Aerosolized lancovutide in adolescents (≥12 years) and adults with cystic fibrosis - a randomized trial.

Abstract Background Lancovutide activates a chloride channel (TMEM-16A) other than the cystic fibrosis (CF) transmembrane conductance regulator protein and could benefit CF patients. Methods In this randomized, multi-center, double-blind, placebo-controlled, parallel-group trial 161 patients ≥12 years with a confirmed diagnosis of CF were randomized to either placebo (saline) or active drug in 3 different dosing schemes of 2.5mg inhaled lancovutide (once daily, every other day or twice a week) for eight weeks. The primary endpoint was the change in the forced expiratory volume in 1 second (FEV1) percent predicted. Secondary endpoints included further lung function parameters (FEV1 (absolute), functional vital capacity percent predicted, forced expiratory flow percent predicted, pulse oximetry), quality of life assessment, pulmonary exacerbations, hospitalization due to pulmonary exacerbations, time to first pulmonary exacerbation, duration of anti-inflammatory, mucolytic or antibiotic treatment, and safety. Results There was no significant difference in the change in FEV1 percent predicted, quality of life, other lung function parameters, pulmonary exacerbations or requirement of additional treatment between groups. Overall, the inhalation of lancovutide was safe although a higher rate of adverse events, especially related to the respiratory system, occurred as compared to placebo. Conclusions Lancovutide did not improve FEV1 percent predicted when compared to placebo (NCT00671736)

The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation by cyclic AMP (cAMP). Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR gene mutation, and sweat chloride concentrations close to normal values. In vivo demonstration of abnormal CFTR protein function would be an important diagnostic aid in this situation. Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening. METHODS/DESIGN: We adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na(+)) transport in response to the Na(+ )channel inhibitor amiloride, and CFTR-mediated chloride (Cl(-)) secretion in response to isoproterenol, a β-agonist in a Cl(- )free solution. The study will include 20 children with CF and 20 healthy control children. CF children will be included only if they carry 2 CF-causing mutations in the CFTR gene or have sweat chloride concentrations > 60 mEq/L or both. The healthy children will be recruited among the siblings of the CF patients, after verification that they do not carry the familial mutation. DISCUSSION: A preliminary study of 3 adult control subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

MUCOVISCIDOSE (PROFIL EVOLUTIF D'UNE POPULATION NEE ENTRE 1976 ET 1986)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

INFLUENCE DE LA POLLUTION ATMOSPHERIQUE SUR LA GRAVITE DE LA BRONCHIOLITE DU NOURRISSON DE MOINS DE 6 MOIS (A PROPOS DE 190 NOURRISSONS LYONNAIS ETUDIES AU COURS DE L'HIVERS 1999-2000)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Métabolisme glucidique dans la mucoviscidose (comparaison des données du holter glycémique à celles de l'hyperglycémie provoquée par voie orale et intraveineuse et aux index homa)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Evaluation de l'ototoxicité induite par les aminosides chez les patients atteints de mucoviscidose (étude rétrospective à propos de 66 patients)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

State Constitutions post-1989: the amendment process and its causes

Esta dissertação pretende contribuir para o conhecimento de dimensões pouco estudadas do processo político estadual, especialmente a política constitucional nos estados brasileiros. Propomos estudar então o processo de emendamento às Constituições Estaduais. Para tanto levantamos os textos das Constituições Estaduais promulgadas após 1989 e suas emendas aprovadas entre 1989 e 2014. A partir dos dados levantados desenvolvemos uma análise descritiva das Constituições e das Emendas aprovadas com o objetivo de identificar padrões e características do constitucionalismo estadual. Além da análise descritiva também comparamos três unidades de medida de extensão constitucional, a quantidade de artigos, de palavras e de dispositivos. Nas análises descritivas encontramos variabilidade tanto na extensão Constitucional quanto no tamanho do emendamento. A fim de identificar fenômenos associados à variabilidade no emendamento desenvolvemos uma análise simplificada em que optamos por modelos estáticos e bivariados. Dentre os testes efetuados destacamos três resultados. A constitucionalização de políticas públicas parece afetar significativamente o emendamento de forma que parte do processo legislativo utiliza a alteração constitucional para avançar a agenda. A maior fragmentação do sistema político leva a aprovação de emendas mais extensas. E finalmente que parte do emendamento às Constituições Estaduais é explicado pelas alterações efetuadas à Constituição Federal.Our main purpose in this masters thesis is advancing the research on Brazilians state politics not yet adequately studied, mainly the state constitutional policy. Therefore, we intend an analysis on the amendment process of state Constitutions. Our first step was gathering the state Constitutions and their amendments between 1989 and 2014 and performing an exploratory descriptive analysis. Along with the descriptive analysis, we perform comparisons amongst three methods of measuring constitutional length, the number of articles, number of words and number of constitutional provisions. As a result of the exploratory analysis, we found considerable variability on state constitutional and amendment length. In order to identify possible phenomena related to amendment variability we perform a simplified analysis based on static and bivariate models. Amongst the performed tests, three results are noteworthy. The amount of public policies on Constitutional texts seem to increase the amendment. Higher party system fragmentation correlates with lengthier approved amends. Lastly, the state constitutional change shows an echo of the Federal Constitutional amendments

Phénotypes de génotypes rares de la mucoviscidose (description clinique)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF