[Excess weight in patients with cystic fibrosis: is it always beneficial?]

INTRODUCTION: The primary objective of this study was to find out the prevalence of overweight and obese status, as well as their association to pulmonary function, total cholesterol and vitamin D in patients with cystic fibrosis (CF). MATERIALS AND METHODS: This is a multicenter descriptive and cross-sectional study. Twelve Spanish hospitals participated. 451 patients with CF were included. Adults were classified according to body mass index (BMI) and children were classified according to BMI percentiles (WHO tables). Pearson's correlation, Anova, Student's t-test and multiple linear regression were conducted. RESULTS: Mean age was 12.3 (range 4-57) years old, 51% were male and 18% had pancreatic sufficiency. Participants were classified in five nutritional status categories: 12% were malnourished; 57%, at nutritional risk; 24%, normally nourished; 6%, overweight; and 1%, obese. Pulmonary function in overweight or obese patients (91 ± 19%) was better than in malnourished patients (77 ± 24%) (p = 0.017). However, no difference was observed between those at nutritional risk (86 ± 19%) or normally nourished (90 ± 22%) groups. Overweight and obese patients had higher levels of total cholesterol (p = 0.0049), a greater proportion of hypercholesterolemia (p = 0.001), as well as lower levels of 25 OH vitamin D (p = 0.058). CONCLUSIONS: Prevalence of overweight and obese was 6 and 1%. Excess weight status does not offer any benefit in pulmonary function in comparison to normally nourished patients.

[VITAMIN D AND CHRONIC LUNG COLONIZATION IN PEDIATRIC AND YOUNG ADULTS CYSTIC FIBROSIS PATIENTS]. / VITAMINA D Y COLONIZACIONES PULMONARES CRÓNICAS EN PACIENTES PEDIÁTRICOS Y ADULTOS JÓVENES CON FIBROSIS QUÍSTICA.

INTRODUCTION AND OBJECTIVES: evaluate vitamin D status and its association with chronic lung colonisation in Cystic Fibrosis patients. MATERIAL AND METHODS: descriptive cross-sectional multicenter study. From November 2012 to April 2014, at 12 national hospitals, 377 patients with Cystic Fibrosis were included. Vitamin D levels < 30 ng/ml were classified as insufficient. Chronic colonisation was considered if they had at least two positive cultures in the past year. RESULTS: the median age was 8.9 years (2 months to 20 years). 65% had insufficient levels of vitamin D. There was an inverse correlation between age and vitamin D levels (r = -0.20 p < 0.001). Those diagnosed by screening, were younger and had higher levels of vitamin D. There was an inverse correlation between the number of colonisations and vitamin D levels (r = -0.16 p = 0.0015). Adjusting for age, pancreatic status and diagnosis by screening, colonization by S. aureus in 6 years, increased the risk of insufficient levels of vitamin D: OR 3.17 (95% CI 1.32 to 7.61) (p = 0.010) and OR 3.77 (95% CI 1.37 to 10 , 37) (p = 0.010), respectively. CONCLUSIONS: despite adequate supplementation, more than half of our patients did not achieve optimal levels of vitamin D. Regardless of age, diagnosis by screening or pancreatic status, chronic colonization by Pseudomonas sp. in children and adolescents and S. Aureus in infants and preschoolars increases the risk of developing vitamin D deficiency in these patients.

Introducción y objetivos: conocer la situación en la que se encuentran los pacientes con fibrosis quística en relación con sus niveles de vitamina D y su asociación con las colonizaciones pulmonares crónicas. Material y métodos: estudio multicéntrico transversal. Participaron 12 hospitales nacionales. De noviembre a abril del 2012 al 2014 se incluyeron 377 pacientes con fibrosis quística. Se consideraron insuficientes niveles de vitamina D < 30 ng/ml. Presentar al menos dos cultivos positivos en el último año fue considerado un criterio de colonización crónica. Resultados: los pacientes tenían una mediana de edad de 8,9 años (2 meses­20 años). Un 65% presentaban niveles insuficientes de vitamina D. Se observó una correlación inversa entre edad y niveles de vitamina D (r = -0,20 p < 0,001). Los diagnosticados por cribado eran más jóvenes y tenían niveles de vitamina D más altos. Los niveles de vitamina D presentaron una correlación inversa con el número de colonizaciones pulmonares (r = -0,16 p = 0,0015). Ajustando por edad, función pancreática y diagnóstico mediante cribado, la colonización por S. Aureus en menores de seis años y por Pseudomonas sp. en los mayores de esa edad, incrementaban el riesgo de presentar niveles insuficientes de vitamina D: OR 3,17 (IC95% 1,32-7,61) (p=0,010) y OR 3,77 (IC95% 1,37- 10,37)(p = 0,010), respectivamente. Conclusiones: a pesar de una suplementación adecuada, más de la mitad de nuestros pacientes no alcanzan niveles óptimos de vitamina D. La colonización crónica por Pseudomonas sp. en escolares y adolescentes y por S. Aureus en lactantes y preescolares se asocia de forma independiente con la deficiencia de vitamina D.

Review and evaluation of the methodological quality of the existing guidelines and recommendations for inherited neurometabolic disorders.

BACKGROUND: Inherited neurometabolic disorders (iNMDs) represent a group of almost seven hundred rare diseases whose common manifestations are clinical neurologic or cognitive symptoms that can appear at any time, in the first months/years of age or even later in adulthood. Early diagnosis and timely treatments are often pivotal for the favorable course of the disease. Thus, the elaboration of new evidence-based recommendations for iNMD diagnosis and management is increasingly requested by health care professionals and patients, even though the methodological quality of existing guidelines is largely unclear. InNerMeD-I-Network is the first European network on iNMDs that was created with the aim of sharing and increasing validated information about diagnosis and management of neurometabolic disorders. One of the goals of the project was to determine the number and the methodological quality of existing guidelines and recommendations for iNMDs. METHODS: We performed a systematic search on PubMed, the National Guideline Clearinghouse (NGC), the Guidelines International Network (G-I-N), the Scottish Intercollegiate Guideline Network (SIGN) and the National Institute for Health and Care Excellence (NICE) to identify all the published guidelines and recommendations for iNMDs from January 2000 to June 2015. The methodological quality of the selected documents was determined using the AGREE II instrument, an appraisal tool composed of 6 domains covering 23 key items. RESULTS: A total of 55 records met the inclusion criteria, 11 % were about groups of disorders, whereas the majority encompassed only one disorder. Lysosomal disorders, and in particular Fabry, Gaucher disease and mucopolysaccharidoses where the most studied. The overall methodological quality of the recommendation was acceptable and increased over time, with 25 % of the identified guidelines strongly recommended by the appraisers, 64 % recommended, and 11 % not recommended. However, heterogeneity in the obtained scores for each domain was observed among documents covering different groups of disorders and some domains like 'stakeholder involvement' and 'applicability' were generally scarcely addressed. CONCLUSIONS: Greater efforts should be devoted to improve the methodological quality of guidelines and recommendations for iNMDs and AGREE II instrument seems advisable for new guideline development. The elaboration of new guidelines encompassing still uncovered disorders is badly needed.

Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases.

BACKGROUND: Advances in the diagnosis and treatment of urea cycle disorders (UCDs) have led to a higher survival rate. The purpose of this study is to describe the characteristics of patients with urea cycle disorders in Spain. METHODS: Observational, cross-sectional and multicenter study. Clinical, biochemical and genetic data were collected from patients with UCDs, treated in the metabolic diseases centers in Spain between February 2012 and February 2013, covering the entire Spanish population. Heterozygous mothers of patients with OTC deficiency were only included if they were on treatment due to being symptomatic or having biochemistry abnormalities. RESULTS: 104 patients from 98 families were included. Ornithine transcarbamylase deficiency was the most frequent condition (64.4%) (61.2% female) followed by type 1 citrullinemia (21.1%) and argininosuccinic aciduria (9.6%). Only 13 patients (12.5%) were diagnosed in a pre-symptomatic state. 63% of the cases presented with type intoxication encephalopathy. The median ammonia level at onset was 298 µmol/L (169-615). The genotype of 75 patients is known, with 18 new mutations having been described. During the data collection period four patients died, three of them in the early days of life. The median current age is 9.96 years (5.29-18), with 25 patients over 18 years of age. Anthropometric data, expressed as median and z-score for the Spanish population is shown. 52.5% of the cases present neurological sequelae, which have been linked to the type of disease, neonatal onset, hepatic failure at diagnosis and ammonia values at diagnosis. 93 patients are following a protein restrictive diet, 0.84 g/kg/day (0.67-1.10), 50 are receiving essential amino acid supplements, 0.25 g/kg/day (0.20-0.45), 58 arginine, 156 mg/kg/day (109-305) and 45 citrulline, 150 mg/kg/day (105-199). 65 patients are being treated with drugs: 4 with sodium benzoate, 50 with sodium phenylbutyrate, 10 with both drugs and 1 with carglumic acid. CONCLUSIONS: Studies like this make it possible to analyze the frequency, natural history and clinical practices in the area of rare diseases, with the purpose of knowing the needs of the patients and thus planning their care.

[Use of illicit drugs over gestation and their neonatal impact. Comparison between periods 1982-1988 and 2002-2008]. / Consumo de drogas durante la gestación y su repercusión neonatal. Análisis de los períodos 1982-1988 y 2002-2008.

BACKGROUND AND OBJECTIVE: The use of illicit drugs during pregnancy becomes a high risk situation. Our objective is to determine the currently prevalence, pregnancy, delivery and newborn's characteristics of mothers who use illicit drugs. PATIENTS AND METHODS: Retrospective study of children exposed prenatally to illicit drugs in the Neonatology's Unit of the Hospital del Mar during 2002-2008 and comparison with 1982-1988 data. RESULTS: Heroin use is lower currently and it is always associated with other drugs, mainly inhaled or smoked. There is an increase of the maternal age (28.4 years), an improved gestational control (60.5%) and more newborns are attended in shelters (13.1%). Methadone programs provide better overall results. Human immunodeficiency virus (HIV) (25%) and hepatitis B (BHV) (2.5%) infections have decreased. Placental abruption rate in cocaine users is very high (11%). By comparing both periods, there were statistically significant differences in maternal age, gestational control, delivery way, neonatal withdrawal syndrome treatment and newborn destination. CONCLUSIONS: Drug abuse remains prevalent in native pregnants. Heroin use has decreased. At present, there is a better gestational control and less HIV and HBV infections. The gestational age and somatometric parameters have not changed over the years. Methadone programs improve the deleterious aspects of opioid use. Placental abruption in pregnancy and neurobehavioral disorders in newborn are common in cocaine users.