The impact of an easy access drug supply management policy law on the consumption and abuse of opioids in Catalonia : A population-based study

Background: Over the last two decades, the rise in opioid prescription has worsened health outcomes worldwide, increasing both levels of abuse and mortality rates. In order to reduce the scale of this public health problem, new policies have been implemented in many countries. In 2012, Spain adopted new legislation on opioid prescription (the ROE law), which meant that practitioners no longer needed to obtain extra authorisation in order to prescribe strong opioids. The objective of the paper is to assess the impact of this law on opioid use and abuse in Catalonia, Spain. Methods: We established two measures of the use of strong and weak opioids: DDDs, and abuse. We used benzodiazepines and antidepressants as controls, and adjusted for age, sex, drug co-payment level, death or near death, cancer diagnosis, morbidity group, and type of prescription. The data were obtained from administrative and dispensing drug databases in a population of 7.5 million inhabitants. We estimated two-way fixed effects using difference in difference models. Results: The ROE law impacted reducing the monthly use of strong opioids by 0.903 DDDs, representing a 3.15% decrease in the mean monthly use of strong opioids. However, abuse rose 1.86 times compared with the average pre-ROE value, which represents an increase of 11,190 months of opioid abuse (i.e., an 11.33% of all monthly opioids use). Conclusion: The abolition of the duplicate prescription programme for strong opioids led to a reduction in the average monthly use of strong opioids, but an increase in abuse

Do governments care about socioeconomic inequalities in health? Narrative review of reports of EU-15 countries

Altres ajuts: Fundació "La Caixa"Socioeconomic inequalities in health have been an issue in all European countries since the publication of the "Black Report" in the United Kingdom in 1980. However, data show that nowadays there are important socioeconomic health inequalities within EU countries. The purpose of this paper is to review EU-15 government reports that address socioeconomic inequalities in health. We reviewed 101 reports. The pioneer countries in analyzing this topic have a Beveridge-type health system, and they are the leaders over time. The top socioeconomic indicators used are education level, social class, deprivation level of the area, and nationality. Given the current COVID-19 pandemic situation and its economic consequences, EU governments need to continue monitoring the existing inequalities in health and to act transversely in all public policies

Geographical, Socioeconomic, and Gender Inequalities in Opioid Use in Catalonia

Background: In recent years, worldwide opioid use has seen a sharp increase, especially for the treatment of chronic non-cancer pain. Catalonia is no exception to this trend. However, no recent studies have addressed the socioeconomic and gender inequalities in opioid use in the different geographical areas of Catalonia. Methods: We performed an ecological study to analyse the associations between socioeconomic status, gender and the use of opioids in the 372 Health Areas of Catalonia. Robust Poisson models were performed to analyse the data provided from the Central Register of Insured Persons and dispensing data from the Electronic Prescription Database. Results: The results show that socioeconomic status has a major impact on opioid use, with the most deprived areas presenting the highest levels of use. There are major inequalities in the DDD/1,000 inhabitants per areas. Moreover, women have much higher utilization rates than men, especially in more deprived areas. The greatest difference is observed in the use of weak opioids in women: the DDD/1,000 inhabitants per day was 2.34 in the area with the lowest use, compared with 22.18 in the area with the highest use. Conclusions: Our findings suggest that stronger action is needed to promote best practices in prescribing for chronic pain and to reduce socioeconomic and gender variation between geographical areas. This study provides a model for routine monitoring of opioid prescription for targeted interventions aimed at lowering high-dose consumption in specifically identified areas

Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% Gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence

Diseño y primeros resultados de una cámara PET para animales pequeños basada en cristales LYSO continuos y fotomulplicadores sensibles a la posición

[ES] En este artículo presentamos el diseño de un nuevo escáner PET para animales pequeños basado en una tecnología completamente innovadora. Los resultados preliminares son muy prometedores, permitiendo obtener imágenes funcionales de alta resolución con una instrumentación compacta y de bajo coste. Los prototipos desarrollados se encuentran actualmente en pruebas en diversos centros de investigación médica, obteniéndose imá- genes de alta calidad en los campos de oncología, neurología y cardiología. Este diseño puede ser fácilmente extendido a cámaras PET dedicadas a la exploración del cerebro o de la mama. La innovación más notable de la presente tecnología consiste en el uso de un único cristal continuo por módulo, a diferencia de otras cámaras PET comerciales donde se utilizan cientos de cristales pixelados. El uso de un único cristal continuo permite abaratar el coste de fabricación, al tiempo que mejora las características de funcionamiento: resolución intrínseca en posición de 1,2 mm, resolución en energía media del 14%, resolución en la profundidad de interacción de 3 mm, sensibilidad > 4% y campo de visión transaxial de 80 mm de diámetro. En el presente artículo se describen en detalle el diseño de esta nueva cámara PET, los principios de funcionamiento, el método utilizado para su calibración y se anticipan algunas imágenes "in vivo" del miocardio y el cerebro de un ratón, permitiendo apreciar de forma preliminar la resolución y calidad alcanzadas.[EN] In this paper we present the design of a new small animal PET scanner based on a completely innovative technology. The achieved results are very promising, showing the possibility to obtain high resolution functional images with a compact and low cost scanner. Several prototypes have been developed and are currently being used at different research medical institutions. High resolution images are being obtained in application fields like oncology, neurology and cardiology. This technology can be easily applied in PET cameras for brain or breast exploration. The most significant innovation of the design is the fact of using a single crystal per module instead of hundreds of pixellated crystals as in other commercial PETs. It has the advantage of decreasing the manufacturing costs and simultaneously improves its performance: 1.2 mm position intrinsic resolution, mean energy resolution as good as 14%, 3 mm depth of interaction resolution, sensitivity above 4%, and 80 mm diameter of transaxial field of view. In this paper we describe in detail the design of this new PET camera, its principle, the calibration methodology and also some preliminary "in vivo" images of a mouse myocardium and brain, showing the achieved image resolution and qualityBenlloch Baviera, JM.; González Martínez, AJ.; Carrilero, V.; Catret, JV.; Correcher, C.; Lerche, CW.; Morera, C.... (2007). Diseño y primeros resultados de una cámara PET para animales pequeños basada en cristales LYSO continuos y fotomulplicadores sensibles a la posición. Revista de física médica. 8(2):315-321. http://hdl.handle.net/10251/79285S3153218

periscope: sub-genomic RNA identification in SARS-CoV-2 genomic sequencing data

We have developed periscope, a tool for the detection and quantification of sub-genomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed “sub-genomic RNAs”. sgRNAs are produced through discontinuous transcription which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L which is located in the 5’ UTR. TRS-L is immediately preceded by a leader sequence. This leader sequence is therefore found at the 5’ end of all sgRNA. We applied periscope to 1,155 SARS-CoV-2 genomes from Sheffield, UK and validated our findings using orthogonal datasets and in vitro cell systems. Using a simple local alignment to detect reads which contain the leader sequence we were able to identify and quantify reads arising from canonical and non-canonical sgRNA. We were able to detect all canonical sgRNAs at expected abundances, with the exception of ORF10. A number of recurrent non-canonical sgRNAs are detected. We show that the results are reproducible using technical replicates and determine the optimum number of reads for sgRNA analysis. In VeroE6 ACE2+/− cell lines, periscope can detect the changes in the kinetics of sgRNA in orthogonal sequencing datasets. Finally, variants found in genomic RNA are transmitted to sgRNAs with high fidelity in most cases. This tool can be applied to all sequenced COVID-19 samples worldwide to provide comprehensive analysis of SARS-CoV-2 sgRNA

Differential Phenotypic and Functional Profiles of TcCA-2 -Specific Cytotoxic CD8+ T Cells in the Asymptomatic versus Cardiac Phase in Chagasic Patients

It has been reported that the immune response mediated by T CD8+ lymphocytes plays a critical role in the control of Trypanosoma cruzi infection and that the clinical symptoms of Chagas disease appear to be related to the competence of the CD8+ T immune response against the parasite. Herewith, in silico prediction and binding assays on TAP-deficient T2 cells were used to identify potential HLA-A*02:01 ligands in the T. cruzi TcCA-2 protein. The TcCA-2-specific CD8+ T cells were functionality evaluated by Granzyme B and cytokine production in peripheral blood mononuclear cells (PBMC) from Chagas disease patients stimulated with the identified HLA-A*02:01 peptides. The specific cells were phenotypically characterized by flow cytometry using several surface markers and HLA-A*02:01 APC-labeled dextramer loaded with the peptides. In the T. cruzi TcCA-2 protein four T CD8+ epitopes were identified which are processed and presented during Chagas disease. Interestingly, a differential cellular phenotypic profile could be correlated with the severity of the disease. The TcCA-2-specific T CD8+ cells from patients with cardiac symptoms are mainly effector memory cells (TEM and TEMRA) while, those present in the asymptomatic phase are predominantly naive cells (TNAIVE). Moreover, in patients with cardiac symptoms the percentage of cells with senescence features is significantly higher than in patients at the asymptomatic phase of the disease. We consider that the identification of these new class I-restricted epitopes are helpful for designing biomarkers of sickness pathology as well as the development of immunotherapies against T. cruzi infection.This work was supported by grants SAF2012-35777 and SAF2013-48527-R from Programa Estatal I+D+i (MINECO); Network of Tropical Diseases Research RICET, grants RD12/0018/0021 and RD12/0018/0018 (MSSSI, Spain) and FEDER. MS and BC were also supported by grant FIS, 2009SGR385 from ISCIII (MSSSI, Spain). Coauthor Concepción Marañón is employed by Genomic Medicine Department, GENYO. Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government. Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government provided support in the form of salaries for author Concepción Marañón, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the author contributions section.Peer reviewe