RESUMEN
BACKGROUND: Current systemic therapies for metastatic pancreatic ductal adenocarcinoma are associated with poor outcomes with a 5-year overall survival rate under 5%. We aimed to assess the safety and antitumour activity of mitazalimab, a human CD40 agonistic IgG1 antibody, with modified FOLFIRINOX (mFOLFIRINOX; fluorouracil, leucovorin, oxaliplatin, and irinotecan), in chemotherapy-naive patients with metastatic pancreatic ductal adenocarcinoma. METHODS: OPTIMIZE-1 was a single-arm, multicentre, phase 1b/2 study which enrolled adults with histologically-confirmed metastatic pancreatic ductal adenocarcinoma and European Cooperative Oncology Group performance status 0 or 1 in 14 university hospitals in Belgium, France, and Spain. The primary endpoint of phase 1b was to determine the recommended phase 2 dose of intravenous mitazalimab (450 µg/kg or 900 µg/kg) when combined with intravenous mFOLFIRINOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2, fluorouracil 2400 mg/m2). In the first 21-day treatment cycle, mitazalimab was administered on days 1 and 10, and mFOLFIRINOX on day 8. In subsequent 14-day cycles mitazalimab was administered 2 days after mFOLFIRINOX. The phase 2 primary endpoint was objective response rate. Activity and safety analyses were conducted on the full analysis set (all patients who received the combination of mitazalimab at the recommended phase 2 dose and mFOLFIRINOX for at least two treatment cycles) and safety set (all patients who received any study treatment), respectively. Enrolment is complete, and data represents a primary analysis of the ongoing trial. The trial is registered at Clinicaltrials.gov (NCT04888312). FINDINGS: Between Sept 29, 2021, and March 28, 2023, 88 patients were screened and 70 patients were enrolled (40 [57%] were female and 30 [43%] were male). In phase 1b, 900 µg/kg mitazalimab was determined as the recommended phase 2 dose. Overall, five patients received 450 µg/kg mitazalimab; 65 received 900 µg/kg mitazalimab. No dose-limiting toxicities were observed at 450 µg/kg, and one dose-limiting toxicity was observed at 900 µg/kg. 57 patients were evaluated for activity, and all 70 patients were included in the safety set. At data cutoff on Nov 14, 2023, median follow-up was 12·7 months (95% CI 11·1-15·7). Of the 57 patients, 29 (51%) remained on study and 18 (32%) remained on treatment. The primary endpoint (objective response rate >30%) was met (objective response rates in 23 [40%]; one-sided 90% CI ≥32 of 57 patients). The most common grade 3 or worse adverse events were neutropenia (18 [26%] of 70 patients), hypokalaemia (11 patients [16%]), and anaemia and thrombocytopenia (eight patients [11%]). Serious adverse events were reported in 29 (41%) of 70 patients, the most common being vomiting (five [7%] of 70 patients), decreased appetite (four [6%]), and diarrhoea and cholangitis (three [4%] of 70 patients for each), none considered related to mitazalimab. No treatment-related deaths were reported. INTERPRETATION: Mitazalimab with mFOLFIRINOX demonstrated manageable safety and encouraging activity, warranting continued development in a phase 3, randomised, controlled trial. The results from OPTIMIZE-1 pave the way for further exploration and confirmation of a novel immunotherapy treatment regimen for metastatic pancreatic ductal adenocarcinoma, which is a complex and aggressive cancer with very low survival rates and restricted treatment options. FUNDING: Alligator Bioscience.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático , Fluorouracilo , Irinotecán , Leucovorina , Oxaliplatino , Neoplasias Pancreáticas , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Persona de Mediana Edad , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Anciano , Irinotecán/administración & dosificación , Fluorouracilo/administración & dosificación , Oxaliplatino/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Anticuerpos Monoclonales Humanizados/administración & dosificación , AdultoRESUMEN
BACKGROUND: Sequential nab-paclitaxel plus gemcitabine followed by modified FOLFOX-6 (oxaliplatin, leucovorin, and 5-fluorouracil) (nab-P/Gem-mFOLFOX) showed a good safety and clinical profile in metastatic pancreatic ductal adenocarcinoma (mPDAC) in the phase I SEQUENCE trial. METHODS: The safety and efficacy of sequential nab-P/Gem-mFOLFOX was compared with standard nab-paclitaxel plus gemcitabine (nab-P/Gem) as first-line treatment in a multi-institutional, randomized, open-label, phase II trial in patients with untreated mPDAC. We randomly assigned patients in a 1:1 ratio to receive nab-P/Gem on days 1, 8, and 15 followed by mFOLFOX on day 29 of a 6-week cycle (experimental group) or nab-P/Gem on days 1, 8, and 15 of a 4-week cycle (control group). The primary end point was the 12-month overall survival rate. RESULTS: A total of 157 patients were randomly assigned: 78 to nab-P/Gem-mFOLFOX and 79 to nab-P/Gem. Patients receiving nab-P/Gem-mFOLFOX had a 12-month overall survival of 55.3% (95% confidence interval [CI], 44.2 to 66.5) versus 35.4% (95% CI, 24.9 to 46) in the control group (P=0.02). Similarly, the 24-month survival was 22.4% (95% CI, 13 to 31.8) with nab-P/Gem-mFOLFOX versus 7.6% (95% CI, 1.8 to 13.4) with control treatment. The median overall survival was 13.2 months (95% CI, 10.1 to 16.2) with nab-P/Gem-mFOLFOX and 9.7 months (95% CI, 7.5 to 12) with nab-P/Gem (hazard ratio for death, 0.68; 95% CI, 0.48 to 0.95). The safety profile showed a higher incidence of grade 3 or higher neutropenia (35 of 76 vs. 19 of 79 patients, P=0.004), grade 3 or higher thrombocytopenia (18 of 78 vs. 6 of 79 patients, P=0.007), and two treatment-related deaths (2.6%) with nab-P/Gem-mFOLFOX compared with none with control treatment. CONCLUSIONS: Sequential nab-P/Gem-mFOLFOX showed a significantly higher 12-month survival when compared with the standard nab-P/Gem treatment; this came with greater treatment toxicity. (Funded by Celgene; EuCT number, 2014-005350-19; ClinicalTrials.gov number, NCT02504333.)
Asunto(s)
Albúminas , Gemcitabina , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/efectos adversos , Paclitaxel/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológicoRESUMEN
Sickle cell disease (SCD) is an inherited autosomal recessive hemoglobin disorder caused by the presence of hemoglobin S, a mutant abnormal hemoglobin caused by a nucleotide change in codon 6 of the ß-globin chain gene. SCD involves a chronic inflammatory state, exacerbated during vaso-occlusive crises, which leads to end-organ damage that occurs throughout the lifespan. SCD is associated with premature mortality in the first years of life. The process of sickling provokes asplenia in the first years of life with an increased risk of infection by encapsulated germs. These complications can be life-threatening and require early diagnosis and management. The most important interventions recommend an early diagnosis of SCD to ensure that affected newborns receive immediate care to reduce mortality and morbidity. The newborn screening program in the region of Murcia for SCD began in March 2016. We aimed to determine the incidence of sickle cell anemia and other structural hemoglobinopathies in the neonatal population of the region of Murcia, an area of high migratory stress, and to systematically assess the benefit of newborn screening for SCD, leading to earlier treatment, as well as to offer genetic counseling to all carriers. The prevalence of SCD in our region is similar to others in Spain, except for Catalonia and Madrid. The newborns with confirmed diagnoses of SCD received early attention, and all the carriers received genetic counseling.
RESUMEN
BACKGROUND: Cystinuria is an inherited metabolic disease involving the defective transport of cystine and the dibasic amino acids in the renal proximal tubules that causes the formation of stones in the urinary system. In our regional child health program, cystinuria is included in newborn metabolic screening. Our objectives are the phenotypic characterization of our cystinuric pediatric cohort and to present our experience in neonatal cystinuria screening. METHODS: The study of clinical cases of pediatric patients diagnosed with cystinuria over a period of 32 years. All patients were studied at demographic, clinical, laboratory, radiological, and therapeutic levels. RESULTS: We diagnosed 86 pediatric patients with cystinuria; 36% of them had the homozygous biochemical phenotype. 95.3% of the patients were detected by neonatal metabolic screening. We performed urine biochemical analyses of parents with additional diagnoses of 63 adult patients. The mean follow-up time was 16.8 ± 8.5 years. 11.6% of patients developed one or more episodes of urinary tract infection during that period. Chronic kidney disease, proteinuria, and hypertension were uncommon (1.2%). 10.5% developed kidney stones at the mean age of presentation of 7.78 ± 7.6 years; 33% were recurrent. The risk of developing lithiasis was higher for homozygous biochemical-phenotype patients. Hypercalciuria was a significant risk factor in the development of lithiasis. CONCLUSIONS: Our clinical data suggest that diagnosing cystinuria through neonatal screening could be a useful strategy for the detection of presymptomatic cases, in order to establish preventive measures, as well as for the detection of relatives at risk. A higher resolution version of the Graphical abstract is available as Supplementary information.
Asunto(s)
Cistinuria , Cálculos Renales , Litiasis , Humanos , Recién Nacido , Cistinuria/diagnóstico , Cistinuria/genética , Cistinuria/terapia , Tamizaje Neonatal , Cálculos Renales/diagnóstico , Cálculos Renales/epidemiología , FenotipoRESUMEN
This paper explores global differences in travel risk perception based on i) attitudes towards travel abroad, and ii) the time required to plan travel. Baseline data from 2019 is compared with data from 2020, the first year of the COVID-19 pandemic. A methodology based on Big Data is developed through the Skyscanner metasearch engine, working with 20,756 million flight searches and 1979 million flight picks worldwide. We conduct an exploratory analysis by region, followed by a cluster analysis of 45 countries. We argue that the findings respond to uncertainty avoidance, with clear differences between Europe, America and Asia-Pacific. This knowledge has marketing implications for tourist destinations in terms of what marketing messages to convey and the best time to introduce marketing campaigns for each country or group of countries, so that the opportunity for reactivation of tourism is maximised.
RESUMEN
BACKGROUND: Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). METHODS: In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. RESULTS: CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. CONCLUSIONS: CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.
RESUMEN
Objetivo: Analizar la efectividad del uso del mindfulness durante el embarazo, el parto y el posparto, y describir los diferentes métodos de mindfulness. Metodología: Se realizó una revisión bibliográfica, acorde con el objetivo, de estudios publicados entre 2014 y 2019 en las bases de datos PubMed, CINAHL, WOS y Scopus, en el periodo de marzo-abril de 2019. Resultados: Se localizaron 124 estudios, de los que finalmente se seleccionaron 22. De éstos, el 54,5% utilizaron mindfulness basado en terapias cognitivas (MBCT). Un 50% de los estudios muestra efectividad del uso del mindfulness en cuanto a descenso de la ansiedad y la depresión; sin embargo, el 13,6% refiere que estos aspectos no mejoran. Conclusiones: Existe evidencia científica respecto al uso del mindfulness, y el MBCT es la terapia más utilizada. El uso del mindfulness mejora, entre otros aspectos, la ansiedad, la depresión, el miedo al parto, el estrés, las náuseas y los vómitos. (AU)
Objective: To analyze the effectiveness of the mindfulness use in pregnancy, delivery and postpartum, and describe the different mindfulness methods. Methodology: A bibliographic review was carried out according to the objective of studies published between 2014-2019, in the databases: PubMed, CINAHL, WOS and Scopus, in the period March-April 2019. Results: A total of 124 studies were located and 22 were finally selected. Of these, 54.5% used mindfulness based on cognitive therapies (MBCT). 50% of the studies show effectiveness of the use of mindfulness, in terms of decreased anxiety and depression; however, in 13.6% they report that these aspects do not improve. Conclusions: There is scientific evidence of the use of mindfulness, with MBCT being the most widely used therapy. The use of mindfulness improves, among others, anxiety, depression, fear of childbirth, stress, nausea and vomiting. (AU)
Asunto(s)
Humanos , Atención Plena , Parto , Periodo Posparto , EmbarazoRESUMEN
Newborn Screening Programs (NSP) in Spain were born in the city of Granada in 1968. Till the 1980s, they were developed around the so-called "National Plan for Preventing Subnormality", covering up to 30% of the Spanish newborns. From 1982, when the health system management was transferred to the different autonomous regions, the NSP began to expand, and the bases to transform them into an organized and multidisciplinary activity, integrated and coordinated from the National Health System were settled. Despite this expansion, it is not until the 1990s when their coverage reaches almost 100% newborns in Spain. NSP grew up asymmetrically across the different autonomous regions. In 2005 and 2006 the scientific societies SEQC (Spanish Society of Clinical Chemistry) and AECNE (Spanish Society of Newborn Screening), coordinated by the Health Promotion Area of the General Directorate of Public Health, gathered together the necessary information to elaborate a report on the NSP in Spain addressed to the Interterritorial Council of the National Health System. In July 2013, that Council approved the seven diseases that should be part of each region newborn screening panel, being the first step towards the NSP harmonization in Spain. Currently, the NSP include between 8 and 29 diseases in their panels, thus more still more efforts are needed in order to achieve a higher uniformity.
Los Programas de Cribado Neonatal (PCN) nacen en España en Granada en el año 1968. Posteriormente, y hasta los años 80, se fueron desarrollando en torno al llamado "Plan Nacional de Prevención de la Subnormalidad" con una cobertura cercana al 30% de los recién nacidos españoles. A partir de 1982, con el inicio de la gestión de la sanidad a las comunidades autónomas (CCAA), los PCN se expandieron y se comenzaron a sentar las bases para que éstos se convirtieran en una actividad organizada y multidisciplinar, integrados y coordinados desde el Sistema de Salud. A pesar de dicha expansión no es hasta el inicio de la década de los 90 cuando se consigue una cobertura próxima al 100% de los RN en España. Los PCN fueron creciendo de forma muy asimétrica en las diferentes CCAA y en los años 2005 y 2006 las Sociedades Científicas SEQC (Sociedad Española de Química Clínica) y AECNE (Asociación Española de Cribado Neonatal), con la coordinación del Área de Promoción de la Salud de la Dirección General de Salud Pública, recopilaron la información y elaboraron un informe, sobre los PCN en España para el Consejo Interterritorial del sistema Nacional de Salud (CISNS). En julio de 2013 este Consejo aprobó las siete enfermedades que debían formar parte del panel de detección de los PCN territoriales, primer paso hacia la armonización de estos programas. Actualmente, los PCN incluyen entre 8 y 29 enfermedades por lo que es necesario seguir trabajando para conseguir una mayor uniformidad.
Asunto(s)
Tamizaje Neonatal/historia , Tamizaje Neonatal/organización & administración , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Recién Nacido , EspañaRESUMEN
In recent years, different techniques to address the problem of observability in traffic networks have been proposed in multiple research projects, being the technique based on the installation of automatic vehicle identification sensors (AVI), one of the most successful in terms of theoretical results, but complex in terms of its practical application to real studies. Indeed, a very limited number of studies consider the possibility of installing a series of non-definitive plate scanning sensors in the elements of a network, which allow technicians to obtain a better conclusions when they deal with traffic network analysis such as urbans mobility plans that involve the estimation of traffic flows for different scenarios. With these antecedents, the contributions of this paper are (1) an architecture to deploy low-cost sensors network able to be temporarily installed on the city streets as an alternative of rubber hoses commonly used in the elaboration of urban mobility plans; (2) a design of the low-cost, low energy sensor itself, and (3) a sensor location model able to establish the best set of links of a network given both the study objectives and of the sensor needs of installation. A case of study with the installation of as set of proposed devices is presented, to demonstrate its viability.
RESUMEN
Incidental findings on newborn screening (NBS) are results that are not the target of screening within a given NBS program, but rather are found as a result of the screening and resulting diagnostic workup for that target. These findings may not have an immediate clinical impact on the newborn, but are sometimes an additional benefit of NBS programs and may be considered secondary targets of NBS programs. This work describes four case reports that had incidental findings on the NBS, which eventually led to the diagnosis of another metabolic disease instead of the one that was initially suspected. The first case was a new defect in the cationic amino acid transporter-2 (CAT-2), which was oriented as an arginase-1 deficiency in the newborn. The second case was a maternal glutaric aciduria type 1 (GA-1) that mimicked a carnitine transporter deficiency in the newborn. The third report was a case of lysinuric protein intolerance (LPI), which appeared as high levels of citrulline on the NBS. The fourth case was a mother with homocystinuria that was diagnosed during the biochemical study of vitamin B12 status. All cases provide new or interesting data that will help guide differential diagnosis in the future.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Encefalopatías Metabólicas/diagnóstico , Cardiomiopatías/diagnóstico , Carnitina/deficiencia , Glutaril-CoA Deshidrogenasa/deficiencia , Homocistinuria/diagnóstico , Hiperamonemia/diagnóstico , Enfermedades Musculares/diagnóstico , Tamizaje Neonatal/métodos , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Encefalopatías Metabólicas/sangre , Cardiomiopatías/sangre , Carnitina/sangre , Pruebas con Sangre Seca , Femenino , Glutaril-CoA Deshidrogenasa/sangre , Homocistinuria/sangre , Humanos , Hiperamonemia/sangre , Recién Nacido , Masculino , Enfermedades Musculares/sangreRESUMEN
No disponible
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Tamizaje Neonatal , Espectrometría de Masas en Tándem , Diagnóstico PrecozRESUMEN
RATIONALE: Obstructive sleep apnea (OSA) has been associated with increased cancer mortality, but whether it is also associated with cancer incidence is unknown. OBJECTIVES: To investigate whether OSA is associated with increased cancer incidence in a large clinical cohort. METHODS: A multicenter, clinical cohort study including consecutive patients investigated for suspected OSA between 2003 and 2007 in seven Spanish teaching hospitals. Apnea-hypopnea index (AHI) and percent nighttime with oxygen saturation less than 90% (TSat(90)) were used as surrogates of OSA severity, both as continuous variables and categorized by tertiles. Cox proportional hazards regression analyses were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for cancer incidence after adjusting for confounding variables. MEASUREMENTS AND MAIN RESULTS: A total of 4,910 patients were analyzed (median follow-up, 4.5 yr; interquartile range, 3.4-5.2). Compared with the lower TSat(90) category (<1.2%), the adjusted hazards (95% CI) of cancer incidence for increasing categories were 1.58 (1.07-2.34) for TSat(90) 1.2-12% and 2.33 (1.57-3.46) for TSat(90) greater than 12%. Continuous TSat(90) was also associated with cancer incidence (adjusted HR, 1.07 [1.02-1.13] per 10-unit increase in TSat(90)). In stratified analyses, TSat(90) was associated with cancer incidence in patients younger than 65 years (adjusted HR, 1.13 [95% CI, 1.06-1.21] per 10-unit increase in TSat(90)) and males (adjusted HR, 1.11 [95% CI, 1.04-1.17] per 10-unit increase in TSat(90)). AHI was not associated with cancer incidence in the adjusted analyses, except for patients younger than 65 years (adjusted HR for AHI >43 vs. <18.7, 1.66; 95% CI, 1.04-2.64). CONCLUSIONS: Increased overnight hypoxia as a surrogate of OSA severity was associated with increased cancer incidence. This association seems to be limited to men and patients younger than 65 years of age.
Asunto(s)
Neoplasias/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Factores de Edad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , España/epidemiologíaRESUMEN
Fundamento y objetivo. La detección precoz de errores innatos del metabolismo mediante espectrometría de masas en tándem permite ampliar el cribado tradicional de fenilcetonuria e hipotiroidismo primario congénito a aminoacidopatías, acidurias orgánicas y alteraciones de la beta-oxidación mitocondrial. En la Región de Murcia también se detecta la fibrosis quística y la deficiencia de biotinidasa. El objetivo de este estudio es describir nuestra experiencia en el cribado neonatal ampliado y definir la prevalencia de cada uno de los errores congénitos del metabolismo detectados precozmente. Pacientes y método. El programa de cribado metabólico neonatal expandido se ha realizado desde marzo de 2007 hasta octubre de 2010 y ha permitido analizar un total de 71.595 recién nacidos utilizando técnicas como la espectrometría de masas en tándem, el fluoroinmunoensayo o técnicas colorimétricas. Resultados. Se han detectado 38 pacientes (prevalencia 1:1.884) mediante espectrometría de masas en tándem, 13 se han diagnosticado de fibrosis quística (prevalencia 1:5.507), 38 de hipotiroidismo primario congénito (prevalencia 1:1.884) y uno por deficiencia de biotinidasa. La frecuencia global de metabolopatías es de 1:804. El valor predictivo positivo para los resultados obtenidos por espectrometría de masas en tándem fue de 20,25%. Hubo 2 falsos negativos (que fueron diagnosticados posteriormente de fibrosis quística y aciduria metilmalónica) y se detectaron 6 pacientes no neonatales. Conclusiones. Nuestros datos apoyan la necesidad de unificar el cribado neonatal en todas las comunidades españolas para la detección de un panel de enfermedades metabólicas y proporcionar a cada recién nacido las mismas oportunidades para el diagnóstico precoz(AU)
Background and objective. The early detection of inborn errors of metabolism by mass spectrometry allows expanding the traditional neonatal screening of phenylketonuria and congenital hypothyroidism to test for aminoacidopathies, fatty acid oxidation disorders and organic acid metabolic disorders. Cystic fibrosis and biotinidase deficiency screening is implemented in the Region of Murcia. The aim of the study is to describe our experience in the expanded neonatal screening and to define the prevalence of each of the metabolic disorders early detected. Patients and methods. Since March 2007 until October 2010, a total of 71,595 neonates were screened with this expanded program by mass spectrometry, fluoroimmunoassay or colorimetric methods. Results. Thirty-eight patients (prevalence 1:1,884) were diagnosed of inborn errors of metabolism by mass spectrometry, 13 patients of cystic fibrosis (prevalence 1:5,507), 38 of congenital hypothyroidism (prevalence 1:1,884) and one of biotinidase deficiency. To date, the global frequency of inborn errors of metabolism is estimated to be 1:804. The positive predictive value for the results obtained by mass spectrometry was 20.25%. Two false negative patients were not identified (cystic fibrosis and methylmalonic aciduria patients) and 6 non neonatal patients were detected through expanded neonatal screening. Conclusions. Our data support the necessity of unifying the set of metabolic diseases to be screened in all Regions of Spain for early detection of a defined panel of inborn errors of metabolism and to provide every newborn the same opportunities to be early diagnosed(AU)
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Tamizaje Neonatal/métodos , Errores Innatos del Metabolismo/epidemiología , Espectrometría de Masas en Tándem/métodos , Fibrosis Quística/epidemiología , Diagnóstico Precoz , Hipotiroidismo Congénito/epidemiología , Deficiencia de Biotinidasa/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVE: The early detection of inborn errors of metabolism by mass spectrometry allows expanding the traditional neonatal screening of phenylketonuria and congenital hypothyroidism to test for aminoacidopathies, fatty acid oxidation disorders and organic acid metabolic disorders. Cystic fibrosis and biotinidase deficiency screening is implemented in the Region of Murcia. The aim of the study is to describe our experience in the expanded neonatal screening and to define the prevalence of each of the metabolic disorders early detected. PATIENTS AND METHODS: Since March 2007 until October 2010, a total of 71,595 neonates were screened with this expanded program by mass spectrometry, fluoroimmunoassay or colorimetric methods. RESULTS: Thirty-eight patients (prevalence 1:1,884) were diagnosed of inborn errors of metabolism by mass spectrometry, 13 patients of cystic fibrosis (prevalence 1:5,507), 38 of congenital hypothyroidism (prevalence 1:1,884) and one of biotinidase deficiency. To date, the global frequency of inborn errors of metabolism is estimated to be 1:804. The positive predictive value for the results obtained by mass spectrometry was 20.25%. Two false negative patients were not identified (cystic fibrosis and methylmalonic aciduria patients) and 6 non neonatal patients were detected through expanded neonatal screening. CONCLUSIONS: Our data support the necessity of unifying the set of metabolic diseases to be screened in all Regions of Spain for early detection of a defined panel of inborn errors of metabolism and to provide every newborn the same opportunities to be early diagnosed.
Asunto(s)
Pruebas Genéticas , Tamizaje Neonatal , Acil-CoA Deshidrogenasa/sangre , Acil-CoA Deshidrogenasa/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Deficiencia de Biotinidasa/sangre , Deficiencia de Biotinidasa/diagnóstico , Deficiencia de Biotinidasa/epidemiología , Colorimetría , Hipotiroidismo Congénito/sangre , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/epidemiología , Fibrosis Quística/sangre , Fibrosis Quística/diagnóstico , Fibrosis Quística/epidemiología , Diagnóstico Precoz , Femenino , Pruebas Genéticas/métodos , Humanos , Técnicas para Inmunoenzimas , Recién Nacido , Errores Innatos del Metabolismo Lipídico/sangre , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/epidemiología , Masculino , Errores Innatos del Metabolismo/sangre , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/epidemiología , Tamizaje Neonatal/métodos , Tamizaje Neonatal/organización & administración , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , España/epidemiología , Espectrometría de Masas en TándemRESUMEN
OBJECTIVE: To describe the long-term efficacy of transtympanic steroids (TTS) using methyl-prednisolone in the treatment of Ménière's disease (MD). DESIGN: Descriptive prospective study. MAIN OUTCOME MEASURES: Pure-tone average (PTA) corresponding to the conversational frequencies on the audiogram (0.5, 1, 2, and 3 kHz), visual analog scale on tinnitus annoyance, and number of vertigo spells 24 months after treatment. RESULTS: Thirty-four MD patients referred to a tertiary center were treated with TTS. All patients were diagnosed as probable or definitive MD (following American Academy of Otolaryngology-Head and Neck Surgery 1995 criteria) and treated by TTS (3 consecutive doses). Data from 32 patients were achieved after 12 months. Forty-eight percent of the patients reduced the PTA in 10 or more decibels, average improvement was 8.6 dB compared with initial PTA (p = 0.004). Tinnitus relief was achieved by 81.5% of the patients. Number of vertigo spells was reduced from 4.3 to 0.3 after 12 months (p = 0.002); 81% of the patients were free of vertigo spells, and 92.6% had 1 or less spells of vertigo. Data from 29 patients were achieved after 24 months. A reduction of PTA in 10 or more decibels was shown by the 33.3% of the sample, and PTA improved in 3.3 dB compared with initial PTA (nonsignificant). Tinnitus relief was achieved in 78% of the patients. Number of vertigo spells was reduced from 4.3 to 0.5 (p = 0.033). Seventy-eight percent of the cases were free of vertigo, and 96% had none or 1 spell. Because of an increase in any of the symptoms, 12 patients (35.2%) required retreatment with 1 or 2 series of TTS (1-3 doses) along the 2-year period. Two patients of the sample (6.25%) required transtympanic gentamicin for vertigo control due to lack of benefit with TTS (14 and 18 mo since TTS). CONCLUSION: Transtympanic steroids in this cohort were associated with good preservation of hearing. Tinnitus control is achieved in more than 70% of the patients, and number of vertigo spells can be dramatically reduced in more than 90% of the patients after a 24-month follow-up.