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Background: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV)., Objectives: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia., Methods: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi 2 , ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI)., Results: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population., Conclusions: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded., (Copyright © 2023 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: To assess the potential of next-generation sequencing (NGS) technologies to characterize cases diagnosed with autosomal recessive (ar) or sporadic (s) macular dystrophies (ar/sMD) and describe their mutational spectrum., Methods: A cohort of 1036 families was classified according to their suspected clinical diagnosis-Stargardt disease (STGD), cone and cone-rod dystrophy (CCRD) or other maculopathies (otherMD). Molecular studies included genotyping microarrays, Sanger sequencing, NGS, and sequencing of intronic regions of the ABCA4 gene. Clinical reclassification was done after the genetic study., Results: At the end of the study, 677 patients (65%) had a confirmed genetic diagnosis, representing 78%, 63%, and 38% of STGD, CCRD, and otherMD groups of patients, respectively. ABCA4 is the most mutated gene in all groups, and a second pathogenic variant was found in 76% of STGD patients with one previously identified mutated ABCA4 allele. Autosomal dominant or X-linked mutations were found in 5% of cases together with not-MD genes (CHM, EYS, RHO, RPGR, RLBP1, OPA1, and USH2A among others) leading to their reclassification. Novel variants in the very rare genes PLA2G5 and TTLL5 revealed additional phenotypic associations., Conclusions: This study provides for the first time a genetic landscape of 1036 ar/sMD families according to their suspected diagnosis. The analysis of >200 genes associated with retinal dystrophies and the entire locus of ABCA4 increase the rate of characterization, even regardless of available clinical and familiar data. The use of the suspected a priori diagnosis referred by the clinicians, especially in the past, could lead to clinical reclassifications to other inherited retinal dystrophies.

Primary Care (PC) and community are the priority health sites for the detection and management of frailty. There are good guidelines (Strategy and consensus of the National Health Service, ADVANTAGE European Joint Action, recommendations of the Program of Prevention and Health Promotion Activities of the Spanish Society of Family and Community Medicine PAPPS-semFYC, Fisterra guideline); however, its implementation is not taking place with the expected magnitude or speed, also considering the influence of the COVID-19 pandemic. The detection and management of frailty requires multidisciplinary work by professionals who usually carry out their activity at the first level of care (physicians, nurses, social workers), with others whose integration is advisable (nutritionists, physiotherapists, etc.); and counting on others of reference (geriatricians). On the other hand, it is necessary to work with comprehensive approaches based on good coordination between PC and the Community, with various experiences in this regard. The support by the Information and Communication Technologies (ICT) can be very interesting, with tools for both users and careers (e.g., VIVIFRAIL), as well as for social and health professionals (e.g., VALINTAN or WHO ICOPE-Handbook App). Strategies to intervene in fragility in a more effective and systematic way must be consolidated: with an adequate professional training, establishment of campaigns and dissemination ways for visualizing its relevance and extend their intervention, prioritization of the most effective programmed assistance activities (highlighting fragility), multidisciplinary work with coordination and participation of the different healthcare and community levels and of the patients themselves, and providing the PC with adequate resources.

Objectives: This study aimed to ascertain if there is a defined pattern of injury related to the percentage of attained adult height and classify injuries according to maturity status bands., Design: Prospective cohort study., Methods: From 1998-2019, 63 elite male soccer players of at least the U12 category from a Spanish LaLiga club's academy were followed until reaching their final height. Medical staff recorded injuries following the FIFA consensus and measured height 2-3 times per season. The percentage of adult height at which each injury occurred was calculated using the player's closest height to the injury and his final adult height. Injuries were classified in maturity bands, pre-peak-height-velocity (PHV) <88%, circa-PHV 88%-96%, and post-PHV >96%., Results: There were 509 injuries among the 63 players. Growth-related injuries occurred at a median (IQR) of 91.2% (86.7%-95.2%) of adult height, predominating in pre-PHV and PHV bands. Muscle injuries predominantly occurred at post-PHV, with 77.78% of those conditions occurring within that time frame and at 98.7% (96%-99.5%) of adult height. Likewise, knee and ankle joint/ligament injuries predominated at post-PHV (87% and 65% of total cases, respectively) occurring at 99.0% (97.9%-99.9%) and 98.4% (89.2%-99.4%) of adult height, respectively., Conclusions: Injuries follow a specific pattern according to the percentage of adult height., (Copyright © 2020 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.

Purpose: To define genotype-phenotype correlations in the largest cohort study worldwide of patients with biallelic ABCA4 variants, including 434 patients with Stargardt disease (STGD1) and 72 with cone-rod dystrophy (CRD)., Design: Cohort study., Methods: We characterized 506 patients with ABCA4 variants using conventional genetic tools and next-generation sequencing technologies. Medical history and ophthalmologic data were obtained from 372 patients. Genotype-phenotype correlation studies were carried out for the following variables: variant type, age at symptom onset (AO), and clinical phenotype., Results: A total of 228 different pathogenic variants were identified in 506 ABCA4 patients, 50 of which were novel. Genotype-phenotype correlations showed that most of the patients with biallelic truncating variants presented with CRD and that these cases had a significantly earlier AO than patients with STGD1. Three missense variants are associated with CRD for the first time (c.1804C>T; p.[Arg602Trp], c.3056C>T; p.[Thr1019Met], and c.6320G>C; p.[Arg2107Pro]). Analysis of the most prevalent ABCA4 variant in Spain, c.3386G>T; p.(Arg1129Leu), revealed that is correlated to STGD1, later AO, and foveal sparing., Conclusions: Our study, conducted in the largest ABCA4-associated disease cohort reported to date, updates the genotype-phenotype model established for ABCA4 variants and broadens the mutational spectrum of the gene. According to our observations, patients with ABCA4 presenting with 2 truncating variants may first present features of STGD1 but eventually develop rod dysfunction, and specific missense variants may be associated with a different phenotype, underscoring the importance of an accurate genetic diagnosis. Also, it is a prerequisite for enrollment in clinical trials, and to date, no other treatment has been approved for STGD1., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Antibiotic combinations that include macrolides have shown lower mortality rates than β-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a β-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a β-lactam (FQ ± BL)., Methods: We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause., Results: Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies., Conclusions: The combination of a β-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Vincristine (VCR), an important component of childhood acute lymphoblastic leukemia (ALL) therapy, can cause sensory and motor neurotoxicity. This neurotoxicity could lead to dose reduction or treatment discontinuation, which could in turn reduce survival. In this line, several studies associated peripheral neurotoxicity and polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR. Nowadays, it is well known that these genes are regulated by microRNAs (miRNAs) and SNPs in miRNAs could modify their levels or function. Therefore, the aim of this study was to determine whether SNPs in miRNAs could be associated with VCR-induced neurotoxicity. To achieve this aim, we analyzed all the SNPs in miRNAs (minor allele frequency (MAF) ≥ 0.01) which could regulate VCR-related genes in a large cohort of Spanish children with B-cell precursor ALL (B-ALL) homogeneously treated with LAL/SHOP protocols. We identified the A allele of rs12402181 in the seed region of miR-3117-3p, that could affect the binding with ABCC1 and RALBP1 gene, and C allele of rs7896283 in pre-mature sequence of miR-4481, which could be involved in peripheral nerve regeneration, significantly associated with VCR-induced neurotoxicity. These findings point out the possible involvement of two SNPs in miRNA associated with VCR-related neurotoxicity.

Purpose: Ventilator-associated tracheobronchitis (VAT) has been suggested as an intermediate process between tracheobronchial colonization and ventilator-associated pneumonia (VAP) in patients receiving mechanical ventilation. The aim of this study was to evaluate the ability of C-reactive protein (CRP) and procalcitonin (PCT) to differentiate between VAT and VAP., Methods: Pre-planned analysis of the prospective multinational TAVeM database, performed on 2960 patients receiving mechanical ventilation for >48 h, including 689 patients with VA-LRTI. Patients with the diagnosis of VAT or VAP microbiologically documented and with one measurement of CRP and/or PCT on the day of diagnosis were included., Results: Four hundred and four patients (mean age 63 years, 298 men, ICU mortality 40%) were studied, 207 with VAT and 197 with VAP. On the day of infection diagnosis, the median CRP was elevated in both groups but significantly higher in VAP (18 mg/dL vs. 14 mg/dL, p = .001). Median PCT was also significantly higher in VAP (2.1 ng/dL vs. 0.64 ng/d L, p < .001). Both biomarkers could not help distinguish between VAT and VAP., Conclusion: Although PCT and CRP presented lower values in VAT as compared to VAP, there was a marked overlap of both biomarkers values in both VA-LRTI not allowing adequate discrimination., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the impact of the recommendations of the SEMICYUC (2012) on severe influenza A., Design: A prospective multicenter observational study was carried out., Setting: ICU., Patients: Patients infected with severe influenza A (H1N1) from the GETGAG/SEMICYUC registry., Interventions: Analysis of 2 groups according to the epidemic period of the diagnosis (2009-2011; 2013-2015)., Variables: Demographic, temporal, comorbidities, severity, treatments, mortality, late diagnosis and place of acquisition., Results: A total of 2,205 patients were included, 1,337 (60.6%) in the first period and 868 (39.4%) in the second one. Age and severity on admission were significantly greater in the second period, as well as co-infection. With regard to the impact of the recommendations, in the second period the diagnosis was established earlier (70.8 vs. 61.1%, P<.001), without changes in the start of treatment. Patients received less corticosteroid treatment (39.7 vs. 44.9%, P<.05), more NIMV was used (47.4 vs. 33.2%, P<.001) and more vaccination was made (11.1 vs. 1.7%, P<.001), without changes in mortality (24.2 vs. 20.7%). A decrease in nosocomial infection was also noted (9.8 vs. 16%, P<.001). Patients needed less MV with more days of ventilation, more vasopressor drug use and more ventral decubitus., Conclusions: The management of patients with severe influenza A (H1N1) has changed over the years, though without changes in mortality. The recommendations of the SEMICYUC (2012) have allowed earlier diagnosis and improved corticosteroid use. Pending challenges are the delay in treatment, the vaccination rate and the use of NIMV., (Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)

Association studies in osteosarcoma risk found significant results in intergenic regions, suggesting that regions which do not codify for proteins could play an important role. The deregulation of microRNAs (miRNAs) has been already associated with osteosarcoma. Consequently, genetic variants affecting miRNA function could be associated with risk. This study aimed to evaluate the involvement of all genetic variants in pre-miRNAs described so far in relationship to the risk of osteosarcoma. We analyzed a total of 213 genetic variants in 206 pre-miRNAs in two cohorts of osteosarcoma patients (n = 100) and their corresponding controls (n = 256) from Spanish and Slovenian populations, using Goldengate Veracode technology (Illumina). Four polymorphisms in pre-miRNAs at 14q32 miRNA cluster were associated with osteosarcoma risk in the Spanish population (rs12894467, rs61992671, rs58834075 and rs12879262). Pathway enrichment analysis including target genes of these miRNAs pointed out the WNT signaling pathways overrepresented. Moreover, different single nucleotide polymorphism (SNP) effects between the two populations included were observed, suggesting the existence of population differences. In conclusion, 14q32 miRNA cluster seems to be a hotspot for osteosarcoma susceptibility in the Spanish population, but not in the Slovenian, which supports the idea of the existence of population differences in developing this disease.

Purpose: To provide a comprehensive overview of the molecular basis of autosomal dominant retinitis pigmentosa (adRP) in Spanish families. Thus, we established the molecular characterization rate, gene prevalence, and mutational spectrum in the largest European cohort reported to date., Methods: A total of 258 unrelated Spanish families with a clinical diagnosis of RP and suspected autosomal dominant inheritance were included. Clinical diagnosis was based on complete ophthalmologic examination and family history. Retrospective and prospective analysis of Spanish adRP families was carried out using a combined strategy consisting of classic genetic techniques and next-generation sequencing (NGS) for single-nucleotide variants and copy number variation (CNV) screening., Results: Overall, 60% of our families were genetically solved. Interestingly, 3.1% of the cohort carried pathogenic CNVs. Disease-causing variants were found in an autosomal dominant gene in 55% of the families; however, X-linked and autosomal recessive forms were also identified in 3% and 2%, respectively. Four genes (RHO, PRPF31, RP1, and PRPH2) explained up to 62% of the solved families. Missense changes were most frequently found in adRP-associated genes; however, CNVs represented a relevant disease cause in PRPF31- and CRX-associated forms., Conclusions: Implementation of NGS technologies in the adRP study clearly increased the diagnostic yield compared with classic approaches. Our study outcome expands the spectrum of disease-causing variants, provides accurate data on mutation gene prevalence, and highlights the implication of CNVs as important contributors to adRP etiology.

The locus CDKN2A/B (9p21.3), which comprises the tumor suppressors genes CDKN2A and CDKN2B and the long noncoding RNA (lncRNA) known as ANRIL (or CDKN2B-AS), was associated with childhood acute lymphoblastic leukemia (ALL) susceptibility in several genome wide association studies (GWAS). However, the variants associated in the diverse studies were different. Recently, new and independent SNPs deregulating the locus function were also identified in association with ALL risk. This diversity in the results may be explained because different variants in each population could alter CDKN2A/B locus function through diverse mechanisms. Therefore, the aim of this study was to determine whether the annotated risk variants in the CDKN2A/B locus affect the susceptibility of B cell precursor ALL (B-ALL) in our Spanish population and explore if other SNPs altering additional regulatory mechanisms could be also involved. We analyzed the four SNPs proposed by GWAs and two additional SNPs in miRNA binding sites in 217 pediatric patients with B-ALL and 330 healthy controls. The SNPs rs2811712, rs3731249, rs3217992 and rs2811709 were associated with B-ALL susceptibility in our Spanish population. ALL subtypes analyses showed that rs2811712 was associated with B-hyperdiploid ALL. These results provide evidence for the influence of genetic variants at CDKN2A/B locus with the risk of developing B-ALL.

Systematic reviews on osteosarcoma have concluded that CTLA4 rs231775 AA genotype influences risk for the disease in the Chinese population. Remarkably, rs231775 shows different frequencies in different human populations. Therefore, it would be interesting to know whether this SNP is related to the risk of osteosarcoma in other populations. The present study aimed to evaluate the association between rs231775 and the susceptibility of osteosarcoma in the Spanish population. We performed an updated meta-analysis including a total of 538 cases and 623 controls. The genotypic association analyses showed that the CTLA4 rs231755 was associated with osteosarcoma susceptibility in the Spanish population. When meta-analysis was performed, the results displayed that CTLA4 rs231775 AA genotype was associated with the risk of developing osteosarcoma in all analyzed populations (OR=2.07; 95% CI: 1.48-2.89).The rs231775 AA genotype could be considered as a susceptibility marker in osteosarcoma Keywords: CTLA4, rs231775, +49A/G and osteogenic sarcoma.

Objectives: Methotrexate (MTX), the key drug in childhood B-cell acute lymphoblastic leukemia (B-ALL) therapy, often causes toxicity. An association between genetic variants in MTX transport genes and toxicity has been found. It is known that these transporters are regulated by microRNAs (miRNAs), and miRNA single nucleotide polymorphisms (SNPs) interfere with miRNA levels or function. With regard to B-cell ALL, we have previously found rs56103835 in miR-323b that targets ABCC4 associated with MTX plasma levels. Despite these evidences and that nowadays a large amount of new miRNAs have been annotated, studies of miRNA polymorphisms and MTX toxicity are almost absent. Therefore, the aim of this study was to determine whether there are other variants in miRNAs associated with MTX levels., Patients and Methods: Blood samples of 167 Spanish patients with pediatric B-cell ALL treated with the LAL-SHOP protocol were analyzed. We selected all the SNPs described in pre-miRNAs with a minor allele frequency more than 1% (213 SNPs in 206 miRNAs) that could regulate MTX transporters because the miRNAs that target MTX transporter genes are not completely defined. Genotyping was performed with VeraCode GoldenGate platform., Results: Among the most significant results, we found rs56292801 in miR-5189, rs4909237 in miR-595, and rs78790512 in miR-6083 to be associated with MTX plasma levels. These miRNAs were predicted, in silico, to regulate genes involved in MTX uptake: SLC46A1, SLC19A1, and SLCO1A2., Conclusion: In this study, we detected three SNPs in miR-5189, miR-595, and miR-6083 that might affect SLC46A1, SLC19A1, and SLCO1A2 MTX transport gene regulation and could affect MTX levels in patients with pediatric B-cell ALL.

Vincristine is a component of acute lymphoblastic leukemia (ALL) treatment with the potential to induce peripheral neuropathy. Recently, the CEP72 rs924607 TT genotype was found to be associated with vincristine-induced toxicity during the continuation phase in pediatric ALL patients treated on the Total XIIIB and COG AALL0433 protocols at St Jude Children's Research Hospital and Children's Oncology Group. This finding could provide a base for safer dosing of vincristine. Nevertheless, there are variations in vincristine regimens among ALL treatment protocols and phases in different populations. Therefore, the aim of this study was to determine whether the CEP72 rs924607 TT genotype is a useful marker of vincristine neuropathy during induction therapy among Spanish children with B-ALL treated on the LAL-SHOP protocols. No association was found between neurotoxicity during the induction phase and the rs924607 TT genotype. This lack of association could be because of population differences and/or differences in neurotoxicity etiology between induction and continuation phases of treatment.

Objective: To determine in patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) the association between the isolation of potential pathogens in a conventional sputum culture and comorbidities., Patients and Methods: The ESMI study is a multicenter observational study. Patients with AE-COPD admitted to the Internal Medicine departments of 70 hospitals were included. The clinical characteristics, treatments, and comorbidities were gathered. The results of conventional sputum cultures were recorded., Results: A total of 536 patients were included, of which 161 produced valid sputum and a potentially pathogenic microorganism was isolated from 88 subjects (16.4%). The isolation of Pseudomonas aeruginosa (30.7%) was associated with a greater severity of the lung disease (previous admissions [P= 0.026], dyspnea scale [P=0.047], post-broncodilator forced expiratory volume in 1 second (FEV1) [P=0.005], and the BODEx index [P=0.009]); also with higher prevalence of cor pulmonale (P=0.017), heart failure (P=0.048), and cerebrovascular disease (P=0.026). Streptococcus pneumoniae (26.1%) was associated with more comorbidity according to number of diseases (P=0.018); notably, peripheral artery disease (P=0.033), hypertension (P=0.029), dyslipidemia (P=0.039), osteoporosis (P=0.0001), and depression (P=0.005)., Conclusion: Patients with AE-COPD and P. aeruginosa present higher severity of COPD, while those with S. pneumoniae present greater comorbidity. The potentially pathogenic microorganism obtained in the sputum culture depends on the associated comorbidities.

Background and Objective: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare respiratory disease closely associated with smoking. The aim of the study is to know the reality of PLCH in the Catalonian population., Material and Methods: We included all patients diagnosed of PLCH in 8 different Catalonian hospitals from April 2011 to December 2012. Epidemiologic, clinical, radiological, functional, diagnostic and therapeutic variables were collected, both at the beginning and at the last visit of the process., Results: Thirty two patients were included. Overall, patients were middle-aged (38 years), with no gender predominance. Most of them were smokers (71.9%). The main pulmonary function values (forced vital capacity 75.9%, forced expiratory volume in one second 68.9%, diffusing capacity of the lung for carbon monoxide 59.6%) and radiological findings (cysts 89.7%, nodules 60.3%) showed no significant changes during evolution. However, the disease progressed with a worsening lung function in 34.4% of cases. The analysis of the functional outcome (forced vital capacity, forced expiratory volume in one second, and diffusing capacity of the lung for carbon monoxide) did not reveal significant differences according to the persistence or not of smoking (P<0.05)., Conclusion: Our patients with PLCH had similar clinical and radiological characteristics to those described in other populations. The results observed regarding the relationship with smoking suggest that there may be other factors beyond smoking, which influence on the evolution of the disease. It therefore seems advisable to design prospective studies to investigate this aspect., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)

Purpose: Information about healthcare-associated pneumonia (HCAP) in critically ill patients is scarce., Methods: This prospective study compared clinical presentation, outcomes, microbial etiology, and treatment of HCAP, community-acquired pneumonia (CAP), and immunocompromised patients (ICP) with severe pneumonia admitted to 34 Spanish ICUs., Results: A total of 726 patients with pneumonia (449 CAP, 133 HCAP, and 144 ICP) were recruited during 1 year from April 2011. HCAP patients had more comorbidities and worse clinical status (Barthel score). HCAP and ICP patients needed mechanical ventilation and tracheotomy more frequently than CAP patients. Streptococcus pneumoniae was the most frequent pathogen in all three groups (CAP, 34.2 %; HCAP, 19.5 %; ICP, 23.4 %; p = 0.001). The overall incidence of Gram-negative pathogens, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa was low, but higher in HCAP and ICP patients than CAP. Empirical treatment was in line with CAP guidelines in 73.5 % of patients with CAP, in 45.5 % of those with HCAP, and in 40 % of those with ICP. The incidence of inappropriate empirical antibiotic therapy was 6.5 % in CAP, 14.4 % in HCAP, and 21.8 % in ICP (p < 0.001). Mortality was highest in ICP (38.6 %) and did not differ between CAP (18.4 %) and HCAP (21.2 %)., Conclusions: HCAP accounts for one-fifth of cases of severe pneumonia in patients admitted to Spanish ICUs. The empirical antibiotic therapy recommended for CAP would be appropriate for 90 % of patients with HCAP in our population, and consequently the decision to include coverage of multidrug-resistant pathogens for HCAP should be cautiously judged in order to prevent the overuse of antimicrobials.

Objectives: To describe the severity of the 2009 influenza A/H1N1v illness among pregnant women admitted to Spanish intensive care units., Design and Patients: Prospective, observational, multicenter study conducted in 148 Spanish intensive care units. We reviewed demographic and clinical data from the Spanish Society of Intensive Care Medicine database reported from April 23, 2009, to February 15, 2010. We included women of reproductive age (15-44 yrs) with confirmed A/H1N1v infection admitted to intensive care units., Main Results: Two hundred thirty-four women of reproductive age were admitted to intensive care units, 50 (21.4%) of them pregnant. Seven deaths were recorded in pregnant and 22 in nonpregnant women. Among intensive care unit admissions, there were no statistically significant differences between pregnant women and nonpregnant in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment scores, chest x-rays, inotrope requirement, or need for mechanical ventilation or steroid therapy. Mortality risk was significantly associated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and obesity. Viral pneumonia was more frequent in pregnant women than in nonpregnant women, with an odds ratio (adjusted for asthma, time from onset influenza symptoms to hospital admission and obesity) of 4.9 (95% confidence interval: 1.4-17.2). The development of primary viral pneumonia in women of reproductive age appeared to be related to the time of commencement of antiviral treatment, the lowest rates being reported with initiation of antiviral therapy within 48 hrs of symptom onset (63.6% vs. 82.6%, p = .03). However, antiviral therapy was started within this time span in only 14% of pregnant women., Conclusions: More than 20% of women of reproductive age admitted to intensive care unit for pH1N1 infection were pregnant. Pregnancy was significantly associated with primary viral pneumonia. Pregnant women should receive prompt treatment with oseltamivir within 48 hrs of the onset of influenza symptoms.

Background and Objective: The impact of pandemic influenza A (H1N1)v infection is still unknown but it is associated with a high case-fatality rate., Methods: This was a prospective, observational, multicentre study conducted in 144 Spanish intensive care units. Demographic and clinical data were reviewed for all cases of pandemic influenza A (H1N1)v infection reported from 23 June 2009 through 11 February 2010 and confirmed by reverse transcriptase PCR assay., Results: Out of 872 cases reported by statewide surveillance, data for the first 131 deceased patients were analysed. Thirty-seven patients (28.2%) died within the first 14 days. The median age of these patients was 46 years (interquartile range 35-58) and 60.3% were male. Twenty-eight patients (21.4%) did not present with any comorbidities on admission. Forty-six per cent of patients were reported to be obese and 22 (16.8%) had COPD. The vast majority of the patients (72.5%) had viral pneumonia; 95.4% of these had bilateral patchy alveolar opacities (predominantly basal), affecting three or four quadrants. One hundred and fifteen patients (87.8%) developed multi-organ dysfunction syndrome. Ninety-seven patients (74%) required vasopressor drugs, 37 (27.2%) received renal replacement therapy, and 47 (35.1%) received intravenous corticosteroids on admission to the intensive care unit. Only 68 patients (51.9%) received empirical antiviral treatment., Conclusions: One-third of patients with pandemic influenza A (H1N1)v infection died within the first two weeks and these were young patients, with rapidly progressive viral pneumonia as the primary cause of admission. Obese patients were at high risk but one in four patients did not present with any risk factors on admission. Only half the patients received empirical antiviral therapy and this was administered late., (© 2010 The Authors. Respirology © 2010 Asian Pacific Society of Respirology.)

Background: There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described., Methods: A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period., Results: Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period., Conclusion: Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection.

Background and Objectives: To describe the characteristics of immigrant women's newborns in our environment, and to compare them with those of native women., Patients and Methods: All newborns attended in the Neonatology Unit of Hospital del Mar in Barcelona, Spain, between January 2007-December 2008 were included (n=3,177). Pregnant immigrant women were classified in six regions. Twelve diagnoses were defined and their relative risks were calculated. The results were compared with the results obtained in a previous study of the period 2003-2004., Results: There were 1,373 native newborns and 1,743 of immigrant origin. Immigrant women showed a higher rate of HBsAg carrier status (RR 4.33), neonatal infection risk (RR 1.24) and also macrosomia (RR 1.4). There were 6 HIV positive pregnant immigrant women compared with 8 Spanish women, and drug abuse was lower in the immigrant group (RR 0.15). There were no significant differences in the rate of other diagnoses. In the comparative rates between both periods there was an increased rate of immigrant women's newborn. We did not find any differences in the mean birth weight among newborns of immigrant women during both periods of time. HIV and hepatitis C infection remained higher in native pregnant women and hepatitis B infection in immigrant women and gypsy native women., Conclusions: The study shows similar results between the two periods with persistence of complications secondary to an inadequate prenatal care, lower drug abuse and moderate increase in HIV and VHC infection in immigrant women and hepatitis B infection in immigrant women and gypsy native women., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Aim: In order to assess whether the use of metronidazole during pregnancy is associated with a higher risk of congenital malformations, a meta-analysis was conducted., Methods: All epidemiological studies (cohort and case-control) which estimate risk of congenital malformations after exposure to metronidazole during early pregnancy were included in the meta-analysis. To obtain a summary odds ratio, the Mantel-Haenszel method was used. A test to verify absence of heterogeneity was also performed., Results: One unpublished case-control and four published cohort studies fulfilled the inclusion criteria and were not statistically heterogeneous. A summary odds ratio was calculated for metronidazole exposure during the first trimester: OR = 1.08, 95% CI: 0.90-1.29, heterogeneity test chi2 = 4.72, P = 0.32., Conclusions: This meta-analysis did not find any relationship between metronidazole exposure during the first trimester of pregnancy and birth defects.

Objective: To develop a risk stratification model to assess open heart surgery mortality in Catalonia (Spain) in order to use risk-adjusted hospital mortality rates as an approach to analyze quality of care., Methods: Data were prospectively collected through a specific data-sheet during 6 1/2 months in consecutive adult patients subjected to open heart surgery. The dependent variable was surgical mortality, and independent variables included were presurgical (sociodemographic data, clinical antecedents, morphological and functional studies) and surgical. The model was built on a subsample (70% of study population) through univariate and logistic regression analysis and validated in the rest of the sample., Results: The total sample was of 1309 procedures in seven hospitals; 47% of them were valve procedures. The overall crude mortality rate was 10.9% and varied among centers (range, 2.8-14.8%). Risk factors included in the model received a weight based on the logistic regression coefficient and a score was generated for each patient. The factors with the highest weight were patient older than 80 and second reoperation. Score was stratified in five categories of increasing risk. There was a good agreement between observed and predicted mortality rates in the validation group. Overall patient distribution was as follows: 52% low risk level, 16% fair, 13% high, 12% very high, and 6% extremely high risk level. Mortality rate increased from 4.2% in the low risk to 54.4% in the highest risk group. Case mix adjustment was performed through the risk score level. There were statistically significant differences in the risk profiles of patients admitted among centers. After adjustment by risk profiles, there were no differences in mortality by hospital., Conclusion: A risk stratification model through a multicentric, prospective and exhaustive collection of data in all types of open heart procedures was developed. In spite of wide differences on crude rates and in the risk profiles of patients admitted, we did not find statistically significant differences in adjusted mortality rates among centers. Timely and accurate information about surgical outcomes can lead to improvements in clinical practice and quality of care.

From last years eighty's decade the number of women with HIV infection have significantly increased. To know the epidemiological and clinic trades in this group we studied retrospectively 476 HIV infected patients attending in a General Hospital from January 1986 to June 1993. Seventy nine (16.5%) were female and 397 male. The mean female group was 25.8 years, 61.9% were IVDUs and 30.4% heterosexual transmission. This last transmission route was more important between females than males (5%) (p < 0.001) and in 1992 the 55% of women been infected by this way. The mean CD4 count was 643 cel/ml in the female group at the diagnostic time and 21.7% developed antigenaemia without difference with the male group. 59.7% of women were no symptoms at the diagnosis time and 14.3% were AIDS, no differences with men, but more in the female group developed AIDS along following time 39.5% in front of 24.7% in the male group (p < 0.05). Disseminated Tuberculosis (DTB) (29.1%) and Wasting Syndrome (WS) (29.1%) were the more frecuent AIDS defining conditions in the female group. The more frecuent complications were: Oropharynx Candidiasis 39.1%, Esophagus Candidiasis 6.3%, WS 11%, DTB 12.65%, PCP 10.12% and Neoplasias 5.06%. Fourteen women became pregnant during HIV infection, no clinical nor immunological differences were observed in this group with the control. The treatment (66%) and following (46.8%), compliance was better between women than men. The rise of women with HIV infection, the poor development in this group described by some authors, so far gynecological aspect and vertical transmission makes HIV infection in women an major health problem.