs were unaffected. Genetic analysis revealed that blaOXA-235, blaOXA-236, and blaOXA-237 were bracketed between two ISAba1 insertion sequences. In addition, the presence of these acquired β-lactamase genes might result from a transposition-mediated mechanism. This highlights the propensity of A. baumannii to acquire multiple carbapenem resistance determinants.

Epidemiology of major depressive episode in a southern European country: Results from the ESEMeD-Spain project

BACKGROUND Information of the epidemiology of Major Depressive Episode (MDE) in Spain, one of the biggest southern European countries, is scarce and heterogeneous. The objective of this study was to assess the epidemiology of the disorder in the Spanish sample of the ESEMeD project. METHODS The ESEMED-Spain project is a cross-sectional, general population, household survey conducted with a representative sample of Spanish non-institutionalized adult population. The survey instrument was the CIDI 3.0, a structured diagnostic interview to assess disorders and treatment. RESULTS Lifetime prevalence was 10.6% while 12-month prevalence was 4.0%. A monotonic increase in lifetime overall prevalence was found from the youngest to the 50-64 cohort, declining then in the oldest group. Median age of onset was 30.0. Being a woman (OR=2.7), previously married (OR=1.8), unemployed or disabled to work (OR=2.9) was associated to higher risk of 12-month-MDE. The highest comorbid associations were with dysthymia (OR=73.1) and panic disorder (OR=41.8). LIMITATIONS 1. Psychiatric diagnoses were made by trained lay interviewers and this could have an imperfect sensitivity/specificity; 2. Individuals with mental illness could have more frequently rejected to participate in the survey; 3. Age-related recall bias could have affected the accuracy of age of onset estimates. CONCLUSIONS The study shows that prevalence MDE in Spain is lower than in other Western countries. Important findings are the early age of onset, the high proportion of chronicity, and the high female/male ratio. Taken together, results offer a complex picture of the epidemiology of MDE in Spain, when compared to other countries in Europe. The role of cultural factors is discussed.

Comparison of Different Valuation Methods for Population Health Status Measured by the EQ‐5D in Three European Countries

OBJECTIVE The purpose of this study was to analyze and compare different valuation methods for population health status measured by the EuroQol-5D (EQ-5D) in three European countries. METHODS A representative survey of the noninstitutionalized population aged 18 and above was conducted in three European countries (Germany, The Netherlands, and Spain). A total of 11,932 respondents were interviewed using the EQ-5D self-classifier. Health state values based on community preferences (EQ-5D index) were calculated for each country using four different value sets: national value sets based on the time trade-off (TTO) and the visual analogue scale (VAS), the UK TTO-based value set and the European VAS-based value set. Linear regression analysis was conducted to evaluate the factors associated with different EQ-5D index scores depending on the value set used. Loss of quality-adjusted life-years (QALYs) was calculated for each country using the four value sets by multiplying the age and gender-specific values with the respective population size. RESULTS In all countries, means of all EQ-5D index scores were higher for men than women, and decreased with age. Index scores calculated using the national value set based on TTO were higher than those calculated using the UK TTO-based value set and, also, slightly higher than those calculated using the European VAS-based value set or the national value set based on the VAS. The mean loss of QALYs estimated for Germany per inhabitant varied between 0.062 (national value set based on TTO) and 0.094 (European VAS-based value set). In The Netherlands, the mean loss of QALYs per inhabitant ranged from 0.090 (national value set based on TTO) to 0.125 (national value set based on VAS). In Spain, the mean loss of QALYs per inhabitant ranged between 0.072 (national value set based on TTO) and 0.085 (European VAS-based value set). CONCLUSIONS In general, the differences among countries and valuations were rather small; nevertheless, some important variations should be taken into account while applying different valuation methods to the EQ-5D descriptive system. The associations between sociodemographic variables and health state scores remained the same across countries regardless of which value sets were used. Using different valuation methods lead to different QALY losses. To overcome this problem in international surveys aimed to compare health state scores or QALYs, it is advisable to use a single valuation method, making these scores comparable.

Psychometric properties of the twelve item World Health Organization Disability Assessment Schedule II (WHO-DAS II) in Spanish primary care patients with a first major depressive episode

BACKGROUND Psychometric information on the World Health Organization Disability Assessment Schedule II (WHO-DAS II) in depressive primary care (PC) patients is scarce and has been obtained with the 36-item version of the instrument. The main objective of this study was to analyse the dimensionality, internal consistency and construct validity of the 12-item WHO-DAS II in a large sample of Spanish PC patients with a first diagnosed major depressive episode. METHOD Data were collected between December 2006 and July 2007. A total of 3615 adult (18 years or older) PC patients from 17 regions of Spain with a first diagnosed major depressive episode participated in the study. The 12-item WHO-DAS II and a battery of instruments assessing sociodemographic characteristics, depression severity (PHQ-9), quality of life (EQ-5D) and chronic health conditions were administered by the family physician during the consultation. RESULTS The principal component analysis and the subsequent confirmatory factor analysis indicated that the 12-item WHO-DAS II is one-dimensional. The instrument showed adequate internal consistency (alpha=0.89) and construct validity because it was significantly associated with quality of life and depression severity (convergent validity) and was able to discriminate between patients on sick leave and those that were working (discriminative validity). LIMITATIONS The test-retest reliability and sensitivity to change of the instrument was not examined due to the cross-sectional design of the study. CONCLUSIONS The 12-item WHO-DAS II is a reliable, valid and useful tool for assessing overall disability in PC patients with depression.

Effectiveness of Pharmacist Care in the Improvement of Adherence to Antidepressants: A Systematic Review and Meta-Analysis

Background Pharmacists can play a decisive role in the management of ambulatory patients with depression who have poor adherence to antidepressant drugs. Objective To systematically evaluate the effectiveness of pharmacist care in improving adherence of depressed outpatients to antidepressants. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. RCTs were identified through electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, Institute for Scientific Information Web of Knowledge, and Spanish National Research Council) from inception to April 2010, reference lists were checked, and experts were consulted. RCTs that evaluated the impact of pharmacist interventions on improving adherence to antidepressants in depressed patients in an outpatient setting (community pharmacy or pharmacy service) were included, Methodologic quality was assessed and methodologic details and outcomes were extracted in duplicate. Results: Six RCTs were identified. A total of 887 patients with an established diagnosis of depression who were initiating or maintaining pharmacologic treatment with antidepressant drugs and who received pharmacist care (459 patients) or usual care (428 patients) were included in the review. The most commonly reported interventions were patient education and monitoring, monitoring and management of toxicity and adverse effects, adherence promotion, provision of written or visual information, and recommendation or implementation of changes or adjustments in medication. Overall, no statistical heterogeneity or publication bias was detected. The pooled odds ratio, using a random effects model, was 1.64 (95% CI 1.24 to 2.17). Subgroup analysis showed no statistically significant differences in results by type of pharmacist involved, adherence measure, diagnostic tool, or analysis strategy. Conclusions: These results suggest that pharmacist intervention is effective in the improvement of patient adherence to antidepressants. However, data are still limited and we would recommend more research in this area, specifically outside of the US.

The 12-item World Health Organization Disability Assessment Schedule II (WHO-DAS II): a nonparametric item response analysis

BackgroundPrevious studies have analyzed the psychometric properties of the World Health Organization Disability Assessment Schedule II (WHO-DAS II) using classical omnibus measures of scale quality. These analyses are sample dependent and do not model item responses as a function of the underlying trait level. The main objective of this study was to examine the effectiveness of the WHO-DAS II items and their options in discriminating between changes in the underlying disability level by means of item response analyses. We also explored differential item functioning (DIF) in men and women.MethodsThe participants were 3615 adult general practice patients from 17 regions of Spain, with a first diagnosed major depressive episode. The 12-item WHO-DAS II was administered by the general practitioners during the consultation. We used a non-parametric item response method (Kernel-Smoothing) implemented with the TestGraf software to examine the effectiveness of each item (item characteristic curves) and their options (option characteristic curves) in discriminating between changes in the underliying disability level. We examined composite DIF to know whether women had a higher probability than men of endorsing each item.ResultsItem response analyses indicated that the twelve items forming the WHO-DAS II perform very well. All items were determined to provide good discrimination across varying standardized levels of the trait. The items also had option characteristic curves that showed good discrimination, given that each increasing option became more likely than the previous as a function of increasing trait level. No gender-related DIF was found on any of the items.ConclusionsAll WHO-DAS II items were very good at assessing overall disability. Our results supported the appropriateness of the weights assigned to response option categories and showed an absence of gender differences in item functioning.

Factor structure, internal consistency and construct validity of the Sheehan Disability Scale in a Spanish primary care sample

RATIONALE, AIMS AND OBJECTIVES The Sheehan Disability Scale (SDS) is a three-item instrument that measures disability in three inter-related domains: work, family life/home responsibilities and social/leisure activities. The main objective of the present study was to examine the factor structure, reliability and construct validity of the SDS in a wide Spanish sample of primary care (PC) patients. METHODS One phase cross-sectional survey. A total of 3815 patients, aged 18 years or older attending PC for a medical visit, were interviewed between October 2005 and March 2006. The interviews included the Structured Clinical Interview for DSM-IV Axis I Disorders for depressive and anxiety disorders, the Mini-International Neuropsychiatric Interview for the rest of mental disorders, a medical conditions checklist, the 2.0 version of the 12-item Short-Form Health Survey (SF-12) for measuring quality of life and the SDS. RESULTS The principal component analysis and the subsequent confirmatory factor analysis indicated that the SDS is one-dimensional (normed fit index = 0.990, non-normed fit index = 0.987, comparative fit index = 0.991, goodness-of-fit index = 0.993, standardized root mean-square residual = 0.037, root mean-square error of approximation = 0.053). The internal consistency of the scale was good (α = 0.83) and it was significantly associated with the physical and mental component of the SF-12. Concerning discriminative validity, patients with major depression or panic disorder scored higher on the SDS than patients with chronic medical conditions or with no chronic pathology. We also found that a cut-off point of 8 in the SDS adequately discriminated between patients with and without depression (area under the curve = 0.814, sensitivity = 81.60%, specificity = 70.60%). CONCLUSIONS The SDS seems a reliable, valid and useful clinical tool for measuring disability in Spanish PC patients.

Factors affecting collaboration between general practitioners and community pharmacists: a qualitative study

BackgroundAlthough general practitioners (GPs) and community pharmacists (CPs) are encouraged to collaborate, a true collaborative relationship does not exist between them. Our objective was to identify and analyze factors affecting GP-CP collaboration.MethodsThis was a descriptive-exploratory qualitative study carried out in two Spanish regions: Catalonia (Barcelona) and Balearic Islands (Mallorca). Face-to-face semi-structured interviews were conducted with GPs and CPs from Barcelona and Mallorca (January 2010-February 2011). Analysis was conducted using Colaizzi’s method.ResultsThirty-seven interviews were conducted. The factors affecting the relationship were different depending on timing: 1) Before collaboration had started (prior to collaboration) and 2) Once the collaboration had been initiated (during collaboration). Prior to collaboration, four key factors were found to affect it: the perception of usefulness; the Primary Care Health Center (PCHC) manager’s interest; the professionals’ attitude; and geography and legislation. These factors were affected by economic and organizational aspects (i.e. resources or PCHC management styles) and by professionals’ opinions and beliefs (i.e. perception of the existence of a public-private conflict). During collaboration, the achievement of objectives and the changes in the PCHC management were the key factors influencing continued collaboration. The most relevant differences between regions were due to the existence of privately-managed PCHCs in Barcelona that facilitated the implementation of collaboration. In comparison with the group with experience in collaboration, some professionals without experience reported a skeptical attitude towards it, reporting that it might not be necessary.ConclusionsFactors related to economic issues, management and practitioners’ attitudes and perceptions might be crucial for triggering collaboration. Interventions and strategies derived from these identified factors could be applied to achieve multidisciplinary collaboration.

Exploring Bacterial Diversity in Hospital Environments by GS-FLX Titanium Pyrosequencing

Understanding microbial populations in hospital environments is crucial for improving human health. Hospital-acquired infections are an increasing problem in intensive care units (ICU). In this work we present an exploration of bacterial diversity at inanimate surfaces of the ICU wards of the University Hospital A Coruña (Spain), as an example of confined hospital environment subjected to selective pressure, taking the entrance hall of the hospital, an open and crowded environment, as reference. Surface swab samples were collected from both locations and recovered DNA used as template to amplify a hypervariable region of the bacterial 16S rRNA gene. Sequencing of the amplicons was performed at the Roche 454 Sequencing Center using GS-FLX Titanium procedures. Reads were pre-processed and clustered into OTUs (operational taxonomic units), which were further classified. A total of 16 canonical bacterial phyla were detected in both locations. Members of the phyla Firmicutes (mainly Staphylococcus and Streptococcus) and Actinobacteria (mainly Micrococcaceae, Corynebacteriaceae and Brevibacteriaceae) were over-represented in the ICU with respect to the Hall. The phyllum Proteobacteria was also well represented in the ICU, mainly by members of the families Enterobacteriaceae, Methylobacteriaceae and Sphingomonadaceae. In the Hall sample, the phyla Proteobacteria, Bacteroidetes, Deinococcus-Thermus and Cyanobacteria were over-represented with respect to the ICU. Over-representation of Proteobacteria was mainly due to the high abundance of Enterobacteriaceae members. The presented results demonstrate that bacterial diversity differs at the ICU and entrance hall locations. Reduced diversity detected at ICU, relative to the entrance hall, can be explained by its confined character and by the existence of antimicrobial selective pressure. This is the first study using deep sequencing techniques made in hospital wards showing substantial hospital microbial diversity.

Evidence-based medicine: is it a bridge too far?

AimsThis paper aims to describe the contextual factors that gave rise to evidence-based medicine (EBM), as well as its controversies and limitations in the current health context. Our analysis utilizes two frameworks: (1) a complex adaptive view of health that sees both health and healthcare as non-linear phenomena emerging from their different components; and (2) the unified approach to the philosophy of science that provides a new background for understanding the differences between the phases of discovery, corroboration, and implementation in science.ResultsThe need for standardization, the development of clinical epidemiology, concerns about the economic sustainability of health systems and increasing numbers of clinical trials, together with the increase in the computer’s ability to handle large amounts of data, have paved the way for the development of the EBM movement. It was quickly adopted on the basis of authoritative knowledge rather than evidence of its own capacity to improve the efficiency and equity of health systems. The main problem with the EBM approach is the restricted and simplistic approach to scientific knowledge, which prioritizes internal validity as the major quality of the studies to be included in clinical guidelines. As a corollary, the preferred method for generating evidence is the explanatory randomized controlled trial. This method can be useful in the phase of discovery but is inadequate in the field of implementation, which needs to incorporate additional information including expert knowledge, patients’ values and the context.ConclusionEBM needs to move forward and perceive health and healthcare as a complex interaction, i.e. an interconnected, non-linear phenomenon that may be better analysed using a variety of complexity science techniques.