Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Anal Dysplasia Screening in People Living with HIV: Long-Term Follow-Up in a Large Cohort from Northwest Spain.

Anal squamous cell carcinoma (SCC) is not a common disease in the general population, although its incidence is higher in people living with human immunodeficiency virus (PLWH). Anal SCC is caused by human papillomavirus (HPV) infection and arises from premalignant lesions termed squamous intraepithelial lesions (SILs). SIL surveillance programs are based on the early detection and treatment of SILs, especially those with a higher risk of transforming into cancer. An anal surveillance program has been under development in our institution since 2011. In this context, we performed a retrospective cohort study at the anal dysplasia unit of Álvaro-Cunqueiro Hospital (Spain). Epidemiological and clinical data were gathered from our Infectious Diseases Sample Collection (an open sample cohort including PLWH) from January 2011 to January 2022. A total of 493 PLWH were considered, 122 (24.7%) of whom were diagnosed with anal dysplasia at baseline, including 2 cases of anal SCC. Briefly, most of individuals were young men (median age, 38 years old) born in Spain (76%), whose vaccination rate before their inclusion in the program was scarce (<3%). Throughout the study period, 81 (16.4%) cases were diagnosed with high-grade squamous-intraepithelial lesions (HSILs) and 3 with anal SCC. At the baseline, severe immunosuppression (i.e., nadir CD4+ lymphocyte count below 200 cell/µL), and prior diagnosis of condyloma acuminata were more frequent within the group with SILs. Conversely, the baseline CD4+ lymphocyte count was similar among both groups. HPV-16 was related to a higher risk of HSILs (odds ratio: 2.76). At the end of the follow-up, 385 PLWH had been retained in care; one patient had died of anal cancer. Anal dysplasia was common (25% of cases), especially among patients infected by HPV-16, diagnosed with condyloma acuminata, and who were severely immunosuppressed. HPV-16 was the main risk factor for the presentation of HSILs.

The imperative for quality control programs in Monkeypox virus DNA testing by PCR: CIBERINFEC quality control.

To evaluate molecular assays for Mpox diagnosis available in various clinical microbiology services in Spain through a quality control (QC) approach. A total of 14 centers from across Spain participated in the study. The Reference Laboratory dispatched eight serum samples and eight nucleic acid extracts to each participating center. Some samples were spiked with Mpox or Vaccinia virus to mimic positive samples for Mpox or other orthopox viruses. Participating centers provided information on the results obtained, as well as the laboratory methods used. Among the 14 participating centers seven different commercial assays were employed, with the most commonly used kit being LightMix Modular Orthopox/Monkeypox (Mpox) Virus (Roche®). Of the 12 centers conducting Mpox determinations, concordance ranged from 62.5% (n = 1) to 100% (n = 11) for eluates and from 75.0% (n = 1) to 100% (n = 10) for serum. Among the 10 centers performing Orthopoxvirus determinations, a 100% concordance was observed for eluates, while for serum, concordance ranged from 87.5% (n = 6) to 100% (n = 4). Repeatedly, 6 different centers reported a false negative in serum samples for Orthopoxvirus diagnosis, particularly in a sample with borderline Ct = 39. Conversely, one center, using the TaqMan™ Mpox Virus Microbe Detection Assay (Thermo Fisher), reported false positives in Mpox diagnosis for samples spiked with vaccinia virus due to cross-reactions. We observed a positive correlation of various diagnostic assays for Mpox used by the participating centers with the reference values. Our results highlight the significance of standardization, validation, and ongoing QC in the microbiological diagnosis of infectious diseases, which might be particularly relevant for emerging viruses.

The Modification of the Illumina® CovidSeq™ Workflow for RSV Genomic Surveillance: The Genetic Variability of RSV during the 2022-2023 Season in Northwest Spain.

There is growing interest in the molecular surveillance of the Respiratory Syncytial Virus and the monitorization of emerging mutations that could impair the efficacy of antiviral prophylaxis and treatments. A simple, scalable protocol for viral nucleic acid enrichment could improve the surveillance of RSV. We developed a protocol for RSV-A and B amplification based on the Illumina CovidSeq workflow using an RSV primer panel. A total of 135 viral genomes were sequenced from nasopharyngeal samples through the optimization steps of this panel, while an additional 15 samples were used to test the final version. Full coverage of the G gene and over 95% of the coverage of the F gene, the target of the available RSV antivirals or monoclonal antibodies, were obtained. The F:K68N mutation, associated with decreased nirsevimab activity, was detected in our facility. Additionally, phylogenetic analysis showed several sublineages in the 2022-2023 influenza season in Europe. Our protocol allows for a simple and scalable simultaneous amplification of the RSV-A and B whole genome, increasing the yield of RSV sequencing and reducing costs. Its application would allow the world to be ready for the detection of arising mutations in relation to the widespread use of nirsevimab for RSV prevention.

Mortality reduction in older COVID-19-patients hospitalized in Spain during the second pandemic wave from the SEMI-COVID-19 Registry.

In 2020, the COVID-19 pandemic followed a two-wave pattern in most countries. Hospital admission for COVID-19 in one wave or another could have affected mortality, especially among the older persons. The objective of this study was to evaluate whether the admission of older patients during the different waves, before SARS-CoV-2 vaccination was available, was associated with a different mortality. We compared the mortality rates of patients hospitalized during 2020 before (first wave) and after (second wave) July 7, 2020, included in the SEMI-COVID-19 Registry, a large, multicenter, retrospective cohort of patients admitted to 126 Spanish hospitals for COVID-19. A multivariate logistic regression analysis was performed to control for changes in either the patient or disease profile. As of December 26, 2022, 22,494 patients had been included (17,784 from the first wave and 4710 from the second one). Overall mortality was 20.4% in the first wave and 17.2% in the second wave (risk difference (RD) - 3.2%; 95% confidence interval (95% CI) - 4.4 to - 2.0). Only patients aged 70 and older (10,973 patients: 8571 in the first wave and 2386 in the second wave) had a significant reduction in mortality (RD - 7.6%; 95% CI - 9.7 to - 5.5) (unadjusted relative risk reduction: 21.6%). After adjusting for age, comorbidities, variables related to the severity of the disease, and treatment received, admission during the second wave remained a protective factor. In Spain, patients aged 70 years and older admitted during the second wave of the COVID-19 pandemic had a significantly lower risk of mortality, except in severely dependent persons in need of corticosteroid treatment. This effect is independent of patient characteristics, disease severity, or treatment received. This suggests a protective effect of a better standard of care, greater clinical expertise, or a lesser degree of healthcare system overload.

Efecto neuroprotector del sulfato de magnesio en prematuros. Análisis tras instaurar su protocolo de administración antenatal en un hospital terciario / Neuroprotective effect of magnesium sulfate in premature infants: Analysis after establishing an antenatal administration protocol in a tertiary care hospital

Introducción: En 2016 se desarrolló en nuestro centro un protocolo de administración antenatal de sulfato de magnesio en gestantes con riesgo de parto pretérmino inminente como método para disminuir el riesgo de parálisis cerebral (PC). Material y métodos: Se realizó un estudio observacional y retrospectivo en un hospital de nivel IIIC con objetivo principal de comparar la incidencia de PC previa y posteriormente a la puesta en marcha de este protocolo. Con respecto a los objetivos secundarios, a destacar la incidencia de déficit cognitivo, enterocolitis necrosante y mortalidad en ambos grupos. Los pacientes incluidos fueron recién nacidos prematuros por debajo de 32 semanas de edad gestacional nacidos en los años 2011-2012 (previo a la instauración del protocolo) y 2016-2018 (posteriormente a la instauración del protocolo, cuyas madres habían recibido sulfato de magnesio como neuroprotector). Las características clínicas y epidemiológicas de ambos grupos fueron comparables entre sí. Resultados: Se recogieron datos de un total de 523 pacientes, 263 y 260 de cada grupo. Con respecto al objetivo principal, no se encontraron diferencias estadísticamente significativas. Se objetivó, en el grupo de pacientes nacidos entre 2016-2018 y con edad gestacional entre 26+0 y 27+6 semanas, cuyas madres recibieron sulfato de magnesio, una reducción estadísticamente significativa de la mortalidad y del riesgo de enterocolitis necrosante grave. Conclusiones: En nuestro trabajo, el sulfato de magnesio administrado a madres en riesgo de parto prematuro, no disminuyó el riesgo de desarrollar PC. (AU)

Introduction: In 2016, a protocol was developed in our hospital for the antenatal administration of magnesium sulfate in pregnant women at risk of imminent preterm birth as a method to reduce the risk of cerebral palsy (CP). Material and methods: We conducted a retrospective observational study in a level IIIC hospital with the primary objective of comparing the incidence of CP before and after the implementation of this protocol. Among the secondary outcomes, we ought to highlight the incidence of cognitive deficits and necrotizing enterocolitis and the mortality in both groups. The sample consisted of preterm newborns delivered before 32 weeks of gestation in 2011-2012 (prior to the implementation of the protocol) and in 2016-2018 (after the implementation of the protocol, whose mothers had received magnesium sulfate for neuroprotection). The clinical and epidemiological characteristics of both groups were comparable. Results: We collected data for a total of 523 patients, 263 and 260 in each group. As regards the primary outcome, we did not find statistically significant differences between groups. We observed a statistically significant reduction in mortality and the risk of severe necrotizing enterocolitis in the group of patients born in the 2016-2018 period and between 26+0 and 27+6 weeks of gestation, whose mothers had received magnesium sulfate. Conclusions: In our study, the administration of magnesium sulfate to mothers at risk of preterm birth did not decrease the risk of developing CP. (AU)

Neuroprotective effect of magnesium sulfate in premature infants. Analysis after establishing an antenatal administration protocol in a tertiary care hospital.

INTRODUCTION: In 2016, a protocol was developed in our hospital for the antenatal administration of magnesium sulfate in pregnant women at risk of imminent preterm birth as a method to reduce the risk of cerebral palsy (CP). MATERIAL AND METHODS: We conducted a retrospective observational study in a level IIIC hospital with the primary objective of comparing the incidence of CP before and after the implementation of this protocol. Among the secondary outcomes, we ought to highlight the incidence of cognitive deficits and necrotizing enterocolitis and the mortality in both groups. The sample consisted of preterm newborns delivered before 32 weeks of gestation in 2011-2012 (prior to the implementation of the protocol) and in 2016-2018 (after the implementation of the protocol, whose mothers had received magnesium sulfate for neuroprotection). The clinical and epidemiological characteristics of both groups were comparable. RESULTS: We collected data for a total of 523 patients, 263 and 260 in each group. As regards the primary outcome, we did not find statistically significant differences between groups. We observed a statistically significant reduction in mortality and the risk of severe necrotizing enterocolitis in the group of patients born in the 2016-2018 period and between 26+0 and 27+6 weeks of gestation, whose mothers had received magnesium sulfate. CONCLUSIONS: In our study, the administration of magnesium sulfate to mothers at risk of preterm birth did not decrease the risk of developing CP.

High-flow nasal cannula oxygen therapy for the treatment of acute respiratory failure secondary to SARS-CoV-2 pneumonia out of ICU.

INTRODUCTION AND OBJECTIVES: High-flow nasal cannula oxygen therapy (HFNC) has been successfully used for the treatment of acute hypoxaemic respiratory failure (AHRF) secondary to SARS-CoV-2 pneumonia and being effective in reducing progression to invasive mechanical ventilation. The objective of this study was to assess the usefulness of HFNC on a hospital ward for the treatment of AHRF secondary to SARS-CoV-2 pneumonia and its impact on the need for intensive care unit (ICU) admission and endotracheal intubation. Other objectives include identifying potential physiological parameters and/or biomarkers for predicting treatment failure and assessing the clinical course and survival. METHODS: Observational study based on data collected prospectively between March 2020 and February 2021 in a single hospital on patients diagnosed with AHRF secondary to SARS-CoV-2 pneumonia who received HFNC outside an ICU. RESULTS: One hundred and seventy-one patients out of 1090 patients hospitalised for SARS-CoV-2 infection. HFNC was set as the ceiling of treatment in 44 cases; 12 survived (27.3%). Among the other 127 patients, intubation was performed in 25.9% of cases with a mortality of 11.8%. Higher creatinine levels (OR 1.942, 95% CI 1.04; 3.732; p = 0.036) and Comorbidity-Age-Lymphocyte-LDH (CALL) score (OR 1.273, 95% CI 1.033; 1.617; p = 0.033) were associated with a higher risk of intubation. High platelet count at HFNC initiation was predictive of good treatment response (OR 0.935, 95% CI 0.884; 0.983; p = 0.012). CONCLUSIONS: HFNC outside an ICU is a treatment with high success rate in patients with AHRF secondary to SARS-CoV-2 pneumonia, including in patients in whom this therapy was deemed to be the ceiling of treatment.

Factors associated with the gender gap in the STEM sector: Comparison of theoretical and empirical concept maps and qualitative SWOT analysis.

Science, Technology, Engineering, and Mathematics (STEM) degrees represent a future employment scenario with low unemployment rates due to the high demand for qualified personnel. However, the STEM sector also represents an educational field marked by horizontal segregation and the gender gap. Different factors play a role in deciding which higher education studies to pursue. From a theoretical and empirical approach, this study aims to identify which factors are associated with the gender gap in the STEM higher education sector. Furthermore, as a research question, it is proposed: are the factors identified at a theoretical and empirical level associated with the gender gap in the STEM higher education sector the same? The empirically validated questionnaire "Questionnaire with university students on STEM studies in Higher Education" (QSTEMHE) was applied to the student community of public and private universities in Spain in 2021, using simple random probability sampling to answer the research question and objective. A final sample of 2101 participants of different genders belonging to different branches of knowledge was obtained. The data analysis was carried out using qualitative methodology and the phenomenological method, following different stages. Firstly, a theoretical conceptual map of the main factors identified in the literature and their authors was composed. Secondly, an empirical conceptual map has been designed with the factors identified in the narratives of the study participants. Finally, these maps were complemented with a SWOT analysis based on the participants' discourses. As a result, it has been observed that there are extrinsic and intrinsic factors and that social constructs and gender stereotypes strongly influence the perception of men, women, and professions and the masculinisation and feminisation of these. Outreach interventions should be proposed from the institutional educational spheres to alleviate existing biases about studies and professions.

Short- and long-term prognosis of patients with community-acquired Legionella or pneumococcal pneumonia diagnosed by urinary antigen testing.

OBJECTIVES: To analyze the differences in short- and long-term prognosis and the predictors of survival between patients with community-acquired Legionella and Streptococcus pneumoniae pneumonia, diagnosed early by urinary antigen testing (UAT). METHODS: Prospective multicenter study conducted in immunocompetent patients hospitalized with community-acquired Legionella or pneumococcal pneumonia (L-CAP or P-CAP) between 2002-2020. All cases were diagnosed based on positive UAT. RESULTS: We included 1452 patients, 260 with community-acquired Legionella pneumonia (L-CAP) and 1192 with community-acquired pneumococcal pneumonia (P-CAP). The 30-day mortality was higher for L-CAP (6.2%) than for P-CAP (5%). After discharge and during the median follow-up durations of 11.4 and 8.43 years, 32.4% and 47.9% of patients with L-CAP and P-CAP died, and 82.3% and 97.4% died earlier than expected, respectively. The independent risk factors for shorter long-term survival were age >65 years, chronic obstructive pulmonary disease, cardiac arrhythmia, and congestive heart failure in L-CAP and the same first three factors plus nursing home residence, cancer, diabetes mellitus, cerebrovascular disease, altered mental status, blood urea nitrogen ≥30 mg/dl, and congestive heart failure as a cardiac complication during hospitalization in P-CAP. CONCLUSION: In patients diagnosed early by UAT, the long-term survival after L-CAP or P-CAP was shorter (particularly after P-CAP) than expected, and this shorter survival was mainly associated with age and comorbidities.

Proof of concept of the potential of a machine learning algorithm to extract new information from conventional SARS-CoV-2 rRT-PCR results.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been and remains one of the major challenges modern society has faced thus far. Over the past few months, large amounts of information have been collected that are only now beginning to be assimilated. In the present work, the existence of residual information in the massive numbers of rRT-PCRs that tested positive out of the almost half a million tests that were performed during the pandemic is investigated. This residual information is believed to be highly related to a pattern in the number of cycles that are necessary to detect positive samples as such. Thus, a database of more than 20,000 positive samples was collected, and two supervised classification algorithms (a support vector machine and a neural network) were trained to temporally locate each sample based solely and exclusively on the number of cycles determined in the rRT-PCR of each individual. Overall, this study suggests that there is valuable residual information in the rRT-PCR positive samples that can be used to identify patterns in the development of the SARS-CoV-2 pandemic. The successful application of supervised classification algorithms to detect these patterns demonstrates the potential of machine learning techniques to aid in understanding the spread of the virus and its variants.

Enhancing SARS-CoV-2 Surveillance through Regular Genomic Sequencing in Spain: The RELECOV Network.

Millions of SARS-CoV-2 whole genome sequences have been generated to date. However, good quality data and adequate surveillance systems are required to contribute to meaningful surveillance in public health. In this context, the network of Spanish laboratories for coronavirus (RELECOV) was created with the main goal of promoting actions to speed up the detection, analyses, and evaluation of SARS-CoV-2 at a national level, partially structured and financed by an ECDC-HERA-Incubator action (ECDC/GRANT/2021/024). A SARS-CoV-2 sequencing quality control assessment (QCA) was developed to evaluate the network's technical capacity. QCA full panel results showed a lower hit rate for lineage assignment compared to that obtained for variants. Genomic data comprising 48,578 viral genomes were studied and evaluated to monitor SARS-CoV-2. The developed network actions showed a 36% increase in sharing viral sequences. In addition, analysis of lineage/sublineage-defining mutations to track the virus showed characteristic mutation profiles for the Delta and Omicron variants. Further, phylogenetic analyses strongly correlated with different variant clusters, obtaining a robust reference tree. The RELECOV network has made it possible to improve and enhance the genomic surveillance of SARS-CoV-2 in Spain. It has provided and evaluated genomic tools for viral genome monitoring and characterization that make it possible to increase knowledge efficiently and quickly, promoting the genomic surveillance of SARS-CoV-2 in Spain.

Impact of severe lymphopenia on the early prediction of clinical outcome in hospitalized patients with pneumococcal community-acquired pneumonia.

PURPOSE: To evaluate the impact of an optimal and reproducible cutoff value set according to a predefined lymphopenia scale as an early predictor of in-hospital mortality and other outcomes in patients hospitalized with pneumococcal pneumonia and positive urinary antigen at admission to the emergency department. METHODS: An observational cohort study was conducted based on analysis of a prospective registry of consecutive immunocompetent adults hospitalized for pneumococcal pneumonia in two tertiary hospitals. Generalized additive models were constructed to assess the smooth relationship between in-hospital mortality and lymphopenia. RESULTS: We included 1173 patients. Lymphopenia on admission was documented in 686 (58.4%). No significant differences were observed between groups regarding the presence of comorbidities. Overall, 299 (25.5%) patients were admitted to intensive care and 90 (7.6%) required invasive mechanical ventilation. Fifty-nine (5%) patients died, among them 23 (38.9%) in the first 72 h after admission. A lymphocyte count < 500/µL, documented in 282 (24%) patients, was the predefined cutoff point that best predicted in-hospital mortality. After adjustment, these patients had higher rates of intensive care admission (OR 2.9; 95% CI 1.9-4.3), invasive mechanical ventilation (OR 2.2; 95% CI 1.2-3.9), septic shock (OR 1.8; 95% CI 1.1-2.9), treatment failure (OR 2.1; 95% CI 1.2-3.5), and in-hospital mortality (OR 2.2; 95% 1.1-4.9). Severe lymphopenia outperformed PSI score in predicting early and 30-day mortality in patients classified in the higher-risk classes. CONCLUSION: Lymphocyte count < 500/µL could be used as a reproducible predictor of complicated clinical course in patients with an early diagnosis of pneumococcal pneumonia.

Nosocomial COVID-19: A Nationwide Spanish Study.

INTRODUCTION: SARS-CoV-2 is a highly contagious virus, and despite professionals' best efforts, nosocomial COVID-19 (NC) infections have been reported. This work aimed to describe differences in symptoms and outcomes between patients with NC and community-acquired COVID-19 (CAC) and to identify risk factors for severe outcomes among NC patients. METHODS: This is a nationwide, retrospective, multicenter, observational study that analyzed patients hospitalized with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from March 1, 2020, to April 30, 2021. NC was defined as patients admitted for non-COVID-19 diseases with a positive SARS-CoV-2 test on the fifth day of hospitalization or later. The primary outcome was 30-day in-hospital mortality (IHM). The secondary outcome was other COVID-19-related complications. A multivariable logistic regression analysis was performed. RESULTS: Of the 23,219 patients hospitalized with COVID-19, 1,104 (4.8%) were NC. Compared to CAC patients, NC patients were older (median 76 vs. 69 years; p < 0.001), had more comorbidities (median Charlson Comorbidity Index 5 vs. 3; p < 0.001), were less symptomatic (p < 0.001), and had normal chest X-rays more frequently (30.8% vs. 12.5%, p < 0.001). After adjusting for sex, age, dependence, COVID-19 wave, and comorbidities, NC was associated with lower risk of moderate/severe acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR]: 0.72; 95% confidence interval [CI]: 0.59-0.87; p < 0.001) and higher risk of acute heart failure (aOR: 1.40; 1.12-1.72; p = 0.003), sepsis (aOR: 1.73; 1.33-2.54; p < 0.001), and readmission (aOR: 1.35; 1.03-1.83; p = 0.028). NC was associated with a higher case fatality rate (39.1% vs. 19.2%) in all age groups. IHM was significantly higher among NC patients (aOR: 2.07; 1.81-2.68; p < 0.001). Risk factors for increased IHM in NC patients were age, moderate/severe dependence, malignancy, dyspnea, moderate/severe ARDS, multiple organ dysfunction syndrome, and shock; odynophagia was associated with lower IHM. CONCLUSIONS: NC is associated with greater mortality and complications compared to CAC. Hospital strategies to prevent NC must be strengthened.

Coste efectividad de la estrategia de cribado de citomegalovirus en recién nacidos mayores de 34 semanas de bajo peso para la edad gestacional / Cost-effectiveness of a cytomegalovirus screening strategy in neonates born after 34 weeks small for gestational age

Introducción: El citomegalovirus (CMV) es una de las infecciones congénitas más frecuentes, con una prevalencia del 0,3-2,4%. En España, al no formar parte del cribado gestacional, se realiza screening de los recién nacidos con factores de riesgo y, en muchos centros, de los que presentan bajo peso para la edad gestacional (BPEG). Para ello se realiza, generalmente, determinación de Polymerase Chain Reaction (PCR) del virus en orina y/o ecografía transfontanelar en busca de imágenes compatibles. El objetivo del estudio es evaluar el rendimiento de la PCR de CMV en orina y ecografía transfontanelar, en recién nacidos >34 semanas asintomáticos, sin factores de riesgo, con BPEG. El objetivo secundario es evaluar el coste-efectividad. Material y métodos: Estudio observacional, descriptivo y retrospectivo, entre enero y diciembre de 2019, en un hospital de tercer nivel (IIIC). Incluye recién nacidos >34 semanas, sin factores de riesgo con BPEG, con PCR de CMV en orina y/o ecografía transfontanelar realizada. (AU)

Introduction: Infection by cytomegalovirus (CMV) is one of the most common congenital infections, with a global prevalence of 0.3%-2.4%. In Spain, CMV screening is not performed during pregnancy, but rather in neonates with risk factors, and, in many hospitals, in those born small for gestational age (SGA). Screening is usually performed by measurement of the viral load in urine by polymerase chain reaction (PCR) and/or head ultrasound in search of compatible features. The aim of the study was to assess the yield of the CMV PCR test in urine and head ultrasound examination in asymptomatic neonates born SGA after 34 weeks’ gestation. The secondary objective was to assess the cost-effectiveness of this strategy. Design and methods: We conducted an observational and retrospective study between January and December 2019 in a tertiary care hospital. It included neonates delivered after 34 weeks, SGA and without additional risk factors assessed with a CMV PCR test in urine and/or head ultrasound. (AU)

Relación entre la estación del año y la gravedad de los síntomas en pacientes con fibromialgia / Relationship between season of the year and severity of symptoms in patients with fibromyalgia

Antecedentes y objetivo: Es frecuente que los pacientes con fibromialgia refieran que ciertas estaciones del año agravan sus síntomas. Como objetivo primario se determinó la asociación entre síntomas claves de la fibromialgia y estación del año. Como objetivo secundario se determinó la existencia de diferencias en función de los niveles de ansiedad o depresión.Material y métodoMuestra de conveniencia formada por 471 participantes con fibromialgia evaluados antes de iniciar un tratamiento multidisciplinar. Se recogieron datos demográficos y meteorológicos y se evaluaron, mediante instrumentos estandarizados, la intensidad del dolor, la funcionalidad, la fatiga, la rigidez, la calidad del sueño, así como la ansiedad y la depresión.ResultadosLos diferentes grupos estacionales fueron homogéneos en edad, género, nivel educativo, estado marital y situación laboral. No se encontraron diferencias significativas en intensidad del dolor (F=1,334; p=0,265), funcionalidad (F=0,402; p=0,669), fatiga (F=0,714; p=0,490), rigidez (F=0,299; p=0,741), ansiedad (F=0,376; p=0,687), depresión (F=0,608; p=0,545), distrés psicológico (F=0,261; p=0,770), duración del sueño (F=1,507; p=0,223) o el índice de problemas de sueño (F=0,343; p=0,710).ConclusionesNo se han encontrado diferencias en la intensidad de los síntomas de la fibromialgia ni en los porcentajes de gravedad entre las distintas estaciones del año. La ansiedad ha sido más prevalente que la depresión, posiblemente debido a las propias características de la muestra, con mayoría de pacientes con perfil disfuncional. (AU)

Background and objective: Fibromyalgia patients often report that certain seasons aggravate their symptoms. The main objective was to determinate the association between key symptoms of fibromyalgia and the season of the year. A secondary objective was to determinate the existence of differences based on levels of anxiety or depression.Material and methodConvenience sample made up of 471 participants with fibromyalgia evaluated before starting multidisciplinary treatment. Demographic and meteorological data were collected. Clinical data were assessed with standardized instruments of pain intensity, functionality, fatigue, stiffness, sleep quality, anxiety and depression.ResultsThe different groups of participants were homogeneous for age, gender, educational level, marital status and employment situation. No significant differences were found in pain intensity (F=1.334; P=.265), functionality (F=.402; P=.669), fatigue (F=.714; P=.490), stiffness (F=.299; P=.741), anxiety (F=.376; P=.687), depression (F=.608; P=.545), psychological distress (F=.261; P=.770), sleep quantity (F=1.507; P=.223) or sleep disturbances (F=.343; P=.710).ConclusionsNo differences were found in the intensity of fibromyalgia symptoms, nor in the percentages of severity among the different seasons of the year. Anxiety was more prevalent than depression, possibly due to the characteristics of the sample itself, with the majority of patients with a dysfunctional profile. (AU)

[Relationship between season of the year and severity of symptoms in patients with fibromyalgia]. / Relación entre la estación del año y la gravedad de los síntomas en pacientes con fibromialgia.

BACKGROUND AND OBJECTIVE: Fibromyalgia patients often report that certain seasons aggravate their symptoms. The main objective was to determinate the association between key symptoms of fibromyalgia and the season of the year. A secondary objective was to determinate the existence of differences based on levels of anxiety or depression. MATERIAL AND METHOD: Convenience sample made up of 471 participants with fibromyalgia evaluated before starting multidisciplinary treatment. Demographic and meteorological data were collected. Clinical data were assessed with standardized instruments of pain intensity, functionality, fatigue, stiffness, sleep quality, anxiety and depression. RESULTS: The different groups of participants were homogeneous for age, gender, educational level, marital status and employment situation. No significant differences were found in pain intensity (F=1.334; P=.265), functionality (F=.402; P=.669), fatigue (F=.714; P=.490), stiffness (F=.299; P=.741), anxiety (F=.376; P=.687), depression (F=.608; P=.545), psychological distress (F=.261; P=.770), sleep quantity (F=1.507; P=.223) or sleep disturbances (F=.343; P=.710). CONCLUSIONS: No differences were found in the intensity of fibromyalgia symptoms, nor in the percentages of severity among the different seasons of the year. Anxiety was more prevalent than depression, possibly due to the characteristics of the sample itself, with the majority of patients with a dysfunctional profile.

Cost-effectiveness of a cytomegalovirus screening strategy in neonates born after 34 weeks small for gestational age.

INTRODUCTION: Infection by cytomegalovirus (CMV) is one of the most common congenital infections, with a global prevalence of 0.3%-2.4%. In Spain, CMV screening is not performed during pregnancy, but rather in neonates with risk factors, and, in many hospitals, in those born small for gestational age (SGA). Screening is usually performed by measurement of the viral load in urine by polymerase chain reaction (PCR) and/or head ultrasound in search of compatible features. The aim of the study was to assess the yield of the CMV PCR test in urine and head ultrasound examination in asymptomatic neonates born SGA after 34 weeks' gestation. The secondary objective was to assess the cost-effectiveness of this strategy. DESIGN AND METHODS: We conducted an observational and retrospective study between January and December 2019 in a tertiary care hospital. It included neonates delivered after 34 weeks, SGA and without additional risk factors assessed with a CMV PCR test in urine and/or head ultrasound. RESULTS: The sample included 259 patients. It was divided in 2 groups: group 1, patients with a head circumference, weight and length below the 10th percentile (53 patients; 20.5%), and group 2, patients in whom only the weight was below the 10th percentile (206 patients; 79.5%). The incidence of late preterm birth, twin pregnancy, neonatal admission and exposure to illicit drugs during gestation was higher in group 1. A total of 186 urine PCR tests and 223 head ultrasounds were performed overall, and both tests were performed more frequently in group 1 (P=.002). There was only 1 positive CMV PCR test result in the sample (0.54%), corresponding to a patient in group 2 with no abnormal sonographic findings who remained asymptomatic throughout the follow-up. Two head ultrasound examinations yielded abnormal findings, in both cases unrelated to congenital CMV infection. We performed a cost-effectiveness analysis and determined that the cumulative cost of head ultrasound examinations and urine CMV PCR tests in our sample amounted to Є17 000 for the detection of a single asymptomatic positive case. CONCLUSION: In our population, screening for congenital CMV infection in asymptomatic late preterm and term newborns whose only risk factor is SGA does not seem to be cost effective. It would be necessary to expand the sample to other populations.

Influence of perinatal and childhood exposure to tobacco and mercury in children's gut microbiota.

Background: Early life determinants of the development of gut microbiome composition in infants have been widely investigated; however, if early life pollutant exposures, such as tobacco or mercury, have a persistent influence on the gut microbial community, its stabilization at later childhood remains largely unknown. Objective: In this exposome-wide study, we aimed at identifying the contribution of exposure to tobacco and mercury from the prenatal period to childhood, to individual differences in the fecal microbiome composition of 7-year-old children, considering co-exposure to a width of established lifestyle and clinical determinants. Methods: Gut microbiome was studied by 16S rRNA amplicon sequencing in 151 children at the genus level. Exposure to tobacco was quantified during pregnancy through questionnaire (active tobacco consumption, second-hand smoking -SHS) and biomonitoring (urinary cotinine) at 4 years (urinary cotinine, SHS) and 7 years (SHS). Exposure to mercury was quantified during pregnancy (cord blood) and at 4 years (hair). Forty nine other potential environmental determinants (12 at pregnancy/birth/infancy, 15 at 4 years and 22 at 7 years, such as diet, demographics, quality of living/social environment, and clinical records) were registered. We used multiple models to determine microbiome associations with pollutants including multi-determinant multivariate analysis of variance and linear correlations (wUnifrac, Bray-Curtis and Aitchison ß-diversity distances), single-pollutant permutational multivariate analysis of variance adjusting for co-variates (Aitchison), and multivariable association model with single taxa (MaAsLin2; genus). Sensitivity analysis was performed including genetic data in a subset of 107 children. Results: Active smoking in pregnancy was systematically associated with microbiome composition and ß-diversity (R2 2-4%, p < 0.05, Aitchison), independently of other co-determinants. However, in the adjusted single pollutant models (PERMANOVA), we did not find any significant association. An increased relative abundance of Dorea and decreased relative abundance of Akkermansia were associated with smoking during pregnancy (q < 0.05). Discussion: Our findings suggest a long-term sustainable effect of prenatal tobacco exposure on the children's gut microbiota. This effect was not found for mercury exposure or tobacco exposure during childhood. Assessing the role of these exposures on the children's microbiota, considering multiple environmental factors, should be further investigated.

Identification of 1,2,3-triazolium salt-based inhibitors of Leishmania infantum trypanothione disulfide reductase with enhanced antileishmanial potency in cellulo and increased selectivity.

N-methylation of the triazole moiety present in our recently described triazole-phenyl-thiazole dimerization disruptors of Leishmania infantum trypanothione disulfide reductase (LiTryR) led to a new class of potent inhibitors that target different binding sites on this enzyme. Subtle structural changes among representative library members modified their mechanism of action, switching from models of classical competitive inhibition to time-dependent mixed noncompetitive inhibition. X-ray crystallography and molecular modeling results provided a rationale for this distinct behavior. The remarkable potency and selectivity improvements, particularly against intracellular amastigotes, of the LiTryR dimerization disruptors 4c and 4d reveal that they could be exploited as leishmanicidal agents. Of note, L. infantum promastigotes treated with 4c significantly reduced their low-molecular-weight thiol content, thus providing additional evidence that LiTryR is the main target of this novel compound.