Research and Innovation
http://hdl.handle.net/20.500.12904/15534
2024-03-27T11:59:31Z
2024-03-27T11:59:31Z
Serum levels of proinflammatory lipid mediators and specialized proresolving molecules are increased in patients with severe acute respiratory syndrome coronavirus 2 and correlate with markers of the adaptive immune response
Turnbull, James
Jha, Rakesh R.
Lunt, Eleanor
Irving, William L.
Gohir, Sameer A.
Valdes, Ana M.
Tarr, Alexander W.
Barrett, David A.
Chapman, Victoria
http://hdl.handle.net/20.500.12904/18421
2024-03-21T04:51:26Z
2022-01-01T00:00:00Z
Serum levels of proinflammatory lipid mediators and specialized proresolving molecules are increased in patients with severe acute respiratory syndrome coronavirus 2 and correlate with markers of the adaptive immune response
Turnbull, James; Jha, Rakesh R.; Lunt, Eleanor; Irving, William L.; Gohir, Sameer A.; Valdes, Ana M.; Tarr, Alexander W.; Barrett, David A.; Chapman, Victoria
Abstract Background Specialized proresolution molecules (SPMs) halt the transition to chronic pathogenic inflammation. We aimed to quantify serum levels of pro- and anti-inflammatory bioactive lipids in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, and to identify potential relationships with innate responses and clinical outcome. Methods Serum from 50 hospital admitted inpatients (22 female, 28 male) with confirmed symptomatic SARS-CoV-2 infection and 94 age- and sex-matched controls collected prior to the pandemic (SARS-CoV-2 negative), were processed for quantification of bioactive lipids and anti-nucleocapsid and anti-spike quantitative binding assays. Results SARS-CoV-2 serum had significantly higher concentrations of omega-6–derived proinflammatory lipids and omega-6– and omega-3–derived SPMs, compared to the age- and sex-matched SARS-CoV-2–negative group, which were not markedly altered by age or sex. There were significant positive correlations between SPMs, proinflammatory bioactive lipids, and anti-spike antibody binding. Levels of some SPMs were significantly higher in patients with an anti-spike antibody value >0.5. Levels of linoleic acid and 5,6-dihydroxy-8Z,11Z,14Z-eicosatrienoic acid were significantly lower in SARS-CoV-2 patients who died. Conclusions SARS-CoV-2 infection was associated with increased levels of SPMs and other pro- and anti-inflammatory bioactive lipids, supporting the future investigation of the underlying enzymatic pathways, which may inform the development of novel treatments.
2022-01-01T00:00:00Z
Development and validation of a prognostic model for leflunomide discontinuation with abnormal blood tests during long-term treatment: Cohort study using data from the clinical practice research datalink gold and aurum
Aithal, Guruprasad P.
Fox, Christopher P.
Abhishek, Abhishek
http://hdl.handle.net/20.500.12904/18420
2024-03-21T04:51:19Z
2022-01-01T00:00:00Z
Development and validation of a prognostic model for leflunomide discontinuation with abnormal blood tests during long-term treatment: Cohort study using data from the clinical practice research datalink gold and aurum
Aithal, Guruprasad P.; Fox, Christopher P.; Abhishek, Abhishek
OBJECTIVE: To develop and validate a prognostic model for LEF discontinuation with abnormal blood test results. METHODS: Data from the Clinical Practice Research Datalink Gold and Aurum were used for model development and external validation, respectively. Participants prescribed LEF between 1 January 2007 and 31 December 2019 were followed up from 6 months after the first general practitioner prescription to the earliest of date of outcome, death, 5 year follow-up or 31 December 2019. Candidate prognostic factors were ascertained using theory and data-driven approaches. Penalized Cox regression was performed to develop the risk equation, followed by internal validation using 500 bootstraps to correct for optimism. Multiple imputation was applied to handle missing data. Model performance was assessed in terms of calibration and discrimination. RESULTS: Data for 1487 and 2329 participants contributing 3140 and 5246 person-years follow-up were included in the development and validation cohorts, respectively. Thirteen candidate predictors were included in the model. Epilepsy and either cytopenia or elevated liver enzymes during the first 6 months of shared-care LEF prescription were strong predictors of drug discontinuation with a hazard ratio of 4.39 (95% CI 1.74, 11.06) and 3.06 (2.15, 4.35), respectively. The unadjusted and optimism-adjusted calibration slope in development data was 1.00 (95% CI 0.75, 1.25) and 0.72 (95% CI 0.47, 0.97), respectively. The calibration slope in validation data was 0.91 (95% CI 0.74, 1.07). The model showed prognostic separation with an optimism-adjusted Royston D statistic of 0.73 (95% CI 0.44, 1.02). CONCLUSION: We have developed and externally validated an easy-to-use prognostic model that may be used to risk stratify monitoring for LEF toxicity and to make informed choices about risks when choosing treatments. Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.
2022-01-01T00:00:00Z
Foot and ankle osteoarthritis and cognitive impairment in retired UK soccer players (FOCUS): Protocol for a cross-sectional comparative study with general population controls
Batt, Mark
http://hdl.handle.net/20.500.12904/18419
2024-03-21T04:51:12Z
2022-01-01T00:00:00Z
Foot and ankle osteoarthritis and cognitive impairment in retired UK soccer players (FOCUS): Protocol for a cross-sectional comparative study with general population controls
Batt, Mark
INTRODUCTION: Professional footballers commonly experience sports-related injury and repetitive microtrauma to the foot and ankle, placing them at risk of subsequent chronic pain and osteoarthritis (OA) of the foot and ankle. Similarly, repeated heading of the ball, head/neck injuries and concussion have been implicated in later development of neurodegenerative diseases such as dementia. A recent retrospective study found that death from neurodegenerative diseases was higher among former professional soccer players compared with age matched controls. However, well-designed lifetime studies are still needed to provide evidence regarding the prevalence of these conditions and their associated risk factors in retired professional football players compared with the general male population. OBJECTIVES: To determine whether former professional male footballers have a higher prevalence than the general male population of: (1) foot/ankle pain and radiographic OA; and (2) cognitive and motor impairments associated with dementia and Parkinson's disease. Secondary objectives are to identify specific football-related risk factors such as head impact/concussion for neurodegenerative conditions and foot/ankle injuries for chronic foot/ankle pain and OA. METHODS AND ANALYSIS: This is a cross-sectional, comparative study involving a questionnaire survey with subsamples of responders being assessed for cognitive function by telephone assessment, and foot/ankle OA by radiographic examination. A sample of 900 adult, male, ex professional footballers will be recruited and compared with a control group of 1100 age-matched general population men between 40 and 100 years old. Prevalence will be estimated per group. Poisson regression will be performed to determine prevalence ratio between the populations and logistic regression will be used to examine risk factors associated with each condition in footballers. ETHICS AND DISSEMINATION: This study was approved by the East Midlands-Leicester Central Research Ethics Committee on 23 January 2020 (REC ref: 19/EM/0354). The study results will be disseminated at national and international meetings and submitted for peer-review publication. Copyright © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
2022-01-01T00:00:00Z
ASSERT (acute acral insufficiency fracture augmentation): Randomised controlled, feasibility trial in older people
Ong, Terence
Salem, Khalid
Quraishi, Nasir
Sahota, Opinder
http://hdl.handle.net/20.500.12904/18418
2024-03-21T04:51:05Z
2022-01-01T00:00:00Z
ASSERT (acute acral insufficiency fracture augmentation): Randomised controlled, feasibility trial in older people
Ong, Terence; Salem, Khalid; Quraishi, Nasir; Sahota, Opinder
OBJECTIVE: To determine the feasibility of designing and conducting a definitive trial to evaluate the effectiveness of sacral fracture fixation compared with non-surgical management among older people admitted with a lateral compression pelvic fragility fracture (PFF). DESIGN: Single-site, parallel, two-arm randomised controlled feasibility trial. SETTING: A UK tertiary centre hospital. PARTICIPANTS: Patients aged >=70 years who were ambulating pre-injury requiring hospital admission (within 28 days of injury) with a type 1 lateral compression PFF. INTERVENTIONS: The intervention group received sacral fracture fixation (cement augmentation+/-screw fixation) within 7 days of randomisation. Routine preoperative and postoperative care followed each surgical intervention. The control group received usual care consisting of analgesia, and regular input from the medical and therapy team. PRIMARY AND SECONDARY OUTCOME MEASURES: The feasibility outcomes were the number of eligible patients, willingness to be randomised, adherence to allocated treatment, retention, data on the completeness and variability of the proposed definitive trial outcome measures, and reported adverse events. RESULTS: 241 patients were screened. 13 (5.4%) were deemed eligible to participate. Among the eligible participants, nine (69.2%) were willing to participate. Five participants were randomised to the intervention group and four to the control group. The clinicians involved were willing to allow their patients to be randomised and adhere to the allocated treatment. One participant in the intervention group and two participants in the control group received their allocated treatment. All participants were followed up until 12 weeks post-randomisation, and had an additional safety follow-up assessment at 12 months. Overall, the proportion of completeness of outcome measures was at least 75%. No adverse events were directly related to the trial. CONCLUSIONS: There were significant challenges in recruiting sufficient participants which will need to be addressed prior to a definitive trial. TRIAL REGISTRATION NUMBER: ISRCTN16719542. Copyright © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
2022-01-01T00:00:00Z