Article
Biochemical Research Methods
Adriana Zardini Buzatto, Mai Abdel Jabar, Imran Nizami, Majed Dasouki, Liang Li, Anas M. Abdel Rahman
Summary: Cystic fibrosis is a genetic disease characterized by abnormal accumulation of mucus in various body tracts, caused by mutations in the CFTR gene. Lipid metabolism alterations related to the disease and different genotypic mutations have been uncovered through comprehensive lipidomics analysis, suggesting potential therapeutic targets. Dyslipidemia, particularly in odd-chain and polyunsaturated fatty acyl lipids, was observed in cystic fibrosis patients, alongside affected phosphatidic acids and diacylglycerols influenced by different genotypic mutation classes. Biomarker panels composed of specific lipids were able to classify patients and differentiate those with reduced lung function, providing valuable insights for future research and treatment.
JOURNAL OF PROTEOME RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Evelina Moliteo, Monica Sciacca, Antonino Palmeri, Maria Papale, Sara Manti, Giuseppe Fabio Parisi, Salvatore Leonardi
Summary: There is substantial evidence that patients with cystic fibrosis (CF) have higher oxidative stress levels, which contribute to the progression of chronic lung damage. CF patients exhibit an abnormal proinflammatory environment in their airways even before infection, possibly due to elevated oxidative stress and abnormal lipid metabolism. CFTR deficiency appears to cause a redox imbalance in epithelial cells and extracellular fluids.
Review
Biochemistry & Molecular Biology
Caitlyn Harvey, Sinead Weldon, Stuart Elborn, Damian G. Downey, Clifford Taggart
Summary: The advent of CFTR modulators in cystic fibrosis treatment has transformed the management of the disease, shifting it from being a life-limiting condition to one that can be effectively managed. These genotype-specific therapies have shown significant improvements in various clinical endpoints, but their effects on pathogenic burden and airway infection need further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Rita Padoan, Serena Quattrucci, Annalisa Amato, Vincenzo Carnovale, Donatello Salvatore, Marco Salvatore, Giuseppe Campagna
Summary: This study examined a subgroup of Italian CF patients diagnosed late, with a median age of 36.2 years at diagnosis. Among male patients, 45.9% were diagnosed due to infertility, and there was a low prevalence of pancreatic insufficiency and Pseudomonas aeruginosa infection in late diagnosis patients, suggesting a mild CF phenotype in the majority of cases.
Article
Pharmacology & Pharmacy
Jia Liu, Allison P. Berg, Yiting Wang, Walailak Jantarajit, Katy J. Sutcliffe, Edward B. Stevens, Lishuang Cao, Marko J. Pregel, David N. Sheppard
Summary: This study investigates the action of a new CFTR potentiator, CP-628006, and compares it with the marketed CFTR potentiator ivacaftor. CP-628006 has distinct effects compared to ivacaftor, suggesting a different mechanism of CFTR potentiation. The emergence of CFTR potentiators with diverse modes of action makes therapy with combinations of potentiators a possibility.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Hannah Farley, Sarah Poole, Stephen Chapman, William Flight
Summary: A retrospective single-center cohort study identified 19 adult patients diagnosed with CF, all of whom had a history of chronic respiratory symptoms and the majority of whom had a CFTR genotype considered eligible for CFTR modulator therapy.
POSTGRADUATE MEDICAL JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Oscar Fonseca, Maria Salome Gomes, Maria Adelina Amorim, Ana Cordeiro Gomes
Summary: Cystic fibrosis, a monogenic disease, has a diverse clinical presentation involving chronic lung infection, inflammation, and reduced bone mass. The underlying mechanisms of reduced bone mass in cystic fibrosis patients are still unclear. This review explores the relationship between CFTR dysfunction and intrinsic bone defects, as well as the impact of the proinflammatory environment and chronic infection on bone mass maintenance in CF patients.
Article
Cell & Tissue Engineering
Winnie Khor, Tzyh-Chang Hwang, Chih-Chien Wang, Aliaksandr A. Yarmishyn, Jiunn-Tyng Yeh, Shih-Hwa Chiou, Shih-Jie Chou
Summary: CF is a genetic disease that affects CFTR channel synthesis. While 90% of CF patients benefit from small molecule target therapies, those with nonsense mutations still lack effective treatment. This study generates induced pluripotent stem cells (iPSCs) from CF patients carrying a specific nonsense mutation, providing a valuable resource for future CF research.
STEM CELL RESEARCH
(2022)
Article
Respiratory System
Edmund H. Sears, Alexandra C. Hinton, Sara Lopez-Pintado, Christine W. Lary, Jonathan B. Zuckerman
Summary: The study found that prolonged periods of missed care in cystic fibrosis patients were associated with decreased lung function, especially in adolescents and young adults.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)
Article
Pharmacology & Pharmacy
L. Clara Mok, Antonio Garcia-Uceda, Matthew N. Cooper, Mariette Kemner Van De Corput, Marleen De Bruijne, Nathalie Feyaerts, Tim Rosenow, Kris De Boeck, Stephen Stick, Harm A. W. M. Tiddens
Summary: Newly developed quantitative CT outcomes designed for CF lung disease can assess structural abnormalities. CFTR modulators have the potential to reduce these abnormalities. This study aimed to investigate the effect of CFTR modulators on the progression of structural lung disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Respiratory System
Carla Colombo, Grant A. Ramm, Anders Lindblad, Fabiola Corti, Luigi Porcaro, Federico Alghisi, Irina Asherova, Helen Evans, Nataliya Kashirskaya, Elena Kondratyeva, Peter J. Lewindon, Isabelle de Monestrol, Mark Oliver, Chee Y. Ooi, Rita Padoan, Sahana Shankar, Gianfranco Alicandro
Summary: Cystic-fibrosis-related liver disease (CFLD) is a variable phenotype of CF. CFTR modulator therapies, elexacaftor, tezacaftor, and ivacaftor (ETI), and ivacaftor (IVA), are available for CF patients. Genetic eligibility evaluation showed that 13% of patients without CFLD and 11% of patients with severe CFLD are not eligible for ETI or IVA therapy. Ineligible patients cannot benefit from these new treatments.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Respiratory System
Daniela K. Schluter, Josh S. Ostrenga, Siobhan B. Carr, Aliza K. Fink, Albert Faro, Rhonda D. Szczesniak, Ruth H. Keogh, Susan C. Charman, Bruce C. Marshall, Christopher H. Goss, David Taylor-Robinson
Summary: A previous analysis found that US pediatric CF patients had higher lung function compared to the UK, a difference that remained throughout childhood. There were no significant differences in early growth, nutrition, or infections, but differences in early treatments were observed.
Review
Cell Biology
Francesca Saluzzo, Luca Riberi, Barbara Messore, Nicola Ivan Lore, Irene Esposito, Elisabetta Bignamini, Virginia De Rose
Summary: Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, leading to imbalances in the airway microenvironment and increased susceptibility to infections. CFTR modulators have shown promise in improving airway infections, but their long-term effects remain to be fully understood.
Article
Obstetrics & Gynecology
Rita F. Padoan, Serena Quattrucci, Annalisa Amato, Marco Salvatore, Donatello Salvatore, Giuseppe Campagna
Summary: The study found that preconceptional respiratory function of women with cystic fibrosis (CF) is associated with the duration of pregnancy and birthweight of newborns, and cesarean deliveries are common among young CF women with normal respiratory function.
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
(2021)
Article
Respiratory System
Irushi Ratnayake, Susannah Ahern, Rasa Ruseckaite
Summary: Participants in this study generally supported the usefulness and practicality of PROM implementation in the ACFDR. They believed that PROMs could provide valuable aggregate health-related quality of life data and emphasized the importance of feedback mechanisms for patients and clinicians. Most participants preferred electronic PROM administration for easy integration and support for feedback.
BMJ OPEN RESPIRATORY RESEARCH
(2021)
Article
Respiratory System
Amy Macdougall, Deborah Jarvis, Ruth H. Keogh, Cole Bowerman, Diana Bilton, Gwyneth Davies, Siobhan B. Carrf, Sanja Stanojevic
Summary: Understanding the relationship between weight trajectories and lung function in children with Cystic Fibrosis (CF) can provide guidance for clinical care. The study found that weight at one year and weight trajectories in early childhood are associated with later lung function. Current guidelines may need to be updated to focus more on tracking weight trajectories over time.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Statistics & Probability
Ornulf Borgan, Ruth H. Keogh, Aleksander Njos
Summary: Nested case-control and case-cohort studies are useful for investigating associations between covariates and time-to-event. Multiple imputation can be used to efficiently analyze the full cohort data and supplement the case-control samples with additional controls. Simulations demonstrate efficiency gains compared to traditional analysis.
SCANDINAVIAN JOURNAL OF STATISTICS
(2023)
Article
Mathematical & Computational Biology
C. Bottomley, M. Ooko, A. Gasparrini, R. H. Keogh
Summary: Interrupted time series are increasingly used in assessing population impact of public health interventions. Proper analysis takes into account the auto correlation of the data, which can be addressed using the Prais-Winsten method, the Newey-West method, or autoregressive-moving-average (ARMA) modeling. This study explores the performance of these methods in 20 simulated autocorrelation scenarios and suggests that the Prais-Winsten and ARMA methods perform best in terms of mean square error, while the Prais-Winsten method generally performs better in terms of coverage. The authors recommend using the Prais-Winsten method due to its good statistical properties and decision-free nature.
STATISTICS IN MEDICINE
(2023)
Review
Infectious Diseases
Catriona Macrae, Jayne Ellis, Suzanne H. Keddie, Jane Falconer, John Bradley, Ruth Keogh, Oliver Baerenbold, Heidi Hopkins, Joseph N. Jarvis
Summary: This article systematically evaluated the diagnostic performance of IMMY CrAg LFA in HIV-negative populations through a systematic review. The results showed that this test has high sensitivity and specificity in both serum and cerebrospinal fluid, providing an effective diagnostic method for cryptococcosis in HIV-negative individuals.
BMC INFECTIOUS DISEASES
(2023)
Article
Mathematics, Interdisciplinary Applications
Ruth H. Keogh, Karla Diaz-Ordaz, Nicholas P. Jewell, Malcolm G. Semple, Liesbeth C. de Wreede, Hein Putter
Summary: Multi-state models are used to describe individuals' transitions through different states over time. This paper focuses on the distribution of time spent in different states conditional on the complete pathway taken through the states, known as 'conditional length of stay'. Non-parametric methods for estimating conditional length of stay distributions in the presence of censoring are described, and are applied to estimate conditional length of stay distributions for individuals hospitalised due to Covid-19 in the UK.
LIFETIME DATA ANALYSIS
(2023)
Article
Pediatrics
Emrah Gecili, Cole Brokamp, Erika Rasnick, Pedro M. Afonso, Eleni-Rosalina Andrinopoulou, Judith W. Dexheimer, John P. Clancy, Ruth H. Keogh, Yizhao Ni, Anushka Palipana, Teresa Pestian, Andrew Vancil, Grace C. Zhou, Weiji Su, Christopher Siracusa, Patrick Ryan, Rhonda D. Szczesniak
Summary: This study aimed to investigate the impact of built environment characteristics on rapid decline of lung function in adolescents and young adults with cystic fibrosis (CF). The study found that traffic-related elemental carbon exposure, community material deprivation, and greenspace near the home were associated with rapid decline of CF lung function.
PEDIATRIC PULMONOLOGY
(2023)
Article
Mathematical & Computational Biology
Ruth H. Keogh, Jon Michael Gran, Shaun R. Seaman, Gwyneth Davies, Stijn Vansteelandt
Summary: This article discusses how longitudinal observational data can be used to study the causal effects of time-varying treatments on time-to-event outcomes. It compares two methods: marginal structural models (MSM) and sequential trials approach, and discusses their assumptions and differences in data usage. Simulation study shows that the sequential trials approach is more efficient in estimating the marginal risk difference in most follow-up times, but this efficiency may be reversed at later time points and relies on modelling assumptions. The methods are applied to estimate the effect of dornase alfa on survival in longitudinal observational data from the UK Cystic Fibrosis Registry.
STATISTICS IN MEDICINE
(2023)
Article
Medicine, General & Internal
William J. Hulme, Elsie M. F. Horne, Edward P. K. Parker, Ruth H. Keogh, Elizabeth J. Williamson, Venexia Walker, Tom M. Palmer, Helen J. Curtis, Alex J. Walker, Colm D. Andrews, Amir Mehrkar, Jessica Morley, Brian MacKenna, Sebastian C. J. Bacon, Ben Goldacre, Miguel A. Hernan, Jonathan A. C. Sterne
Summary: A study compared the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England. The results showed that mRNA-1273 had a modest benefit in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 compared to BNT162b2.
BMJ-BRITISH MEDICAL JOURNAL
(2023)
Letter
Public, Environmental & Occupational Health
Elsie M. F. Horne, William J. Hulme, Ruth H. Keogh, Tom M. Palmer, Elizabeth J. Williamson, Edward P. K. Parker, Venexia M. Walker, Rochelle Knight, Yinghui Wei, Kurt Taylor, Louis Fisher, Jessica Morley, Amir Mehrkar, Iain Dillingham, Sebastian Bacon, Ben Goldacre, Jonathan A. C. Sterne
Summary: Understanding how the effectiveness of COVID-19 vaccines changes over time and in response to new variants is crucial for scheduling subsequent doses. Previous research has shown that vaccine effectiveness decreases in a log-linear manner over time and remains consistent across different risk-based subgroups. To further investigate the waning effectiveness beyond 26 weeks and in the era of the Omicron variant, the follow-up period was extended to the earliest of 50 weeks after the second dose or March 31, 2022.
AMERICAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Multidisciplinary Sciences
Ryan Chung, Zhe Xu, Matthew Arnold, David Stevens, Ruth Keogh, Jessica Barrett, Hannah Harrison, Lisa Pennells, Lois G. Kim, Emanuele Diangelantonio, Ellie Paige, Juliet A. Usher-Smith, Angela M. Wood
Summary: Prioritizing individuals for formal CVD risk assessment using eHEART with age- and sex-specific thresholds can lead to more efficient assessment programs with minimal decrease in effectiveness at preventing new CVD events.
Article
Respiratory System
Emily Granger, Gwyneth Davies, Ruth H. Keogh
Summary: This study investigates whether adding hypertonic saline to patients with cystic fibrosis who are already using dornase alfa has additional benefits for lung function or use of intravenous antibiotics. The findings indicate that adding hypertonic saline does not significantly improve lung function or decrease the use of intravenous antibiotics in cystic fibrosis patients.
Editorial Material
Critical Care Medicine
Gwyneth Davies, Ruth H. Keogh
LANCET RESPIRATORY MEDICINE
(2023)
Article
Respiratory System
Rhonda Szczesniak, Eleni-Rosalina Andrinopoulou, Weiji Su, Pedro M. Afonso, Pierre-Regis Burgel, Elizabeth Cromwell, Emrah Gecili, Enas Ghulam, Christopher H. Goss, Nicole Mayer-Hamblett, Ruth H. Keogh, Theodore G. Liou, Bruce Marshall, Wayne J. Morgan, Joshua S. Ostrenga, David J. Pasta, Sanja Stanojevic, Claire Wainwright, Grace C. Zhou, Gabriela Fernandez, Aliza K. Fink, Michael S. Schechter
Summary: The study aims to estimate the rate of lung function decline in cystic fibrosis and examine the impact of different research methods on the results. The findings show that the choice of modeling strategy can affect the estimated rate of decline, but the results are generally reliable under specific scenarios.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)
Review
Infectious Diseases
Tamalee Roberts, Suzanne H. Keddie, Sayaphet Rattanavong, Santiago Rayment Gomez, John Bradley, Ruth H. Keogh, Oliver Barenbold, Jane Falconer, Petra F. Mens, Heidi Hopkins, Elizabeth A. Ashley
Summary: This systematic review and meta-analysis demonstrated high estimated pooled sensitivity and specificity of DAT for the diagnosis of VL, although there were variations in sensitivity and specificity for different patient groups and geographical locations. Standardization of DAT methods and preparations, along with data availability from more geographical locations, are highlighted as areas for improvement in future studies.
BMC INFECTIOUS DISEASES
(2023)
