Valores de referencia y puntos de corte de leptina para identificar anormalidad cardiometabólica en la población española

Antecedentes y objetivo: Estimar los valores de referencia de leptina y calcular los puntos de corte de leptinemia que identifiquen anormalidad cardiometabólica en España. Métodos: Estudio transversal realizado de 2008 a 2010 sobre 11.540 individuos representativos de la población española ≥ 18 años. La información se obtuvo mediante examen físico estandarizado y las analíticas se realizaron en un laboratorio central. La leptinemia se midió por inmunoensayo enzimático. Se definió anormalidad cardiometabólica como la presencia de ≥ 2 de las siguientes anormalidades: presión arterial elevada; triglicéridos elevados; colesterol unido a lipoproteínas de alta densidad bajo; valores altos de resistencia a insulina según homeostasis model assessment; proteína C reactiva y glucosa elevada. Resultados: Los niveles de leptina fueron mayores en mujeres que en varones (media geométrica 21,9 ng/ml y 6,6 ng/ml, respectivamente, p<0.001) y aumentaban con la edad y el índice de masa corporal (p<0,001). La mediana fue 24,5 ng/ml en mujeres (rango intercuartílico P25-P75: 14,1-37,0) y 7,2 ng/ml en varones (P25-P75: 3,3-14,3). La leptinemia fue mayor en sujetos con obesidad general o abdominal, diabetes, hipertensión o síndrome metabólico (p<0.001 en todos los casos). Los valores de leptinemia que identificaron anormalidad cardiometabólica fueron 23,75 ng/ml en mujeres (área bajo la curva 0,722, 72,3% sensibilidad y 58,7% especificidad), y 6,45 ng/ml en varones (área bajo la curva 0,716, 71,4% sensibilidad y 60,2% especificidad). Conclusiones: Estos resultados facilitan la interpretación de los valores de leptinemia en estudios clínicos y poblacionales. La leptina tiene sensibilidad y especificidad moderadas para identificar anormalidad cardiometabólica en ambos sexosLos datos de este análisis proceden del estudio ENRICA, que fue financiado por Sanofi-Aventis. La financiación específica para este análisis procede de los proyectos FIS PI13/02321 y “Cátedra UAM de Epidemiología y Control del Riesgo Cardiovascular”, Madri

Impact of ambulatory blood pressure monitoring on reclassification of hypertension prevalence and control in older people in Spain

This is the submitted version of the following article: Impact of ambulatory blood pressure monitoring on reclassification of hypertension prevalence and control in older people in Spain, Journal of Clinical Hypertension 17.6:453-61 which has been published in final form at http://dx.doi.org/10.1111/jch.12525. This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy wiley.com/WileyCDA/Section/id- 820227.htmlAmbulatory blood pressure monitoring (ABPM) accurately classifies blood pressure (BP) status but its impact on the prevalence and control of hypertension is little known. The authors conducted a cross-sectional study in 2012 among 1047 individuals 60 years and older from the follow-up of a population cohort in Spain. Three casual BP measurements and 24-hour ABPM were performed under standardized conditions. Approximately 68.8% patients were hypertensive based on casual BP (≥140/90 mm Hg or current BP medication use) and 62.1% based on 24-hour ABPM (≥130/80 mm Hg or current BP medication use) (P=.009). The proportion of patients with treatment-eligible hypertension who met BP goals increased from 37.4% based on the casual BP target to 54.1% based on the 24-hour BP target (absolute difference, 16.7%; P<.01). These results were consistent across alternative BP thresholds. Therefore, compared with casual BP, 24-hour ABPM led to a reduction in the proportion of older patients recommended for hypertension treatment and a substantial increase in the proportion of those with hypertension controlData collection was funded by Fondo de Investigación Sanitaria (FIS) grants 09/1626 and 12/1166 (Ministry of Health of Spain) and by the ‘Cátedra UAM de Epidemiología y Control del Riesgo Cardiovascular’. Specific funding for this analysis was obtained from FIS grant PI13/02321

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children