Increased Severity of Mycoplasma pneumoniae Infections in Spanish Children.

BACKGROUND: Since the end of 2023, an elevated incidence and severity of Mycoplasma pneumoniae infections among children in Asia has been noted. Subsequently, this trend was observed in several European countries although limited data are currently available. We conducted a national study to delineate the ongoing M. pneumoniae outbreak in our country. METHODS: A multicenter retrospective observational study was conducted across 32 hospitals in Spain, encompassing patients under 18 years old hospitalized for M. pneumoniae infection from January 2023 to March 2024. Infection was confirmed by positive polymerase chain reaction and/or by 2 serological tests. RESULTS: A total of 623 children were included, with 79% of cases diagnosed in the final 3 months of the study period. Pneumonia was the most common diagnosis (87%). Respiratory symptoms were present in 97% of cases, with 62% requiring oxygen supplementation and 14% requiring admission to the pediatric intensive care unit (PICU). Risk factors for PICU admission included the presence of neurological symptoms, hypoxemia and a history of prematurity. Children admitted to the PICU exhibited significantly higher neutrophil counts upon admission. CONCLUSIONS: We have observed a notable increase in hospital admissions, including PICU support by up to 14%, due to M. pneumoniae infection in our country since November 2023, indicative of a more severe clinical course associated with this pathogen.

Anti-SARS-CoV-2-specific antibodies in human breast milk following SARS-CoV-2 infection during pregnancy: a prospective cohort study.

BACKGROUND: While the presence of SARS-CoV-2 in human breast milk is contentious, anti-SARS-CoV-2 antibodies have been consistently detected in human breast milk. However, it is uncertain when and how long the antibodies are present. METHODS: This was a prospective cohort study including all consecutive pregnant women with confirmed SARS-CoV-2 infection during pregnancy, recruited at six maternity units in Spain and Hong Kong from March 2020 to March 2021. Colostrum (day of birth until day 4 postpartum) and mature milk (day 7 postpartum until 6 weeks postpartum) were prospectively collected, and paired maternal blood samples were also collected. Colostrum samples were tested with rRT-PCR-SARS-CoV-2, and skimmed acellular milk and maternal sera were tested against SARS-CoV-2 specific immunoglobulin M, A, and G reactive to receptor binding domain of SARS-CoV-2 spike protein 1 to determine the presence of immunoglobulins. Then, we examined how each immunoglobulin type in the colostrum was related to the time of infection by logistic regression analysis, the concordance between these immunoglobulins in the colostrum, maternal serum, and mature milk by Cohen's kappa statistic, and the relationship between immunoglobulin levels in mature milk and colostrum with McNemar. RESULTS: One hundred eighty-seven pregnant women with confirmed SARS-CoV-2 infection during pregnancy or childbirth were recruited and donated the milk and blood samples. No SARS-CoV-2 was found in the human breast milk. Immunoglobulin A, G, and M were present in 129/162 (79·6%), 5/163 (3·1%), and 15/76 (19·7%) colostrum samples and in 17/62 (27·42%), 2/62 (3·23%) and 2/62 (3·23%) mature milk samples, respectively. Immunoglobulin A was the predominant immunoglobulin found in breast milk, and its levels were significantly higher in the colostrum than in the mature milk (p-value < 0.001). We did not find that the presence of immunoglobulins in the colostrum was associated with their presence in maternal, the severity of the disease, or the time when the infection had occurred. CONCLUSIONS: Since anti-SARS-CoV-2 antibodies are found in the colostrum irrespective of the time of infection during pregnancy, but the virus itself is not detected in human breast milk, our study found no indications to withhold breastfeeding, taking contact precautions when there is active disease.

Lyme borreliosis in pediatric population: Clinical, diagnostic and therapeutic features.

INTRODUCTION: Lyme borreliosis (LB) in the paediatric population is an understudied entity with certain peculiarities. The objective of this study is to describe the characteristics of paediatric patients with LB, and their diagnostic and therapeutic processes. METHODS: Descriptive and retrospective study in patients up to 14 years old with suspected or confirmed LB between 2015 and 2021. RESULTS: A total of 21 patients were studied: 18 with confirmed LB (50% women; median age 6.4 years old) and 3 false positive of the serology. Clinical features in the 18 patients with LB were: neurological (3, neck stiffness; 6, facial nerve palsy), dermatological (6, erythema migratory), articular (1), and non-specific manifestations (5). Serological diagnosis was confirmatory in 83.3% of cases. A total of 94.4% patients received antimicrobial treatment (median duration, 21 days). All recovered with resolution of symptoms. CONCLUSIONS: LB diagnosis is difficult in the paediatric population and presents clinical and therapeutic peculiarities, with favourable prognosis.

Condrodisplasia punctata ligada ao cromossomo X tipo 1 (CDPX1) - relato de caso com fenótipo atípico / X-linked chondrodysplasia punctata type 1 (CDPX1) - case report with atypical phenotype

A condrodisplasia punctata (CDP) é um grupo de displasias ósseas caracterizadas por calcificações puntiformes nas cartilagens, principalmente epifisárias. Entre as várias formas de CDP, a ligada ao X é rara e foi descrita em 50 pacientes do sexo masculino na literatura. O objetivo deste estudo é descrever um caso atípico de CDPX1 e compará-lo com a literatura prévia. Pré-escolar, sexo masculino, quatro anos, nascido a termo, pequeno para a idade gestacional e sem casos semelhantes na família. Ele evoluiu com baixa estatura desproporcionada, eutrofia, escoliose cervical e dorsal com pectus carinatum, assimetria discreta em membros inferiores, hipertelorismo ocular com esclera azul-acinzentada e queda de cabelo. Não apresentou fraturas ou dores ósseas e teve desenvolvimento neuropsicomotor adequado para a idade. Os exames não mostraram alterações no perfil osteometabólico nem nos hormônios hipofisários. O cariótipo foi 46,XY e o painel genético para displasias esqueléticas mostrou uma variante patogênica em hemizigose no gene ARSL (Arylsulfatase L) chrX:2.934.859 C>T (p.Trp581* ENST00000381134) com diagnóstico de condrodisplasia punctata ligada ao cromossomo X do tipo 1. A CDPX1 está diretamente relacionada à deficiência da atividade da enzima ARSL, o que pode resultar em alterações de desenvolvimento neuropsicomotor, perda auditiva e episódios de insuficiência respiratória. No entanto, estas características não foram apresentadas pelo probando. Assim, o probando apresenta uma forma mais branda de CDPX1. O diagnóstico precoce de displasias esqueléticas como a CDPX1 é importante para o acompanhamento ambulatorial adequado, aconselhamento familiar e prevenção do desenvolvimento de comorbidades a longo prazo.

Chondrodysplasia punctata (CDP) is a group of bone dysplasias characterized by punctate calcifications in the cartilage, mainly epiphyseal. Among the various forms of CDP, the X-linked form is rare and has been described in 50 male patients in the literature. The aim of this study is to describe an atypical case of CDPX1 and compare it with previous literature. Preschooler, male, four years old, born full-term, small for gestational age and with no similar cases in the family. He developed disproportionate short stature, eutrophy, cervical and dorsal scoliosis with pectus carinatum, slight asymmetry in the lower limbs, ocular hypertelorism with blue-gray sclera and hair loss. He did not present fractures or bone pain and had neuropsychomotor development appropriate for his age. The exams showed no changes in the osteometabolic profile or in pituitary hormones. The karyotype was 46,XY and the genetic panel for skeletal dysplasias showed a hemizygous pathogenic variant in the ARSL gene (Arylsulfatase L) chrX:2.934.859 C>T (p.Trp581* ENST00000381134) diagnosed with X-linked chondrodysplasia punctata type 1. CDPX1 is directly related to the deficiency of ARSL enzyme activity, which can result in changes in neuropsychomotor development, hearing loss and episodes of respiratory failure. However, these characteristics were not presented by the proband. Thus, the proband has a milder form of CDPX1. Early diagnosis of skeletal dysplasias such as CDPX1 is important for adequate outpatient follow-up, family counseling and prevention of the development of long-term comorbidities.

DELEÇÃO 14q24.1: características fenotípicas e resposta ao uso hormônio do crescimento recombinante humano / 14q24.1 DELETION: phenotypic characteristics and response to the use of recombinant human growth hormone

As alterações cromossômicas estruturais no cromossomo 14 são incomuns e podem levar a um espectro variado de manifestações clínicas, incluindo hipotonia, atraso no desenvolvimento psicomotor, déficits cognitivos e dismorfismos faciais. O fenótipo específico é influenciado pela localização, extensão e pontos de interrupção da deleção. Este relato de caso tem como objetivo detalhar o fenótipo e genótipo de uma pré-escolar com deleção 14q24.1, além de documentar a resposta ao tratamento com hormônio do crescimento recombinante humano (rhGH). A paciente, uma prematura nascida com medidas adequadas para a idade gestacional e filha de pais não consanguíneos, apresentou desconforto respiratório e dificuldades de deglutição no período neonatal, necessitando de gastrostomia até o primeiro ano de vida. Entre o nascimento e os dois anos e seis meses, ela apresentou uma redução da velocidade de crescimento e baixa estatura desproporcional. Foram observados também inclinação palpebral superior bilateral, baixa inserção das orelhas, fissura palatina posterior, dentição irregular, micrognatia, retrognatia, escoliose, encurtamento do fêmur direito com marcha antálgica, agenesia do rim esquerdo e posicionamento pélvico do rim direito. Além disso, a paciente exibiu atraso no desenvolvimento neuropsicomotor. A análise genética revelou uma deleção no braço longo do cromossomo 14 de aproximadamente 231 Kb. Com o tratamento com rhGH, observou-se melhora na taxa de crescimento e na estatura final. A evolução clínica do caso indica que a administração de rhGH, associada ao acompanhamento clínico rigoroso e ao tratamento das comorbidades, pode contribuir para a melhoria dos parâmetros antropométricos.

Structural chromosomal changes on chromosome 14 are uncommon and can lead to a diverse spectrum of clinical manifestations, including hypotonia, delayed psychomotor development, cognitive deficits, and facial dysmorphisms. The specific phenotype is influenced by the location, extent, and breakpoints of the deletion. This case report aims to detail the phenotype and genotype of a preschooler with 14q24.1 deletion, in addition to documenting the response to treatment with recombinant human growth hormone (rhGH). The patient, a premature female, born with appropriate measurements for gestational age and daughter of non-consanguineous parents, presented respiratory discomfort and swallowing difficulties in the neonatal period, requiring gastrostomy until the first year of life. Between birth and two years and six months, she presented a reduction in growth speed and disproportionate short stature. Bilateral upper eyelid tilt, low ear insertion, posterior cleft palate, irregular dentition, micrognathia, retrognathia, scoliosis, shortening of the right femur with antalgic gait, agenesis of the left kidney and pelvic positioning of the right kidney were also observed. Furthermore, the patient exhibited delayed neuropsychomotor development. Genetic analysis revealed a deletion on the long arm of chromosome 14 of approximately 231 Kb. With rhGH treatment, an improvement in growth rate and final height was observed. The clinical evolution of the case indicates that the administration of rhGH, associated with strict clinical monitoring and treatment of comorbidities, can contribute to the improvement of anthropometric parameters.

Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.

INTRODUCTION: Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. OBJECTIVE: To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. METHODS: This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. RESULTS: The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. CONCLUSION: A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

Changes in the epidemiology of invasive fungal disease in a Pediatric Hematology and Oncology Unit: the relevance of breakthrough infections.

BACKGROUND: Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time. METHODS: Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome. RESULTS: Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674). CONCLUSIONS: In this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates.

Biochemical and Hematological Indexes of Liver Dysfunction in Horses.

In the present review, the authors, based on the multiple functions performed by the liver, analyze the multiple biochemical and hematological changes as an expression of altered liver function in the horse. The liver performs important metabolic functions related to the synthesis, degradation, and excretion of various substances. Modification of these functions can be evaluated and diagnosed by determining serum concentrations of several serum analytes, including enzymes and other endogenous substances. Hepatocellular enzymes, such as sorbitol dehydrogenase-SDH and glutamate dehydrogenase-GLDH, are released following hepatocellular necrosis. Hepatobiliary enzymes, such as γ-glutamyl transferase-GGT, increase in response to necrosis, cholestasis, and other alterations in bile conducts. Serum concentrations of mainly endogenous and exogenous substances that the liver should synthesize or eliminate, such as proteins (albumin and globulins), bile acids, urea, glucose, total and direct bilirubin, and coagulation factors, and fibrinogen should be included in the liver function test profile. The interpretation of laboratory tests of liver function will allow the diagnosis of functional loss of the organ. Some of the analytes considered provide information on the prognosis of liver disease. This review will provide an accurate and objective interpretation of the common biochemical and hematological tests in use in the diagnosis of equine hepatic disease patients, aiding still further the veterinary activity on the applied equine clinical cases.

Household Transmission of SARS-CoV-2 and Long-term Immunity in Children: A Prospective Study in Northern Spain.

BACKGROUND: The role of children in SARS-CoV-2 transmission and their immune response after infection have been profoundly discussed. Hereby, we analyze both aspects in a Spanish pediatric population. METHODS: Prospective, multicentre, longitudinal study performed from July 2020 to September 2021 in children up to 14 years old. Venous blood samples were collected every 6 months and serum was analyzed for antibodies against SARS-CoV-2 using a spike (S) and a nucleocapsid (N) protein assays. Household contacts of seropositive children were tested. Household transmission, antibody dynamics, and durability were analyzed. RESULTS: Two hundred children were recruited and 28 had SARS-CoV-2 antibodies at the end of the study, resulting in an overall seroprevalence of 16.6% (95% CI: 9.5%-19.6%). Most of children (18/28) were secondary cases. The secondary attack rate (SAR) was lower in households with pediatric index cases than in those with adult index cases ( P = 0.023). The median antibody titers in the first positive serology, for the seropositive patients, were 137 BAU/mL (IQR 83.3-427.4) for the S-assay and 132.5 COI (IQR 14.5-170.5) for the N-assay without significant differences between symptomatic and asymptomatic children. The median time between the RT-PCR and the last serology was 7.5 months (IQR 5.2-8.8), and the duration of SARS-CoV-2 antibodies after infection was proven to be at least 18 months. There were no cases of seroreversion. CONCLUSIONS: (1) Children are not the main drivers of SARS-CoV-2 household transmission. (2) They maintain SARS-CoV-2 antibodies for up to 18 months after infection and the titers are similar between symptomatic and asymptomatic children.

Borreliosis de Lyme en población pediátrica: peculiaridades clínicas, diagnósticas y terapéuticas / Lyme borreliosis in pediatric population: Clinical, diagnostic and therapeutic features

Introducción: La borreliosis de Lyme (BL) es una entidad poco estudiada en pediatría, pero con ciertas peculiaridades. El objetivo de este estudio es conocer las características de los pacientes pediátricos con sospecha y/o confirmación de BL. Métodos: Estudio descriptivo y retrospectivo en menores de 14 años con diagnóstico clínico y/o serológico, sospechoso o confirmado, de BL entre 2015 y 2021. Resultados: Se estudiaron 21 pacientes: 18 con diagnóstico final de BL (50% mujeres; mediana de edad 6,4 años) y 3 falsos positivos. En los casos de BL, las manifestaciones clínicas presentadas fueron: neurológicas (3, meningitis; 6, parálisis facial), dermatológicas (6, eritema migratorio), articulares (uno) e inespecíficas (2). El diagnóstico serológico fue confirmatorio en el 83,3% de los casos. El 94,4% recibió antibioterapia (mediana de duración 21 días) y la evolución fue satisfactoria en todos los casos. Conclusiones: El diagnóstico de la BL es difícil en la población pediátrica y presenta peculiaridades clínicas y terapéuticas, pero el pronóstico es favorable.(AU)

Introduction: Lyme borreliosis (LB) in the paediatric population is an understudied entity with certain peculiarities. The objective of this study is to describe the characteristics of paediatric patients with LB, and their diagnostic and therapeutic processes. Methods: Descriptive and retrospective study in patients up to 14 years old with suspected or confirmed LB between 2015 and 2021. Results: A total of 21 patients were studied: 18 with confirmed LB (50% women; median age 6.4 years old) and 3 false positive of the serology. Clinical features in the 18 patients with LB were: neurological (3, meningitis; 6, facial nerve palsy), dermatological (6, erythema migrans), articular (one), and non-specific manifestations (2). Serological diagnosis was confirmatory in 83.3% of cases. A total of 94.4% patients received antimicrobial treatment (median duration 21 days). All recovered with resolution of symptoms. Conclusions: LB diagnosis is difficult in the paediatric population and presents clinical and therapeutic peculiarities, with favourable prognosis.(AU)

Change on the Circulation of Respiratory Viruses and Pediatric Healthcare Utilization during the COVID-19 Pandemic in Asturias, Northern Spain.

(1) Background: The COVID-19 pandemic and the implementation of restrictions and nonpharmaceutical interventions (NPIs) changed the trends in respiratory viral circulation and the pattern in pediatric healthcare utilization; (2) Methods: A retrospective, multicenter observational study designed to analyze the impact of the pandemic on pediatric healthcare utilization and the viral circulation pattern in children in a region in Northern Spain was carried out. Viral diagnostics data from all nasal or pharyngeal swabs collected in children in Asturias during the periods of March 2018−September 2019 and March 2020−September 2021 were analyzed, as well as the number of pediatric hospitalizations and emergency visits; (3) Results: A total of 14,640 samples were collected during the pandemic period. Of these, at least one respiratory virus was detected in 2940 (20.1%) while 5568/10,298 samples were positive in the pre-pandemic period (54.1%); p < 0.001. The detection of both enveloped and non-enveloped viruses decreased among periods (p < 0.001). After week 14, 2020, enveloped viruses were no longer detected until one year later, while non-enveloped viruses continued to be detected in children. Overall, a mean of 4946.8 (95% CI 4519.1−5374.4) pediatric emergency visits per month during the period 2018−2019 as compared to 2496.5 (95% CI 2086.4−2906.5) for 2020−2021 occurred (p < 0.001). The mean of pediatric hospitalizations also significantly decreased between periods, as follows: 346.6 (95% CI 313−380.2) in 2018−2019 vs. 161.1 (95% CI 138.4−183.8); p < 0.001; (4) Conclusions: Our study showed a remarkably reduction in pediatric hospitalizations and emergency visits and a change in the pattern of viral circulation during the COVID-19 pandemic in Asturias. The usual seasonal respiratory viruses, namely influenza or RSV were nearly absent in the pediatric population during the pandemic.

Variation in SARS-CoV-2 seroprevalence in children in the region of Asturias, Northern Spain.

BACKGROUND: Updated seroprevalence estimates are important to describe the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) landscape and to guide public health decisions. The aims are to describe longitudinal changes in seroprevalence in children in a region in Northern Spain and to analyze factors associated with SARS-CoV-2 seropositivity. METHODS: Prospective multicenter longitudinal study with subjects recruited from July to September 2020. Children (up to 14 years old) were included and followed up until September 2021. Venous blood samples were collected every six months during three testing rounds and were analyzed for SARS-CoV-2 antibodies. The data regarding epidemiological features, contact tracing, symptoms, and virological tests were collected. The evolution of SARS-CoV-2 seroprevalence during the study and the differences between children with positive and negative SARS-CoV-2 antibody tests were analyzed. RESULTS: Two hundred children were recruited (50.5% girls, median age 9.7 years). The overall seroprevalence increased from round 1 [1.5%, 95% confidence interval (CI) 0.3%-4.3%] to round 2 (9.1%, 95% CI 4.6%-12.7%) and round 3 (16.6%, 95% CI 9.5%-19.6%) (P < 0.001). Main changes occurred in children aged zero to four years (P = 0.001) who lived in urban areas (P < 0.001). None of the children who were previously positive became seronegative. Following multivariable analysis, three variables independently associated with SARS-CoV-2 seropositivity were identified: close contact with coronavirus disease 2019 (COVID-19) confirmed or suspected cases [odds ratio (OR) = 3.9, 95% CI 1.2-12.5], previous positive virological test (OR = 17.1, 95% CI 3.7-78.3) and fatigue (OR = 18.1, 95% CI 1.7-193.4). CONCLUSIONS: SARS-CoV-2 seroprevalence in children has remarkably increased during the time of our study. Fatigue was the only COVID-19-compatible symptom that was more frequent in seropositive than in seronegative children.

Trends and Pattern of Antibiotic Use in Children in Northern Spain, Interpreting Data about Antibiotic Consumption in Pediatric Outpatients.

Monitoring of antibiotic prescription and consumption behavior is crucial. The Access, Watch, and Reserve (AWaRe) classification of antibiotics has been recently introduced in order to measure and improve patterns of antibiotic use. In this study, retrospective data about systemic antibiotic consumption (expressed in defined daily dose per 1000 inhabitants per day (DID)) in pediatric outpatients in a region in northern Spain (around 100,000 children up to 14 years old) from 2005 to 2018 were analyzed and compared with antibiotic consumption in general population in Spain. The pattern of use was analyzed by the percentage of the current AWaRe categories, the Access-to-Watch index, and the amoxicillin index. Data were calculated annually and compared into two periods. Mean antibiotic consumption in pediatric outpatients was 14.0 DID (CI 95% 13.38-14.62). It remained stable throughout the study and was lower than consumption in general population in Spain, particularly from 2016. Changes in the consumption of the main active principles have led to an improvement in the three metrics of the pattern of use. It is important to have a thorough knowledge of the methodology applied in studies about antibiotic consumption. There is a lack of an optimal standardized metric for the pediatric population.

Evaluation of five widely used serologic assays for antibodies to SARS-CoV-2.

Reliable diagnostic technologies are pivotal to the fight against COVID-19. While real-time reverse transcription-polymerase chain reaction (rRT-PCR) remains the gold standard, commercial assays for antibodies against (SARS-CoV-2) have emerged. We sought to examine 5 widely used commercial methods. We measured antibodies against SARS-CoV-2 with assays, Abbott-IgG, Roche-IgT (total antibodies, isotype-unspecific), EUROIMMUN-IgG, EUROIMMUN-IgA, DiaSorin-IgG, in 191 serum samples from patients with rRT-PCR proven COVID-19 between days 0 and 47 after the onset of clinical symptoms and in biobank samples collected in 2018. The assays were calibrated using the manufacturers' instructions; results are in multiples of the assay specific cut-offs (Abbott, Roche, EUROIMMUN) or in arbitrary units (AU/mL, DiaSorin). The assays for IgG and IgT have approximately the same sensitivity and specificity for detecting seroconversion which starts at approximately day 3 after symptom onset, sensitivity reached 93% on day 16 and was 100% for each assay on day 20. The assay for IgA antibodies was superior in sensitivity and had a lower specificity than the others. Bivariate non-parametric correlation coefficients ranged between 0.738 and 0.991. Commercial assays for IgG or total antibodies against SARS-CoV-2 are largely equivalent for establishing seroconversion but differ at high antibody titres. Increased sensitivity to detect seroconversion is afforded by including IgA antibodies. Further international efforts to harmonise assays for antibodies against SARS-CoV-2 are urgently needed.

Treating Full Depth Cartilage Defects with Intraosseous Infiltration of Plasma Rich in Growth Factors: An Experimental Study in Rabbits.

OBJECTIVE: Intraarticular (IA) administration of platelet-rich plasma (PRP) has been proposed as a new strategy to halt osteoarthritis (OA) progression. In patients with severe OA, its potential is limited because it is unable to reach the subchondral bone, so a new strategy is needed, and intraosseous (IO) infiltration has been suggested. The purpose is to assess the impact of IA together with IO infiltration of plasma rich in growth factors (PRGF) in serum hyaluronic acid (HA) and type II collagen cleavage neoepitope (C2C) levels. DESIGN: A total of 32 rabbits were included in the study and randomly divided into 2 groups: control and treatment. A 4-mm chondral defect was created in the medial femoral condyle and IA followed by IO infiltration were performed. Serum C2C and HA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests before infiltration and 28, 56, and 84 days post-infiltration. RESULTS: Significant lower C2C serum levels were obtained in treatment group (IA + IO infiltration of PRGF) at 84 days post-infiltration than in control group (IA infiltration of PRGF + IO infiltration of saline solution), while no significant differences between groups were reported at any other study times. Regarding HA, at 56 days post-infiltration, greater significant levels were seen in the treatment group. However, at 84 days post-infiltration, no significant differences were obtained, although lower levels were reported in the treatment group. CONCLUSIONS: Despite inconclusive, the results suggest that the combination of IA and IO infiltration with PRGF may enhance cartilage and subchondral bone regeneration, but further studies are needed.

Evolución del consumo de antibióticos a nivel extrahospitalario en Asturias, España (2005-2018) / Evolution of antibiotic consumption in pediatric outpatients of Asturias, Spain (2005-2018)

Introducción: El consumo de antibióticos en España es elevado y más del 90% de las prescripciones se realizan en ámbito extrahospitalario. La exposición a antibióticos en la edad infantil es alta. El objetivo de este estudio es describir la evolución del consumo extrahospitalario de antibióticos en la población pediátrica del Principado de Asturias entre 2005 y 2018.Material y métodos: Estudio descriptivo y retrospectivo del consumo de antibacterianos de uso sistémico (grupo J01 de la clasificación ATC, Anatomical Therapeutic Chemical Classification) en ámbito extrahospitalario en la población pediátrica (0-13 años) del Principado de Asturias entre 2005 y 2018. Se compara el consumo, medido en número de dosis diarias definidas (DDD) por 1.000 habitantes y día (DHD), en 3 periodos de tiempo.Resultados: El consumo medio de antibacterianos en la población pediátrica asturiana (2005-2018) fue de 14 DHD (IC95% 13,4-14,6), con un aumento hasta 2009 (15,2 DHD) y descenso a partir de 2015 (11,9 DHD en 2018). A lo largo del estudio se detectó: 1) un aumento del consumo de amoxicilina (p=0,027), que supera al de amoxicilina-clavulánico desde el año 2011; 2) un consumo estable de macrólidos, con un aumento de azitromicina (p<0,001) y un descenso de claritromicina (p=0,001); 3) un descenso del consumo de cefalosporinas (p<0,001); 4) un aumento del consumo de quinolonas (p=0,002).Conclusiones: El consumo de antibióticos a nivel extrahospitalario en la población pediátrica del Principado de Asturias entre los años 2005 y 2018 ha experimentado un descenso mantenido en los últimos años y una mejora evolutiva del patrón de uso. (AU)

Introduction: Data about consumption of antibiotics in Spain are worrisome. They are mainly prescribed in the community sector and there is a high exposure to antibiotics in the pediatric population. The aim of this study is to describe the evolution of antibiotic consumption in the pediatric population of Asturias during 2005-2018 period.Material and methods: Retrospective and descriptive study using data about consumption of antibacterial agents for systemic use (J01 group of the Anatomical Therapeutic Chemical Classification) in pediatric outpatients in Principado de Asturias between 2005 and 2018. Data, expressed as defined daily dose (DDD) per 1000 inhabitants per day (DID), in three periods were compared.Results: Mean antibiotic consumption in pediatric outpatients in Principado de Asturias (2005-2018) was 14 DID (CI95% 13.4-14.6). Consumption increased until 2009 (15.2 DID) and decreased from 2015 onwards (11.9 DID in 2018). Remarkable data along the study were: 1) increase in amoxicillin consumption (p=0.027), that have exceeded that of amoxicillin-clavulanate since 2011; 2) steady consumption of macrolides, with an increase in azithromycin (p<0.001) and a decrease in clarithromycin (p=0.001); 3) reduction of cephalosporins consumption (p<0.001); 4) increase in quinolones consumption (p=0.002).Conclusions: Global antibiotic consumption in pediatric outpatients in Principado de Asturias between 2005 and 2018 has experienced a constant decrease lately and an improvement in patterns of antibacterial use. (AU)

Evolution of antibiotic consumption in pediatric outpatients of Asturias, Spain (2005-2018).

INTRODUCTION: Data about consumption of antibiotics in Spain are worrisome. They are mainly prescribed in the community sector and there is a high exposure to antibiotics in the pediatric population. The aim of this study is to describe the evolution of antibiotic consumption in the pediatric population of Asturias during 2005-2018 period. METHODS: Retrospective and descriptive study using data about consumption of antibacterial agents for systemic use (J01 group of the Anatomical Therapeutic Chemical Classification) in pediatric outpatients in Asturias between 2005 and 2018. Data, expressed as defined daily dose (DDD) per 1000 inhabitants per day (DID), in three periods were compared. RESULTS: Mean antibiotic consumption in pediatric outpatients in Asturias (2005-2018) was 14 DID (CI95% 13.4-14.6). Consumption increased until 2009 (15.2 DID) and decreased from 2015 onwards (11.9 DID in 2018). Remarkable data along the study were: 1) increase in amoxicillin consumption (p = 0.027), that have exceeded that of amoxicillin-clavulanate since 2011; 2) steady consumption of macrolides, with an increase in azithromycin (p < 0.001) and a decrease in clarithromycin (p = 0.001); 3) reduction of cephalosporins consumption (p < 0.001); 4) increase in quinolones consumption (p = 0.002). CONCLUSIONS: Global antibiotic consumption in pediatric outpatients in Asturias between 2005 and 2018 has experienced a constant decrease lately and an improvement in patterns of antibacterial use.

Cell and Cell Free Therapies in Osteoarthritis.

Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients' function, decreasing quality of life. There are many limitations regarding OA conventional therapies-pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies' efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.