Método de detección de Salmonella en alimentos bajo el marco de la UNE-EN ISO 17025

Motivación: En la actualidad, la contaminación microbiana de los alimentos constituye un problema que genera grandes pérdidas en el sector público y privado y un riesgo para salud pública por intoxicación alimentaria. Uno de los microorganismos más comunes y peligrosos que causan estas intoxicaciones alimentarias a nivel europeo y mundial es Salmonella. Por ello la ley exige el cumplimiento de ciertos protocolos a las empresas y laboratorios que realizan los controles para la detección de Salmonella.En este proyecto se desarrolló un método de detección de Salmonella para la obtención de la acreditación a la ISO 17025.Métodos: Se contaminó artificialmente 5 alimentos diferentes con Salmonella (WCDM 00030) y se evaluaron, además de los parámetros específicos de la ISO (condiciones de repetitividad o reproducibilidad), otros parámetros tales como límite de detección, efecto matricial, presencia de otros microorganismos etc.Resultados: El porcentaje de recuperación obtenido según el nivel de contaminación no difirió estadísticamente de lo esperado; además, el elevado número de resultados negativos que se obtuvieron sugiere que se manejaron niveles de contaminación en torno al límite de detección. También se observó que la presencia de otros microorganismos o el efecto matricial no alteraron el resultado en lo referido a la detección de Salmonella. Por último, la variación de las condiciones en las que se realizaron los ensayos para algunos de los alimentos no alteró significativamente los resultados obtenidos, por lo que el método desarrollado en este trabajo respeta los parámetros específicos descritos en la normativa ISO 17025.Conclusiones: El método desarrollado cumple con la normativa exigida para la obtención de la ISO 17025 en la competencia metodológica para la detección de Salmonella en alimentos. Además, este método reduce el tiempo de detección habitual de 5 días (para métodos en los que se usan medios de cultivo) a menos de 48 h mejorando así la competitividad frente a otros laboratorios

Benefit of tolvaptan in the management of hyponatraemia in patients with diuretic‐refractory congestive heart failure: the SEMI‐SEC project

Aims: Hyponatraemia is an electrolyte disorder that occurs in advanced congestive heart failure (HF) and worsens prognosis. We explored the usefulness of tolvaptan, which has shown promising results in the treatment of this condition. Methods and results: This study is based on a retrospective national registry (2011-15) of patients hospitalized with refractory HF and hyponatraemia who agreed to receive tolvaptan when standard treatment was ineffective. The benefit of tolvaptan was analysed according to the following criteria: normalization ([Na+] >= 135mmol/L) or increased sodium levels [Na+] >= 4mEq/L on completion of treatment, and increase in urine output by 300 or 500mL at 48h. Factors associated with tolvaptan benefit were explored. A total of 241 patients were included, 53.9% of whom had ejection fraction = 4mEq/L and/or +300mL in urine output (54.4% both). Conclusions: An increase in sodium levels and/or improvement in urine output was observed in patients admitted for HF and refractory hyponatraemia under tolvaptan treatment. Tolvaptan may be useful in this setting, in which no effective proven alternatives are available

Tráfico inverso: una actividad ilícita emergente en la cadena de suministro de medicamentos en España

AGRADECIMIENTOS : A Eugenio Ces Gens, Begoña Rocha Blanco, Mª Jesús Silva Villar y Ana Vilar Carneiro, Inspectores de Farmacia de Servicios Sanitarios que también han colaborado de forma activa en estas actuaciones; a Antonio Fernández- Campa García-Bernardo, Secretario General Técnico de la Consellería de Sanidade de la Xunta de Galicia, por su apoyo continuo a la Inspección de Servicios Sanitarios; a Enrique Gomez Bastida, director de la Agencia de Protección de la Salud en el Deporte, por su implicación con las Inspecciones de Servicios Sanitarios en la lucha contra este fenómeno mientras estuvo al frente del Grupo de Investigaciones de la Seguridad Social.Objetivos: La inversión de los circuitos de comercialización de medicamentos en la red de distribución es una actividad ilícita emergente en España y compromete seriamente la salud pública. Los almacenes farmacéuticos pasan a abastecerse de medicamentos a través de oficinas de farmacias, en lugar de ponerlos a su disposición, y las oficinas de farmacia pasan a hacer actividades de suministro a éstos en lugar de dispensarlos a los pacientes. Se ha extendido en el territorio nacional debido a la diferencia de precios entre España y el resto de países de la Unión Europea. El objetivo fue explicar la operativa de estos agentes y dar a conocer una metodología de trabajo inspector efectiva. Material y Métodos: Probar la inversión del canal de suministro de medicamentos entre los agentes: estudio de datos de compras frente a ventas, de entregas y trazabilidad de los pedidos, y de los sistemas de información de facturación al Servicio de Salud. No necesita la colaboración del establecimiento inspeccionado. Resultados: Cuando no se tenía un tipo de infracción administrativa específica ni se conocía la operativa de estas organizaciones: sanciones entre 3.000-78.000 euros como faltas graves. Con un tipo de infracción específico recogido como falta muy grave en la normativa, y una metodología de investigación implementada: sanciones entre 600.000- 1.000.000 euros. Conclusiones: La inspección farmacéutica es el principal actor en la lucha contra esta actividad ilícita. Exige un esfuerzo de colaboración interadministrativa. La vía penal, con el apoyo del Grupo de Investigaciones de la Seguridad Social, es una alternativa en determinados casos.Aim: The inversion of medicinal products marketing and distribution network circuits is an emergent illegal activity that results in serious threat to public health. Wholesale distributors obtain medicinal products from high street pharmacies instead of supplying them; and pharmacies become involved in wholesale distribution instead of focusing strictly on their legitimate function of dispensing the medicines to individual patients. This practice has expanded in the country due to price differentials between Spain and other European states. This activity is known as “reverse pharmaceutical traffic”. The aims were to explain the operation of the agents involved and provide an effective inspection methodology. Materials and Methods: Based on proving the inversion of the supply channel among the agents involved, hindered by a systematic and deliberate impediment to the inspection tasks. Such methodology includes activities like studies of purchasing data against sales, deliveries against sales, and analysis of the billing information systems to the Health Service. Not needing the cooperation of the inspected institution. Results: with no specific type of administrative infringement defined and no knowledge of the illicit operations of these organizations: sanctions between 3,000 and 78,000 € defined as serious offenses. With a specific type of infringement defined as very serious offenses and a research methodology implemented: sanctions between 600,000 and 1,000,000 €. Conclusion: Pharmaceutical inspection is the main actor in the fight against this illegal activity. It requires a major effort in inter-administrative collaboration. The penal system with support of the special police “Grupo de Investigaciones de la Seguridad Social” is alternative in some cases

Rationale, design and preliminary results of the GALIPEMIAS study (prevalence and lipid control of familial dyslipidemia in Galicia, northwest Spain)

[Abstract] Aims. There is little information on the familial nature of dyslipidemias in the Spanish population. This knowledge could have potential diagnostic and treatment implications. The objective of the GALIPEMIAS study was to determine the prevalence of familial dyslipidemia in Galicia, as well as determine the degree of lipid control in the participants. Prevalence of atherosclerotic cardiovascular disease (ASCVD) was also estimated. This paper presents the design, methodology and selected preliminary results. Methodology. A cross‐sectional study was performed in the population aged ≥18 years using cluster sampling and then random sampling. A sample of 1000 subjects was calculated and divided into three sequential phases with a specific methodology for each one. Phase I: selection of subjects from the general population and collection of informed consent documents; Phase II: collection of data from the digital clinical history to select subjects with dyslipidemia according to study criteria; Phase III: personal interview, blood analysis, family tree, and definitive diagnosis of dyslipidemia. Prevalence of different diseases and active medication was analysed. Corrected prevalence (to the reference population) of different risk factors and ASCVD was estimated. Results. Phase I participation was 89.5%. We extracted complete information from 93% of the participants (Phase II). According to the study′s own criteria, 56.5% (n = 527) of the participants had some form of dyslipidemia and almost 33.7% of them had familial dyslipidemia with autosomal dominant inherit pattern. The corrected prevalence of ASCVD was 5.1% (95% CI 3.1‐7.2). Conclusions. Dyslipidemia was the most prevalent cardiovascular risk factor in our population with an autosomal dominant inheritance pattern in one out of every three dyslipidemia cases. Approximately, 5.1% of the sample population aged ≥18 has suffered an episode of ACVD

Lack of replication of interactions between polymorphisms in rheumatoid arthritis susceptibility: case-control study

Introduction: Approximately 100 loci have been definitively associated with rheumatoid arthritis (RA) susceptibility. However, they explain only a fraction of RA heritability. Interactions between polymorphisms could explain part of the remaining heritability. Multiple interactions have been reported, but only the shared epitope (SE) × protein tyrosine phosphatase nonreceptor type 22 (PTPN22) interaction has been replicated convincingly. Two recent studies deserve attention because of their quality, including their replication in a second sample collection. In one of them, researchers identified interactions between PTPN22 and seven single-nucleotide polymorphisms (SNPs). The other showed interactions between the SE and the null genotype of glutathione S-transferase Mu 1 (GSTM1) in the anti-cyclic citrullinated peptide-positive (anti-CCP+) patients. In the present study, we aimed to replicate association with RA susceptibility of interactions described in these two high-quality studies. Methods: A total of 1,744 patients with RA and 1,650 healthy controls of Spanish ancestry were studied. Polymorphisms were genotyped by single-base extension. SE genotypes of 736 patients were available from previous studies. Interaction analysis was done using multiple methods, including those originally reported and the most powerful methods described. Results: Genotypes of one of the SNPs (rs4695888) failed quality control tests. The call rate for the other eight polymorphisms was 99.9%. The frequencies of the polymorphisms were similar in RA patients and controls, except for PTPN22 SNP. None of the interactions between PTPN22 SNPs and the six SNPs that met quality control tests was replicated as a significant interaction term the originally reported finding or with any of the other methods. Nor was the interaction between GSTM1 and the SE replicated as a departure from additivity in anti-CCP+ patients or with any of the other methods. Conclusions: None of the interactions tested were replicated in spite of sufficient power and assessment with different assays. These negative results indicate that whether interactions are significant contributors to RA susceptibility remains unknown and that strict standards need to be applied to claim that an interaction exists

Development and validation of a clinical score to estimate progression to severe or critical state in Covid-19 pneumonia hospitalized patients

The prognosis of a patient with Covid-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. A retrospective study was performed of patients admitted with Covid-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, analytical, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. During the study period 1,152 patients presented with Covid-19 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 hours of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤5%, 6-25%, and >25% exhibited disease progression, respectively. A simple risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis.Carlos III Health Institute, Spain, Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER)Instituto de Salud Carlos II

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass