Forty years of Tuberculous meningitis: The new face of an old enemy.

BACKGROUND: Tuberculous meningitis (TBM) occurs in 1-5% of cases of tuberculosis. Without early treatment, mortality and permanent disability rates are high. METHODS: A retrospective study performed at a tertiary hospital in Madrid (Spain) to describe clinical, diagnostic, and therapeutic aspects of TBM and analyze epidemiological trends over forty years, divided into two intervals (1979-1998 and 1999-2018). RESULTS: Overall, TBM was diagnosed in 65 patients (1.8% of new tuberculosis diagnoses), 48 in the first period and 17 in the second one. Median age at diagnosis increased from 38.5 to 77 years (p = 0.003). The proportion of non-HIV immunosuppressed patients increased (from 2.1% to 29.4%, p < 0.001), while the percentage of patients with a history of drug-abuse decreased (from 33.3% to 5.9%, p = 0.027). The median time between the onset of neurological symptoms and lumbar puncture increased from seven to 15 days (p = 0.040). The time between the onset of symptoms and the initiation of tuberculostatic treatment also increased from eleven to 18 days (p = 0.555). Results from image, biochemical, and microbiological tests showed no differences between both periods. A decreasing trend was observed in survival rates at 1-week (from 97.9% to 64.7%, p < 0.001), 1-month (from 91.7% to 58.8%, p = 0.002) and 1-year (from 85.4% to 47.1%, p = 0.002) after TBM diagnosis. CONCLUSIONS: The profile of patients diagnosed with TBM has changed from a young HIV-infected patient with a history of drug addiction to an elderly patient with non-HIV immunosuppression. Diagnosis and start of treatment both experienced a noticeable delay in the second period, which could help explain the increase in mortality observed across the two periods.

Spread of a new Chlamydia trachomatis variant from men who have sex with men to the heterosexual population after replacement and recombination in ompA and pmpH genes.

OBJECTIVES: Sexually transmitted infections are frequently related to outbreaks in high-risk populations due to the dense sexual networks. We wanted to determine the dissemination of a Chlamydia trachomatis variant characterized by the pmpH-recombinant gene between L and G genotypes, which was previously described in a high-risk population. METHODS: A total of 449 samples were analysed in two periods ranging from 2009 to 2015 for detection of the pmpH-recombinant gene. For those samples yielding positive amplification, a sampling was selected for phylogenetic reconstructions based on sequencing of five chromosomal genes. RESULTS: Globally this variant was found in 113 of the 449 samples (25%). During the first years (2009-13), this variant was found almost exclusively in rectal samples (30/112 samples) of men who have sex with men and in only one non-rectal sample (1/63). In 2014, this variant was also found in urethral and pharyngeal samples (1/24 and 1/7, respectively). However, in 2015, an epidemiological change was observed as the proportion of this variant had increased in rectal samples (20/51; 39%) and non-rectal samples, including cervical samples (51/142; 36.4%). The molecular characterization revealed the replacement of the ompA gene belonging to subtype G in samples recovered from 2009 to 2013 by the ompA gene belonging to subtype J after 2013. CONCLUSIONS: Our data would support the evidence that subtype J could be a 'subtype bridge' between different sexual networks, as subtype J has been found in men who have sex with men and heterosexual populations in similar proportions. This work reveals the necessity of implementing molecular surveillance in extra-rectal samples to help us understand the gaps in transmission.

Efficiency of pragmatic search strategies to update clinical guidelines recommendations.

BACKGROUND: A major challenge in updating clinical guidelines is to efficiently identify new, relevant evidence. We evaluated the efficiency and feasibility of two new approaches: the development of restrictive search strategies using PubMed Clinical Queries for MEDLINE and the use of the PLUS (McMaster Premium Literature Service) database. METHODS: We evaluated a random sample of recommendations from a national guideline development program and identified the references that would potentially trigger an update (key references) using an exhaustive approach. We designed restrictive search strategies using the minimum number of Medical Subject Headings (MeSH) terms and text words required from the original exhaustive search strategies and applying broad and narrow filters. We developed PLUS search strategies, matching Medical Subject Headings (MeSH) and Systematized Nomenclature of Medicine (SNOMED) terms with guideline topics. We compared the number of key references retrieved by these approaches with those retrieved by the exhaustive approach. RESULTS: The restrictive approach retrieved 68.1 % fewer references than the exhaustive approach (12,486 versus 39,136), and identified 89.9 % (62/69) of key references and 88 % (22/25) of recommendation updates. The use of PLUS retrieved 88.5 % fewer references than the exhaustive approach (4,486 versus 39,136) and identified substantially fewer key references (18/69, 26.1 %) and fewer recommendation updates (10/25, 40 %). CONCLUSIONS: The proposed restrictive approach is a highly efficient and feasible method to identify new evidence that triggers a recommendation update. Searching only in the PLUS database proved to be a suboptimal approach and suggests the need for topic-specific tailoring.

La investigación biomédica, el mercado, los clínicos, la seguridad y la responsabilidad social corporativa posfase III: retener la confianza / Biomedical research, the market, clinicians, safety and corporate social responsibility post-phase III: maintaining confidence

Introducción: Los ensayos controlados aleatorios son el gold standar occidental respecto a la toma de decisiones, tanto para los clínicos como para los gestores o responsables de políticas comunitarias. En este poderoso despliegue de esfuerzo investigador existen grados variables de conflictos de intereses y los clínicos, que no somos ajenos a eso, estamos entrando en un mar de dudas acerca de la seguridad, dimensión que emerge como un elemento diacrítico, irrenunciable. El objeto del estudio fue toda evaluación crítica y la selección sobre editoriales, ensayos clínicos o metaanálisis publicados en soporte físico o vía web, acreditados internacionalmente, que resultaran más relevantes y que abordaran como objetivo primario la seguridad de los pacientes. Pacientes y métodos: Investigación evaluativa que se llevó a cabo en el Complejo Hospitalario Torrecárdenas, perteneciente al Servicio Andaluz de Salud. Sistema Sanitario Público de Andalucía, en el contexto de una unidad formativa acreditada (Mejora_F) en 2008, denominada «transferencia del conocimiento biomédico desde la bibliografía». Resultados: Los artículos analizados fueron 170 (el 75% en inglés, con predominio de New England Journal of Medicine [>50%], seguida de Journal Of the American Medical Association, The Lancet, British Medical Journal, Journal of American Geriatrics, Medicina Clínica, Revista Clínica Española e Infectología). De los 170 artículos elegibles, seleccionamos 5 tópicos clave por su impacto como los más representativos por su frecuencia de citación. Representaron, a nuestro juicio, «una bandera roja» de seguridad los siguientes: betaestimulantes de acción larga y aumento de mortalidad en asma; neurolépticos en ancianos y prolongación del intervalo QT asociado a muerte súbita; tiazolidindiona en diabetes de tipo ii y efectos negativos cardiovasculares; potenciación de estatinas-ezetimiba y discutible asociación con mayor mortalidad por cáncer, y tratamiento intensivo en diabetes y probable aumento de mortalidad. Conclusiones: Lo que realmente importa en biomedicina es qué efectos provoca una estrategia dada en los pacientes reales, no en los puntos intermedios. Los clínicos no deberíamos apoyar resultados parciales de diseños basados en datos intermedios -indudablemente menos costosos y más rápidos- sin conocer adecuadamente la seguridad de la estrategia erigida para alcanzarlos. Sólo así nos constituimos en verdaderos garantes de la seguridad, sólo así, y en ausencia de conflictos de intereses, podremos mantener la confianza dada (AU)

Introduction: Randomised controlled trials (RCTs) are the gold standard in the western world for decision making, as much for the clinicians as for the agencies or managers for community policies. In this powerful deployment of investigative effort there are variable degrees of conflict of interests, and the clinicians, not foreign to this, are entering a sea of doubts on safety, a dimension that emerges like a diacritical, inalienable element. The aim of the study was to select and ctically evaluate editorials, clinical trials and/or meta-analyses published on physical support, or the more important internationally credited websites, which has patient safety as their primary objective. Patients and Methods: Evaluative study performed in the Torrecardenas Hospital, of the Andalucian Public Health Service (SSPA), in the context of an accredited training unit (Mejora_F), so called "transference of the biomedical knowledge from the bibliography" from 2008 to 2009. Results: Analyzed articles: 170 (75 % in English, with predominance of N Eng J Med >50 %; followed by Journal Of the American Medical Association, The Lancet, British Medical Journal, Journal of American Geriatrics; Med Clin, Rev Clin Esp.; and Infectología). From 170 eligible articles we selected 5 key topoi due to their impact as the most representative owing to their citation frequency. They represented, in our judgment, "a red flag" of safety: long-acting beta-stimulators or LABS and increase in mortality in asthma; neuroleptics in the elderly and extension of the QT interval associated with sudden death; thiazolidinediones in type II diabetes and negative cardiovascular effects; promotion of statins-ezetimibe and the debatable association with major mortality for cancer, and intensive treatment in diabetes and probable increase in mortality. Conclusions: What really maters in biomedicine is that it leads to a given strategy in real patients, not the intermediate points. Clinicians should not support partial results of designs based on intermediate information -undoubtedly less costly and more rapid- without adequately knowing the safety of the strategy built to reach them. Only in this way we can be real guarantors of safety, and only in this way, and in absence of conflicts of interests we will be able to support the given confidence (AU)

[Biomedical research, the market, clinicians, safety and corporate social responsibility post-phase III: maintaining confidence]. / La investigación biomédica, el mercado, los clínicos, la seguridad y la responsabilidad social corporativa posfase III: retener la confianza.

INTRODUCTION: Randomised controlled trials (RCTs) are the gold standard in the western world for decision making, as much for the clinicians as for the agencies or managers for community policies. In this powerful deployment of investigative effort there are variable degrees of conflict of interests, and the clinicians, not foreign to this, are entering a sea of doubts on safety, a dimension that emerges like a diacritical, inalienable element. The aim of the study was to select and ctically evaluate editorials, clinical trials and/or meta-analyses published on physical support, or the more important internationally credited websites, which has patient safety as their primary objective. PATIENTS AND METHODS: Evaluative study performed in the Torrecardenas Hospital, of the Andalucian Public Health Service (SSPA), in the context of an accredited training unit (Mejora_F), so called "transference of the biomedical knowledge from the bibliography" from 2008 to 2009. RESULTS: Analyzed articles: 170 (75 % in English, with predominance of N Eng J Med >50 %; followed by Journal Of the American Medical Association, The Lancet, British Medical Journal, Journal of American Geriatrics; Med Clin, Rev Clin Esp.; and Infectología). From 170 eligible articles we selected 5 key topoi due to their impact as the most representative owing to their citation frequency. They represented, in our judgment, "a red flag" of safety: long-acting beta-stimulators or LABS and increase in mortality in asthma; neuroleptics in the elderly and extension of the QT interval associated with sudden death; thiazolidinediones in type II diabetes and negative cardiovascular effects; promotion of statins-ezetimibe and the debatable association with major mortality for cancer, and intensive treatment in diabetes and probable increase in mortality. CONCLUSIONS: What really maters in biomedicine is that it leads to a given strategy in real patients, not the intermediate points. Clinicians should not support partial results of designs based on intermediate information - undoubtedly less costly and more rapid - without adequately knowing the safety of the strategy built to reach them. Only in this way we can be real guarantors of safety, and only in this way, and in absence of conflicts of interests we will be able to support the given confidence.

BCG specificity of an inhibitory seric factor from tuberculosis anergic patients that acts on non-adherent PPD reactive cells.

The effect of tuberculosis anergic immune sera adsorbed with BCG was studied on cocultures of adherent and non-adherent cells from PPD+ tuberculosis patient (TBP PPD+). This effect on the cocultures was quantified by lymphocyte transformation (LT) test using PPD as antigen. Only those cocultures with non-adherent cells from TBP PPD+ patients treated with anergic sera, inhibited the LT response induced by PPD, whereas sera adsorption with BCG eliminated the inhibitory effect.

[Fatal food poisoning by parathion]. / Intoxicación alimentaria mortal por paratión.

A case of family food poisoning by the organophosphate insecticide (OPI) parathion is revised. Poisoning was involuntary, affecting four brothers in one family that ate eggplant floured with parathion, which was mistaken for flour. As a result, 2 patients died suddenly and the other two had cardiorespiratory arrest, one dying from this while hospitalized, the other discharged without further consequences. The clinical diagnosis of poisoning was confirmed by the below-normal levels of plasmatic cholinesterase. Presence of parathion was detected in the gastric juices and blood of those poisoned as well as in the sample of the fried eggplant. We emphasize the need for public information campaigns on the storage and use of OPI in order to avoid this kind of accidents.

Characterization of an inhibitory seric factor from tuberculosis anergic patients that acts on non-adherent PPD reactive cells.

Non-adherent cells from PPD+ tuberculosis patients (TBP PPD+) and from healthy individuals treated with whole tuberculosis anergic immune sera or with its protein A-Sepharose IgG fraction, or with sera fraction separated by PPD-Sepharose chromatography, were submitted to immunofluorescence assays. Anti-human IgG or IgM FITC-conjugate were used to reveal the assays, and results were expressed by a fluorescence percentage or fluorescence index. The presence of IgG over the surface of PPD+ non-adherent cells was detected. High fluorescence percentages were observed only in those PPD+ cells treated with whole anergic serum or with its IgG fraction. Positive fluorescence index values were obtained only in those PPD+ cells treated with anergic serum, meanwhile fluorescence index was always negative when non-bound fractions from PPD-Sepharose were used. Results suggest that non-adherent population are the cell targets for the serum inhibitory factor, which previously has been detected to inhibit antigen response in PPD reactive cells and, point out the specific behavior of this factor, since it was eliminate by PPD-Sepharose chromatography. The IgG nature of the factor was demonstrated by SDS-PAGE and immunoelectrophoresis.