10957 research outputs found
Sort by
A British Society of Gastrointestinal and Abdominal Radiology multi-centre audit of imaging investigations in inflammatory bowel disease
Full text linkObjectives
To evaluate current UK practice for inflammatory bowel disease (IBD) imaging against recommendations from published international literature.
Methods
A retrospective multi-centre audit was undertaken evaluating imaging modalities, protocols, and pathways used to investigate IBD both in outpatient and inpatient settings during January-December 2022. Reporting practices and training provisions were also recorded.
Results
Forty-one centres contributed: 35 centres provided complete data, whereas 6 centres provided incomplete data. Magnetic resonance enterography (MRE) was the most common modality for small bowel imaging across UK centres, comprising 13 099/18 784 (69.7%) investigations. There was regional variability in other modalities used, with 5 centres performing 81% of all intestinal ultrasound and 3 centres performing 65% of all small bowel follow-through. Compared with outpatients, inpatients with suspected IBD were significantly more likely to be imaged with techniques imparting ionising radiation whether scanned either in-hours (p = 0.005) or out-of-hours (p < 0.001). Non-ionising radiation imaging modalities were significantly less available out-of-hours (p < 0.0001). Sequences included in MRE protocols were variable. Disparity in imaging follow-up for patients prescribed biologic therapies was observed.
Conclusions
Considerable variation in UK IBD imaging practice has been identified. Improvements must be made to reduce the regional inequality of patient access to different imaging modalities and decrease reliance on ionising radiation for inpatients. Further research to standardise and optimise imaging pathways should be undertaken to improve uniformity, with emphasis placed on training and education.
Advances in knowledge
This multi-centre audit showed considerable IBD imaging practice variation between UK centres, particularly for imaging modalities used between inpatient and outpatient groups and in-hours versus out-of-hours
Structural Design and Immunogenicity of a Novel Self-Adjuvanting Mucosal Vaccine Candidate for SARS-CoV-2 Expressed in Plants
Full text linkMucosal vaccination for COVID‐19 to boost preexisting though insufficient systemic and local/mucosal immunity remains an attractive prospect but there are currently no licensed mucosal vaccines against this infection. Here, using a plant expression system, we developed a novel mucosal vaccine platform for respiratory viruses and demonstrated its application in the context of SARS‐CoV‐2 infection. In addition to the antigen itself, the PCF (Platform CTB‐Fc) vaccine candidate incorporates two molecular adjuvants, the IgG‐Fc antibody fragment and the nontoxic cholera toxin B subunit (CTB), with the first targeting the vaccine to IgG receptors on antigen‐presenting cells, and the second providing local adjuvanticity by targeting cellular gangliosides in the mucosae. We demonstrated that this vaccine candidate is highly immunogenic in mice, inducing virus‐neutralising systemic and mucosal antibodies as well as tissue resident memory T cells in the lungs. We also demonstrated that SRBD‐PCF is recognised by immune cells from exposed or vaccinated individuals, and that circulating antibodies also bind to the antigen within the vaccine, forming immune complexes (IC). Finally, with a view of respiratory delivery, we demonstrated that the vaccine can be aerosolised without loss of material or biological activity, and that it is noncytotoxic and nonhaemolytic to human cells. Furthermore, we demonstrate that the plant expression system represents a suitable platform to produce these complex, multifunctional macromolecules capable of simultaneously binding to multiple targets. Our data strongly support the case for a safe, self‐adjuvanting mucosal COVID‐19 vaccine development, as means to boosting both systemic and mucosal immunity
Considerations for drug trials in hypertrophic cardiomyopathy.
Full text linkHypertrophic cardiomyopathy (HCM) is a heterogeneous condition with potentially serious manifestations. Management has traditionally comprised therapies to palliate symptoms and implantable cardioverter-defibrillators to prevent sudden cardiac death. The need for disease-modifying therapies has been recognized for decades. More recently, an increasing number of novel and repurposed therapies hypothesized to target HCM disease pathways have been evaluated, culminating in the recent regulatory approval of mavacamten, a novel oral myosin inhibitor. HCM poses several unique challenges for clinical trials, which are important to recognize when designing trials and interpreting findings. This manuscript discusses the key considerations in the context of recent and ongoing randomized trials, including the roles of genotype, phenotype and symptom status in patient selection, the evidence base for clinical and mechanistic outcome measurements, trial duration and sample size
Digital cognitive behavioural self-management programme for fatigue, pain, and faecal incontinence in inflammatory bowel disease (IBD-BOOST): a multicentre, parallel, randomised controlled trial
Full text linkBackground
Fatigue, pain, and faecal urgency or incontinence are common, debilitating symptoms in inflammatory bowel disease (IBD). We developed IBD-BOOST, a digital, interactive, facilitator-supported, self-management intervention, and aimed to assess its effects compared with care as usual in relieving these symptoms and improving quality of life.
Methods
This multicentre, parallel, randomised controlled trial was conducted online in the UK, with allocation concealment maintained. Participants aged 18 years or older with IBD who rated the impact of fatigue, pain, and faecal urgency or incontinence as 5 or more on a 0–10 scale in a UK national survey were invited. Participants were randomly assigned (1:1) to the online IBD-BOOST programme or care as usual for 6 months via computer-generated randomisation. Primary outcomes were UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ) and Global Rating of Symptom Relief at 6 months post-randomisation. All randomly assigned participants were included in the intention-to-treat and harms analysis. This trial is registered with ISRCTN.com (ISRCTN71618461) and is closed.
Findings
Between Jan 20, 2020, and July 27, 2022, 4449 participants were invited to participate, and 780 participants were randomly assigned: 391 to IBD-BOOST and 389 to care as usual. 524 (67%) of 780 participants were female and 253 (32%) were male. At 6 months, there were no statistically significant differences for UK-IBDQ between the care as usual group (unadjusted mean 62·09 [SD 14·42]) and the IBD-BOOST group (unadjusted mean 60·85 [SD 16·08]; treatment effect estimate: adjusted mean difference –1·67 [95% CI –4·13 to 0·80], p=0·19) or for Global Rating of Symptom Relief (unadjusted mean 3·65 [2·75] vs 4·13 [2·81]; adjusted mean difference 0·44 [95% CI –0·56 to 1·44], p=0·39). Complier-averaged causal effects analysis demonstrated that participants who complied with IBD-BOOST reported lower UK-IBDQ scores than those who would have complied in the care as usual group (mean difference –2·39 [95%CI –4·34 to –0·45], p=0·016). Adverse events and serious adverse events were similar between the IBD-BOOST group (55 [14%] of 391) and care as usual group (79 [20%] of 389). There was one possible treatment-related serious adverse event in the IBD-BOOST group (recurrent sleep disorder) and no deaths.
Interpretation
IBD-BOOST did not statistically significantly improve disease-specific quality of life or Global Rating of Symptom Relief in patients with IBD with fatigue, pain, or faecal urgency or incontinence compared with care as usual. People who complied with the intervention appeared to derive benefit. Future research should focus on enhancing compliance with interventions and targeting them to individuals most likely to benefit
Phenotyping Functional Gait Disorder: An Exploratory Analysis of Existing Frameworks
No full textBackground
Gait impairment in functional neurological disorder is a disabling problem. Clinical phenotypes of functional gait vary considerably and there is no gold standard method for describing or classifying them. Six frameworks have been proposed in the literature to date.
Objectives
The primary aim of this study was to evaluate the ability of existing frameworks to classify a sample of functional gait disorder videos. The secondary aim was to assess inter‐rater agreement on these classifications.
Methods
An observational study with inter‐rater reliability assessment was completed. Raters examined each video and allocated the most suitable phenotype, per framework. Descriptive statistics were used to report the proportion of videos classified by each framework. Krippendorf‐alpha was used to analyze inter‐rater agreement.
Results
Thirty‐four videos were examined by five raters, using six phenotypic frameworks. The frameworks proposed by Fung (2016), and Baik and Lang (2007) categorized a median of 85% and 82% of the videos, respectively, whereas Lempert (1991), Jordbru (2012), Nonnekes (2020), and Baizabal‐Carvallo (2020), classified 53–65% of cases. Inter‐rater agreement on all frameworks was low (K‐alpha: 0.287–0.507).
Conclusion
Existing phenotypic frameworks have limited ability to categorize a sample of functional gait disorder videos. None of the frameworks examined were able to categorize all of the videos, with the framework proposed by Fung (2016) classifying the greatest number of videos. Inter‐rater agreement was consistently low for each of the six frameworks. These findings have implications for the future development of a valid, reliable, and comprehensive phenotypic classification framework for FGD
Comparing access to, and outcomes following, TAVI by biological sex
Full text linkIntroduction
European valvular heart disease guidelines define women as a ‘special group’. To explore what factors have led us to consider more than 50% of the global population special, we assessed access to transcatheter aortic valve implantation (TAVI) by sex on national and local levels and studied post-TAVI outcomes by sex within our centre.
Methods
Population statistics from census data were compared against British Cardiovascular Intervention Society (BCIS) audit and local data.
Using the National Institute for Cardiovascular Outcomes Research TAVI database, a retrospective analysis of 1049 consecutive patients from 2013 to 2023 was conducted at our UK tertiary centre.
Primary outcomes were all-cause death, a three-point composite of major adverse cardiac events (MACE) comprising death, non-fatal myocardial infarction and non-fatal stroke during TAVI admission, and post-TAVI survival.
Results
Nationally, females comprise 60% of over 75-year-olds; however, TAVI was performed more frequently in males: nationally (55.2% vs 44.8%, p<0.01) and locally (53.2% vs 46.8%, p<0.01). Males were 1.82 times more likely to undergo TAVI.
Locally, females undergoing TAVI were older and had worse renal function, higher frailty and greater transvalvular gradients. Males had more cardiovascular comorbidity.
In-hospital mortality and MACE did not differ by sex. Median survival was longer in females (1350 days vs 1728 days, p=0.02). Regression analysis demonstrated female sex as a predictor of increased survival (HR 0.73, 95% CI 0.61 to 0.88, p<0.01). Chronic obstructive pulmonary disease, atrial fibrillation, frailty and poor mobility were identified as predictors of reduced survival.
Conclusion
In this retrospective, observational study, we have demonstrated an under-representation of females undergoing TAVI. This observation is likely of multifactorial cause, including different disease recognition, referral, investigation and treatment practices.
We observed no difference in procedural death or MACE, but longer female survival, despite higher baseline age, frailty and renal impairment
Cardiac dysfunction during adverse maternal outcomes in hypertensive disorders of pregnancy
Full text linkIntroduction
Hypertensive disorders of pregnancy are associated with significant cardiac remodeling and diastolic dysfunction during pregnancy and are important contributors to maternal morbidity and mortality. Whether acute adverse maternal outcomes during hypertensive disorders of pregnancy are associated with abnormal left ventricular geometry and function has not been widely studied.
Material and Methods
A prospective observational study was conducted on 255 women with hypertensive disorders of pregnancy who underwent transthoracic echocardiography during the peripartum period. Maternal echocardiographic parameters, including left ventricular morphology and function, were analyzed to determine their association with composite adverse maternal outcomes by univariate and multivariate analyses. The composite adverse maternal outcome was defined as at least one of the following: admission to a high dependency unit (an intermediate‐care ward, providing enhanced cardiac monitoring), acute renal injury, adverse cardiopulmonary events, stroke, and disseminated intravascular coagulation.
Results
Adverse maternal outcomes occurred in 68 (26.7%) participants. Women with adverse outcomes had significantly higher left atrial volume index (28.8 [23.4–32.3] mL/m2 vs. 26.6 [22.2–30.9] mL/m2, p = 0.045) and E/e' ratio (7.8 [6.6–9.2] vs. 7.0 [5.9–8.1], p = 0.002) compared to those without complications. Other diastolic indices, namely, mitral inflow E/A and tissue‐Doppler e' velocities at the lateral and septal mitral annulus, showed no statistically significant between‐group. In multivariable analysis, both left atrial volume index and E/e' ratio remained independently associated with adverse maternal outcomes after adjusting for maternal factors and clinical variables. Right ventricular indices, such as tricuspid annular plane systolic excursion and systolic velocity S', were independently associated with adverse maternal outcomes, while fractional area change remained unchanged, indicating hyperkinetic circulatory adaptation rather than enhanced intrinsic right systolic function.
Conclusions
Cardiac abnormalities, particularly in left ventricular diastolic function and in right ventricular function, are more common in women with adverse maternal outcomes in hypertensive disorders of pregnancy than in hypertensive women without adverse maternal outcomes. Further studies are needed to determine whether these echocardiographic abnormalities could help identify women at increased risk of complications
Identifying Poor Responders to STN DBS in Parkinson Disease: The Role of Rapid Disease Progression in the First Year in Optimal Responders to Levodopa
Full text linkBackground
The factors contributing to a poor response to subthalamic nucleus deep brain stimulation (STN‐DBS) in Parkinson's disease (PD) are not yet fully understood. Accordingly, predicting the outcome might be challenging particularly in those who display an optimal response to the Levodopa challenge test.
Objective
To determine which factors may contribute to poor outcome of STN‐DBS in PD.
Methods
We performed a retrospective analysis of consecutive PD patients treated with STN‐DBS. Motor and non‐motor variables were retrieved before surgery and at 1‐year follow‐up. Patients were divided into poor and good DBS responders by a cut‐off value of less than 20% improvement of UPDRS‐II in the OFF‐medication ON‐stimulation condition at 1 year.
Results
Thirty‐two (26.2%) of 122 patients were categorised as poor responders. Before surgery, poor responders had significantly less impairment in activity of daily living and less severe motor severity. Response to levodopa challenge test was similar between poor and good responders. Significant worsening of axial symptoms at 1‐year follow‐up in the off‐medication off‐stimulation condition was found in poor responders. On multivariable linear regression analysis, only the relative change of activity of daily living by dopaminergic medications before surgery predicted its improvement by neurostimulation at 1‐year follow‐up.
Conclusions
Candidates for surgery with less impairment in activities of daily living may have less favourable outcomes after STN‐DBS, despite an optimal response during the pre‐operative Levodopa challenge. The worsening of axial symptoms due to disease progression might contribute to poorer outcomes, underscoring the need for better identification of these symptoms before surgery
Smoking Cessation Advisors’ Perspectives on Pregnant Women’s Attitudes on the Risks and Consequences of Smoking While Pregnant
Full text linkSmoking while pregnant is known to increase infant mortality, morbidity and can have adverse effects on children’s physical and mental development. Despite strong evidence and public health efforts, cessation support for pregnant smokers remains inconsistent across UK maternity services. Objectives: To investigate smoking cessation advisors’ perspectives on pregnant women’s attitudes and beliefs about smoking during pregnancy and the perceived risks to the unborn child. Methods: Ten smoking cessation advisors, from ten different hospital sites in London and Kent, participated in a focus group. Data were audio-recorded, transcribed verbatim, and thematically analysed. Results: Three main themes were identified: (1) building a positive relationship, (2) pregnant smokers’ awareness of health risks, and (3) informative techniques used by smoking cessation advisors. While based on a single focus group, the findings suggest that while many pregnant smokers recognise the health risks, this awareness alone may not lead to cessation. Conclusions: Adopting a person-centred approach that considers pregnant smokers’ knowledge, beliefs, and emotional readiness may help advisors deliver timely and appropriate information to encourage cessation. Practice implications could benefit from a more structured yet flexible framework to guide sensitive discussions about smoking risks and to reinforce the potential benefits of quitting for both maternal and foetal wellbeing
Seroprevalence of measles antibodies in children with cancer: results of a 2024 UK service evaluation
Full text linkObjective
To assess measles seroprevalence and testing practices in children with cancer in the UK.
Design
Multicentre evaluation of measles serology data for children on active treatment for cancer between January and March (Q1) 2024.
Setting
Eleven UK paediatric oncology centres (eight principal treatment centres and three shared care units).
Patients
Children aged <18 years on active cancer treatment with measles serology data at diagnosis and/or following revised UK Health Security Agency guidance in Q1 2024.
Results
A total of 695 eligible patients were included with a median age of 5.2 years (IQR 3.3–10.8 years). Baseline measles serology was tested in 545 patients with 89.0% positive for IgG antibodies. Cross-sectional testing of patients in Q1 2024 was undertaken in 289 patients with 78.5% measles seropositivity. Of the 121 patients tested at both time points who were measles seropositive at diagnosis, 23 (19.0%) were seronegative at retest. Most patients who lost pre-existing humoral immunity had an underlying diagnosis of leukaemia (n=16) followed by non-solid central nervous system (CNS) tumour (n=3), CNS tumour (n=2), lymphoma (n=1) and other (n=1). Although the odds of losing immunity were higher in haematological malignancy groups, this was not statistically significant (OR=1.44, 95% CI 0.52 to 3.99).
Conclusions
Children with cancer can lose pre-existing humoral immunity to measles during treatment. Variability in testing practices and rising measles cases nationally requires a standardised approach. Retesting measles serostatus during national outbreaks is important to identify susceptible patients who may require postexposure intravenous immunoglobulin
Access Repository Dashboard
Do you manage Open Research Online? Become a CORE Member to access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard! 👇