Publications by authors named "J Robert Macey"

102 Publications

Rapid Improvement After Starting Elexacaftor-tezacaftor-ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease.

Am J Respir Crit Care Med 2021 Feb 18. Epub 2021 Feb 18.

Groupe Hospitalier Cochin-Hotel Dieu, AP-HP, Pulmonary Department and Adult CF Centre, Paris, France.

Rationale: Elexacaftor-tezacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator modulator combination, developed for cystic fibrosis (CF) patients with at least one Phe508del mutation.

Objectives: To evaluate the effects of elexacaftor-tezacaftor-ivacaftor in CF patients with advanced respiratory disease.

Methods: A prospective observational study, including all patients aged ≥12 years and with ppFEV1<40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at one and three months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries.

Main Results: Elexacaftor-tezacaftor-ivacaftor was initiated in 245 patients with a median [IQR] ppFEV1=29 [24; 34]. Mean (95% confidence interval) absolute increase in ppFEV1 was +15.1 (+13.8,+16.4; P<0.0001) and in weight was +4.2 kg (+3.9, +4.6; P<0.0001). The number of patients requiring long-term oxygen, non-invasive ventilation and/or enteral tube feeding decreased by 50%, 30% and 50%, respectively (P<0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only two were transplanted and one died. By September 2020 only five patients were still on transplantation path. Compared with the previous two years, a two-fold decrease in the number of lung transplantations in CF patients was observed in 2020, while the number of death without transplantation remained stable.

Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended.
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http://dx.doi.org/10.1164/rccm.202011-4153OCDOI Listing
February 2021

Evidence of two deeply divergent co-existing mitochondrial genomes in the Tuatara reveals an extremely complex genomic organization.

Commun Biol 2021 Jan 29;4(1):116. Epub 2021 Jan 29.

Department of Anatomy, University of Otago, PO Box 913, Dunedin, 9054, New Zealand.

Animal mitochondrial genomic polymorphism occurs as low-level mitochondrial heteroplasmy and deeply divergent co-existing molecules. The latter is rare, known only in bivalvian mollusks. Here we show two deeply divergent co-existing mt-genomes in a vertebrate through genomic sequencing of the Tuatara (Sphenodon punctatus), the sole-representative of an ancient reptilian Order. The two molecules, revealed using a combination of short-read and long-read sequencing technologies, differ by 10.4% nucleotide divergence. A single long-read covers an entire mt-molecule for both strands. Phylogenetic analyses suggest a 7-8 million-year divergence between genomes. Contrary to earlier reports, all 37 genes typical of animal mitochondria, with drastic gene rearrangements, are confirmed for both mt-genomes. Also unique to vertebrates, concerted evolution drives three near-identical putative Control Region non-coding blocks. Evidence of positive selection at sites linked to metabolically important transmembrane regions of encoded proteins suggests these two mt-genomes may confer an adaptive advantage for an unusually cold-tolerant reptile.
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http://dx.doi.org/10.1038/s42003-020-01639-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846811PMC
January 2021

Understanding the Five-Year Outcomes of Abusive Head Trauma in Children: A Retrospective Cohort Study.

Dev Neurorehabil 2021 Jan 22:1-7. Epub 2021 Jan 22.

Kids Rehab, The Children's Hospital at Westmead , NSW, Australia.

Understanding the long-term medical and developmental outcomes for children who survive abusive head trauma (AHT) is important to ensure necessary supports and services are available. This study examined the retrospective global and specific medical and developmental outcomes of 55 children with AHT who were treated at The Children's Hospital at Westmead. Global outcomes were assessed using the Kings Outcome Scale of Childhood Head Injury (KOSCHI). Five years post-injury, one child had died and two had made a complete recovery. Forty-five children (81.8%) had a moderate or severe disability, an increase from 64.5% at acute discharge. At follow-up, the main impairments were behavioral problems (53%), vision impairment (44%), fine motor difficulties (26%), gross motor problems (26%), communication problems (24%) and 16% had seizures. A Spearman's Rank correlation revealed that only 41% of variance in KOSCHI scores five years post-injury could be accounted for KOSCHI scores at the time of acute discharge (rs(55) = 0.638, < .001), and many children's presentation was worse at follow-up. Therefore, all children presenting with AHT need long term follow up regardless of early indications of good recovery.
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http://dx.doi.org/10.1080/17518423.2020.1869340DOI Listing
January 2021

Dermatologist and Patient Perceptions of Treatment Success in Alopecia Areata and Evaluation of Clinical Outcome Assessments in Japan.

Dermatol Ther (Heidelb) 2021 Jan 10. Epub 2021 Jan 10.

Medical Development Unit, Eli Lilly Japan K.K., Kobe, Japan.

Introduction: The content validity and treatment success thresholds of clinical outcome assessments (COAs) for alopecia areata (AA)-including the Alopecia Areata-Investigator Global Assessment™ (AA-IGA™), Scalp Hair Assessment Patient-Reported Outcome™ (PRO), and clinician-reported outcome (ClinRO) and PRO measures for eyebrows, eyelashes, eye irritation, and nails-were established in interviews with dermatologists and patients in North America. This study aimed to confirm the content validity and treatment success thresholds of these measures with clinicians and patients in Japan.

Methods: Qualitative interviews were conducted in Japan with dermatologists with AA expertise and adults with AA who experienced ≥ 50% scalp hair loss. Interviews included concept elicitation and cognitive interview questions. Data were analyzed using thematic and framework techniques.

Results: Seven dermatologists and 15 patients participated. Scalp hair loss was the most important sign/symptom of AA and the greatest treatment priority. Dermatologists and patients understood the AA-IGA™, Scalp Hair Assessment PRO™, and other COAs, and found these measures to be appropriate, relevant, and clinically meaningful. Dermatologists and patients confirmed that achieving ≤ 20% scalp hair loss (AA-IGA™/Scalp Hair Assessment PRO™ categories 0 or 1) indicated treatment success for patients with ≥ 50% scalp hair loss. Categories 0 or 1 on the other COAs represented treatment success.

Conclusion: This study confirmed the content validity and treatment success thresholds of the AA-IGA™, Scalp Hair Assessment PRO™, and other ClinRO and PRO measures for AA in Japan. These findings were aligned with interview results in North America and support the use of these measures in AA treatment studies.
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http://dx.doi.org/10.1007/s13555-020-00477-6DOI Listing
January 2021

The demise of a wonder: Evolutionary history and conservation assessments of the Wonder Gecko Teratoscincus keyserlingii (Gekkota, Sphaerodactylidae) in Arabia.

PLoS One 2021 7;16(1):e0244150. Epub 2021 Jan 7.

Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), Passeig Marítim de la Barceloneta, Barcelona, Spain.

Effective biodiversity conservation planning starts with genetic characterization within and among focal populations, in order to understand the likely impact of threats for ensuring the long-term viability of a species. The Wonder Gecko, Teratoscincus keyserlingii, is one of nine members of the genus. This species is distributed in Iran, Afghanistan, and Pakistan, with a small isolated population in the United Arab Emirates (UAE), where it is classified nationally as Critically Endangered. Within its Arabian range, anthropogenic activity is directly linked to the species' decline, with highly localised and severely fragmented populations. Here we describe the evolutionary history of Teratoscincus, by reconstructing its phylogenetic relationships and estimating its divergence times and ancestral biogeography. For conservation implications of T. keyserlingii we evaluate the genetic structure of the Arabian population using genomic data. This study supports the monophyly of most species and reveals considerable intraspecific variability in T. microlepis and T. keyserlingii, which necessitate broad systematic revisions. The UAE population of T. keyserlingii likely arrived from southern Iran during the Pleistocene and no internal structure was recovered within, implying a single population status. Regional conservation of T. keyserlingii requires improved land management and natural habitat restoration in the species' present distribution, and expansion of current protected areas, or establishment of new areas with suitable habitat for the species, mostly in northern Abu Dhabi Emirate.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244150PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790289PMC
January 2021

The Clinical Use of Lung MRI in Cystic Fibrosis: What, Now, How?

Chest 2020 Dec 17. Epub 2020 Dec 17.

Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH.

To assess airway and lung parenchymal damage noninvasively in cystic fibrosis (CF), chest MRI has been historically out of the scope of routine clinical imaging because of technical difficulties such as low proton density and respiratory and cardiac motion. However, technological breakthroughs have emerged that dramatically improve lung MRI quality (including signal-to-noise ratio, resolution, speed, and contrast). At the same time, novel treatments have changed the landscape of CF clinical care. In this contemporary context, there is now consensus that lung MRI can be used clinically to assess CF in a radiation-free manner and to enable quantification of lung disease severity. MRI can now achieve three-dimensional, high-resolution morphologic imaging, and beyond this morphologic information, MRI may offer the ability to sensitively differentiate active inflammation vs scarring tissue. MRI could also characterize various forms of inflammation for early guidance of treatment. Moreover, functional information from MRI can be used to assess regional, small-airway disease with sensitivity to detect small changes even in patients with mild CF. Finally, automated quantification methods have emerged to support conventional visual analyses for more objective and reproducible assessment of disease severity. This article aims to review the most recent developments of lung MRI, with a focus on practical application and clinical value in CF, and the perspectives on how these modern techniques may converge and impact patient care soon.
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http://dx.doi.org/10.1016/j.chest.2020.12.008DOI Listing
December 2020

Quantification of MRI T2 Interstitial Lung Disease Signal-Intensity Volume in Idiopathic Pulmonary Fibrosis: A Pilot Study.

J Magn Reson Imaging 2020 Nov 25. Epub 2020 Nov 25.

Centre de Recherche Cardio-Thoracique de Bordeaux, Univ. Bordeaux, INSERM U1045, CIC 1401, Bordeaux, France.

Background: Imaging has played a pivotal role in the diagnosis of idiopathic pulmonary fibrosis (IPF). Recent reports suggest that T -weighted MRI could be sensitive to monitor signal-intensity modifications of the lung parenchyma, which may relate to the disease activity in IPF. However, there is a lack of automated tools to reproducibly quantify the extent of the disease, especially using MRI.

Purpose: To assess the feasibility of T interstitial lung disease signal-intensity volume quantification using a semiautomated method in IPF.

Study Type: Single center, retrospective.

Population: A total of 21 adult IPF patients and four control subjects without lung interstitial abnormalities.

Field Strength/sequence: Both free-breathing ultrashort echo time (TE) lung MRI using the spiral volume interpolated breath hold examination (VIBE) sequence (3D-UTE) and T -BLADE at 1.5T.

Assessment: Semiautomated segmentation of the lung volume was done using 3D-UTE and registered to the T -BLADE images. The interstitial lung disease signal-intensity volume (ISIV) was quantified using a Gaussian mixture model clustering and then normalized to the lung volume to calculate T -ISIV. The composite physiological index (CPI) and forced vital capacity (FVC) were measured as known biomarkers of IPF severity. Measurements were performed independently by three readers and averaged. The reproducibility between measurements was also assessed.

Statistical Tests: Reproducibility was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Correlations were assessed using Spearman test. Comparison of median was assessed using the Mann-Whitney test.

Results: The reproducibility of T -ISIV was high, with ICCs = 0.99. Using Bland-Altman analysis, the mean differences were found between -0.8 to 0.1. T -ISIV significantly correlated with CPI and FVC (rho = 0.48 and 0.50, respectively; P < 0.05). T -ISIV was significantly higher in IPF than in controls (P < 0.05).

Data Conclusion: T -ISIV appears to be able to reproducibly assess the volumetric extent of abnormal interstitial lung signal-intensity modifications in patients with IPF, and correlate with disease severity.

Level Of Evidence: 4 TECHNICAL EFFICACY STAGE: 1.
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http://dx.doi.org/10.1002/jmri.27454DOI Listing
November 2020

Treatment Preferences of Patients with Chronic Obstructive Pulmonary Disease: Results from Qualitative Interviews and Focus Groups in the United Kingdom, United States, and Germany.

Chronic Obstr Pulm Dis 2021 Jan;8(1)

Value Evidence and Outcomes, GlaxoSmithKline plc., Collegeville, Pennsylvania, United States.

Background: A wide range of therapeutic regimens, including single-inhaler triple therapies (SITTs), are now available for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Thus, an improved understanding of patient preferences may be valuable to inform physician prescribing decisions. This study was performed to assess the factors considered by patients when making decisions about their COPD treatments using qualitative techniques.

Methods: In the United Kingdom, United States and Germany, individual qualitative interviews (n=10 per country) and focus groups (1 per country; [United Kingdom, n=4; United States, n=6; Germany, n=6 participants]) were conducted. Interviews and focus groups were semi‑structured, lasting approximately 60 minutes, and focused on treatment preferences. Data were analyzed according to emerging themes identified from the interviews; qualitative thematic analysis of the data was performed using specialist software.

Results: In interviews and focus groups, efficacy, ease of use, and lower frequency of use were favored attributes for current treatment, while side effects, medication taste, and more complex administration techniques were key dislikes. In interviews, most participants would consider a switch in medication, mainly for improved efficacy, but also to reduce medication frequency or following physician advice. Overall, efficacy and ease of use were the 2 most important attributes reported in interviews in all 3 countries.

Conclusion: Patients with COPD have preferences for certain attributes of medication, highlighting the multi-faceted nature of treatment effectiveness and the importance of the delivery device.These results were subsequently used to inform the design of a discrete choice experiment.
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http://dx.doi.org/10.15326/jcopdf.8.1.2020.0131DOI Listing
January 2021

The Role of Patients in Alopecia Areata Endpoint Development: Understanding Physical Signs and Symptoms.

J Investig Dermatol Symp Proc 2020 11;20(1):S71-S77

Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.

Meaningful patient input to understand disease experience and patient expectations for improvement with treatment is essential for the selection and development of outcome measures for alopecia areata (AA) clinical trials. This study explored the physical signs and symptoms of AA through 30 semistructured interviews with adult (n = 25) and adolescent (n = 5) patients experienced with severe or very severe AA. Scalp hair loss was overwhelmingly the most important sign and symptom of AA. Nearly all patients (90%) considered scalp hair loss in their top three most bothersome physical signs and symptoms of AA, with 77% (n = 23) naming scalp hair loss as the most bothersome symptom. Other identified signs and symptoms in the top three most bothersome included eyebrow, eyelash, nose, body, and facial hair loss, as well as eye irritation and nail damage and/or appearance. Eyebrow (16%, n = 4), eyelash (4%, n = 1), nasal (4%, n = 1), and body (4%, n = 1) hair loss were identified by seven adult patients as the most bothersome signs and symptoms of AA. Conceptual saturation confirmed that a comprehensive understanding of this patient population's physical AA-related signs and symptoms was obtained. These findings indicate that the primary objective for new AA treatments for this patient population should be meaningful improvement in scalp hair growth to address the most troubling unmet need.
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http://dx.doi.org/10.1016/j.jisp.2020.05.006DOI Listing
November 2020

"'You lose your hair, what's the big deal?' I was so embarrassed, I was so self-conscious, I was so depressed:" a qualitative interview study to understand the psychosocial burden of alopecia areata.

J Patient Rep Outcomes 2020 Sep 11;4(1):76. Epub 2020 Sep 11.

Patient-Focused Outcomes Center of Expertise, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.

Background: Alopecia areata (AA) is characterized by hair loss that can affect the scalp and body. This study describes the psychosocial burden of AA.

Methods: Participants diagnosed with AA who had experienced ≥50% scalp hair loss according to the Severity of Alopecia Tool (SALT) were identified by clinicians. A semi-structured interview guide, developed with expert clinician input, included open-ended questions to explore patients' experiences of living with AA. Data were thematically analyzed to identify concepts and relationships.

Results: Participants (n = 45, 58% female, mean age 33.3 years [range 15-72], mean SALT 67.2 [range 0-100]) described the AA diagnosis as "devastating". Both males and females reported emotional and psychological impacts of AA including feeling sad/depressed (n = 21), embarrassed/ashamed (n = 10) and angry/frustrated (n = 3). Patients felt helpless (n = 5) due to the unpredictability of disease recurrence, and anxious (n = 19) about judgement from others. Many patients avoided social situations (n = 18), which impaired relationships and increased isolation. Coping strategies included concealment of hair loss through wigs or make-up, although fear of the displacement of these coverings also caused anxiety and the avoidance of activities that could result in scalp exposure (n = 22). Some patients became more accepting of AA over time, which lessened the emotional impact, though efficacious treatment was still desired. A conceptual framework was developed, and a conceptual model was created to depict the relationship between the physical signs/symptoms and the associated psychosocial effects of AA.

Conclusion: AA impairs patients' emotional and psychological wellbeing, relationships and lifestyles. Greater disease awareness and effective treatments are needed.
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http://dx.doi.org/10.1186/s41687-020-00240-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483696PMC
September 2020

Development of Clinician-Reported Outcome (ClinRO) and Patient-Reported Outcome (PRO) Measures for Eyebrow, Eyelash and Nail Assessment in Alopecia Areata.

Am J Clin Dermatol 2020 Oct;21(5):725-732

Department of Dermatology, Yale School of Medicine, 333 Cedar Street, LMP 5040, New Haven, CT, 06520, USA.

Background: Eyebrow and eyelash hair loss and nail damage-in addition to scalp hair loss-are important signs/symptoms of alopecia areata (AA) to patients and deserve assessment in AA clinical trials.

Objectives: Our objective was to develop clinician-reported outcome (ClinRO) and patient-reported outcome (PRO) measures and accompanying photoguides to aid in the assessment of AA-related eyebrow, eyelash and nail signs/symptoms.

Methods: Iterative rounds of qualitative, semi-structured interviews were conducted with US expert dermatologists and North American patients with AA. Patients with eyebrow, eyelash and nail involvement were purposefully sampled. Interview transcripts were qualitatively analyzed.

Results: Dermatologists (n = 10) described eyebrow and eyelash loss as concerning for affected patients and, along with nail appearance, as deserving assessment. Dermatologist data informed the development of single item, 4-point Likert-type ClinRO and PRO measures of current eyebrow loss, eyelash loss and nail appearance and a PRO measure of eye irritation. Patients (n = 45, age 15-72 years) confirmed the importance and relevance of these signs/symptoms. Interim revision resulted in measures that were understood by and relevant to patients. Dermatologists (n = 5) and patients (n = 10, age 21-54 years) participated in the development of the eyebrow, eyelash and nail photoguides and confirmed that they included photos that appropriately represented different severity levels and were helpful to derive and standardize ratings across raters.

Conclusions: The ClinRO and PRO measures for eyebrow, eyelash and nail appearance, with their accompanying photoguides and the PRO Measure for Eye Irritation provide clear and meaningful assessments of outcomes important to patients with AA.
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http://dx.doi.org/10.1007/s40257-020-00545-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473969PMC
October 2020

The tuatara genome reveals ancient features of amniote evolution.

Nature 2020 08 5;584(7821):403-409. Epub 2020 Aug 5.

Ngatiwai Trust Board, Whangarei, New Zealand.

The tuatara (Sphenodon punctatus)-the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana-is an iconic species that is endemic to New Zealand. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights into the ancestral amniotes. Here we analyse the genome of the tuatara, which-at approximately 5 Gb-is among the largest of the vertebrate genomes yet assembled. Our analyses of this genome, along with comparisons with other vertebrate genomes, reinforce the uniqueness of the tuatara. Phylogenetic analyses indicate that the tuatara lineage diverged from that of snakes and lizards around 250 million years ago. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Our genome sequence analysis identifies expansions of proteins, non-protein-coding RNA families and repeat elements, the latter of which show an amalgam of reptilian and mammalian features. The sequencing of the tuatara genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. Our study also provides important insights into both the technical challenges and the cultural obligations that are associated with genome sequencing.
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http://dx.doi.org/10.1038/s41586-020-2561-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116210PMC
August 2020

Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function.

J Cyst Fibros 2020 Jun 23. Epub 2020 Jun 23.

Université de Paris, Institut Cochin, Paris, France; Respiratory Medicine and National Reference Cystic Fibrosis Reference Center, Cochin Hospital; Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France; ERN-Lung CF network.

Background: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV.

Methods: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV<40 or ppFEV≥90 in comparison with those with ppFEV [40-90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers.

Results: 827 patients were classified into 3 subgroups according to ppFEV at treatment initiation (ppFEV<40, n = 121; ppFEV [40-90[, n = 609; ppFEV≥90, n = 97). Treatment discontinuation rate was higher in ppFEV<40 patients (28.9%) than in those with ppFEV [40-90[(16.4%) or ppFEV≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV occurred in the ppFEV [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV<40 (+0.5%, P = 0.03) but not in those with ppFEV≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV<40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups.

Conclusion: Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function but the characteristics and magnitude of the response vary depending on ppFEV at baseline.
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http://dx.doi.org/10.1016/j.jcf.2020.06.012DOI Listing
June 2020

Management of initial colonisations with Burkholderia species in France, with retrospective analysis in five cystic fibrosis Centres: a pilot study.

BMC Pulm Med 2020 Jun 5;20(1):159. Epub 2020 Jun 5.

CRCM pédiatrique, Service de Pneumo-Allergologie pédiatrique, Hôpital des Enfants, Centre Hospitalier Universitaire de Toulouse, 330 avenue de Grande-Bretagne - TSA 40031, 31059, Toulouse cedex 9, France.

Background: Whereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome.

Methods: We performed a retrospective review of the primary colonisations (PC), defined as newly positive sputum cultures, observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected.

Results: Seventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher forced expiratory volume in 1 second and forced vital capacity at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. The management of PC was shown to be heterogeneous, thus impairing the statistical power of our study. Large prospective studies are needed to define whom to treat, when, and how.

Conclusions: Pending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia 1 month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of intravenous beta-lactam + oral or intravenous fluoroquinolone + inhaled aminoglycoside.
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http://dx.doi.org/10.1186/s12890-020-01190-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275364PMC
June 2020

Volumetric quantification of lung MR signal intensities using ultrashort TE as an automated score in cystic fibrosis.

Eur Radiol 2020 Oct 15;30(10):5479-5488. Epub 2020 May 15.

Univ. Bordeaux, F-33000, Bordeaux, France.

Objectives: The study aimed to validate automated quantification of high and low signal intensity volumes using ultrashort echo-time MRI, with CT and pulmonary function test (PFT) as references, to assess the severity of structural alterations in cystic fibrosis (CF).

Methods: This prospective study was performed in a single center between May 2015 and September 2017. Participants with CF completed clinical examination, CT, MRI, and PFT the same day during routine clinical follow-up (M0), and then 1 year after (M12) except for CT. Using MRI, percentage high (%MR-HSV), low (%MR-LSV), and total abnormal (%MR-TSV) signal intensity volumes were recorded, as well as their corresponding attenuation values using CT (%CT-HAV, %CT-LAV, %CT-TAV, respectively). Automated quantifications and visual Bhalla score were evaluated independently by two observers. Correlations were assessed using the Spearman test, comparisons using the Mann-Whitney test, and reproducibility using the intraclass correlation coefficient (ICC).

Results: A total of 30 participants were enrolled (median age 27 years, 18 men). At M0, there was a good correlation between %MR-HSV and %CT-HAV (ρ = 0.70; p < 0.001) and %MR-LSV and %CT-LAV (ρ = 0.60; p < 0.001). Automated MR metrics correlated to PFTs and Bhalla score (p < 0.05) while %MR-TSV was significantly different between CF with and without respiratory exacerbation (p = 0.01) at both M0 and M12. The variation of %MR-HSV correlated to the variation of FEV1% at PFT (ρ = - 0.49; p = 0.008). Reproducibility was almost perfect (ICCs > 0.95).

Conclusions: Automated quantification of abnormal signal intensity volumes relates to CF severity and allows reproducible cross-sectional and longitudinal assessment.

Trial Registration: Clinical trial identifier: NCT02449785 KEY POINTS: • Cross-sectionally, the automated quantifications of high and low signal intensity volumes at UTE correlated to the quantification of high and low attenuation using CT as reference. • Longitudinally, the variation of high signal intensity volume at UTE correlated to the variation of pulmonary function test and was significantly reduced in CF with an improvement in exacerbation status. • Automated quantification of abnormal signal intensity volumes are objective and reproducible tools to assess structural alterations in CF and follow-up longitudinally, for both research and clinical purposes.
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http://dx.doi.org/10.1007/s00330-020-06910-wDOI Listing
October 2020

Development of the Scalp Hair Assessment PRO™ measure for alopecia areata.

Br J Dermatol 2020 12 26;183(6):1065-1072. Epub 2020 May 26.

Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.

Background: Valid patient-reported outcome (PRO) measures are required to evaluate alopecia areata (AA) treatments.

Objectives: To develop a content-valid and clinically meaningful PRO measure to assess AA scalp hair loss with scores comparable with the five-response-level Alopecia Areata Investigator Global Assessment (AA-IGA™).

Methods: A draft PRO measure was developed based on input from 10 clinical experts in AA. The PRO measure was cognitively debriefed, modified and finalized through two rounds of qualitative semistructured interviews with patients with AA who had experienced ≥ 50% scalp hair loss. Data were thematically analysed.

Results: Adults (round 1: n = 25; round 2: n = 15) and adolescents aged 15-17 years (round 1: n = 5) in North America participated. All patients named scalp hair loss as a key AA sign or symptom. Patients demonstrated the ability to self-report their current amount of scalp hair using percentages. In round 1 not all patients interpreted the measurement concept consistently; therefore, the PRO was modified to clarify the measurement concept to improve usability. Following modifications, patients in round 2 responded without difficulty to the PRO measure. Patients confirmed that they could use the five-level response scale to rate their scalp hair loss: no missing hair, 0%; limited, 1-20%; moderate, 21-49%; large, 50-94%; nearly all or all, 95-100%. Almost all patients deemed hair regrowth resulting in ≤ 20% scalp hair loss a treatment success.

Conclusions: The Scalp Hair Assessment PRO™ is a content-valid, clinically meaningful assessment of distinct gradations of scalp hair loss for evaluating AA treatment for patients with ≥ 50% hair loss at baseline.
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http://dx.doi.org/10.1111/bjd.19024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754291PMC
December 2020

The Alopecia Areata Investigator Global Assessment scale: a measure for evaluating clinically meaningful success in clinical trials.

Br J Dermatol 2020 10 3;183(4):702-709. Epub 2020 Apr 3.

Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.

Background: Content-valid and clinically meaningful instruments are required to evaluate outcomes of therapeutic interventions in alopecia areata (AA).

Objectives: To develop an Investigator's Global Assessment (IGA) to interpret treatment response in AA treatment studies.

Methods: Qualitative interviews were conducted in the USA with expert dermatologists and with patients with AA who had experienced ≥ 50% scalp-hair loss. Thematic data analysis identified critical outcomes and evaluated the content validity of the new IGA.

Results: Expert clinicians (n = 10) judged AA treatment success by the amount of scalp-hair growth (median 80% scalp hair). Adult (n = 25) and adolescent (n = 5) patients participated. Scalp-hair loss was the most bothersome AA sign/symptom for most patients. Perceived treatment success - short of 100% scalp hair - was the presence of ~ 70-90% scalp hair (median 80%). Using additional clinician and patient insights, the Alopecia Areata Investigator Global Assessment (AA-IGA™) was developed. This clinician-reported outcome assessment is an ordinal, static measure comprising five severity categories of scalp-hair loss. Nearly all clinicians and patients in this study agreed that, for patients with ≥ 50% scalp-hair loss, successful treatment would be hair regrowth resulting in ≤ 20% scalp-hair loss.

Conclusions: We recommend using the Severity of Alopecia Tool to assess the extent (0-100%) of scalp-hair loss. The AA-IGA is a robust ordinal measure providing distinct and clinically meaningful gradations of scalp-hair loss that reflects patients' and expert clinicians' perspectives and treatment expectations. What is already known about this topic? The Severity of Alopecia Tool is widely used to assess the extent of scalp-hair loss in patients with alopecia areata. Guidelines define treatment success as a 50% improvement in scalp hair, and clinical trials have used dynamic thresholds of 50% and 90%. However, there is no clinical consensus on these endpoints, and patient perspectives on treatment success are unknown. What does this study add? Through qualitative interviews with 10 expert dermatologists and 30 patients with alopecia areata who had experienced ≥ 50% scalp-hair loss, we developed the Alopecia Areata Investigator Global Assessment (AA-IGA™) to measure five clinically meaningful gradations of alopecia areata scalp-hair loss that reflects patients' and clinicians' perspectives and expectations of treatment success in alopecia areata treatment studies. What are the clinical implications of this work? The AA-IGA is a robust ordinal measure that can inform clinical evaluation of alopecia areata treatment outcomes. The AA-IGA can be used to determine clinically meaningful treatment success for alopecia areata, with success defined by patients and clinicians as reaching ≤ 20% scalp-hair loss. Linked Comment: Blome. Br J Dermatol 2020; 183:609.
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http://dx.doi.org/10.1111/bjd.18883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586961PMC
October 2020

GamCog: A measurement instrument for miscognitions related to gamblification, gambling, and video gaming.

Psychol Addict Behav 2020 Feb 7;34(1):242-256. Epub 2019 Nov 7.

Gamifiction Group, Faculty of Information Technology and Communication Sciences, Tampere University.

"Gamblification" is a rapidly emerging form of media convergence between the more chance-based activity of gambling and the more skill-based activity of (video) gaming, for example in the competitive video gaming known as esports. The marriage of video gaming and gambling has been theorized as bringing about new forms of gambling-related cognitive processes in individuals and affecting the ways in which they approach and evaluate gambling situations. As such, a pertinent research problem is whether existing measurement instruments designed to identify gambling related cognitions can be employed in this new context and population, and if not, how they can be adapted. Therefore, in this study, we investigate the psychometric properties of Gambling Related Cognitions Scale (GRCS) and a series of items developed following a review of existing literature. We employ 3 separate data sets gathered from video game players who also gamble ( = 442; 391; and 335). The results indicate that the GRCS is not a robust measure to use for video game players who gamble; the new GamCog measure was, therefore, developed to address this gap. The study implies that the most significant cognitive differences between video game players and the wider population are the ways in which concepts of skill and luck are perceived, potentially due to the sense of personal agency engendered by video games. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/adb0000526DOI Listing
February 2020

Quantification of MRI T2-weighted High Signal Volume in Cystic Fibrosis: A Pilot Study.

Radiology 2020 01 29;294(1):186-196. Epub 2019 Oct 29.

From the Univ. Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, F-33000 Bordeaux, France (I.B., P.B., F.L., G.D.); Inserm, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, F-33000 Bordeaux, France (I.B., P.B., F.L., G.D.); and CHU de Bordeaux, Service d'Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d'Exploration Fonctionnelle Respiratoire, Unité de Pneumologie Pédiatrique, CIC 1401, F-33600 Pessac, France (I.B., F.H., J.M., S.B., P.B., F.L., G.D.).

Background In patients with cystic fibrosis (CF), pulmonary structures with high MRI T2 signal intensity relate to inflammatory changes in the lung and bronchi. These areas of pathologic abnormalities can serve as imaging biomarkers. The feasibility of automated quantification is unknown. Purpose To quantify the MRI T2 high-signal-intensity lung volume and T2-weighted volume-intensity product (VIP) by using a black-blood T2-weighted radial fast spin-echo sequence in participants with CF. Materials and Methods Healthy individuals and study participants with CF were prospectively enrolled between January 2017 and November 2017. All participants underwent a lung MRI protocol including T2-weighted radial fast spin-echo sequence. Participants with CF also underwent pulmonary function tests the same day. Participants with CF exacerbation underwent repeat MRI after their treatment with antibiotics. Two observers supervised automated quantification of T2-weighted high-signal-intensity volume (HSV) and T2-weighted VIP independently, and the average score was chosen as consensus. Statistical analysis used the Mann-Whitney test for comparison of medians, correlations used the Spearman test, comparison of paired medians used the Wilcoxon signed rank test, and reproducibility was evaluated by using intraclass correlation coefficient. Results In 10 healthy study participants (median age, 21 years [age range, 18-27 years]; six men) and 12 participants with CF (median age, 18 years [age range, 9-40 years]; eight men), T2-weighted HSV was equal to 0% and 4.1% (range, 0.1%-17%), respectively, and T2-weighted VIP was equal to 0 msec and 303 msec (range, 39-1012 msec), respectively ( < .001). In participants with CF, T2-weighted HSV or T2-weighted VIP were associated with forced expiratory volume in 1 second percentage predicted (ρ = -0.88 and ρ = -0.94, respectively; < .001). In six participants with CF exacerbation and follow-up after treatment, a decrease in both T2-weighted HSV and T2-weighted VIP was observed ( = .03). The intra- and interobserver reproducibility of MRI were good (intraclass correlation coefficients, >0.99 and >0.99, respectively). Conclusion In patients with cystic fibrosis (CF), automated quantification of lung MRI high-signal-intensity volume was reproducible and correlated with pulmonary function testing severity, and it improved after treatment for CF exacerbation. © RSNA, 2019 See also the editorial by Revel and Chassagnon in this issue.
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http://dx.doi.org/10.1148/radiol.2019190797DOI Listing
January 2020

Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis.

Am J Respir Crit Care Med 2020 01;201(2):188-197

Respiratory Medicine and National Reference Cystic Fibrosis Reference Center, Cochin Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation. To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting. The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations. Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV (ppFEV) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV (+3.67%), an increase in body mass index (+0.73 kg/m), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV, without improvement in body mass index or decrease in intravenous antibiotic courses. Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.
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http://dx.doi.org/10.1164/rccm.201906-1227OCDOI Listing
January 2020

Patient-reported outcomes in patients with cystic fibrosis with a G551D mutation on ivacaftor treatment: results from a cross-sectional study.

BMC Pulm Med 2019 Aug 13;19(1):146. Epub 2019 Aug 13.

Vertex Pharmaceuticals Incorporated, Boston, MA, USA.

Background: Clinical studies demonstrate that ivacaftor (IVA) improves health-related quality of life (HRQoL) in patients aged ≥6 years with cystic fibrosis (CF). The real-world impact of IVA and standard of care (SOC) in groups of patients with G551D and F508del mutations, respectively, was assessed using a survey comprising disease-specific and generic HRQoL measures.

Methods: Patients with CF aged ≥12 years, or aged 6-11 years with caregiver support, with either (1) a G551D mutation and receiving IVA (G551D/IVA) for ≥3 months, or (2) homozygous for F508del and receiving SOC before lumacaftor/IVA availability (F508del/SOC), were eligible to participate in a cross-sectional survey. Demographic and clinical characteristics, and HRQoL measures were compared between patient groups, and multiple regression analyses were conducted.

Results: After differences in patient demographic and clinical characteristics were controlled for, significantly better scores were observed in the G551D/IVA group than in the F508del/SOC group on multiple domains of the validated Cystic Fibrosis Questionnaire-Revised and the EuroQol 5-dimensions 5-level questionnaire.

Conclusions: G551D/IVA patients reported better HRQoL than F508del/SOC patients on generic and disease-specific measures in a real-world setting.
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http://dx.doi.org/10.1186/s12890-019-0887-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693259PMC
August 2019

The effect of smell and taste of milk during tube feeding of preterm infants (the Taste trial): a protocol for a randomised controlled trial.

BMJ Open 2019 07 17;9(7):e027805. Epub 2019 Jul 17.

Neonatal Intensive Care Unit and Newborn Research, The Royal Women's Hospital, Melbourne, Victoria, Australia.

Introduction: Smell and taste of milk are not generally considered when tube feeding preterm infants. Preterm infants have rapid growth, particularly of the brain, and high caloric needs. Enteral feeding is often poorly tolerated which may lead to growth failure and long-term neurodevelopmental impairment. Smell and taste are strong stimulators of digestion and metabolism. We hypothesise that regular smell and taste during tube feeding will improve weight z-scores of very preterm infants at discharge from hospital.

Methods And Analysis: Taste is a randomised, unblinded two-centre trial. Infants born at <29 weeks' gestation and/or <1250 g at birth and admitted to a participating neonatal intensive care unit are eligible. Randomisation occurs before infants receive two hourly feeds for 24 hours. Infants are randomised to either smell and taste of milk with each tube feed or tube feeding without the provision of smell and taste. The primary outcome is weight z-score at discharge. Secondary outcomes include: days to full enteral feeds, duration of parenteral nutrition, rate of late-onset sepsis, post menstrual age at removal of nasogastric tube and at discharge from hospital, anthropometric data and neurodevelopmental outcomes at 2 years of corrected age.

Ethics And Dissemination: Human Research Ethics Committees of Mater Misericordiae (trial reference number: HREC/16/MHS/112) and the Royal Women's Hospital (trial reference number: 17/21) last approved the trial protocol (version 4.2; Date: 18 December 2018) and recruitment commenced in May 2017 and November 2017, respectively. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences.

Trial Registration Number: ACTRN12617000583347.
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http://dx.doi.org/10.1136/bmjopen-2018-027805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661682PMC
July 2019

Automated Volumetric Quantification of Emphysema Severity by Using Ultrashort Echo Time MRI: Validation in Participants with Chronic Obstructive Pulmonary Disease.

Radiology 2019 07 4;292(1):216-225. Epub 2019 Jun 4.

From the Université Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, Bordeaux, France (I.B., P.B., P.O.G., F.L., G.D.); Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM U1045, Université Bordeaux Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France (I.B., P.B., P.O.G., F.L., G.D.); and CHU de Bordeaux, Service d'Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d'Exploration Fonctionnelle Respiratoire, CIC 1401, France (I.B., P.B., P.O.G., C.D., J.M., F.L., G.D.).

Background The validity of three-dimensional (3D) ultrashort echo time (UTE) MRI for the assessment of emphysema in patients with chronic obstructive pulmonary disease (COPD) at high spatial resolution is, to the knowledge of the authors, unknown. Purpose To assess whether noncontrast agent-enhanced 3D UTE MRI at submillimeter spatial resolution can be used to determine the extent of emphysema by using both qualitative visual scoring and fully automated volumetric quantification. Materials and Methods Twenty-eight participants with COPD and 10 control participants (mean age, 70 years ± 7 [standard deviation] and 64 years ± 4, respectively) were prospectively enrolled between 2015 and 2017. Participants underwent pulmonary function testing, CT, and MRI. CT was used as the reference standard. Qualitative scoring of emphysema extent was performed by two readers. Fully automated quantification of percentage of low-attenuation volume by using a threshold of -950 HU (%LAV) at CT and percentage of low-signal-intensity volume by using an adaptive threshold of 0.20 (%LSV) at MRI were the respective emphysema indexes. Comparison of means was performed by using Student test, correlation was determined by using Pearson test, agreement was found by using weighted κ index, and reproducibility was determined by using intraclass correlation coefficient. Diagnostic performance was assessed by calculating the area under the receiver operating characteristics curve (AUC). Results With qualitative scoring, agreement between UTE MRI and CT was good (weighted κ, 0.79; 95% confidence interval: 0.71, 0.83). With automated volumetric quantification, %LSV was significantly correlated with %LAV in participants with COPD (, -0.80; < .001) and correlated with forced expiratory volume in 1 second percentage predicted (, -0.55; = .002). %LSV was significantly higher in participants with COPD than in control participants ( < .001). The diagnostic performance and reproducibility of %LSV were good (AUC, 1.00 [95% confidence interval: 0.88, 1.00], and intraclass correlation coefficient, > 0.99, respectively). Conclusion A fully automated method with three-dimensional ultrashort echo time MRI reproducibly quantified the volumetric extent of emphysema in participants with chronic obstructive pulmonary disease. © RSNA, 2019
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http://dx.doi.org/10.1148/radiol.2019190052DOI Listing
July 2019

CT evaluation of hyperattenuating mucus to diagnose allergic bronchopulmonary aspergillosis in the special condition of cystic fibrosis.

J Cyst Fibros 2019 07 12;18(4):e31-e36. Epub 2019 Feb 12.

CHU de Bordeaux, Service d'Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d'Exploration Fonctionnelle Respiratoire, Unité de Pneumologie pédiatrique, Service de Parasitologie-Mycologie, CIC 1401, F-33600 Pessac, France; Univ. Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, F-33000 Bordeaux, France; Inserm, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, F-33000 Bordeaux, France. Electronic address:

Background: Mucus plugging (MP), central bronchiectasis (CB), and consolidation/atelectasia (CA) are conventional CT signs to diagnose allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF). Hyperattenuating mucus (HAM) has recently been described and may improve diagnostic accuracy. The goal of our study was to compare HAM versus conventional CT signs to diagnose ABPA in CF. Secondary objectives were to determine the optimal threshold of HAM quantitatively and to assess the diagnostic value of HAM using chest radiograph (CXR).

Methods: The study was retrospective and included 137 patients with CF, aged >6-year-old. The presence of HAM, CB, MP and CA were determined by two radiologists in consensus. HAM was quantified using an absolute mean density value (AMD) and a ratio between mucus and paraspinal muscle (DRM). Sensitivity (Se), Specificity (Sp) and Youden's J-index were calculated. The Cystic Fibrosis Conference Consensus criteria were chosen as Gold Standard.

Results: 23 out of 137 CF patients had ABPA. Using CT, the most sensitive structural alteration was MP (Se = 91%), followed by CB (Se = 87%) and CA (Se = 70%) whereas specificities were 28%, 19% and 58%, respectively. Conversely, HAM had the highest specificity (Sp = 100%) whereas Se was 69%. HAM had the highest Youden's J-index (p < 0.001) Quantitative optimal thresholds were AMD > 78 HU (Se/Sp = 71%/98%) and DRM > 1.3 (Se/Sp = 82%/97%). HAM was unseen using CXR (Se = 0%).

Conclusion: HAM is the most specific CT biomarker of ABPA in CF, with good sensitivity. Our study suggests that characterization of mucus density may improve the accuracy of imaging criteria to diagnose ABPA early.
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http://dx.doi.org/10.1016/j.jcf.2019.02.002DOI Listing
July 2019

Measurement of Utilities Associated with Parenteral Support Requirement in Patients with Short Bowel Syndrome and Intestinal Failure.

Clin Ther 2018 11 2;40(11):1878-1893.e1. Epub 2018 Nov 2.

Salford Royal NHS Foundation Trust, Salford, United Kingdom.

Purpose: Short bowel syndrome (SBS) is the main cause of intestinal failure. Intravenous supplementation (parenteral support [PS]) helps patients regain health but can affect patients' health-related quality of life (HRQoL). The value of health states associated with the number of days on PS per week is unknown in the United Kingdom. The objectives of the present study were to develop health state vignettes for SBS and PS, and to estimate health state utilities by using the time trade-off (TTO) technique.

Methods: Vignettes were developed and reviewed through various processes. Eight states described the impact of 0 days (weaned off PS) through to 7 days on PS; each state comprised the conditions, symptoms, treatments, and impacts related to EuroQol-5 dimensions. A sample of the UK general public viewed each state in interviews; they provided ratings using a visual analog scale and utility scores using the TTO. Participants completed background questionnaires.

Findings: One hundred participants rated and valued each health state. Visual analog scale and utility scores showed a steady decline for the health states associated with increasing numbers of days on PS. With "full health" equivalent to a utility score of 1, the most burdensome state was "7 days on PS" (mean [SD] utility score, 0.36 [0.35]), whereas weaned off ("0 days on PS") showed the least burden (0.82 [0.22]).

Implications: More days of PS are perceived by members of the public to have an increasing negative impact on HRQoL. Therapies aimed at reducing the number of days on PS may be beneficial for improving patients' HRQoL.
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http://dx.doi.org/10.1016/j.clinthera.2018.09.009DOI Listing
November 2018

A molecular phylogenetic hypothesis for the Asian agamid lizard genus Phrynocephalus reveals discrete biogeographic clades implicated by plate tectonics.

Zootaxa 2018 Sep 3;4467(1):1-81. Epub 2018 Sep 3.

Genomics, Department of Biosciences, Merritt College, 12500 Campus Drive, Oakland, CA 94619, USA Museum of Vertebrate Zoology, University of California, Berkeley, CA 94720, USA.

Phylogenetic relationships of the agamid lizard genus Phrynocephalus are described in the context of plate tectonics. A near comprehensive taxon sampling reports three data sets: (1) mitochondrial DNA from ND1 to COI (3' end of ND1, tRNAGln, tRNAIle, tRNAMet, ND2, tRNATrp, tRNAAla, tRNAAsn, tRNACys, tRNATyr, and the 5' end of COI) with 1761 aligned positional sites (1595 included, 839 informative), (2) nuclear RAG-1 DNA with 2760 aligned positional sites (342 informative), and (3) 25 informative allozyme loci with 213 alleles (107 informative when coded as presence/absence). It is hypothesized that Phrynocephalus phyletic patterns and speciation reflect fault lines of ancient plates now in Asia rejuvenated by the more recent Indian and Arabian plate collisions. Molecular estimates of lineage splits are highly congruent with geologic dates from the literature.  A southern origin for the genus in Southwest Asia is resolved in phylogenetic estimates and a northern origin is statistically rejected. On the basis of monophyly and molecular evidence several taxa previously recognized as subspecies are recognized as species: P. hongyuanensis, P. sogdianus, and P. strauchi as "Current Status"; Phrynocephalus bannikovi, Phrynocephalus longicaudatus, Phrynocephalus turcomanus, and Phrynocephalus vindumi are formally "New Status". Phylogenetic evaluation indicates a soft substrate habitat of sand for the shared ancestor of modern Phrynocephalus. Size diversity maximally overlaps in the Caspian Basin and northwestern Iranian Plateau. The greatest species numbers of six in sympatry and regional allopatry are found in the southern Caspian Basin and southern Helmand Basin, both from numerous phylogenetic lineages in close proximity attributed to tectonic induced events.
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http://dx.doi.org/10.11646/zootaxa.4467.1.1DOI Listing
September 2018

3D ultrashort echo time MRI of the lung using stack-of-spirals and spherical k-Space coverages: Evaluation in healthy volunteers and parenchymal diseases.

J Magn Reson Imaging 2018 12 11;48(6):1489-1497. Epub 2018 Sep 11.

University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France.

Background: Ultrashort echo time (UTE) has been shown to improve lung MRI quality in three dimensions. The evaluation of 3D-UTE stack-of-spirals VIBE (3D-USV) sequence for parenchymal diseases and a comparison of performance with that of a spherical mode of acquisition is needed.

Purpose: To assess MRI quality using a prototypical 3D-USV sequence and to compare performance with that of a spherical acquisition using Pointwise Encoding Time Reduction with Radial Acquisition (PETRA).

Study Type: Monocenter, prospective.

Population: Twelve healthy volunteers and 32 adult patients with either cystic fibrosis (CF; n = 16) or interstitial lung disease (ILD; n = 16).

Field Strength/sequence: Both free-breathing 3D-USV and PETRA were completed at 1.5T.

Assessment: In healthy volunteers, visual analysis of imaging quality was scored using a Likert scale. Quantitative evaluation of apparent signal ratio (Sr) and contrast ratio (Cr) was measured. Patients with CF and ILD completed both computed tomography (CT) and MRI. Depiction of structural alterations was assessed using dedicated clinical scores. All evaluations were done in consensus by two readers.

Statistical Tests: Comparison of means was assessed using the Wilcoxon signed rank test. Concordance and agreement between CT and MRI were assessed using the intraclass correlation coefficient (ICC) and kappa test.

Results: In controls, 3D-USV yielded lower artifacts owing to better automatic respiratory synchronization than PETRA (P < 0.001). However, Sr and Cr of 3D-USV were found significantly lower by 2.25- and 2.36-fold, respectively (P < 0.001). In patients, 3D-USV and PETRA showed comparable performances to assess airway severity in CF (Bhalla score, ICC = 0.89 and ICC = 0.92, respectively) and presence of structural alterations in ILD such as honeycombing (kappa = 0.68 and kappa = 0.69, respectively).

Data Conclusion: 3D-USV enables high-resolution morphological imaging of the lung without need of an external device to compensate respiratory motions. Automation and robustness of the method may facilitate clinical application for both airway and interstitial lung investigations.

Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1489-1497.
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http://dx.doi.org/10.1002/jmri.26212DOI Listing
December 2018

Evaluating the Impact and Benefits of Fluticasone Furoate/Vilanterol in Individuals with Asthma or COPD: A Mixed-Methods Analysis of Patient Experiences.

Adv Ther 2018 09 13;35(9):1378-1399. Epub 2018 Aug 13.

ICON plc, San Francisco, CA, USA.

Introduction: This study evaluated patients' experiences with fluticasone furoate/vilanterol (FF/VI) combination therapy in UK patients with asthma or chronic obstructive pulmonary disease (COPD).

Methods: Participants aged ≥ 18 years, with self-reported, physician-diagnosed asthma or COPD (≥ 1 year) who had been receiving FF/VI (≥ 3 months) were recruited from UK primary care. This two-phase, mixed-methods study consisted of a semi-structured, telephone-interview phase (qualitative) and a self-completed online/paper-survey phase (quantitative).

Results: The telephone-interview phase included 50 individuals [asthma, n = 25; COPD, n = 25; mean age (SD) 56.7 years (13.3); 50% female]. Of these, 21 with asthma reported that their condition was stable/well controlled and 13 with COPD felt their condition was manageable. Most participants found FF/VI easy to use (asthma, 25; COPD, 23), easy to integrate into their daily routine (asthma, 25; COPD, 24), and able to control symptoms for ≥ 24 h (asthma, 14; COPD, 16). During the survey phase, 199 individuals were recruited [asthma, n = 100; COPD, n = 99; mean age (SD) 63.6 years (15.1); 59.3% female]. Most participants were satisfied/very satisfied with the efficacy of FF/VI in terms of all-day symptom relief (asthma, 84%; COPD, 75%) and found FF/VI easy/very easy to fit into their daily routine (asthma, 99%; COPD, 96%), easy/very easy to use (asthma, 97%; COPD, 92%), and convenient/very convenient to take as instructed (asthma, 95%; COPD, 93%). Significantly more individuals with asthma (87% versus 46%, P < 0.001) and numerically more individuals with COPD (84% versus 76%, P = 0.055) were satisfied/very satisfied with FF/VI compared with their most recent previous maintenance medication.

Conclusion: The majority of individuals in this study had confidence in FF/VI and were satisfied or very satisfied with various key attributes of the treatment.

Trial Registration: GSK study HO-15-15503/204888.

Funding: GSK.
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http://dx.doi.org/10.1007/s12325-018-0760-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133131PMC
September 2018

Depression, posttraumatic stress and relationship distress in parents of very preterm infants.

Arch Womens Ment Health 2018 08 3;21(4):445-451. Epub 2018 Mar 3.

Mater Mothers' Hospital, Brisbane, Australia.

To determine the prevalence, associated factors, and relationships between symptoms of depression, symptoms of posttraumatic stress (PTS), and relationship distress in mothers and fathers of very preterm (VPT) infants (< 32 weeks). Mothers (n = 323) and fathers (n = 237) completed self-report measures on demographic and outcome variables at 38 days (SD = 23.1, range 9-116) postpartum while their infants were still hospitalised. Of mothers, 46.7% had a moderate to high likelihood of depression, 38.1% had moderate to severe symptoms of PTS, and 25.1% were in higher than average relationship distress. The corresponding percentages in fathers were 16.9, 23.7, and 27%. Depression was positively associated with having previous children (p = 0.01), speaking little or no English at home (p = 0.01), financial stress (p = 0.03), and recently accessing mental health services (p = 0.003) for mothers, and financial stress (p = 0.005) and not being the primary income earner (p = 0.04) for fathers. Similar associations were found for symptoms of PTS and relationship distress. Being in higher relationship distress increased the risk of depression in both mothers (p < .001) and fathers (p = 0.03), and PTS symptoms in mothers (p = 0.001). For both mothers and fathers, depression was associated with more severe PTS symptoms (p < .001). Fathers of VPT infants should be screened for mental health problems alongside mothers, and postpartum parent support programs for VPT infants should include strategies to improve the couple relationship.
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http://dx.doi.org/10.1007/s00737-018-0821-6DOI Listing
August 2018