Recurrent wheezing during the first 3 years of life in a birth cohort of moderate-to-late preterm infants.

BACKGROUND: Data addressing short- and long-term respiratory morbidity in moderate-late preterm infants are limited. We aim to determine the incidence of recurrent wheezing and associated risk and protective factors in these infants during the first 3 years of life. METHODS: Prospective, multicenter birth cohort study of infants born at 32+0 to 35+0  weeks' gestation and followed for 3 years to assess the incidence of physician-diagnosed recurrent wheezing. Allergen sensitization and pulmonary function were also studied. We used multivariate mixed-effects models to identify risk factors associated with recurrent wheezing. RESULTS: A total of 977 preterm infants were enrolled. Rates of recurrent wheezing during year (Y)1 and Y2 were similar (19%) but decreased to 13.3% in Y3. Related hospitalizations significantly declined from 6.3% in Y1 to 0.75% in Y3. Independent risk factors for recurrent wheezing during Y2 and Y3 included the following: day care attendance, acetaminophen use during pregnancy, and need for mechanical ventilation. Atopic dermatitis on Y2 and male sex on Y3 were also independently associated with recurrent wheezing. Palivizumab prophylaxis for RSV during the first year of life decreased the risk or recurrent wheezing on Y3. While there were no differences in rates of allergen sensitization, pulmonary function tests (FEV0.5 ) were significantly lower in children who developed recurrent wheezing. CONCLUSIONS: In moderate-to-late premature infants, respiratory symptoms were associated with lung morbidity persisted during the first 3 years of life and were associated with abnormal pulmonary function tests. Only anti-RSV prophylaxis exerted a protective effect in the development of recurrent wheezing.

Simplifying the human lumbar spine (L3/L4) material in order to create an elemental structure for the future modeling.

The human lumbar spine incorporates the best joints in nature due to its optimal static and dynamic behavior against the internal and external loads. Developing an elemental structure based on this joint requires simplification in terms of the materials employed by keeping the mechanical and anatomical behaviors of the human lumbar spine. In the present study, the finite element (FE) of two motion segments of the human lumbar spine (L3/L4) was developed based on the CT scan data as the base for vertebrae geometry, verified geometry properties for another part of two motion segments, and combination of materials and loads obtained from the validated resources. Then, simplification occurred in four continuous steps such as omitting the annual fibers of annual matrix, representing the material of the annual matrix to the nucleus, demonstrating the material of annual matrix to the endplates too, and omitting the trabecular part of vertebrae. The present study aimed to propose the method for developing the basic structure of the human lumbar spine by simplifying its materials in the above-mentioned steps, analyzing the biomechanical effects of these four steps in terms of their internal and external responses, and validating the data obtained from the FE method. The validated simplified way introduced in this study can be used for future research by making implants, prosthesis, and modeling based on the human lumbar spine in other fields such as industrial design, building structures, or joints, which results in making the model easier, cheaper, and more effective.

Antibiotic resistance and population structure of cystic fibrosis Pseudomonas aeruginosa isolates from a Spanish multi-centre study.

The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population in Spain, not represented by the epidemic clones widely distributed across Europe, with multiple combinations of virulence factors and high antimicrobial resistance rates (except for colistin).

Antibiotic prescription patterns in Spanish cystic fibrosis patients: results from a national multicenter study.

OBJECTIVE: Information about antibiotic prescription patterns for cystic fibrosis (CF) patients and, specifically, about inhaled treatment strategies for their management is lacking in Spain due to the absence of a national patient registry. In this study we present data about antibiotic prescription in the Spanish CF context that were obtained in a multicenter study, being inhaled treatment strategies the special focus of this work. METHODS: Twenty-four specialized CF units (12 adult, 12 pediatric) from 17 tertiary-care hospitals covering all Spanish Autonomous Communities provided sputa and clinical data from 15 consecutive patients. Data about antibiotic and non-antibiotic therapies prescribed to these patients during the year prior inclusion (2013) were retrospectively collected. RESULTS: The multicenter study included 341 CF patients from all age groups and clinical status. The prevalence of oral, inhaled and intravenous therapies was 89% (n = 302), 80% (n = 273) and 31% (n = 105), respectively. The most prevalent oral agents were ciprofloxacin (n = 177, 59%), cotrimoxazole (n = 109, 36%) and amoxicillin-clavulanate (n = 99, 33%), whereas ceftazidime (n = 53, 50%), tobramycin (n = 43, 41%) and meropenem (n = 41, 49%) were the most prevalent intravenous ones. Two or more different inhaled antibiotics were administered to 67 patients (24%), 51 of them receiving 2 drugs continuously in alternating schemes. Nebulization of intravenous specific antibiotics was common (n = 39) and, in some cases, was used for maintenance purposes. CONCLUSIONS: These results show that the treatment of CF patients is evolving more rapidly than clinical consensus guidelines. Clinical trials evaluating new specific inhaled combinations and new alternative treatment regimes of the existing ones are needed.

Objetivos: Existen actualmente pocos datos acerca de las pautas de tratamiento antimicrobiano administradas a los pacientes con fibrosis quística (FQ) en España, sobre todo en lo que se refiere a la antibioterapia inhalada. Esta escasez de conocimiento se debe principalmente a la ausencia de un registro nacional de datos de pacientes. En 2013 se llevó a cabo el primer estudio multicéntrico español focalizado en la microbiología de la FQ. En este trabajo presentamos los patrones de prescripción de antimicrobianos administrados durante un año a los pacientes incluidos en dicho estudio.Métodos: Se contó con la participación de 24 unidades de FQ (12 de adultos y 12 de pediatría) procedentes de 17 hospitales españoles. Cada unidad reclutó a 15 pacientes de manera consecutiva, que aportaron muestras respiratorias y datos clínicos. Se recogieron de manera retrospectiva los tratamientos antibióticos y no antibióticos administrados a estos pacientes durante el año previo a su inclusión en el estudio.Resultados: Se incluyeron 341 pacientes con FQ de todos los rangos de edad y de gravedad clínica. La prevalencia de antibioterapia oral, inhalada e intravenosa fue del 89% (n = 302), 80% (n = 273) y 31% (n = 105), respectivamente. Los fármacos administrados con mayor frecuencia por vía oral fueron ciprofloxacino (n = 177, 59%), cotrimoxazol (n = 109, 36%) y amoxicilina-clavulánico (n = 99, 33%), siendo ceftazidima (n = 53, 50%), tobramicina (n = 43, 41%) y meropenem (n = 41, 49%) los más frecuentes por vía intravenosa. Se administraron dos o más antibióticos por vía inhalada a 67 pacientes (24%), habiendo recibido 51 de ellos 2 antibióticos simultáneamente de manera rotatoria. La nebulización de antibióticos con formulación intravenosa fue una práctica común (n = 39) y, en algunos casos, se utilizó durante un tiempo prolongado como terapia de mantenimiento.Conclusiones: Los esquemas de tratamiento observados en este estudio demuestran que la terapia antibiótica de la FQ evoluciona más rápidamente que las recomendaciones reflejadas en las guías clínicas. Es necesario evaluar estos nuevos esquemas con estudios clínicos, así como con otros fármacos inhalados de reciente aparición y su papel en los esquemas existentes.

Risk factors for bronchiolitis, recurrent wheezing, and related hospitalization in preterm infants during the first year of life.

BACKGROUND: Airway diseases are highly prevalent in infants and cause significant morbidity. We aimed to determine the incidence and risk factors for respiratory morbidity in a Spanish cohort of moderate-to-late preterm (MLP) infants prospectively followed during their first year of life. METHODS: SAREPREM is a multicenter, prospective, longitudinal study. Preterm infants born at 32-35 weeks of gestation with no comorbidities were enrolled within 2 weeks of life and followed at 2-4 weeks, 6, and 12 months of age. Multivariate mixed-models were performed to identify independent risk factors associated with (i) development of bronchiolitis, (ii) recurrent wheezing, or (iii) related hospital admissions. RESULTS: Overall, 977 preterm infants were included, and 766 (78.4%) completed follow-up. Of those, 365 (47.7%) developed bronchiolitis during the first year, 144 (18.8%) recurrent wheezing, and 48 (6.3%) were hospitalized. While low birthweight, day care attendance (DCA) and school-age siblings were significantly and independently associated with both the development of bronchiolitis and recurrent wheezing, lower maternal age increased the risk for bronchiolitis and respiratory-related hospitalizations. Lastly, mechanical ventilation was associated with a higher risk of bronchiolitis and history of asthma in any parent increased the likelihood of developing recurrent wheezing. CONCLUSIONS: In this study, several non-modifiable parameters (family history of asthma, low birthweight, need for mechanical ventilation) and modifiable parameters (young maternal age, DCA, or exposure to school-age siblings) were identified as significant risk factors for the development of bronchiolitis and recurrent wheezing during the first year of life in MLP infants.

Spanish consensus on the prevention and treatment of Pseudomonas aeruginosa bronchial infections in cystic fibrosis patients.

Pseudomonas aeruginosa is the main pathogen in bronchopulmonary infections in cystic fibrosis (CF) patients. It can only be eradicated at early infection stages while reduction of its bacterial load is the therapeutic goal during chronic infection or exacerbations. Neonatal screening and pharmacokinetic/pharmacodynamic knowledge has modified the management of CF-patients. A culture based microbiological follow-up should be performed in patients with no infection with P.aeruginosa. At initial infection, inhaled colistin (0,5-2MU/tid), tobramycin (300mg/bid) or aztreonam (75mg/tid) with or without oral ciprofloxacin (15-20mg/kg/bid, 2-3weeks) are recommended. In chronic infections, treatment is based on continuous administration of colistin or with a 28-day on-off regimen with tobramycin or aztreonam. During mild-moderate exacerbations oral ciprofloxacin (2-3weeks) can be administered while serious exacerbations must be treated with intravenous combination therapy (beta-lactam with an aminoglycoside or a fluoroquinolone). Future studies will support antibiotic rotation and/or new combination therapies. Epidemiological measures are also recommended to avoid new P.aeruginosa infections and "patient-to-patient transmission" of this pathogen.