PELFI Project: Recruitment and Sociodemographic Characteristics of Immigrant and Autochthonous Families from Alicante and Barcelona City Subcohorts

Este artículo corresponde al “Proyecto de Estudios Longitudinales de Familias Inmigradas (PELFI)” del Subprograma de Inmigración y Salud del CIBERESP y describe el trabajo de campo basal y principales características socio-demográficas de dos sub-cohortes de familias inmigrantes y autóctonas. El diseño es observacional prospectivo. La población de estudio se definió como una muestra no probabilística de 180 familias de origen colombiano, ecuatoriano y marroquí y 50 españolas. Se entrevistó a 473 personas adultas entre 18 y 65 años (59,8% mujeres, 68,5% ocupados/as) y a 304 adolescentes entre 12 y17 años (53,9% mujeres, 27,1% nacidos en España pero de padres inmigrados) de cada familia, mediante dos cuestionarios diseñados ad hoc. La tasa de cooperación fue del 82,0% con una velocidad media de reclutamiento de 1,3 familias diarias. En total, se reclutó a 250 familias, 82 procedentes de Ecuador, 82 de Colombia, 29 de Marruecos y 57 españolas. Los adultos inmigrados llevaban una media de 13 años en España. La combinación de técnicas no probabilísticas permitió el acceso y velocidad de reclutamiento. Este estudio aporta información clave para el diseño y mejora de este tipo de cohortes en familias inmigradas.This study is a part of the multi-centre project “Platform of Longitudinal Studies of Immigrant Families (PELFI)” of the Immigration and Health Subprogram of the CIBER-ESP. It describes the field work and data collection of two sub-cohorts of immigrant and native families, and their main socio-demographic characteristics. Prospective observational cohort study in carried out in Barcelona and Alicante, Spain. The study population is a non-probabilistic sample of 180 families of Colombian, Ecuadorian and Moroccan origin and 50 families of Spanish origin. We interviewed adults aged 18-65 years and adolescents aged 12-17 years in each family, through two questionnaires (adolescent/adult). The cooperation rate was 82.0% with an average recruitment rate of 1.3 families per day. In total, 250 families have been recruited, 82 from Ecuador, 82 from Colombia, 29 from Morocco and 57 from Spain. A total of 473 adults (59.8% women and 68.5% employed) were surveyed. Immigrant adults have an average of 13 years living in Spain. A total of 304 adolescents (53.9% female, 27.1% born in Spain but with immigrant parents) were surveyed. The combination of non-probabilistic techniques promoted access and improved recruitment speed. This study provides key information for the design and improvement of cohort studies with immigrant families.Proyectos Fondo Investigación Sanitaria números PI14/01146 y PI14/02005 e Instituto de Salud Carlos III-FEDER

Phage inducible islands in the gram-positive cocci

The SaPIs are a cohesive subfamily of extremely common phage-inducible chromosomal islands (PICIs) that reside quiescently at specific att sites in the staphylococcal chromosome and are induced by helper phages to excise and replicate. They are usually packaged in small capsids composed of phage virion proteins, giving rise to very high transfer frequencies, which they enhance by interfering with helper phage reproduction. As the SaPIs represent a highly successful biological strategy, with many natural Staphylococcus aureus strains containing two or more, we assumed that similar elements would be widespread in the Gram-positive cocci. On the basis of resemblance to the paradigmatic SaPI genome, we have readily identified large cohesive families of similar elements in the lactococci and pneumococci/streptococci plus a few such elements in Enterococcus faecalis. Based on extensive ortholog analyses, we found that the PICI elements in the four different genera all represent distinct but parallel lineages, suggesting that they represent convergent evolution towards a highly successful lifestyle. We have characterized in depth the enterococcal element, EfCIV583, and have shown that it very closely resembles the SaPIs in functionality as well as in genome organization, setting the stage for expansion of the study of elements of this type. In summary, our findings greatly broaden the PICI family to include elements from at least three genera of cocci

Steroid hormone-related polymorphisms associate with the development of bone erosions in rheumatoid arthritis and help to predict disease progression: Results from the REPAIR consortium

Here, we assessed whether 41 SNPs within steroid hormone genes associated with erosive disease. The most relevant finding was the rheumatoid factor (RF)-specific effect of the CYP1B1, CYP2C9, ESR2, FcγR3A, and SHBG SNPs to modulate the risk of bone erosions (P = 0.004, 0.0007, 0.0002, 0.013 and 0.015) that was confirmed through meta-analysis of our data with those from the DREAM registry (P = 0.000081, 0.0022, 0.00074, 0.0067 and 0.0087, respectively). Mechanistically, we also found a gender-specific correlation of the CYP2C9rs1799853T/T genotype with serum vitamin D3 levels (P = 0.00085) and a modest effect on IL1β levels after stimulation of PBMCs or blood with LPS and PHA (P = 0.0057 and P = 0.0058). An overall haplotype analysis also showed an association of 3 ESR1 haplotypes with a reduced risk of erosive arthritis (P = 0.009, P = 0.002, and P = 0.002). Furthermore, we observed that the ESR2, ESR1 and FcγR3A SNPs influenced the immune response after stimulation of PBMCs or macrophages with LPS or Pam3Cys (P = 0.002, 0.0008, 0.0011 and 1.97•10−7). Finally, we found that a model built with steroid hormone-related SNPs significantly improved the prediction of erosive disease in seropositive patients (PRF+ = 2.46•10−8) whereas no prediction was detected in seronegative patients (PRF− = 0.36). Although the predictive ability of the model was substantially lower in the replication population (PRF+ = 0.014), we could confirm that CYP1B1 and CYP2C9 SNPs help to predict erosive disease in seropositive patients. These results are the first to suggest a RF-specific association of steroid hormone-related polymorphisms with erosive disease

Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation

BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.Tis project was funded in part by CRIS CANCER FOUNDATION

Latent tuberculosis infection, tuberculin skin test and vitamin D status in contacts of tuberculosis patients: a cross-sectional and case-control study

<p>Abstract</p> <p>Background</p> <p>Deficient serum vitamin D levels have been associated with incidence of tuberculosis (TB), and latent tuberculosis infection (LTBI). However, to our knowledge, no studies on vitamin D status and tuberculin skin test (TST) conversion have been published to date. The aim of this study was to estimate the associations of serum 25-hydroxyvitamin D₃(25[OH]D) status with LTBI prevalence and TST conversion in contacts of active TB in Castellon (Spain).</p> <p>Methods</p> <p>The study was designed in two phases: cross-sectional and case-control. From November 2009 to October 2010, contacts of 42 TB patients (36 pulmonary, and 6 extra-pulmonary) were studied in order to screen for TB. LTBI and TST conversion cases were defined following TST, clinical, analytic and radiographic examinations. Serum 25(OH)D levels were measured by electrochemiluminescence immunoassay (ECLIA) on a COBAS^®410 ROCHE^®analyzer. Logistic regression models were used in the statistical analysis.</p> <p>Results</p> <p>The study comprised 202 people with a participation rate of 60.1%. Only 20.3% of the participants had a sufficient serum 25(OH)D (≥ 30 ng/ml) level. In the cross-sectional phase, 50 participants had LTBI and no association between LTBI status and serum 25(OH)D was found. After 2 months, 11 out of 93 negative LTBI participants, without primary prophylaxis, presented TST conversion with initial serum 25(OH)D levels: a:19.4% (7/36): < 20 ng/ml, b:12.5% (4/32):20-29 ng/ml, and c:0%(0/25) ≥ 30 ng/ml. A sufficient serum 25(OH)D level was a protector against TST conversion a: Odds Ratio (OR) = 1.00; b: OR = 0.49 (95% confidence interval (CI) 0.07-2.66); and c: OR = 0.10 (95% CI 0.00-0.76), trends p = 0.019, adjusted for high exposure and sputum acid-fast bacilli positive index cases. The mean of serum level 25(OH)D in TST conversion cases was lower than controls,17.5 ± 5.6 ng/ml versus 25.9 ± 13.7 ng/ml (p = 0.041).</p> <p>Conclusions</p> <p>The results suggest that sufficient serum 25(OH)D levels protect against TST conversion.</p

The RD-Connect Genome-Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases.

Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Delta variant break-through infections in nursing home residents following vaccination with Comirnaty®COVID‐19 vaccine were characterized. In total, 201 participants (median age, 87 years;range, 64–100; 133 female) from two nursing homes in the Valencian community (Spain)were included. SARS‐CoV‐2‐Spike (S) antibody responses were determined by a lateralflow immunocromatography (LFIC) assay and by quantitative electrochemiluminescentassay in LFIC‐negative participants. SARS‐CoV‐2‐S‐IFNγT cells were enumerated by flowcytometry in 10 participants. Nasopharyngeal SARS‐CoV‐2 RNA loads were quantified byreal‐time polymerase chain reaction assays. Vaccine breakthrough COVID‐19 due to theDelta variant occurred in 39 residents (median age, 87 years; range, 69–96; 31 female) ata median of 6.5 months after vaccination (nine requiring hospitalization). Breakthroughinfections occurred at a higher rate(p< 0.0001) in residents who had not been previouslyinfected with SARS‐CoV‐2 (naïve) (33/108; 18%) than in those with prior diagnosis ofSARS‐CoV‐2 infection (experienced) (6/93; 6.4%), and were more likely (p< 0.0001) todevelop in residents who tested negative by LFIC (20/49) at 3 months after vaccinationas compared to their LFIC‐positive counterparts (19/142). Among LFIC‐negativeresidents, a trend towards lower plasma anti‐RBD antibody levels was noticed in thosedeveloping breakthrough infection (p=0.16).SARS‐CoV‐2 RNA loads in nasopharyngealspecimens were lower in SARS‐CoV‐2‐experienced residents (p< 0.001) and in thosetesting positive by LFIC (p=0.13). The frequency of SARS‐CoV‐2‐S‐reactive T cells at3monthswassimilarinLFIC‐negative residents with (n=7) or without (n=3)breakthrough infection. Prior history of SARS‐CoV‐2 infection and detection ofS‐reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta‐variant breakthrough infection in nursing home residents at midterm after Comirnaty®COVID‐19 vaccination.We are grateful to the Vice‐presidency and Ministry of Equality andInclusive Policies of the Valencia Community, the Corporate Associationof Residences and Services for People with Dependency of the ValencianCommunity (AERTE), the Valencia Health System nursing homedepartmental committees, and the staff and residents of the participantnursing homes for their collaboration in developing the ProVaVacprogram. We would also like to thank Ana Berenguer, General Directorof Analysis and Public Policies of the Presidency of the Generalitat.Ignacio Torres (Río Hortega Contract; CM20/00090) and Eliseo Albert(Juan Rodés Contract; JR20/00011) hold contracts funded by the HealthInstitute Carlos III (co‐financed by the European Regional DevelopmentFund, ERDF/FEDER). This study received no public or private funds.Peer reviewe

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S