Epidemiology of Herpes Zoster in Spain

[ES] El Herpes Zóster (HZ) resulta de la reactivación de la infección latente por el virus de la varicela-zóster (VVZ) y es una patología frecuente que está asociada a estados de inmunosupresión y al envejecimiento. Se presenta el análisis de la información disponible en cuanto a incidencia y hospitalizaciones por Herpes Zóster y por su principal complicación, la Neuralgia Post-Herpética, en España entre 1998 y 2018. El HZ es una entidad de la edad adulta, las formas graves y las complicaciones del zóster ocurren más en las edades avanzadas de la vida. La eventual incorporación al calendario de la vacunación de HZ en los adultos necesitará de una monitorización estrecha del HZ en los próximos años. [EN] Herpes Zoster (HZ) is the reactivation of latent infection by the varicella-zoster virus (VVZ) and is a pathology associated with states of immunosuppression and aging. The analysis of the available information regarding incidence and hospitalizations for HZ and Post-herpetic Neuralgia in Spain between 1998 and 2018 is presented. HZ is a mainly adult entity. Complications like Post-herpetic Neuralgia occur more frequently in advanced ages of life. The eventual recommendation of vaccination against HZ in adults will require close monitoring of HZ in the coming years.N

Epidemiología del Herpes Zóster en España

[ES]El Herpes Zóster (HZ) resulta de la reactivación de la infección latente por el virus de la varicela-zóster (VVZ) y es una patología frecuente que está asociada a estados de inmunosupresión y al envejecimiento. Se presenta el análisis de la información disponible en cuanto a incidencia y hospitalizaciones por Herpes Zóster y por su principal complicación, la Neuralgia Post-Herpética, en España entre 1998 y 2018. El HZ es una entidad de la edad adulta, las formas graves y las complicaciones del zóster ocurren más en las edades avanzadas de la vida. La eventual incorporación al calendario de la vacunación de HZ en los adultos necesitará de una monitorización estrecha del HZ en los próximos años. [EN]Herpes Zoster (HZ) is the reactivation of latent infection by the varicella-zoster virus (VVZ) and is a pathology associated with states of immunosuppression and aging. The analysis of the available information regarding incidence and hospitalizations for HZ and Post-herpetic Neuralgia in Spain between 1998 and 2018 is presented. HZ is a mainly adult entity. Complications like Post-herpetic Neuralgia occur more frequently in advanced ages of life. The eventual recommendation of vaccination against HZ in adults will require close monitoring of HZ in the coming years

Exploring genetic factors involved in huntington disease age of onset. E2F2 as a new potential modifier gene

Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor

El reto de profesionalizar la salud pública

Somos profesionales de la salud pública, aunque nuestras familias siguen sin saber a qué nos dedicamos. No es lo contrario de la salud privada: es la salud de y para toda la población. Dada la complejidad que esta definición entraña y la confusión semántica inherente al adjetivo “público”, los profesionales de la salud pública nos enfrentamos con frecuencia al reto de tener que justificar nuestra existencia.N

Quality More Than Quantity: The Use of Carbohydrates in High-Fat Diets to Tackle Obesity in Growing Rats

This research was supported by funds provided by the Abbott Laboratories S.A.Childhood obesity prevention is important to avoid obesity and its comorbidities into adulthood. Although the energy density of food has been considered a main obesogenic factor, a focus on food quality rather that the quantity of the different macronutrients is needed. Therefore, this study investigates the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on metabolic abnormalities and its impact on obesity in growing rats fed a high-fat diet (HFD). Growing rats were fed on HFD containing carbohydrates with different digestion rates: a HFD containing rapid-digesting carbohydrates (OBE group) or slow-digesting carbohydrates (ISR group), for 4 weeks and the effect on the metabolism and signaling pathways were analyzed in different tissues. Animals from OBE group presented an overweight/obese phenotype with a higher body weight gain and greater accumulation of fat in adipose tissue and liver. This state was associated with an increase of HOMA index, serum diacylglycerols and triacylglycerides, insulin, leptin, and pro-inflammatory cytokines. In contrast, the change of carbohydrate profile in the diet to one based on slow digestible prevented the obesity-related adverse effects. In adipose tissue, GLUT4 was increased and UCPs and PPARg were decreased in ISR group respect to OBE group. In liver, GLUT2, FAS, and SRBP1 were lower in ISR group than OBE group. In muscle, an increase of glycogen, GLUT4, AMPK, and Akt were observed in comparison to OBE group. In conclusion, this study demonstrates that the replacement of rapidly digestible carbohydrates for slowly digestible carbohydrates within a highfat diet promoted a protective effect against the development of obesity and its associated comorbidities.Abbott Laboratories S.A

Molecular Pathways Leading to Induction of Cell Death and Anti-Proliferative Properties by Tacrolimus and mTOR Inhibitors in Liver Cancer Cells

Background/Aims: Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with portal hypertension and/or increased bilirubinemia, but without vascular-associated diseases. Tumor recurrence, which is the main drawback for the survival of patients submitted to OLT for HCC, has been related to tumor-related variables and the immunosuppressive therapies. We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. This study identified the role of the immunosuppressant partners such as FK506-binding proteins (FKBPs) in the induction of cell death and arrest of cell proliferation by immunosuppressants in two representative liver cancer cells. Methods: The regulation of endoplasmic reticulum (ER) stress, apoptosis/autophagy, cell proliferation, and FKBPs expression was determined in Tacrolimus-, Sirolimus- and Everolimus-treated primary human hepatocytes, and hepatoma HepG2 and Huh7 cell lines. The functional repercussion of FKBPs on cell death and proliferation was also addressed using the siRNA technology. The assessed antitumoral properties of the immunosuppressants were associated to microRNAs (miRNAs) pattern. Results: The enhanced pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with increased protein kinase RNA-like endoplasmic reticulum kinase (PERK)-related ER stress, Ser15 P-p53/p53 ratio and p21 protein expression that may counterbalance the risk of proliferative upregulation caused by enhanced Thr172 P-Cdk4/ Cdk4 activation in liver cancer cells. The inhibition of the mTOR pathway by Sirolimus and Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired translation likely at a very early step of the elongation phase. Tacrolimus and mTOR inhibitors increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role. Interestingly, the administration of immunosuppressants yields a specific pattern of miRNAs. Tacrolimus and mTOR inhibitors decreased miR-92a-1-5p, miR-197-3p, miR-483-3p and miR- 720, and increased miR-22-3p, miR-376a-3p, miR-663b, miR-886-5p, miR-1300 and miR-1303 expressions in HepG2 cells. Conclusion: The more potent pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with an increased activation of PERK and p53 signaling, and p21 protein expression. FKBP12 and FKBP51 appeared to be the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in HepG2 cells. The observed effects of immunosuppressants were related to a specific miRNA signature in liver cancer cellsEspaña Ministry of Economy and Competitiveness (MINECO) cofinanced by the ERDF (BFU2016-75352-P AEI/FEDER, EU

Skills for Preventive Medicine and Public Health: Proposal after a comparative and participative approach

Parte de este trabajo fue presentado en la XXXV Reunión Científica de la Sociedad Española de Epidemiología y XII Congresso da Associação Portuguesa de Epidemiologia celebrada el 6 de septiembre de 2017 en Barcelona, en formato póster, con el título «Competencias de la especialidad medicina preventiva y salud pública: una nueva visión». También en el XIX Congreso Nacional y VIII Internacional de la SEMPSPH celebrado en Valencia el 16 de mayo de 2017 fue presentado en la ponencia titulada «Pasado, presente y futuro de la formación MIR».[ES] Introducción: El desarrollo normativo de la Ley 44/2003, a través del Real Decreto 639/2014, inició el proceso de reorganización de la Formación Sanitaria Especializada (FSE). El objetivo de este trabajo es elaborar una propuesta de competencias específicas para la especialidad de Medicina Preventiva y Salud Pública mediante un análisis comparado y proceso participativo. Métodos: Cuatro fases: 1) análisis y extracción de competencias de documentación de organismos oficiales; 2) consulta dirigida a personas clave; 3) consulta abierta a residentes y personas implicadas en la FSE, y 4) difusión a la Comisión Nacional de la Especialidad y público general. Resultados: 1) Se extrajeron 543 competencias y 67 categorías de 7 fuentes primarias (Austria, Canadá, ECDC, Estados Unidos, Francia, Reino Unido y OPS). Se produjeron 126 competencias en 12 categorías. 2) Participaron 10 personas clave, 64 competencias fueron modificadas, 10 eliminadas y 9 nuevas. 3) Hubo 32 respuestas: 132 competencias en 12 categorías. Propuesta final: 145 competencias en 21 categorías, organizadas en 3 bloques: competencias genéricas, técnicas y específicas. Conclusión: La propuesta final es producto de la participación de residentes y personas implicadas en la FSE, partiendo del actual marco y del análisis del desarrollo de la especialidad en el contexto internacional. Se han incorporado conceptos presentes en países de nuestro entorno y cercanos a la práctica. [EN] Introduction: The Royal Decree 639/2014 (‘Core Curriculum’ Decree) has amongst its objectives to modify Specialist Training in Medicine Disciplines. The aim of this project is to elaborate a proposal of specific skills for the specialty of Preventive Medicine and Public Health using a comparative and participative approach. Methods: 1) Comparative analysis of documents published by official institutions; 2) consultation with key informants; 3) open consultation with residents and trainers, and 4) presentation to the National Commission of the Specialty and the general public. Results: 1) 126 competencies were found in 12 categories. 2) 10 key informants, 64 skills modified, 10 removed, and 9 added; 3) 32 responses the first draft contained 132 skills in 12 categories. The final proposal included 145 skills in 21 categories, classified into 3 areas: generic, technical, and specific skills. Conclusion: The final proposal is the product of participation of residents and individuals involved in specialised training, starting from the current framework and international context analysis. Concepts present in countries in this field and close to our professional activity have been included.S

Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE)

OBJECTIVES Comprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist. DESIGN Repeated cross sectional study. SETTING Swiss, German and Canadian research ethics committees (RECs). PARTICIPANTS RCT protocols approved by RECs in 2012 (n=257) and 2016 (n=292). PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcomes were the proportion of reported SPIRIT items per protocol and the proportion of trial protocols reporting individual SPIRIT items. We compared these outcomes in protocols approved in 2012 and 2016, and built regression models to explore factors associated with adherence to SPIRIT. For each protocol, we also extracted information on general trial characteristics and assessed whether individual SPIRIT items were reported RESULTS: The median proportion of reported SPIRIT items among RCT protocols showed a non-significant increase from 72% (IQR, 63%-79%) in 2012 to 77% (IQR, 68%-82%) in 2016. However, in a preplanned subgroup analysis, we detected a significant improvement in investigator-sponsored protocols: the median proportion increased from 64% (IQR, 55%-72%) in 2012 to 76% (IQR, 64%-83%) in 2016, while for industry-sponsored protocols median adherence was 77% (IQR 72%-80%) for both years. The following trial characteristics were independently associated with lower adherence to SPIRIT: single-centre trial, no support from a clinical trials unit or contract research organisation, and investigator-sponsorship. CONCLUSIONS In 2012, industry-sponsored RCT protocols were reported more comprehensively than investigator-sponsored protocols. After publication of the SPIRIT checklist, investigator-sponsored protocols improved to the level of industry-sponsored protocols, which did not improve

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

BACKGROUND We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research

A primary healthcare information intervention for communicating cardiovascular risk to patients with poorly controlled hypertension: The Education and Coronary Risk Evaluation (Educore) study-A pragmatic, cluster-randomized trial

PURPOSE: Uncertainty exists regarding the best way to communicate cardiovascular risk (CVR) to patients, and it is unclear whether the comprehension and perception of CVR varies according to the format used. The aim of the present work was to determine whether a strategy designed for communicating CVR information to patients with poorly controlled high blood pressure (HBP), but with no background of cardiovascular disease, was more effective than usual care in the control of blood pressure (BP) over the course of a year. METHODS: A pragmatic, two-arm, cluster-randomized controlled trial was performed. Consecutive patients aged 40-65 years, all diagnosed with HBP in the last 12 months, and all of whom showed poor control of their condition (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg), were recruited at 22 primary healthcare centres. Eleven centres were randomly assigned to the usual care arm, and 11 to the informative intervention arm (Educore arm). At the start of the study, the Educore arm subjects were shown the "low risk SCORE table", along with impacting images and information pamphlets encouraging the maintenance of good cardiovascular health. The main outcome variable measured was the control of HBP; the secondary outcome variables were SCORE table score, total plasma cholesterol concentration, use of tobacco, adherence to prescribed treatment, and quality of life. RESULTS: The study participants were 411 patients (185 in the Educore arm and 226 in the usual care arm). Multilevel logistic regression showed that, at 12 months, the Educore intervention achieved better control of HBP (OR = 1.57; 1.02 to 2.41). No statistically significant differences were seen between the two arms at 12 months with respect to the secondary outcomes. CONCLUSIONS: Compared to usual care, the Educore intervention was associated with better control of HBP after adjusting for age, baseline SBP and plasma cholesterol, at 12 months.This study was funded by the Spanish Ministry of Science and Innovation via the Instituto de Salud Carlos III, Subprograma de Proyectos de Investigación en Evaluación de Tecnologías Sanitarias y Servicios de Salud (PI 09/90354), and the Fundación de Investigación e Innovación Biomédica en Atención Primaria (FIIBAP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptS