Publications by authors named "D L Hughes"

3,346 Publications

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The Utility of the Low Energy Availability in Females Questionnaire to Detect Markers Consistent With Low Energy Availability-Related Conditions in a Mixed-Sport Cohort.

Int J Sport Nutr Exerc Metab 2021 Jul 20:1-11. Epub 2021 Jul 20.

Australian Catholic University.

The Low Energy Availability in Females Questionnaire (LEAF-Q) was validated to identify risk of the female athlete triad (triad) in female endurance athletes. This study explored the ability of the LEAF-Q to detect conditions related to low energy availability (LEA) in a mixed sport cohort of female athletes. Data included the LEAF-Q, SCOFF Questionnaire for disordered eating, dual-energy X-ray absorptiometry-derived body composition and bone mineral density, Mini International Neuropsychiatric Interview, blood pressure, and blood metabolic and reproductive hormones. Participants were grouped according to LEAF-Q score (≥8 or <8), and a comparison of means was undertaken. Sensitivity, specificity, and predictive values of the overall score and subscale scores were calculated in relation to the triad and biomarkers relevant to LEA. Fisher's exact test explored differences in prevalence of these conditions between groups. Seventy-five athletes (18-32 years) participated. Mean LEAF-Q score was 8.0 ± 4.2 (55% scored ≥8). Injury and menstrual function subscale scores identified low bone mineral density (100% sensitivity, 95% confidence interval [15.8%, 100%]) and menstrual dysfunction (80.0% sensitivity, 95% confidence interval [28.4%, 99.5%]), respectively. The gastrointestinal subscale did not detect surrogate markers of LEA. LEAF-Q score cannot be used to classify athletes as "high risk" of conditions related to LEA, nor can it be used as a surrogate diagnostic tool for LEA given the low specificity identified. Our study supports its use as a screening tool to rule out risk of LEA-related conditions or to create selective low-risk groups that do not need management as there were generally high negative predictive values (range 76.5-100%) for conditions related to LEA.
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http://dx.doi.org/10.1123/ijsnem.2020-0233DOI Listing
July 2021

A Short extension to multiple breath washout provides additional signal of distal airway disease in people with CF: A pilot study.

J Cyst Fibros 2021 Jul 15. Epub 2021 Jul 15.

Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, Manresa Rd, London, United Kingdom; European Cystic Fibrosis Society Lung Clearance Index Core Facility, London, United Kingdom.

Background: Adding a slow vital capacity (SVC) to multiple breath washout (MBW) allows quantification of otherwise overlooked signal from under/un-ventilated lung units (UVLU) and may provide a more comprehensive assessment of airway disease than conventional lung clearance index (LCI).

Methods: We conducted a pilot study on people undergoing MBW tests: 10 healthy controls (HC) and 43 cystic fibrosis (CF) subjects performed an SVC after the standard end of test. We term the new outcome LCI with Short extension (LCI). We assessed (i) CF/ HC differences, (ii) variability (iii) effect of pulmonary exacerbation (PEx)/treatment and (iv) relationship with CF computed tomography (CFCT) scores.

Results: HC/ CF group differences were larger with LCI than LCI (P<0.001). Within the CF group UVLU was highly variable and when abnormal it did not correlate with corresponding LCI. Signal showed little variability during clinical stability (n = 11 CF; 2 visits; median inter-test variability 2.6% LCI 2.5% LCI). PEx signal was significantly greater for LCI both for onset and resolution. Both MBW parameters correlated significantly with total lung CT scores and hyperinflation but only LCI correlated with mucus plugging.

Conclusions: UVLU captured within the LCI varies between individuals; the lack of relationship with LCI demonstrates that new, additional information is being captured. LCI repeatability during clinical stability combined with its larger signal around episodes of PEx may lend it superior sensitivity as an outcome measure. Further studies will build on this pilot data to fully establish its utility in monitoring disease status.
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http://dx.doi.org/10.1016/j.jcf.2021.06.013DOI Listing
July 2021

Predicting 90-day modified Rankin Scale score with discharge information in acute ischaemic stroke patients following treatment.

BMJ Neurol Open 2021 24;3(1):e000177. Epub 2021 Jun 24.

Department of Radiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.

Objectives: To understand variability in modified Rankin Scale scores from discharge to 90 days in acute ischaemic stroke patients following treatment, and examine prediction of 90-day modified Rankin Scale score by using discharge modified Rankin Scale and discharge disposition.

Materials And Methods: Retrospective analysis of acute ischaemic stroke patients following treatment was performed from January 2016 to March 2020. Data collection included demographic and clinical characteristics and outcomes data (modified Rankin Scale score at discharge, 30 days and 90 days and discharge disposition). Pearson's χ test assessed statistical differences in distribution of modified Rankin Scale scores at discharge, 30 days and 90 days. The predictive power of discharge modified Rankin Scale score and disposition quantified the association with 90-day outcome.

Results: A total of 280 acute ischaemic stroke patients (65.4% aged ≥65 years, 47.1% female, 60.7% white) were included in the analysis. The modified Rankin Scale score significantly changed between 30 and 90 days from discharge (p<0.001) after remaining stable from discharge to 30 days (p=0.665). The positive and negative predictive values of an unfavourable long-term outcome for discharge modified Rankin Scale scores of 3-5 were 67.7% (95% CI 60.4% to 75.0%) and 82.0% (95% CI 75.1% to 88.8%), and for non-home discharge disposition were 72.4% (95% CI 64.5% to 80.2%) and 74.5% (95% CI 67.8% to 81.3%), respectively.

Conclusions: Discharge modified Rankin Scale score and non-home discharge disposition are good individual predictors of 90-day modified Rankin Scale score for ischaemic stroke patients following treatment.
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http://dx.doi.org/10.1136/bmjno-2021-000177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231000PMC
June 2021

Performance of the Innova SARS-CoV-2 antigen rapid lateral flow test in the Liverpool asymptomatic testing pilot: population based cohort study.

BMJ 2021 07 6;374:n1637. Epub 2021 Jul 6.

Institute of Population Health Sciences, University of Liverpool, Liverpool, UK.

Objective: To assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres.

Design: Observational cohort study.

Setting: Community LFT pilot at covid-19 testing sites in Liverpool, UK.

Participants: 5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020.

Interventions: Participants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites.

Main Outcome Measures: Sensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease.

Results: Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >10 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>10 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<10 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load.

Conclusions: The Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.
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http://dx.doi.org/10.1136/bmj.n1637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259455PMC
July 2021

Effects of adiposity on the human plasma proteome: observational and Mendelian randomisation estimates.

Int J Obes (Lond) 2021 Jul 5. Epub 2021 Jul 5.

Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.

Background: Variation in adiposity is associated with cardiometabolic disease outcomes, but mechanisms leading from this exposure to disease are unclear. This study aimed to estimate effects of body mass index (BMI) on an extensive set of circulating proteins.

Methods: We used SomaLogic proteomic data from up to 2737 healthy participants from the INTERVAL study. Associations between self-reported BMI and 3622 unique plasma proteins were explored using linear regression. These were complemented by Mendelian randomisation (MR) analyses using a genetic risk score (GRS) comprised of 654 BMI-associated polymorphisms from a recent genome-wide association study (GWAS) of adult BMI. A disease enrichment analysis was performed using DAVID Bioinformatics 6.8 for proteins which were altered by BMI.

Results: Observationally, BMI was associated with 1576 proteins (P < 1.4 × 10), with particularly strong evidence for a positive association with leptin and fatty acid-binding protein-4 (FABP4), and a negative association with sex hormone-binding globulin (SHBG). Observational estimates were likely confounded, but the GRS for BMI did not associate with measured confounders. MR analyses provided evidence for a causal relationship between BMI and eight proteins including leptin (0.63 standard deviation (SD) per SD BMI, 95% CI 0.48-0.79, P = 1.6 × 10), FABP4 (0.64 SD per SD BMI, 95% CI 0.46-0.83, P = 6.7 × 10) and SHBG (-0.45 SD per SD BMI, 95% CI -0.65 to -0.25, P = 1.4 × 10). There was agreement in the magnitude of observational and MR estimates (R = 0.33) and evidence that proteins most strongly altered by BMI were enriched for genes involved in cardiovascular disease.

Conclusions: This study provides evidence for a broad impact of adiposity on the human proteome. Proteins strongly altered by BMI include those involved in regulating appetite, sex hormones and inflammation; such proteins are also enriched for cardiovascular disease-related genes. Altogether, results help focus attention onto new proteomic signatures of obesity-related disease.
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http://dx.doi.org/10.1038/s41366-021-00896-1DOI Listing
July 2021
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