Vacuna de la varicela

La varicela es una enfermedad infecciosa con alta incidencia en niños y mucho menor en adultos. Constituye un importante problema de salud por el gran número de casos que se producen. Su importancia clínica se debe, sin embargo, a sus complicaciones, más frecuentes en adultos, inmunodeficientes y niños de pocos meses. Acarrea importantes costes, no sólo por el consumo de recursos y servicios de salud, tanto en la atención primaria como en la hospitalaria, sino también costes sociales indirectos: pérdida de horas laborales por los familiares o cuidadores, pérdida de horas escolares, necesidad de desplazamientos, etc. No siempre es una enfermedad benigna. La mortalidad, en general baja, al estar vinculada a las complicaciones, resulta también significativamente superior en adultos, lactantes y pacientes afectos de algún tipo de inmunodeficiencia. Anualmente se presentan en España unos 300.000 casos de varicela, que comportan alrededor de 1.000-1500 hospitalizaciones y 5-6 defunciones. Se dispone de vacunas contra esta enfermedad, ya comercializadas en España, que han demostrado ser eficaces y seguras. Existen aún importantes dudas acerca de los efectos sobre la epidemiología de la varicela y del herpes zóster que la generalización del empleo de la vacuna pudiera ocasionar en el futuro. Se discute también cuál es la mejor estrategia para su implementación, en función de los costes de la estrategia elegida, los beneficios obtenidos con cada una de ellas y como pueden modificar la distribución etaria actual de los casos de varicela y de herpes zóster. Algunos países han optado por la vacunación sistemática de todos los niños en el segundo año de vida, complementada por la vacunación de los adolescentes susceptibles y de los sujetos incluidos en determinados grupos con alto riego de padecer varicela grave. Otros, entre los que se cuenta España, a partir de este año, prefieren vacunar de forma sistemática solo a los adolescentes y de forma selectiva a las personas pertenecientes a dichos grupos de riesgo. En cualquier caso, y se elija la estrategia vacunal que se elija, será necesario un seguimiento epidemiológico a largo plazo de la incidencia de varicela en los diferentes grupos de edad (niños, adolescentes y adultos) y sus complicaciones. Similar seguimiento deberá efectuarse sobre la incidencia de herpes zóster. Existen algunas diferencias entre las dos vacunas contra la varicela disponibles de nuestro país (Varilrix®, de GSK, y Varivax®, de Sanofi Pasteur MSD), especialmente en cuanto a las indicaciones aceptadas para cada una de ellas. Según su ficha técnica, Varilrix se encuentra indicada en individuos susceptibles de 13 o más años, pacientes de alto riesgo de padecer varicela grave y contactos susceptibles sanos de estos pacientes (en este caso a partir del año de vida). Varivax, por el contrario, está indicada para la vacunación primaria de individuos de edad igual o superior a 12 meses. En ambas fichas técnicas se contempla su indicación para la profilaxis de los individuos susceptibles tras la exposición a un caso de varicela. Ambas vacunas son estables entre +2/+8ºC, son muy sensibles al calor y deben administrarse por vía subcutánea lo antes posible tras su reconstitución. La vacunación consiste en una sola dosis en los menores de 13 años y dos dosis a partir de esta edad, separadas un mes. No se han efectuado, por el momento, recomendaciones sobre la necesidad de revacunación. Pueden administrarse junto a cualquiera de las vacunas incluidas en el calendario de vacunaciones sistemáticas vigente. Si no se administra simultáneamente a la vacuna triple vírica, debe espaciarse la administración de ambas vacunas un mínimo de 4 semanas. En USA, país donde antes se incorporó la vacuna de la varicela al calendario de vacunaciones sistemáticas (a los 12-18 meses), la efectividad global de la vacuna fue del 87%, especialmente en el primer año después de la vacunación (97%), disminuyendo al 84% a los 2-8 años de recibida la vacuna. La efectividad para la enfermedad moderada-severa fue del 97%.Cierto número de individuos vacunados contra la varicela sigue padeciendo esta enfermedad, ya que la protección conferida por la vacuna no es completa. La incidencia de varicela breakthrough (varicela aparecida en sujetos previamente vacunados) es del 2.5% anual (14.8% en controles históricos previos al inicio de la vacunación sistemática), aumentando al 16% si la fuente de contagio es un contacto familiar (87% en los no vacunados). Es una varicela habitualmente leve, con menos elementos, afectación general y complicaciones que la varicela causada por la infección natural

Key epidemiological indicators and spatial autocorrelation patterns across five waves of COVID-19 in Catalonia

Epidemiology; StatisticsEpidemiología; EstadísticasEpidemiologia; EstadístiquesThis research studies the evolution of COVID-19 crude incident rates, effective reproduction number R(t) and their relationship with incidence spatial autocorrelation patterns in the 19 months following the disease outbreak in Catalonia (Spain). A cross-sectional ecological panel design based on n = 371 health-care geographical units is used. Five general outbreaks are described, systematically preceded by generalized values of R(t) > 1 in the two previous weeks. No clear regularities concerning possible initial focus appear when comparing waves. As for autocorrelation, we identify a wave’s baseline pattern in which global Moran’s I increases rapidly in the first weeks of the outbreak to descend later. However, some waves significantly depart from the baseline. In the simulations, both baseline pattern and departures can be reproduced when measures aimed at reducing mobility and virus transmissibility are introduced. Spatial autocorrelation is inherently contingent on the outbreak phase and is also substantially modified by external interventions affecting human behavior.All the authors acknowledge funding from the Social Observatory of the “la Caixa” Foundation as part of the project LCF/PR/SR20/52550011. Partial funding was also received from the Spanish Ministry of Science and Innovation (PID2020-117029RB-I00). Joan Benach gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. J. Fernández-Gracia was supported by Direcció General de Política Universitària i Recerca from the government of the Balearic Islands through the postdoctoral program Vicenç Mut. J. P. Rodríguez is supported by Juan de la Cierva Formacion program (Ref. FJC2019-040622-I) funded by MCIN/AEI/ https://doi.org/10.13039/501100011033

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis

Homeostasis; PathogenesisHomeostasis; PatogénesisHomeòstasi; PatogènesiProgressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS−/−) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS−/− mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS−/− livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.This work was supported by the MICINN Retos RTI2018-095673-B-I00, PID2020-11782RB-I00, PID2020-117941RB-I00, all of which were co-funded with FEDER funds, AMMF 2018/117, COST Action CA17112 and Comunidad de Madrid S2022/BMD-7409. This project has received funding from the European Horizon’s research and innovation program HORIZON-HLTH-2022-STAYHLTH-02 under agreement No. 101095679. The research group belongs to the validated Research Groups Ref. 970935 Liver Pathophysiology, 920631 Lymphocyte Immunobiology and IBL-6 (imas12-associated). KZ was supported by the China Scholarship Council. SM-G was supported by a predoctoral scholarship from Complutense University

Risc cardiovascular en pacients que consulten a urgències d'un hospital general amb un esdeveniment vascular agut

La malaltia cardiovascular és una de les principals causes de morbimortalitat. Els factors de risc cardiovasculars són diversos. Hi ha moltes guies de prevenció clínica i escales de risc

Review article: The need for more efficient and patient-oriented drug development pathways in NASH—setting the scene for platform trials

Drug development; Non-alcoholic steatohepatitis; Study designsDesenvolupament de fàrmacs; Esteatohepatitis no alcohòlica; Dissenys d'estudiDesarrollo de fármacos; Esteatohepatitis no alcohólica; Diseños de estudioBackground and Aims Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. Platform trials (PT) might help accelerate drug development while lowering overall costs and creating a more patient-centric environment. This review provides a comprehensive and nuanced assessment of the NASH clinical development landscape. Methods Narrative review and expert opinion with insight gained during the EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. Results Although NASH represents an opportunity to use adaptive trial designs, including master protocols for PT, there are barriers that might be encountered owing to distinct and sometimes opposing priorities held by these stakeholders and potential ways to overcome them. The following aspects are critical for the feasibility of a future PT in NASH: readiness of the drug pipeline, mainly from large drug companies, while there is not yet an FDA/EMA-approved treatment; the most suitable design (trial Phase and type of population, e.g., Phase 2b for non-cirrhotic NASH patients); the operational requirements such as the scope of the clinical network, the use of concurrent versus non-concurrent control arms, or the re-allocation of participants upon trial adaptations; the methodological appraisal (i.e. Bayesian vs. frequentist approach); patients' needs and patient-centred outcomes; main regulatory considerations and the funding and sustainability scenarios. Conclusions PT represent a promising avenue in NASH but there are a number of conundrums that need addressing. It is likely that before a global NASH PT becomes a reality, ‘proof-of-platform’ at a smaller scale needs to be provided.JMP reports having received consulting fees from Boehringer-Ingelheim, MSD and Novo Nordisk. He has received speaking fees from Gilead, Intercept, and Novo Nordisk, and travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk. He has received educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD. Funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898. NAdP works for Janssen. QMA is Coordinator of the EU IMI-2 LITMUS consortium, which is funded by the EU Horizon 2020 programme and EFPIA. This multistakeholder consortium includes industry partners. He reports research Grant Funding: Allergan/Tobira, AstraZeneca, Boehringer-Ingelheim, Glaxo SmithKline, Glympse Bio, Intercept, Novartis Pharma AG, Pfizer Ltd. Consultancy: 89Bio, Abbvie/Allergan, Akero, Altimentiv, Altimmune, AstraZeneca, Axcella, Blade, BMS, BNN Cardio, Boehringer-Ingelheim, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly & Company Ltd., Galmed, Genentech, Genfit SA, Gilead, Grunthal, HistoIndex, Indalo, Intercept Pharma Europe Ltd., Inventiva, IQVIA, Janssen, Johnson & Johnson, Madrigal, MedImmune, Medpace, Merck, Metacrine, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, PathAI, Pfizer Ltd., Poxel, ProSciento, Raptor Pharma, Roche, Servier, Shionogi, Terns, The Medicines Company, Viking Therapeutics. Speaker: Abbott Laboratories, Allergan/Tobira, BMS, Clinical Care Options, Falk, Fishawack, Genfit SA, Gilead, Integritas Communications, Kenes, Medscape. Royalties: Elsevier Ltd. PM works for Novartis. MSK is an employee of and a shareholder in Novo Nordisk A/S. JG has received consulting fees from Boehringer-Ingelheim, speaking fees from Echosens and travel expenses from Gilead and Abbie. Funds from ISCIII PI18/00947 and PI21/00691. JRE has received speaking fees from Gilead. FT lab’ work has been supported by the German Research Foundation (DFG, CRC/TR 362) and research grants from Gilead, Allergan, Bristol-Myers Squibb and Inventiva. VR consults for and Intercept, Novo Nordisk, Galmed, Poxel, NGM, Madrigal, Enyo, Sagimet, 89 Bio, Prosciento, Terns, and Theratechnologies, and received grants from Intercept and Gilead

Prevalence and Risk Factors of MASLD and Liver Fibrosis amongst the Penitentiary Population in Catalonia: The PRISONAFLD Study

Metabolic dysfunction-associated steatotic liver disease; Metabolic syndrome; PrisonMalaltia hepàtica esteatòtica associada a disfunció metabòlica; Síndrome metabòlica; PresóEnfermedad hepática esteatósica asociada a disfunción metabólica; Síndrome metabólico; PrisiónBackground and Aims: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence and risk factors of MASLD and MASLD-associated liver fibrosis in the penitentiary population in Catalonia, Spain. Method: A cross-sectional observational study involving eight penitentiary centers. Participants had at least one metabolic disorder and were at a closed-regimen penitentiary. Individuals with concomitant liver diseases and/or alcohol risk consumption were excluded. Significant fibrosis and MASLD were defined as liver stiffness ≥8 kPa and a controlled attenuation parameter ≥275 dB/m by vibration-controlled transient elastography (VCTE), respectively. After exclusions, metabolic inmates with VCTE were analyzed. Logistic regression analysis was performed to identify predictors of MASLD and MASLD-associated significant fibrosis. Results: Out of the 4338 inmates studied, 1290 (29.7%) had metabolic disorders, and 646 (14.9%) underwent VCTE. The mean age was 48.0 years (SD 12.1), and 89.5% were male. MASLD prevalence was 33.9%. Significant fibrosis and MASLD-associated significant fibrosis were found in 16.4% and 9.4% of inmates, respectively. In the multivariate analysis, T2D, waist circumference, MetS, and higher ALT values were identified as independent risk factors for MASLD and MASLD-associated significant fibrosis amongst the prison population. Conclusions: Metabolic disorders including MASLD are highly prevalent among inmates. The prevalence of significant fibrosis seems notably higher than that of the general population, underscoring the need for targeted screening programs and therapeutic interventions in the incarcerated population

Proteomic Analysis of Dysfunctional Liver Sinusoidal Endothelial Cells Reveals Substantial Differences in Most Common Experimental Models of Chronic Liver Diseases

Animal models; Chronic liver disease; Endothelial dysfunctionModels animals; Malaltia hepàtica crònica; Disfunció endotelialModelos animales; Enfermedad hepática crónica; Disfunción endotelialMolecular markers of dedifferentiation of dysfunctional liver sinusoidal endothelial cells (LSEC) have not been fully elucidated. We aimed at deciphering the molecular profile of dysfunctional LSEC in different pathological scenarios. Flow cytometry was used to sort CD11b−/CD32b+ and CD11b−/CD32b− LSEC from three rat models of liver disease (bile duct ligation-BDL; inhaled carbon tetrachloride-CCl4; and high fat glucose/fructose diet-HFGFD). A full proteomic profile was performed applying nano-scale liquid chromatography tandem mass spectrometry (nLC-MS) and analyzed with PEAKS software. The percentage of CD32b− LSEC varied across groups, suggesting different capillarization processes. Both CD32+ and CD32b− LSEC from models are different from control LSEC, but differently expressed proteins in CD32b− LSEC are significantly higher. Heatmaps evidenced specific protein expression patterns for each model. Analysis of biological significance comparing dysfunctional CD32b− LSEC with specialized CD32b+ LSEC from controls showed central similarities represented by 45 common down-regulated proteins involved in the suppression of the endocytic machinery and 63 common up-regulated proteins associated with the actin-dependent cytoskeleton reorganization. In summary; substantial differences but also similarities in dysfunctional LSEC from the three most common models of liver disease were found, supporting the idea that LSEC may harbor different protein expression profiles according to the etiology or disease stage.This work was supported by grants PI18/00947 and AC18/00033 (ENM3 2018) and PI21/00691 from Instituto de Salud Carlos III (ISCIII) and cofounded by the European Union (ERDF/ESF, “Investing in your future”). J.G. is the recipient of a clinical intensification award and D.H. of a Sara Borrell grant, both from ISCIII. M.G. and A.B. have predoctoral fellowships from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) and ISCIII respectively. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is supported by ISCIII. The APC was funded by ISCIII

Hepatitis C antibody prevalence and active hepatitis C infection in HIV-negative gay, bisexual, and other men who have sex with men in Barcelona and Madrid, Spain (March 2018-March 2021)

Objectives: Hepatitis C virus (HCV) has been recognized as a sexually transmitted infection (STI) in HIV-positive men who have sex with men (MSM), with an increased notification in HIV-negative MSM. The aim of this study was to determine the prevalence of HCV antibody and active HCV infection in HIV-negative gay, bisexual, and other MSM (GBMSM), and their characteristics, in Barcelona and Madrid, from March 2018 to March 2021. Methods: Cross-sectional study conducted on 3548 HIV-undiagnosed GBMSM, across four HIV/STI testing centers. Respondents submitted an online, self-administered questionnaire after consultation, which collected information on sociodemographics, sexual health history, HCV knowledge, and substance consumption. Prevalence of HCV antibodies was determined by a reactive result in a rapid anti-HCV test or enzyme-linked immunosorbent assay (ELISA), while active HCV infection was determined by participants who were also positive on an HCV-RNA test. Crude and adjusted Poisson analyses with robust variance are presented for both prevalence and active infection. Results: In total, 97.6% of participants (n = 3463) were HIV-negative. Of those, 18 were found to have HCV antibodies (0.52%), of which nine (0.26%) were also HCV-RNA positive. Those with HCV antibodies were associated to have lived with an HCV (+) person (adjusted prevalence ratio [APR]: 7.84, [95% confidence interval: 2.50-24.53]), using injectable drugs for sex (APR: 6.92, [1.20-39.79]) and testing positive for an STI in the previous year (APR: 4.06, [1.09-15.12]). Presenting an active infection was strongly associated with a previous HCV diagnosis (APR: 100.82 [22.16-458.76]), sexualized injectable drug use (APR: 17.53 [2.70-113.76]), and sharing douching material (APR: 7.45, [2.12-25.95]). Conclusion: Sexual practices with a higher risk of bleeding and sexualized drug use, particularly sexualized injectable drug use, were associated with higher rates of HCV diagnosis in GBMSM. Identifying these practices during consultation, contact tracing new cases and regularly testing those with a previous history of HCV, will facilitate HCV eradication.Both a Health Research Grant (Fondo de Investigación en Salud, FIS P117/02077) and an Intramural Strategy Action Grant (PI17CIII/00037), From the Carlos III Institute, at the Science and Innovation Ministry of the Spain Government, supported this study.S

How did COVID-19 measures impact sexual behaviour and access to HIV/STI services in Panama? Results from a national cross-sectional online survey.

OBJECTIVE: To describe reported changes in sexual behaviours, including virtual sex (sexting and cybersex), and access to HIV/STI testing and care during COVID-19 measures in Panama. METHODS: We conducted an online cross-sectional survey from 8 August to 12 September 2020 among adults (≥18 years) residing in Panama. Participants were recruited through social media. Questions included demographics, access to HIV/STI testing and HIV care, and sexual behaviours 3 months before COVID-19 social distancing measures and during social distancing measures (COVID-19 measures). Logistic regression was used to identify associations between variables and behavioural changes. RESULTS: We recruited 960 participants; 526 (54.8%) identified as cis-women, 366 (38.1%) cis-men and 68 (7.1%) non-binary or another gender. The median age was 28 years (IQR: 23-37 years), and 531 of 957 (55.5%) were of mixed ethnicity (mixed Indigenous/European/Afro-descendant ancestry). Before COVID-19 measures, virtual sex was reported by 38.5% (181 of 470) of cis-women, 58.4% (184 of 315) cis-men and 45.0% (27 of 60) non-binary participants. During COVID-19 measures, virtual sex increased among 17.2% of cis-women, 24.7% cis-men and 8.9% non-binary participants. During COVID-19 measures, 230 of 800 (28.8%) participants reported decreased casual sex compared with pre-COVID-19 measures. Compared with pre-COVID-19 measures, decreased casual sex was reported more frequently during COVID-19 measures by cis-men compared with cis-women (39.2% vs 22.9%, urban/rural adjusted OR (AOR)=2.17, 95% CI 1.57 to 3.01), and by Afro-descendant compared with participants of mixed ethnicity (40.0% vs 29.8%, AOR=1.78, 95% CI 1.07 to 2.94). Compared with no change in virtual sex (16.8%), increased virtual sex (38.5%, AOR=1.78, 95% CI 1.10 to 2.88) and decreased virtual sex (86.7%, AOR=16.53, 95% CI 7.74 to 35.27) were associated with decreased casual sex encounters. During COVID-19 measures, HIV/STI testing could not be obtained by 58.0% (58 of 100) of the participants who needed a test, and interrupted HIV care was reported by 53.3% (8 of 15) of participants living with HIV. CONCLUSIONS: COVID-19 measures in Panama were associated with a decrease in casual sex among cis-men and Afro-descendant people, while access to HIV/STI testing and care was seriously disrupted

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Background: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country