A guide to interpreting estimated median age of survival in cystic fibrosis patient registry reports.

Survival statistics, estimated using data collected by national cystic fibrosis (CF) patient registries, are used to inform the CF community and monitor survival of CF populations. Annual registry reports typically give the median age of survival, though different registries use different estimation approaches and terminology, which has created confusion for the community. In this article we explain how median age of survival is estimated, what its interpretation is, and what assumptions and limitations are involved. Information on survival from birth is less useful for individuals who have already reached a certain age and we propose use of conditional survivor curves to address this. We provide recommendations for CF registries with the aim of facilitating clear and consistent reporting of survival statistics. Our recommendations are illustrated using data from the UK Cystic Fibrosis Registry

Processing, crystallization and oxidation of the Ni-Nb(-Sn) refractory alloy glass system

In this work, the topics of processing, crystallization and isothermal oxidation, below the glass transition temperature, of Ni-Nb(-Sn) based bulk metallic glasses are studied. In addition to the as-cast amorphous structures, the thermally treated amorphous structures, as well as the nanocrystalline and microcrystalline structures are studied. Characterizations were conducted by employing various experimental techniques, such as differential thermal analysis, x-ray diffraction, thermogravimetry, electron microscopy and atom probe tomography. The results show that the microcrystalline structures obey purely parabolic laws. The as-cast amorphous structures of Ni59.35Nb34.45Sn6.2, Ni57Nb34Sn9 and Ni58.85Nb34.45Sn6.2Si0.5 oxidize in a paralinear manner, while Ni70Nb30, Ni62Nb38 and Ni60Nb36Sn3B1 oxidize parabolically. The microcrystalline samples have lower parabolic oxidation rates than the as-cast amorphous structures with the same composition. Thermally treated amorphous- and especially the nanocrystalline- structures show significantly better oxidation resistance than the as-cast structures. The oxidation of the amorphous structure is accompanied by crystallization of Ni-rich intermetallics, among which Ni3Sn is found. Ni3Sn is not found as a product of devitrification in Ar. The results are discussed in terms of thermodynamics and kinetics of oxidation and crystallization.Die Themen dieser Arbeit sind die Herstellung, die Kristallisation und das Oxidationsverhalten von Ni-Nb(-Sn)-basierten metallischen Massivgläsern. Die Oxidationsstudien wurden mit Proben amorpher, mikrokristalliner und nanokristalliner Struktur durchgeführt. Als Methoden der Materialcharakterisierungen dienten die Differentialthermoanalyse, Röntgenbeugung, thermogravimetrische Analyse, Elektronenmikroskopie und tomographische Atomsonde. Die Ergebnisse zeigen, dass das zeitliche Oxidationsverhalten bei mikrokristallinen Strukturen parabolischen Gesetzen folgt. Amorphe Proben der Legierungen Ni59.35Nb34.45Sn6.2, Ni57Nb34Sn9 und Ni58.85Nb34.45Sn6.2Si0.5 oxidieren nach einem paralinearen Gesetz, während Ni70Nb30, Ni62Nb38 und Ni60Nb36Sn3B1 parabolischen Zeitgesetzen folgen. Die parabolischen Oxidationsraten der mikrokristallinen Proben sind niedriger als die der amorphen Proben mit gleicher Zusammensetzung. Die thermisch behandelten amorphen Proben sowie die nanokristallinen Proben zeigen einen höheren Oxidationswiderstand als die im Gusszustand amorphen Proben. Die Oxidation amorpher Proben findet mit Kristallisation in Ni-reichen intermetallischen Phasen, insbesondere Ni3Sn, statt. Bei einer Kristallisation in Ar-Atmosphäre wird die Entstehung von Ni3Sn nicht beobachtet. Die Ergebnisse werden hinsichtlich kinetischer und thermodynamischer Aspekte diskutiert

Bronchodilator responsiveness in wheezy infants and toddlers is not associated with asthma risk factors

Background There are limited data assessing bronchodilator responsiveness (BDR) in infants and toddlers with recurrent wheezing, and factors associated with a positive response. Objectives In a multicenter study of children ≤ 36 months old, we assessed the prevalence of and factors associated with BDR among infants/toddlers with recurrent episodes of wheezing. Methods Forced expiratory flows and volumes using the raised‐volume rapid thoracic compression method were measured in 76 infants/toddlers [mean (SD) age 16.8 (7.6) months] with recurrent wheezing before and after administration of albuterol. Prior history of hospitalization or emergency department treatment for wheezing, use of inhaled or systemic corticosteroids, physician treatment of eczema, environmental tobacco smoke exposure, and family history of asthma or allergic rhinitis were ascertained. Results Using the published upper limit of normal for post bronchodilator change (FEV 0.5  ≥ 13% and/or FEF 25–75  ≥ 24%) in healthy infants, 24% (n = 18) of children in our study exhibited BDR. The BDR response was not associated with any clinical factor other than body size. Dichotomizing subjects into responders (defined by published limits of normal) or by quartile to identify children with the greatest change from baseline (4th quartile vs. other) did not identify any other factor associated with BDR. Conclusions Approximately one quarter of infants/toddlers with recurrent wheezing exhibited BDR at their clinical baseline. However, BDR in wheezy infants/toddlers was not associated with established clinical asthma risk factors. Pediatr Pulmonol. 2012; 47:421–428. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91214/1/21567_ftp.pd

Risk for Asthma in Offspring of Asthmatic Mothers versus Fathers: A Meta-Analysis

Many human epidemiologic studies demonstrate that maternal asthma confers greater risk of asthma to offspring than does paternal disease. However, a handful have shown the opposite. Given this disparity, a meta-analysis is necessary to determine the veracity and magnitude of the "maternal effect."We screened the medical literature from 1966 to 2009 and performed a meta-analysis to compare the effect of maternal asthma vs. paternal asthma on offspring asthma susceptibility. Aggregating data from 33 studies, the odds ratio for asthma in children of asthmatic mothers compared with non-asthmatic mothers was significantly increased at 3.04 (95% confidence interval: 2.59-3.56). The corresponding odds ratio for asthma in children of asthmatic fathers was increased at 2.44 (2.14-2.79). When comparing the odds ratios, maternal asthma conferred greater risk of disease than did paternal asthma (3.04 vs. 2.44, p = 0.037). When analyzing the studies in which asthma was diagnosed by a physician the odds ratios were attenuated and no significant differences were observed (2.85 vs. 2.48, N = 18, p = 0.37). Similarly, no significant differences were observed between maternal and paternal odds ratios when analyzing the studies in which the patient population was 5 years or older (3.15 vs. 2.60, p = 0.14). However, in all cases the trend remained the same, that maternal asthma was a greater risk factor for asthma than paternal.The results show that maternal asthma increases offspring disease risk to a greater extent than paternal disease

Interpretation of Spirometry in Saskatchewan First Nations Adults

Originally Published in: Mark E. Fenton, Brian L. Graham, Sanja Stanojevic, Lorna Whitford, and Laurie Ironstand. Interpretation of Spirometry in Saskatchewan First Nations Adults. Annals of the American Thoracic Society 2018;Vol. 15:1237-1239. DOI: 10.1513/AnnalsATS.201711-909RL Copyright © 2018 the American Thoracic Society The final publication is available at https://doi.org/10.1513/AnnalsATS.201711-909RL.Saskatchewan Health Research FoundationPeer ReviewedThe Canadian First Nations and Inuit communities bear a large burden of respiratory disease, with increased rates of smoking, respiratory infections, asthma, chronic obstructive lung disease, and hospitalizations (1). Identification of respiratory disease and classification has relied on spirometric reference values from white individuals, or in the case of the Global Lung Initiative (GLI) dataset, “other” (2), because there are no published reference values for Canadian First Nations individuals. Several studies have suggested that spirometric values for Canadian Inuit populations may be different from those for white populations (3–7), but these observations are not consistent (7–10). This study investigated whether lung function measured in Plains Cree adults differed from that expected in white adults. Part of the data reported in this letter was presented at the 2014 American Thoracic Society International Conference in abstract form (11)

Inter-test reproducibility of the lung clearance index measured by multiple breath washout

Background: Traditionally the inter-test reproducibility of the lung clearance index (LCI) has been described in terms of absolute change (e.g. 1 unit), however, if LCI is more variable at higher values, interpretation of absolute changes in LCI may be biased. Aims: We assessed whether inter-test reproducibility depends on the LCI value and whether relative changes are better suited to define reproducibility. Methods: Multiple breath nitrogen washout (MBW) was measured at baseline, 1, 3, 6, 9 and 12 months in children aged 3-6 years with CF, and age-matched healthy controls. Reproducibility of the LCI between each pair of measurements was described using Bland Altman limits of agreement (LA), Coefficient of repeatability (CR), and relative change. Results: 148 children contributed 619 MBW measurements. The within-subject SD of the LCI between paired measurements, a measure of variability, increased as the absolute LCI increased. Therefore, using LA or the CR to determine thresholds of inter-test reproducibility will over-estimate clinically relevant changes in patients with higher LCI values. Using relative changes, a physiologically or clinically relevant change in healthy preschool children was calculated to be +/- 15%, whereas it was +/- 30% in CF children. The average relative change in both health and CF was independent of the time interval between measurements. Conclusions: Since LCI variability is proportional to its mean, interpretation of absolute changes will be biased. Changes in LCI greater than +/- 15% can be considered greater than the biological variability of the test in health and may help to identify patients with clinically relevant changes in lung function

Exploring flexible polynomial regression as a method to align routine clinical outcomes with daily data capture through remote technologies

BACKGROUND: Clinical outcomes are normally captured less frequently than data from remote technologies, leaving a disparity in volumes of data from these different sources. To align these data, flexible polynomial regression was investigated to estimate personalised trends for a continuous outcome over time. METHODS: Using electronic health records, flexible polynomial regression models inclusive of a 1st up to a 4th order were calculated to predict forced expiratory volume in 1 s (FEV1) over time in children with cystic fibrosis. The model with the lowest AIC for each individual was selected as the best fit. The optimal parameters for using flexible polynomials were investigated by comparing the measured FEV1 values to the values given by the individualised polynomial. RESULTS: There were 8,549 FEV1 measurements from 267 individuals. For individuals with > 15 measurements (n = 178), the polynomial predictions worked well; however, with < 15 measurements (n = 89), the polynomial models were conditional on the number of measurements and time between measurements. The method was validated using BMI in the same population of children. CONCLUSION: Flexible polynomials can be used to extrapolate clinical outcome measures at frequent time intervals to align with daily data captured through remote technologies

Implementation of prognostic machine learning algorithms in paediatric chronic respiratory conditions: a scoping review.

Machine learning (ML) holds great potential for predicting clinical outcomes in heterogeneous chronic respiratory diseases (CRD) affecting children, where timely individualised treatments offer opportunities for health optimisation. This paper identifies rate-limiting steps in ML prediction model development that impair clinical translation and discusses regulatory, clinical and ethical considerations for ML implementation. A scoping review of ML prediction models in paediatric CRDs was undertaken using the PRISMA extension scoping review guidelines. From 1209 results, 25 articles published between 2013 and 2021 were evaluated for features of a good clinical prediction model using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines.Most of the studies were in asthma (80%), with few in cystic fibrosis (12%), bronchiolitis (4%) and childhood wheeze (4%). There were inconsistencies in model reporting and studies were limited by a lack of validation, and absence of equations or code for replication. Clinician involvement during ML model development is essential and diversity, equity and inclusion should be assessed at each step of the ML pipeline to ensure algorithms do not promote or amplify health disparities among marginalised groups. As ML prediction studies become more frequent, it is important that models are rigorously developed using published guidelines and take account of regulatory frameworks which depend on model complexity, patient safety, accountability and liability