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BACKGROUND Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 casos per 100 000 habitantes ( -62%; P

Introduction: Patients with invasive pneumococcal disease (IPD) may require admission into paediatric intensive care units (PICU). The aim of this study is to analyse the epidemiological, clinical, and microbiological characteristics associated with IPD that may require admission to the PICU. Material and methods: A prospective study was conducted on cases of IPD diagnosed in three Paediatric Hospitals in Barcelona between January 2012 and June 2016. An analysis was made of the associations between the admission to PICU and the epidemiological, clinical, and microbiological variables. Results: A total of 263 cases with IPD were included, of which 19% (n = 50) required admission to PICU. Patients with septic shock (7; 100%), meningitis (16; 84.2%), and those with complicated pneumonia (23; 15.2%) were admitted to the PICU. The most frequent complications were pulmonary (35.2%) and neurological (39.5%). The ratio between admission and non-admission to PICU was 4.7 times higher in subjects with an underlying disease. The serotypes associated with PICU admission were 19A (23% of the total of this serotype), serotype 14 (20%), serotype 3 (17%), and serotype 1 (12.5%). Conclusions: IPD required PICU admission in cases of septic shock and meningitis, and less so with complicated pneumonia. The percentage of admissions is greater in children with an underlying disease. Admission into the PICU involves a longer stay, complications during the acute phase, as well as sequelae, particularly neurological ones. The serotypes of the patients that were admitted to PICU were predominantly vaccine serotypes. Resumen: Introducción: La enfermedad neumocócica invasora (ENI) puede requerir ingreso en la unidad de cuidados intensivos pediátricos (UCIP). El objetivo de este trabajo es analizar las características epidemiológicas, clínicas y microbiológicas asociadas a la ENI que predisponen el ingreso en la UCIP. Material y métodos: Estudio prospectivo de casos diagnosticados con ENI en tres hospitales pediátricos de Barcelona entre enero de 2012 y junio de 2016. Se analizaron las asociaciones entre el ingreso en la UCIP y las variables epidemiológicas, clínicas y microbiológicas. Resultados: Se incluyeron 263 casos con ENI. El 19% (n = 50) requirió ingreso en la UCIP. El 100% (7) de los pacientes con shock séptico, 84,2% (16) con meningitis y 15,2% (23) con neumonía complicada ingresaron en la UCIP. Las complicaciones más frecuentes fueron pulmonares (35,2%) y neurológicas (39,5%). La razón entre ingreso y no ingreso en la UCIP fue 4,17 veces mayor en los sujetos con enfermedad de base. Los serotipos asociados al ingreso en la UCIP fueron el 19A (23% del total de este serotipo), el 14 (20%), el 3 (17%) y el serotipo 1 (12,5%). Conclusiones: La ENI requiere ingreso en la UCIP en caso de shock séptico y meningitis, no así, de entrada, la neumonía complicada. El porcentaje de ingresos es mayor en los niños con enfermedad de base. El ingreso en la UCIP conlleva una estancia más prolongada, así como complicaciones durante la fase aguda y secuelas, sobre todo, neurológicas. Los serotipos de los pacientes que ingresaron en la UCIP fueron, predominantemente, serotipos vacunales.

Introduction: The number of patients with complex chronic conditions (CCC) has increased in the last 20 years or so. There is limited data as regards the prevalence of CCC in the paediatric population and its impact on hospital admissions. The main objectives of this study are to determine the proportion of CCC in the paediatric hospital population and compare them with other groups of patients admitted (acute and chronic). Patients and methods: A descriptive, retrospective study was carried out in a tertiary maternity-paediatric hospital (from December 2016 to November 2017). All patients admitted into the Paediatric Department were recruited with a fortnightly frequency. A series of demographic, clinical, and pregnancy data were collected. In order to identify the level of complexity of the patients, the Clinical Risk Group (CRG) was used, with 3 groups being created: acute, chronic, and CCC. Statistics analysis was performed using SPSS v24. Results: A total of 1433 patients were included. The proportion of CCC on the Paediatric Ward was 14.4%. The CCC were older patients, mainly admitted due to decompensation or progression of their underlying disease, had a longer admission time, and required support in the Paediatric Intensive Care Unit (PICU) more often than that of the other sub-groups. Just under half (44.7%) of the CCC were carriers of a technological device. Of the total of long stays (>1 month), 71.3% had CCC. Conclusions: Patients with CCC require long hospital stays, a greater need of intensive care, and use of technology. New approaches to treatment and follow-up need to be established. They should be cost-effective, and at the same time decrease the impact of the disease on the children and their family. Resumen: Introducción: En las últimas décadas se ha incrementado el número de pacientes crónicos complejos (PCC). Existen pocos datos referentes a la prevalencia de PCC en población pediátrica y su impacto en los ingresos hospitalarios. Los objetivos principales de este trabajo son determinar en nuestro medio la proporción de PCC en hospitalización pediátrica y compararlos con otros grupos de pacientes ingresados (agudos y crónicos). Pacientes y métodos: Estudio descriptivo retrospectivo realizado en un hospital materno-infantil terciario (de diciembre 2016 a noviembre 2017). Se reclutaron a todos los pacientes ingresados en el servicio de Pediatría con una periodicidad quincenal. Se recogieron una serie de variables demográficas, clínicas y de gestión. Para identificar el grado de complejidad de los pacientes se utilizó el sistema de clasificación Clinical Risk Group (CRG) y se crearon 3 grupos: agudos, crónicos y PCC. Para el análisis estadístico se usó SPSS v24. Resultados: Se incluyeron 1.433 pacientes. La proporción de PCC en planta de Pediatría fue del 14,4%. Los PCC fueron pacientes de mayor edad, ingresaron principalmente por descompensación o progresión de su enfermedad de base, estuvieron ingresados más tiempo y precisaron soporte en la Unidad de Cuidados Intensivos Pediátricos (UCIP) con mayor frecuencia que los otros subgupos. Un 44,7% de los PCC era portador de dispositivos tecnológicos. Del total de largas estancias (>1 mes), el 71,3% fue de PCC. Conclusiones: Los PCC requieren de estancias hospitalarias largas, mayor necesidad de cuidados intensivos y uso de tecnología. Es necesario plantear nuevos enfoques de tratamiento y seguimiento que sean costo-eficientes a la vez que disminuyan el impacto de la enfermedad en el niño y su familia.

AIM Escherichia coli (E coli) is a known cause of paediatric bacteraemia. The main objective was to characterise the emergency department (ED) presentations of paediatric E coli bacteraemia and secondarily to identify those related to greater severity. METHODS This was a sub-study of a multicentre cross-sectional prospective registry including all with E coli bacteraemia episodes between 2011 and 2016. We used multiple correspondence and cluster analysis to identify different patterns. RESULTS We included 291 patients and 43 met criteria for severe disease (14.3%, 95% confidence interval 11.2-19.3). We identified four types of paediatric E coli bacteraemia presentations. Two (178 patients, 61.2%) were related to well-appearing previously healthy infants with associated urinary tract infection (UTI). Well-appearing children older than 12 months old with underlying disease (n = 60, 20.6%) and non-well-appearing children of different ages (n = 53, 18.2%) corresponded to the other two types; these had associated UTI infrequently and higher severity rate (15% and 50.9%, respectively, higher when compared with the two previous types, P

Background: Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach. Methods: Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020. Results: Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. Conclusion: Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics. This work was supported by the Departament de Salut, Generalitat de Catalunya (grant number SLT006/17/00109). L.I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program

AIM The aim was to analyze the epidemiological, microbiological and clinical characteristics of patients with complicated pneumococcal pneumonia with pleural effusion (PE) or empyema. METHOD Prospective study in three Catalan hospitals in persons aged

Introduction: There are only a limited number of studies on the impact of influenza in the Spanish child population. The present work intends to increase this knowledge by studying some key aspects, such as the incidence of hospital admissions, clinic variables, comorbidities, and the vaccination status in the hospitalised children. Methods: A retrospective, observational study was conducted by reviewing the medical records of children under 15 years and hospitalised due to community acquired influenza confirmed microbiologically, during 2 ́flu seasons (2014–2015 and 2015–2016). The study was carried out in 10 hospitals of 6 cities, which represent approximately 12% of the Spanish child population. Results: A total of 907 children were admitted to hospital with main diagnosis of influenza infection (447 10 years. Admission to the PICU was required in 10% (92) of the cases, mainly due to acute respiratory failure. Conclusion: Influenza continues to be an important cause of hospitalization in the Spanish child population. Children 50%) of the cases. Many of the severe forms of childhood influenza that occur today could be avoided if current vaccination guidelines were met. Resumen: Introducción: La información existente sobre el impacto de la gripe en la población infantil española es escasa. El presente trabajo pretende aumentar este conocimiento estudiando aspectos clave como la incidencia de hospitalización, clínica, comorbilidades y el estado vacunal en los niños hospitalizados. Métodos: Estudio retrospectivo, observacional, por revisión de historias clínicas, en menores de 15 años hospitalizados por gripe adquirida en la comunidad, confirmada microbiológicamente, durante 2 temporadas gripales (2014-2015 y 2015-2016). El estudio se realizó en 10 hospitales de 6 ciudades, que atienden aproximadamente al 12% de la población infantil española. Resultados: Fueron hospitalizados 907 niños con diagnóstico principal de gripe (447 50%) de los casos. Una gran parte de las formas graves de gripe en población infantil podrían ser evitada si se cumplieran las indicaciones actuales de vacunación.

Surveillance tools to estimate infection rates in young populations are essential to guide recommendations for school reopening and management during viral epidemics. Ideally, field-deployable non-invasive, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We determined SARS-CoV-2 antibody conversion by high-throughput Luminex assays in saliva samples collected weekly in 1,509 children and 396 adults in 22 Summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29thto July 31st2020, between the first and second COVID-19 pandemic waves. Saliva antibody conversion defined as ≥4-fold increase in IgM, IgA and/or IgG levels to SARS-CoV-2 antigens between two visits over a 5-week period was 3.22% (49/1518), or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. To conclude, saliva antibody profiling including three isotypes and multiplexing antigens is a useful and more user-friendly tool for screening pediatric populations to determine SARS-CoV-2 exposure and guide public health policies during pandemics.

COVID-19 affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions.We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA and IgG antibodies against five SARS-CoV-2 spike (S) and nucleocapsid (N) antigens in the context of a contacts and infectivity longitudinal study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain.Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary.In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection. Saliva antibody detection could allow determining COVID-19 prevalence in pediatric populations, alternative to bleeding or nasal swab, and serological diagnosis following vaccination.

Background Understanding the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is critical to guide decision-making for schools in the pandemic. We aimed to describe the transmission of SARS-CoV-2 among children and adult staff in summer schools. Methods During July 2020, we prospectively recruited children and adult staff attending summer schools in Barcelona who had SARS-CoV-2 infection. Primary SARS-CoV-2 infections were identified through (1) a surveillance program in 22 summer schools of 1905 participants, involving weekly saliva sampling for SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) during 2–5 weeks; and (2) cases identified through the Catalonian Health Surveillance System of children diagnosed with SARS-CoV-2 infection by nasopharyngeal RT-PCR. All centers followed prevention protocols: bubble groups, handwashing, face masks, and conducting activities mostly outdoors. Contacts of a primary case within the same bubble were evaluated by nasopharyngeal RT-PCR. Secondary attack rates and the effective reproduction number in summer schools (Re*) were calculated. Results Among the >2000 repeatedly screened participants, 30 children and 9 adults were identified as primary cases. A total of 253 close contacts of these primary cases were studied (median, 9 [interquartile range, 5–10] for each primary case), among which 12 new cases (4.7%) were positive for SARS-CoV-2. The Re* was 0.3, whereas the contemporary rate in the general population from the same areas in Barcelona was 1.9. Conclusions The transmission rate of SARS-CoV-2 infection among children attending school-like facilities under strict prevention measures was lower than that reported for the general population. This suggests that under preventive measures schools are unlikely amplifiers of SARS-CoV-2 transmission, supporting current recommendations for school opening.

Background: We analyzed contagions of coronavirus disease 2019 inside school bubble groups in Catalonia, Spain, in the presence of strong non-pharmaceutical interventions from September to December 2020. More than 1 million students were organized in bubble groups and monitored and analyzed by the Health and the Educational departments. Methods: We had access to 2 data sources, and both were employed for the analysis, one is the Catalan school surveillance system and the other of the educational department. As soon as a positive index case is detected by the health system, isolation is required for all members of the bubble group, in addition to a mandatory proactive systematic screening of each individual. All infected cases are reported. It permits the calculation of the average reproductive number (R*), corresponding to the average number of infected individuals per index case. Results: We found that propagation inside of the bubble group was small. Among 75% index cases, there was no transmission to other members in the classroom, with an average R* across all ages inside the bubble of R* = 0.4. We found a significant age trend in the secondary attack rates, with the R* going from 0.2 in preschool to 0.6 in high school youth. Conclusions: The secondary attack rate depends on the school level and therefore on the age. Super-spreading events (outbreaks of 5 cases or more) in childhood were rare, only occurring in 2.5% of all infections triggered from a pediatric index case.

We aimed to assess the duration of nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA persistence in adults self-confined at home after acute infection; and to identify the associations of SARS-CoV-2 persistence with respiratory virus co-detection and infection transmission. A cross-sectional intra-household study was conducted in metropolitan Barcelona (Spain) during the time period of April to June 2020. Every adult who was the first family member reported as SARS-CoV-2-positive by reverse transcription polymerase chain reaction (RT-PCR) as well as their household child contacts had nasopharyngeal swabs tested by a targeted SARS-CoV-2 RT-PCR and a multiplex viral respiratory panel after a 15 day minimum time lag. Four-hundred and four households (404 adults and 708 children) were enrolled. SARS-CoV-2 RNA was detected in 137 (33.9%) adults and 84 (11.9%) children. Rhinovirus/Enterovirus (RV/EV) was commonly found (83.3%) in co-infection with SARS-CoV-2 in adults. The mean duration of SARS-CoV-2 RNA presence in adults' nasopharynx was 52 days (range 26-83 days). The persistence of SARS-CoV-2 was significantly associated with RV/EV co-infection (adjusted odds ratio (aOR) 9.31; 95% CI 2.57-33.80) and SARS-CoV-2 detection in child contacts (aOR 2.08; 95% CI 1.24-3.51). Prolonged nasopharyngeal SARS-CoV-2 RNA persistence beyond the acute infection phase was frequent in adults quarantined at home during the first epidemic wave; which was associated with RV/EV co-infection and could enhance intra-household infection transmission. Funding: This work was supported by the Kids Corona Project, Hospital Sant Joan de Déu, Barcelona,which received donations from Stavros Niarchos Foundation and Banco de Santander. ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID)

Phenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without disability) and sets of omic factors (genomic, proteomic, and metabolomic) plus markers measured in routine geriatric care. This study was a prevalent case control using stored biospecimens (urine, whole blood, cells, plasma, and serum) from 1522 individuals (identified as robust (R), pre-frail (P), or frail (F)] from the Toledo Study of Healthy Aging (R=178/P=184/F=109), 3 City Bordeaux (111/269/100), Aging Multidisciplinary Investigation (157/79/54) and InCHIANTI (106/98/77) cohorts. The analysis included over 35,000 omic and routine laboratory variables from robust and frail or pre-frail (with/without disability) individuals using a machine learning framework. We identified three protective biomarkers, vitamin D3 (OR: 0.81 [95% CI: 0.68-0.98]), lutein zeaxanthin (OR: 0.82 [95% CI: 0.70-0.97]), and miRNA125b-5p (OR: 0.73, [95% CI: 0.56-0.97]) and one risk biomarker, cardiac troponin T (OR: 1.25 [95% CI: 1.23-1.27]). Excluding individuals with a disability, one protective biomarker was identified, miR125b-5p (OR: 0.85, [95% CI: 0.81-0.88]). Three risks of frailty biomarkers were detected: pro-BNP (OR: 1.47 [95% CI: 1.27-1.7]), cardiac troponin T (OR: 1.29 [95% CI: 1.21-1.38]), and sRAGE (OR: 1.26 [95% CI: 1.01-1.57]). Three key frailty biomarkers demonstrated a statistical association with frailty (oxidative stress, vitamin D, and cardiovascular system) with relationship patterns differing depending on the presence or absence of a disability.

Highlights • Most of the episodes of acute lower-respiratory diseases were not related to SARS-CoV-2 infection. • Human-rhinovirus/enterovirus was the main detection during the pandemics. • SARS-CoV-2 was mainly found causing pneumonia in older children. • Bronchiolitis is possible, but SARS-CoV-2 was found causing a minority of these respiratory episodes. • Clinicians should be aware that SARS-CoV-2 infection could be the agent of lower-respiratory disease in paediatric patients with lymphopenia., Objective This study describes the characteristics of children requiring admission with an acute lower-respiratory disease (ALRD) during the SARS-CoV-2 pandemics. Methods Epidemiological, clinical, and microbiological data from patients with ALRD (pneumonia, bronchiolitis, bronchospasm) admitted to a reference paediatric hospital in Spain during the pandemic peak (week 11–20/2020) were prospectively analysed. Results 110 patients were included. 7 were SARS-CoV-2(+) and they were older in comparison to SARS-CoV-2(-). Among SARS-CoV-2(+) patients, pneumonia was the main clinical diagnosis (6/7) and bronchospasm was absent. Only 1 of 29 infants diagnosed with bronchiolitis was SARS-CoV-2(+). Lower values of leucocytes, lymphocytes, neutrophils, and platelets and higher values of creatinine were found in SARS-CoV-2(+). Human-rhinovirus/enterovirus was the main detection (11/32). There were not differences in PICU admission rates between SARS-CoV-2(+) and (-). Conclusions Most of the ALRD episodes identified during the pandemics were not related to SARS-CoV-2 infection. SARS-CoV-2 was mainly found causing pneumonia in older children.

Volume 57, no. 8, e00363-19, 2019, [https://doi.org/10.1128/JCM.00363-19][1]. This article was published on 26 July 2019 with the title “Invasive Pneumococcal Disease and Influenza Activity in a Pediatric Population: Impact of PCV13 Vaccination in Pandemic and Nonpandemic Influenza Periods.” The

Vaccination with the 13-valent conjugated pneumococcal disease (PCV13) has reduced invasive pneumococcal disease (IPD), but there have been reports of vaccine failures. We performed a prospective study in children aged 2-59 months who received diagnoses of IPD during January 2012-June 2016 in 3 pediatric hospitals in Catalonia, Spain, a region with a PCV13 vaccination coverage of 63%. We analyzed patients who had been age-appropriately vaccinated but who developed IPD caused by PCV13 serotypes. We detected 24 vaccine failure cases. The serotypes involved were 3 (16 cases); 19A (5 cases); and 1, 6B, and 14 (1 case each). Cases were associated with children without underlying conditions, with complicated pneumonia (OR 6.65, 95% CI 1.91-23.21), and with diagnosis by PCR (OR 5.18, 95% CI 1.84-14.59). Vaccination coverage should be increased to reduce the circulation of vaccine serotypes. Continuous surveillance of cases of IPD using both culture and PCR to characterize vaccine failures is necessary.

Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain).A prospective observational study was conducted in patients18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%.35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13.Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

In many areas of southern Europe, the scarcity of water due to climate change will increase, making its availability for irrigation an even more limiting factor for agriculture. One of the main necessary measures of adaptation of the vineyards in these areas will be the implementation of water-saving irrigation strategies and technologies to improve WUE (water use efficiency). The objective of the present study was to evaluate the long-term economic viability/profitability of different deficit irrigation techniques such as regulated deficit irrigation (RDI) and partial root-zone irrigation (PRI) with low water volume/fertilizer applied in a Monastrell vineyard in southeastern Spain to plants grafted on different rootstocks, and to assess the productive, social, and economic efficiency in these semiarid conditions. Through a cost/benefit analysis, socio-economic and environmental criteria for the selection of optimal deficit irrigation strategies and tolerant/water use efficient rootstocks for the vineyards in arid environments are proposed. Our analysis shows a clear conflict between productivity and quality in wine grape production. Productive and economic indices, such as yield, productive WUE (kg m-3), economic efficiency (&euro, m-3), break-even point (kg ha-1), and water productivity (&euro, m-3), were inversely related with berry quality. Besides, high berry quality was closely related with higher production costs. Under the current market of low-priced grapes, if the grower is not rewarded for the quality of the grapes (considering technological, phenolic, and nutraceutical quality), the productivity vision will continue and the cost-effective option will be to produce a lot of grapes, even if at the expense of the berry and wine quality. In this situation, it will be difficult to implement optimized deficit irrigation strategies and sustainable irrigation water use, and the pressure on water resources will increase in semiarid areas. Public policies should encourage vine growers to invest in producing high-quality grapes as a differentiating character, as well as to develop agronomic practices that are environmentally and socially sustainable, by the grapes more adjusted to their real quality and production costs. Only in this way we can implement agronomic measures such as optimized low-input DI (deficit irrigation) techniques and the use of efficient rootstocks to improve WUE and grape quality in semiarid regions in a context of climate change and water-limiting conditions.

The lack of invasive pneumococcal disease (IPD) cost studies may underestimate the eect of pneumococcal polysaccharide conjugated vaccines (PCV). The objective of this study was to estimate the direct costs of hospitalized IPD cases. A prospective study was made in children aged

The objectives were to clarify whether the relationship between physical performance and frailty was independently and jointly mediated by movement behaviors and body composition. We analyzed 871 older adults (476 women) from The Toledo Study for Healthy Aging. Skeletal muscle index (SMI) and fat index (FI) were determined using bone densitometry. Sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) were assessed using accelerometry. The Frailty Trait Scale and The Short Physical Performance Battery (SPPB) were used to evaluate frailty and physical performance, respectively. Simple and multiple mediation analyses were carried out to determine the role of movement behaviors and body composition, adjusted for potential confounders. ST and MVPA acted independently as mediators in the relationship between SPPB and frailty (0.06% for ST and 16.89% for MVPA). FI also acted as an independent mediator in the same relationship (36.47%), while the mediation role of SMI was not significant. MVPA and FI both acted jointly as mediators in this previous relationship explaining 58.15% of the model. Our data support the fact that interventions should simultaneously encourage the promotion of MVPA and strategies to decrease the FI in order to prevent or treat frailty through physical performance improvement.

Background: The objective of this study is to describe incidence and shifts of serotype and clonal distribution of invasive Streptococcus pneumoniae strains in four different age groups (65 years) during a period of intermediate PCV13 vaccination coverage (2011–2016) in Catalonia, Spain. Methods: We included all pneumococcal strains systematically sent to the Catalan support laboratory for molecular surveillance of invasive pneumococcal disease (IPD) located at Hospital Sant Joan de Deu, Barcelona. Two study periods were considered: 2011–13, early PCV13 vaccination period (EVP) and 2014–2016, late vaccination period (LVP). Results: A total of 2142 strains were included in the study. Five years after intermediate introduction of PCV13 in our population, a significant decrease of overall incidence of IPD in children 65 years. Results found when comparing both periods were consistent with IRRs observed year by year. In children 65 years the most frequently isolated serotypes were 3, 19A and 7F vs 3, 14 and 12F, respectively. Regarding clonal complexes (CCs) expressing mainly PCV13 serotypes, significant decreases of the proportions of CC306, CC191 and CC320 were observed, while CC156 showed a significant increase. As for CCs expressing mostly non-PCV13 serotypes, significant increases in ST989, CC53 and CC404 were showed. Conclusions: Despite low vaccine coverage in our setting a significant decrease of incidence of IPD was observed in children younger than 5 years. The modest indirect protection against vaccine serotypes causing IPD in elderly indicate the need for the inclusion of more serotypes in future high-valent PCV and vaccinating old adults should be considered. info:eu-repo/semantics/publishedVersion

Background: There is an urgent need to curb COVID-19 pandemic through early identification of asymptomatic but infectious cases. We aimed to validate and implement an optimized screening method for detection of SARS-CoV-2 RNA combining use of self-collected raw saliva samples, single-step heat-treated virus inactivation and RNA extraction, and direct RT-qPCR. Methods: The study was conducted in Sant Joan de Deu University Hospital (Barcelona, Spain), including: i) method analytical validation against standard RT-qPCR in saliva samples; ii) method diagnostic validation against standard RT-qPCR in nasopharyngeal samples using a prospective cohort of asymptomatic teenagers and young adult players and staff in a youth sports academy; and iii) method implementation through pilot screening of asymptomatic health workers, students, and aid volunteers in the study site. Findings: The direct method had comparable performance to standard RT-qPCR in saliva and high intra- and inter-assay precision. Diagnostic validation included saliva and nasopharyngeal samples serially obtained from 173 participants during 9-12 weeks. At week 0, all saliva and nasopharyngeal samples were negative. In the following weeks, standard RT-qPCR yielded 23 positive results in nasopharyngeal samples. Paired saliva specimens yielded 22 (95·7%) positive and one inconclusive result. A total of 2,709 participants engaged in the pilot screening, with a high rate of participation (83·4% among health workers). Only 17 (0·6%) of saliva samples self-collected by participants were invalid. Saliva was positive in 24 (0·9%) out of 2,692 valid specimens and inconclusive in 27 (1·0%). All 24 saliva-positive and 4 saliva-inconclusive participants were positive by standard RT-PCR in nasopharyngeal samples. Use of a high throughput system allowed fast screening workflow (up to 384 samples in

Background Although home hospitalization has been a well-known and widespread practice for some time in the adult population, it has not been the same case in the pediatric setting. Simultaneously, telemedicine tools are a facilitator of the change in the health care model, which is increasingly focused on home care. In a pioneering way in Spain, the in-home hospitalization program of the Hospital Sant Joan de Déu in Barcelona allows the child to be in their home environment at the time they are being monitored and clinically followed by the professionals. Besides being the preferred option for families, previous experience suggests that pediatric home hospitalization reduces costs, primarily thanks to savings on the structural cost of the stay. Objective The aim of this study is to compare the average cost of a discharge by tele–home care with the usual care and to analyze the main drivers of the differential costs of both care models. Methods A cost-minimization analysis is conducted under a hospital’s perspective, based on observational data, and estimated retrospectively. A historical control group of similar patients in terms of clinical casuistry to children hospitalized at home was used for comparison. Results A 24-hour stay at the hospital costs US $574.19, while the in-home hospitalization costs US $301.71 per day, representing a saving of almost half (48%) of the cost compared to usual care. The main saving drivers were the personnel costs (US $102.83/US $284.53, 35.5% of the total), intermediate noncare costs (US $6.09/US $284.53, 33.17%), and structural costs (US $55.16/US $284.53, 19.04%). Home hospitalization involves a total stay 27.61% longer, but at almost half the daily cost, and thus represents a saving of US $176.70 (9.01%) per 24-hour stay. Conclusions The cost analysis conducted under a hospital perspective shows that pediatric tele–home care is 9% cheaper compared to regular hospital care. These results motivate the most widespread implementation of the service from the point of view of economic efficiency, adding to previous experiences that suggest that it is also preferable from the perspective of user satisfaction.

Background Homocysteine (Hcy) high levels are associated with fractures, bone resorption and an early onset of osteoporosis in elderly persons; a relationship between Hcy and bone formation has also been suggested but is still controversial. Frailty, an independent predictor of fractures and decreased bone mineral density is associated with altered bone metabolism in women. However, no previous works have studied the relationship among frailty, Hcy levels and bone turnover. Methods We studied the association among Hcy, osteoporosis and N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (β-CTX), parathyroid hormone (PTH), calcium and 25-hydroxyvitamin D (25(OH)D) in 631 Spanish women between the ages of 65–78 from the Toledo Study for Healthy Aging (TSHA) cohort, who were classified as highly functional (robust subjects) or non-robust (pre-frail or frail subjects) according to Fried's criteria. Results Hcy was independently associated with β-CTX in the entire population (B = 0.22; 95% CI, 0.09–0.34; p = 0.001) and in the non-robust group (B = 0.24; 95% CI, 0.09–0.39; p = 0.002). Hcy was also associated with PINP in the entire and non-robust populations, but the association was lost after including the levels of β-CTX, but not the other bone biomarkers, in the multivariate analysis. This suggests that the controversial relationship between Hcy and bone formation might be explained, at least to a certain extent, by the confounding effects of β-CTX. Conclusions This work highlights the important implication of frailty status in the association between Hcy and increased bone turnover in older women.

Introduction Frailty is a strong predictor of adverse health events, but its impact on cognitive function is poorly understood. Aim To assess cognitive performance in frailty and to identify the frailty stage where cognitive impairment begins. Methods Data were taken from 2044 people aged ≥65 years without cognitive impairment selected from the Toledo Study for Healthy Aging, a population-based cohort of older adults. Frailty status was assessed by 3 different scales: Frailty Phenotype (FP), Frailty Trait Scale (FTS), and Frailty Index (FI). Neuropsychological assessments of different cognitive domains included the Mini-Mental State Examination, Short and Long-Term Memory Recalling Test, the Boston Naming Test, Verbal Fluency Test, Digit Span Forward, Go/No-go Test, Luria Orders Test, Clock Drawing Test, and Serial Word Learning Test. The relationships between the score of the scales and frailty status (robust, prefrail, and frail for FP and quartiles for FTS and FI) were analyzed using multivariate linear regression models including age, sex, and educative level as possible confounders. Results Participants classified as the worst degree of frailty (frail in FP and fourth quartile of FTS and FI) presented more cognitive domains affected and to a higher extent than moderate frail (prefrail and second quartile and third quartile of FTS and FI) and robust (and first quartile of FTS and FI) participants. Conclusions Cognitive performance progressively declined across the frailty state, regardless of the instrument used to assess frailty. In prefrail participants, cognitive impairment may be an early marker of frailty-dependent cerebral involvement and could be already subject to interventions aimed at reducing the transition to frailty.

Sedentary behaviour (SB) has recently emerged as an independent risk factor for different health outcomes. Older adults accumulate long time in SB. Understanding the role that SB plays on health is crucial for a successful aging. This short systematic review summarizes the current evidence related to the effects of objectively measured SB on frailty, physical performance and mortality in adults >60 years old. The literature search produced 271 records for physical performance (n=119), frailty (n=31), and mortality (n=121). Finally, only 13 articles fulfilled the inclusion criteria and were included in this review. All articles but one included in the physical performance section (n=9) showed a negative association between longer time spent in SB and physical performance. A significant association of SB with higher odds of frailty was found, however this association disappeared after adjusting for cognitive status. Lastly, two of the three included studies showed positive associations between SB and mortality, but this effect decreased or even disappeared in the more adjusted models. In conclusion, there is consistency that SB is negatively associated with physical performance. However, the relationship between objectively measured SB and frailty incidence and mortality rates remains unclear and deserves further research. The use of homogenous criteria to assess SB and the inclusion of more robust research designs will help clarifying the independent effects that SB could have on physical performance, frailty, and mortality. This will ultimately help designing more efficient and comprehensive physical activity guidelines for older adults.

The elderly population is increasing worldwide and in Chile, it is expected to grow rapidly. The World Health Organization (WHO) ICOPE guideline (Integrated Care for Older People) emphasizes the importance of frailty diagnosis to prevent dependence. Frailty in older adults is considered an indicator of vulnerability and poor health outcomes, of multifactorial etiology. Our objective was to investigate the association of activation of coagulation and increased risk of thrombosis with frailty in people older than 64 years. A prevalent-case control study was designed with 28 frail older and 27 robust older adults (non-frail, control group) older than 64 years. Frailty was defined by Fried's Phenotype, Platelet aggregation and activation plasma levels of Thromboxane B2 (TXB2), 8-isoprostane and Growth Differentiation Factor-15 (GDF-15) were determined.Compared to healthy controls, frail older adults, had a) higher percentage of platelet aggregation induction with ADP 4 μM (82.85% (3.35) and 73.41% (3.26), p-value = 0.024) and subaggregant dose of ADP (30.83% (7.47) and 13.25% (3.21), p-value = 0.002); b) higher platelet activation: P-selectin exposure (18.23% (4.41) and 6.96% (1.08), p-value = 0.011), and activated GPIIβ-IIIα (21.51% (3.41) and 8.26% (1.18), p-value = 0.001), at the baseline level and against a subaggregant dose ADP: P-selectin exposure (46.93% (5.95) and 13.41% (3.35), p-value = 0.002) and activated GPIIβ-IIIα (43.29% (6.04) and 26.71% (4.92), p-value = 0.024); c) higher plasma levels of TXB2 (201.8 ng/mL (59.53-236.3) and 45.77 ng/mL (25.14-98.26), p-value0.0001), d) elevated plasma levels of 8-isoprostane (70.94 pg/mL, IQ: 65.89-99,96 and 56.24 pg/mL, IQ: 42.18-74.81, p-value = 0.001), and e) higher plasma GDF-15 levels (2,379 pg/mL, IQ: 1,845-4,121and 1367 pg/mL, IQ: 1190-1747, p-value = 0.0001).Older adults with frailty syndrome have an upregulated platelet activity that may contribute to an increased risk of thrombosis and aspirin resistance. The elevated oxidative stress and increases of GDF-15 levels might be related to altered platelet responsiveness in frail patients.The determination of biomarkers of platelet dysfunction, oxidative stress and cell senescence/mitochondrial dysfunction may contribute to frailty diagnosis, and approaches aimed at regulating platelet function in frail older adults could contribute to its prevention and treatment.

Background: Physical activity (PA) is a recognized contributor to healthy aging. However, the majority of studies exploring its associations with adverse outcomes in cohorts of older adults use single-time PA estimates, which do not consider its dynamic nature. The aim of the present study is to explore the presence of different PA trajectories in the Toledo Study of Healthy Aging and their association with adverse outcomes. Our hypothesis is that prospectively maintaining or increasing PA is associated with a reduced risk of adverse outcomes. Methods: We used data from 1679 participants enrolled in the Toledo Study of Healthy Aging. Trajectories based on the Physical Activity Scale for the Elderly were identified using group-based trajectory modelling. Cox and logistic regression were used to investigate associations between PA trajectories and mortality and hospitalization, and incident and worsening disability, respectively. Mortality was ascertained by linkage to the Spanish National Death Index; disability was evaluated through the Katz Index; and hospitalization was defined as the first admission to Toledo Hospital. Models were adjusted by age, sex, smoking, Charlson Index, education, cognitive impairment, polypharmacy, and Katz Index at Wave 2. Results: We found four PA-decreasing and one PA-increasing trajectories: high PA-consistent (n = 566), moderate PA-mildly decreasing (n = 392), low PA-increasing (n = 237), moderate PA-consistent (n = 191), and low PA-decreasing (n = 293). Belonging to the high PA-consistent trajectory group was associated with reduced risks of mortality as compared with the low PA-decreasing group [hazard ratio (HR) 1.68; 95% confidence interval (CI) = 1.21–2.31] and hospitalization compared with the low PA-increasing and low PA-decreasing trajectory groups (HR 1.24; 95% CI = 1.004–1.54 and HR 1.25; 95% CI = 1.01–1.55, respectively) and with lower rates of incident [odds ratio (OR) 3.14; 95% CI = 1.59–6.19] and worsening disability (OR 2.16; 95% CI = 1.35–3.45) in relation to the low PA-decreasing trajectory group and at follow-up. Increasing PA during late life (low PA-increasing group) was associated with lower incident disability rates (OR 0.38; 95% CI = 0.19–0.82) compared with decreasing PA (low PA-decreasing group), despite similar baseline PA. Conclusions: Our results suggest that sustaining higher PA levels during aging might lead to healthy aging, characterized by a reduction in adverse outcomes. Our study supports the need for enhancing PA participation among older populations, with the goal of reducing personal and economic burden in a worldwide aging population. The present work was funded by grants from the Spanish Ministry of Economy, Industry and Competitiveness, cofinanced by the European Regional Development Funds (RD120001/0043) and the Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CB16/10/00464).

The objective of this study was to analyze the incidence, clinical presentation, and severity of invasive pneumococcal disease (IPD)-causing serotypes and the impact of the 13-valent pneumococcal conjugate vaccination during epidemic and nonepidemic influenza periods in Catalonia, Spain. This was a prospective study in persons aged

Objectives To assess the role of frailty in predicting death and incident disability in older adults with type 2 diabetes mellitus. Design Prospective cohort study. Setting Community dwelling. Participants A total of 1825 individuals ≥65 years old recruited between June 2006 and September 2009 were followed for a median of 5.5 years for mortality and 4.98 years for incident functional disability in activities of daily living. Self-reported diabetes, comorbidities (Charlson index), cardio- and cerebrovascular diseases, drug treatments, Frailty Trait Score (FTS) and Frailty Index (FI), activities of daily living, heart rate, and blood pressure among others were collected at baseline. Main outcome measures Survival analysis (Kaplan-Meier), adjusted Cox proportional-hazards models, and binary logistic regression were used to assess the relationship between frailty, comorbidity, and vascular diseases and time to death and incident disability. Results A total of 363 people had diabetes. Among them, 83 deaths and 84 cases of incident disability occurred during follow-up. People with diabetes died more frequently than those without diabetes [hazard ratio = 1.36, 95% confidence interval (CI) 1.06–1.75; P = .002], showing a poorer functional status at baseline. Survival analysis showed a relationship between frailty quartiles and the risk of death. In the adjusted Cox-models, only age and frailty indices, but not comorbidity or cardio/cerebrovascular diseases, were associated with the risk of death and incident disability after adjusting for measures of frailty. The hazard ratio for death was 1.51 (95% CI 1.28–1.77) and 1.83 (95% CI 1.49–2·26) for each 10 points increase in the FTS and FI; odds ratio for incident disability was 1·64 (95% CI 1.22–2.20) and 1·35 (95% CI 1.09–1.67) when using FI and FTS, respectively. Conclusions Frailty is an important risk factor for death and disability in older adults with diabetes, supporting the recent recommendations that frailty status should be routinely assessed in these patients.

To analyse the changes in eating patterns in Argentina from 1961 to 2011, and to assess changes in overweight and obesity in their socioeconomic and political context, we performed a hierarchical cluster analysis. We used the information from Food Balance Sheets of the United Nations Food and Agriculture Organisation to identify dietary patterns of apparent consumption. Years were grouped into five patterns. The food group with the highest apparent consumption was cereals (30% of total kcal/person/day) although this decreased slightly. Meats were second and their contribution decreased by 12%. The following foods contribution increased during the period: Sugar and milk by 2% and vegetable oils by 6%. The changes observed in the number of kcal/person/day were in line with changes in real wage, and coincided with economic and political crises that Argentina experienced during that period. Changes in eating patterns allow us to interpret that they relate to the increase in overweight and obesity.

The School of Engineering at Universidad Europea de Madrid (UEM) implemented, starting in the 2012–2013 period, a unified academic model based on project-based learning as the methodology used throughout the entire School. This model expects that every year, in each grade, all the students should participate in a capstone project integrating the contents and competencies of several courses. This paper presents the academic context under which this experience has been implemented, and a summary of the work done to design and implement the Project-Based Engineering School at the UEM. The steps followed, the structure used, some sample projects, as well as the difficulties and benefits of implementing the programme are discussed in this paper. The results are encouraging as students are more motivated and the initial set objectives were accomplished. Sin financiación 0.581 SJR (2017) Q1, 84/857 Engineering (miscellaneous); Q2, 302/1261 Education UEM

We read with interest the article by Pouletty et al ,1 in which the authors describe a multicentre compilation of patients with Kawasaki disease (KD) in France, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Other colleagues in Europe and USA have recently reported similar experiences.2–5 We report a prospective case series of paediatric patients that fulfilled clinical diagnostic criteria of KD during the SARS-CoV-2 pandemic in a paediatric referral centre in Barcelona, Spain. KD was defined according to the 2017 criteria of the American Heart Association.6 Assessment of SARS-CoV-2 infection was made by means of quantitative real-time PCR assay (GeneFinder COVID-19 Plus, Elitech; Puteaux, France) in nasopharyngeal samples; stools were tested in patients with diarrhoea. SARS-CoV-2 IgG qualitative determination (SARS-CoV-2 IgG chemiluminescent microparticle immunoassay; Abbot, Chicago, Illinois) was performed during admission. Statistical analyses were performed using SPSS V.25 (IBM). Informed consent was obtained from parents or legal guardians, as was informed assent in patients aged >12 years. From March 23 to May 14, twelve previously healthy patients with KD were admitted to our institution (table 1). The yearly number of patients with KD diagnosed in our centre is around 10–12. Prior to diagnosis, several patients reported gastrointestinal symptoms (10/12, 83.3%; vomiting, diarrhoea and abdominal pain) and neurological symptoms (5/12, 41.6%; irritability, headache, decreased consciousness and febrile seizures). Only patient 10 was referred with respiratory symptoms …

Introduction Skeletal muscle power has been demonstrated to be a stronger predictor of functional limitations than any other physical capability. However, no validated alternatives exist to the usually expensive instruments and/or time-consuming methods to evaluate muscle power in older populations. Our aim was to validate an easily applicable procedure to assess muscle power in large cohort studies and the clinical setting and to assess its association with other age-related outcomes. Methods Forty community dwelling older adults (70–87 years) and 1804 older subjects (67–101 years) participating in the Toledo Study for Healthy Aging were included in this investigation. Sit-to-stand (STS) velocity and muscle power were calculated using the subject's body mass and height, chair height and the time needed to complete five STS repetitions, and compared with those obtained in the leg press exercise using a linear position transducer. In addition, STS performance, physical (gait speed) and cognitive function, sarcopenia (skeletal muscle index (SMI)) and health-related quality of life (HRQoL) were recorded to assess the association with the STS muscle power values. Results No significant differences were found between STS velocity and power values and those obtained from the leg press force-velocity measurements (mean difference ± 95% CI = 0.02 ± 0.05 m·s−1 and 6.9 ± 29.8 W, respectively) (both p > 0.05). STS muscle power was strongly associated with maximal muscle power registered in the leg press exercise (r = 0.72; p Conclusion The STS muscle power test proved to be a valid, and in general, a more clinically relevant tool to assess functional trajectory in older people compared to traditional STS time values. The low time, space and material requirements of the STS muscle power test, make this test an excellent choice for its application in large cohort studies and the clinical setting.

Introduction: The effects of replacing sedentary time with light or moderate- to vigorous-intensity physical activity on frailty are not well known. Aim: To examine the mutually independent associations of sedentary time (ST), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with frailty status in older adults. Methods: A total of 628 people aged 65 years from the Toledo Study of Healthy Aging (TSHA) participated in this cross-sectional study. Frailty was measured using the Frailty Trait Scale. Hip-worn accelerometers were used to capture objective measurements of ST, LPA, and MVPA. Linear regression and isotemporal substitution analyses were used to examine associations of ST, LPA, and MVPA with frailty status. Analyses were also stratified by comorbidity. Results: In single and partition models, LPA and MVPA were negatively associated with frailty. Time in sedentary behavior was not associated with frailty in these models. In the isotemporal substitution models, replacing 30 minutes/d of ST with MVPA was associated with a decrease in frailty [b 2.460; 95% confidence interval (CI): 3.782, 1.139]. In contrast, replacing ST with LPA was not associated with favorable effects on this outcome. However, when the models were stratified by comorbidity, replacing ST with MVPA had the greatest effect on frailty in both the comorbidity (b 2.556; 95% CI: 4.451, 0.661) and the no comorbidity group (b 2.535; 95% CI: 4.343, 0.726). Moreover, the favorable effects of LPA in people with comorbidities was found when replacing 30 minutes/d of ST with LPA (b 0.568; 95% CI: 1.050, 0.086). Conclusions: Substituting ST with MVPA is associated with theoretical positive effects on frailty. People with comorbidity may also benefit from replacing ST with LPA, which may have important clinical implications in order to decrease the levels of physical frailty.

Introduction The actual mechanisms leading to a reduced muscle power and functional ability in older adults are poorly understood. We investigated the association between different force-velocity (F-V) profiles and impaired muscle power, physical and cognitive function, frailty, and health-related quality of life (HRQoL) in older people. Methods Physical function (habitual gait speed, timed up-and-go test, sit-to-stand and stair-climbing ability), cognitive function, HRQoL and frailty were evaluated in 31 older subjects (70–85 years). The F-V relationship and maximal muscle power (Pmax) were assessed in the leg press exercise. The skeletal muscle index (SMI) and fat index, moderate-to-vigorous physical activity (MVPA) and sedentary time were obtained from DXA scans and accelerometry, respectively. Results While some subjects showed a force deficit (FDEF), others presented a velocity deficit (VDEF), both leading to an impaired muscle power [Effect size (ES) = 1.30–1.44], and to a likely-very likely moderate harmful effect in their physical and cognitive function, HRQoL and frailty levels (except the VDEF group for cognitive function) [ES = 0.76–1.05]. Leg muscle mass and specific force were similarly associated with force at Pmax, while MVPA but not sedentary time was related to fat index, force at Pmax, and power values (all p Conclusion Older subjects exhibited different mechanisms (force vs. velocity deficits) leading to impaired muscle power. Both deficits were associated with a lower physical function and quality of life, and a higher frailty, whereas only a force deficit was associated with a lower cognitive function. Interventions aimed at reversing age- and/or disuse-related impairments of muscle power might evaluate the specific responsible mechanism and act accordingly.

Although circulating microRNAs (miRNAs) can modulate gene expression and affect immune system response, little is known about their participation in age-associated frailty syndrome and sarcopenia. The aim of this study was to determine miRNAs as possible biomarkers of age and frailty and their correlation with oxidative and inflammatory state in human blood. Three inflammation-related miRNAs (miR-21, miR-146a, and miR-223) and one miRNA related with the control of melatonin synthesis (miR-483) were analyzed. Twenty-two healthy adults, 34 aged robust, and 40 aged fragile patients were selected for this study. The expression of plasma miRNAs was assessed by RT-qPCR; plasma cytokines (IL-6, IL-8, IL-10, and TNFα) were analyzed by commercial kits, and plasma advanced oxidation protein products (AOPP) and lipid oxidation (LPO) were spectrophotometrically measured. Fragile subjects had higher miR-21 levels than control subjects, whereas miR-223 and miR- 483 levels increased at a similar extend in both aged groups. All cytokines measured increased in aged groups compared with controls, without differences between robust and fragile subjects. The fragile group had a TNFα/IL-10 ratio significantly higher than robust and control groups. Aged groups also had higher AOPP and LPO levels than controls. Women presented higher AOPP and LPO levels and increased expression of miR-483 compared with men. Positive correlations between miR-21 and AOPP and between miR-483 and IL-8 were detected. The expression of miR-21 and the TNFα/IL-10 ratio were correlated positively with the presence of frailty, which suggests that these markers can be considered as possible biomarkers for age-related frailty., This work was partially supported by grants from the Ministerio de Economía, Industria y Competitividad y por el Fondo de Desarrollo Regional Feder, Spain nos. RD12/ 0043/0005, PI13-00981, and CB16-10-00238 and from the Universidad de Granada, Spain no. CEI2014-MPBS31

International audience; Natural rubber demand was 11 million tons in 2014 and is expected to reach 16 million tons by 2025 according to the International Rubber Study Group (IRSG). The expected limitation of natural rubber from Hevea induced an interest for the development of alternative sources of natural rubber. Guayule (Parthenium argentatum Gray L.), being native to the Mexican Chihuahua desert, is a perennial crop of semi-arid area, with the potential of growing in the Mediterranean area. To assess the potential of guayule cultivation, CIRAD (France) and Wageningen University (The Netherlands) have conducted some on-farm guayule trials in southern Europe in partnership within the European based production and exploitation of alternative rubber and latex sources project (EU-PEARLS). Promising agronomic results have led to assess the profitability of a guayule commodity chain in the Mediterranean Europe area. Data on farming practices, biorefinery, costs of inputs were collected from the trials conducted in Spain and France, and from farmers and farmers’ organizations in both countries. At farm level, different cost scenarios were tested, with guayule biomass being the sole output, with annual or biennial harvests. Our results showed that, based on a nine-year field cultivation, the farmer’s breakeven point can be reached at a sale price of €147 ton−1 of dry biomass (at 12 ton ha−1). At factory level, the biorefiner needs to sell water-extracted rubber as latex. By adding solvent extraction, it is possible to extract the remaining percentage of total rubber and the resin. In such case, the biorefiner’s profits rises to €691 ton−1 of extracted rubber, making guayule cultivation profitable. Bagasse sale for electricity production or wood pellets is a bonus to be considered too. Our results showed that, in these conditions, a guayule value chain in Europe could be profitable. We extrapolated the results from our experiments to other Mediterranean countrie’s culture conditions. Our results showed that guayule cultivation would probably be more beneficial in the Southern Mediterranean countries, including Spain, than in the Northern countries (South of France). Introduction of guayule production in the Mediterranean region could contribute to improved sustainability in rural development projects, allow a new economic development of the regions, and contribute to provide a new sustainable crop alternative against the impacts of climate change such as longer and more severe drought stress.

BACKGROUND the association between muscular strength, mortality and hospitalisation with ageing can change depending on sex and the body region analysed (e.g. upper and lower limb muscles). OBJECTIVE to determine the effect of measuring lower and upper extremities muscular strength on the relationship between strength, mortality and hospitalisation risk in elder men and women. DESIGN a population-based cohort study using data from the Toledo Study for Healthy Aging (TSHA). METHODS a Spanish population sample of 1,755 elders aged ≥65 years participated in this study. Upper (handgrip and shoulder) and lower limbs (knee and hip) maximal voluntary isometric strength was obtained using standardised techniques and equipment. Cox proportional hazards model was used to examine mortality and hospitalisation over 5.5 and 3 years of follow-up, respectively. RESULTS after adjustment for potential confounding factors, including co-morbidities and BMI, hazard ratio of death and hospitalisation was significantly lower in the stronger women and men, but showing regional- and sex-specific differences. That is shoulder, knee and hip muscle regions in women and handgrip and shoulder in men (all P < 0.05). There was a cumulative effect of measuring several muscle strengths over the risk of health events (P < 0.05), so that mortality hazard ratio increased by 45% in women and 25% in men per muscular strength (shoulder, grip, knee and hip) in the weaker strength quartile increase (P < 0.01). CONCLUSIONS regional muscle strength is a predictor of medium-term mortality and hospitalisation in elder men and women. Multiple strength measures including lower and upper body limb muscles are better predictors than a single strength measurement.

Visceral fat has a high metabolic activity with deleterious effects on health contributing to the risk for the frailty syndrome. We studied the association between waist to hip ratio (an indirect measure of visceral fat stores) on upper and lower extremities strength. 1741 individuals aged ≥65 participated in this study. The data was obtained from the Toledo Study for Healthy Aging. For each gender, we studied the relationship between the waist-to-hip ratio (WHR), body mass index (BMI) and regional muscle strength (grip, shoulder, knee and hip) using multivariate linear regression and kernel regression statistical models. WHR was higher in men than in women (0.98 ± 0.07 vs. 0.91 ± 0.08, respectively, P

This work has been supported by grants from the Instituto de Salud Carlos III (PI12/1166, PI11/01379, PI13/00288 and RD12/0043/0001 RETICEF) and the European Commission (FRAILOMIC Initiative FP7-HEALTH-2012-Proposal No: 305483-2)

The executive function is a complex set of skills affected during the aging process and translate into subclinical cerebrovascular disease. Postural instability or motor slowness are some clinical manifestations, being consubstantial with the frailty phenotype, genuine expression of aging. Executive dysfunction is also considered a predictor of adverse health events in the elderly. To study whether the executive dysfunction can be used as an early marker for frailty and the viability of use as a predictor of mortality, hospitalization and/or disability in a Mediterranean population. A population-based cohort study using data from the Toledo Study for Healthy Aging (TSHA). 1690 Spanish elders aged ≥65 years underwent a neuropsychological evaluation in order to measure executive function. To assess whether the accumulation of dysfunctions (in severity and amplitude) could increase the predictive value of adverse health events in relation to each dimension separately an executive dysfunction cumulative index was constructed. Cox proportional hazards model was used to examine mortality and hospitalization over 5.02 and 3.1 years of follow-up, respectively. Executive dysfunction is a powerful predictor of mortality, frailty and disability. Cumulative differences in executive function are associated with high risk of frailty and disability, thus, for each one point increment in the executive function index, the risk of death increased by 7 %, frailty by 13% and disability by 11% (P

Introduction Frailty and sarcopenia are correlates of musculoskeletal aging that represent a state of vulnerability increasing the risk of negative health outcomes. Standardized definitions are lacking for both, and sometimes both concepts are used interchangeably. However, no large study has assessed the coexistence of these 2 entities in a cohort of older community-dwelling people. Methods Data were taken from the Toledo Study of Healthy Aging (TSHA), a study of community-dwelling elderly (≥65 years). The study population consists of 1611 participants with frailty and sarcopenia assessments. For sarcopenia, we used 3 criteria: European Working Group on Sarcopenia in Older People (EWGSOP), the Foundation for the National Institutes of Health (FNIH), and the FNIH fitted to the cut-off points of our population [standardized FNIH (sFNIH)]. Frailty was assessed according to the Fried criteria with cut-off points adjusted to our population. We used logistic regression to assess the relationship between sarcopenia and frailty and measures of diagnostic accuracy to evaluate the potential use of sarcopenia as a diagnostic marker for frailty. Results The mean age of the population was 75.42 years (±5.86). Overall, 72 (4.5%) were frail. In addition, 352 (21.8%), 332 (20.6%), and 453 (28.1%) participants were considered sarcopenic according to the EWGSOP, FNIH, and sFNIH criteria, respectively. The prevalence of frailty among those with sarcopenia was 8.2% (29/352), 15.7% (52/332), and 10.4% (47/453). Moreover, among frail people, the prevalence of sarcopenia was 40.27%, 72.2%, and 65.3% according to the used criteria. Sarcopenia showed a low sensitivity ( 97%) for the diagnosis of frailty, with a low intercorrelation (Cramer V = 0.16, 0.40, and 0.30) between the 3 criteria and frailty. Using multivariate logistic regression, frailty was associated with sarcopenia according to EWGSOP [odds ratio (OR) = 1.67, 95% confidence interval (CI) = 0.95, 2.96], FNIH (OR = 10.61, 95% CI = 5.8, 19.4), and sFNIH (OR = 6.63, 95% CI =3.5, 12.53). Conclusion Frailty and sarcopenia are distinct but related conditions. Sarcopenia is not a useful clinical biomarker of frailty, but its absence might be useful to exclude frailty.

Background Muscle power has been proposed to be the primary therapeutic target for resistance training interventions aimed at enhancing physical function in older adults. However, no recommendations exist on ideal testing protocols to assess muscle power in older adults, and the safety of this procedure has not been adequately evaluated in the literature. Methods A systematic review was conducted to identify studies evaluating muscle power exerted by older people in resistance exercises through May 2017. Information from muscle power testing protocols regarding familiarization, warm-up, measuring instrument, exercise, intensity, volume, rest intervals, data collection, and analysis was collected, as well as that regarding adverse events. Reporting bias was evaluated according to the recommendations given by the Cochrane Collaboration group. Results From 65 studies that met inclusion criteria, 3,484 older subjects and 11,841 muscle power tests distributed in 6,105 testing sessions were identified. A full description of the different muscle power testing protocols was conducted. In addition, a risk of adverse events of 0.15%-0.69% (one adverse event every 144-658 muscle power tests) was found. However, adverse events were poorly reported, with most of the studies showing a high risk of reporting bias. Conclusions Major discrepancies were found in muscle power testing protocols among studies. This might limit consensus on designing optimal training programs to improve muscle power and physical function in older adults, and understanding the main mechanisms involved in the age-related loss of muscle power. Finally, muscle power testing was found to be safe in older people with a broad range of health and functional states.

Background Specific mechanisms underlying frailty syndrome are not well known. Frailty can be viewed as a loss of functional reserve resulting in increased vulnerability to stressors. We hypothesize that pathways regulating cellular response to stress are potential players in the development of frailty. The aim of this study was to evaluate the association of the expression of certain genes related to cellular response to stress with the presence of frailty in older patients. Methods A sample of 350 individuals aged 65 years or older (22% frail) was selected from the Toledo Study of Healthy Aging. RNA was extracted from blood and retro-transcribed into complementary DNA. TaqMan Low density Arrays were used for the measurement of expression of genes implicated in cellular response to oxidative stress, genes implicated in inflammation, genes implicated in vascular physiology, and genes related to hypoxia. For data analysis, a logistic regression model was used to assess the relationship of gene expression and frailty. Results Among the analyzed genes, lower expression of genes related to cellular response to hypoxia (hypoxia inducible factor-1α) or to cellular response to oxidative stress (nuclear factor erythroid 2-related factor 2 and its target genes heme oxygenase-2, thioredoxin reductase-1, and superoxide dismutase-2), but not to those related to inflammation or vascular physiology, were significantly associated with the presence of frailty after adjustment for age and sex. These associations remained significant after adjustment by type 2 diabetes and Charlson index of comorbidities. Lower expressions of genes involved in cellular response to stress were also associated with increased risk of functional impairment. Conclusions Reduced expression of several genes implicated in cellular response to oxidative stress or hypoxia is significantly associated with the presence of frailty. These results help to fill the gap of knowledge of this evolving field and provide targets for intervention to promote health and independence in the elderly.

BACKGROUND: Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. METHODS: A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). RESULTS: High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29-0.87) and dependence (OR = 0.33; 95% CI = 0.19-0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22-0.70 and OR = 0.39; 95%CI = 0.21-0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. CONCLUSIONS: Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain. This project was partially funded by a research contract in support of the project “Epidemiological Study of Dementia in Spain” signed by the Pfizer Foundation and Carlos III Institute of Health. The funding agency had no influence in the scientific process including study design, data collection, data analysis, interpretation of results, and writing of the manuscript. Sí