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Extracorporeal Shockwave Therapy for Diabetes Related Foot Ulcers: A Pilot Three-Arm Double-Blinded Randomised Controlled Trial
Full text linkThere is an urgent need for effective interventions to aid diabetes-related foot ulcer (DFU) healing. This study aimed to test the deliverability of a proposed trial of extracorporeal shockwave therapy (ESWT) for DFU healing. A pilot double-blinded randomised controlled trial. Patients with a DFU present for ≥ 4 weeks were randomised to high dose (500 shocks/cm2), low dose (100 shocks/cm2) or sham (0 shocks/cm2) ESWT, plus standard care. Follow-up was for 24 weeks. Primary outcome was deliverability of the trial. Secondary outcomes were healing, quality of life and healthcare resource use. One-hundred and forty-one (15.6%) screened patients were eligible and 74 (52.5%) patients were recruited. Follow-up attendance was 97.3% (72/74), 93.2% (69/74) and 87.8% (65/74) at 6, 12 and 24 weeks. The median DFU healing time was high dose: 54.0 (IQR 119.0), low dose: 78.5 (IQR 61.0) and sham: 83.0 (IQR 85.0) days. The mean EQ-5D-5L utility value at 24 weeks was high dose: 0.621 (95% CI 0.438–0.804), low dose: 0.779 (95% CI 0.683–0.876) and sham: 0.806 (95% CI 0.717–0.895). Healthcare resource use was lowest in the low-dose ESWT arm. The pilot trial has demonstrated that patients with a DFU are willing to engage in the proposed trial and suggest the optimal way to deliver the definitive trial
"This Is What I Should Have Been Feeling": Transformations and Transitions in an LGBTQIA+ Inclusive Rugby Club
Full text linkAcross the UK, LGBTQIA+ sports clubs have become an established feature of the grassroots sporting landscape, with networks such as International Gay Rugby (IGR) expanding rapidly over the past two decades. Their continued growth suggests that many LGBTQIA+ people still perceive mainstream sport as exclusionary or unwelcoming. Yet scholarship remains limited, and studies grounded in Inclusive Masculinity Theory (IMT) frequently posit that declining homophobia has rendered such clubs primarily social spaces rather than sites of necessary protection or transformation.This article applies Multiple and Multidimensional Transitions (MMT) theory to the experiences of 14 gay and bisexual rugby players, to examine the ongoing relevance and value of LGBTQIA+ inclusive sports spaces. It shows how joining an inclusive rugby team prompts a dynamic set of interconnected transitions across psychological, cultural, identity and social domains. By highlighting these ongoing multidimensional processes, MMT demonstrates that LGBTQIA+ sports teams remain vital not merely as alternatives to homophobic environments, but as spaces that actively construct queer belonging and enable more expansive, authentic ways of being in sport
The engaged action hypothesis: Explaining the merits of external focus cues
Full text linkThe attentional focus effect—the theory that focusing on the body during skilled tasks leads to suboptimal results relative to focusing externally—is well established, but it is not known why it holds. The most widely cited explanation is the constrained action hypothesis: Focusing on the body interferes with beneficial automatic motor programs. We argue that increased automaticity may not be the sole or even primary explanation for the attentional focus effect and propose the engaged action hypothesis: An external focus prompts individuals to focus on the task at hand and engage and coordinate relevant muscle groups
A Simple and Robust Machine Learning Method for Segmentation of Thoracic Computed Tomography
Full text linkMachine learning being used as a tool in the field of healthcare offers us a great advantage, with already implemented automated processes like segmentation when it comes to cancer patients and treatments. However, these are not widely used as they are computationally costly and do not give a clear concise validation of whether its predictions are correct or not, along with no indications of the limitations or robustness of the model itself. In this work, we aim to make a faster, less complicated model to segment disease/infection within the lungs, along with giving us a score on its uncertainty in its predictions with a look into its limitations with the intention to apply this model to cancer patients with early stage lung cancer in the future. This will allow clinician’s to make a quick decision on how much to rely on this as a tool for that singular prediction in that moment. The lower the score, the worse the prediction in which the clinician will take over, or if the prediction obtains a high score, clinicians can have more trust and take its results into consideration as it gives a level of confidence behind its prediction. This tool could be the key to shortening wait times in the NHS and freeing up time for clinicians to increase survival rates
Part 1 - imidazolines and the changing face of nasal decongestants
Full text linkImidazolines are sympathomimetic drugs used to treat a range of conditions including nasal congestion, ocular disorders, and hypertension. Imidazolines were discovered over 150 years ago. However, it was research from the 1940s onwards which established the therapeutic benefits of imidazolines. Although there is extensive literature describing imidazolines, the history and timeline of their development is not well documented. This review focuses on the evolution of imidazoline pharmacology particularly those used in nasal decongestants, naphazoline, tetrahydrozoline, xylometazoline and oxymetazoline. These derivatives activate the α1-and α2-adrenergic receptors with varying degrees of selectivity, to provide decongestive relief through vasoconstriction. This reduces swelling of the nasal mucosa, delivering both subjective and objective relief from congestion. Each new imidazoline derivative has improved onset and duration of action, resulting in treatments with enhanced efficacy, tolerability, and safety. Although these advancements allow for less frequent dosing with comparable effects, the importance of correct usage for optimal benefit cannot be overstated. These nasal decongestants are considered safe when used as recommended however, rhinitis medicamentosa, characterized by chronic nasal congestion, can occur with excessive use. Imidazolines are an important class of compounds which have shown improvements in efficacy and safety over time. However, further improvements could be made with more advances in understanding their pharmacology
Part II – imidazolines and rhinitis medicamentosa: how can we tackle the rebound dilemma?
Full text linkRhinitis medicamentosa is the state of chronic congestion experienced from the prolonged or excessive use of nasal vasoconstrictors, typically used in the treatment of nasal congestion. Although a minor ailment, nasal congestion is a bothersome symptom for many allergic and non-allergic rhinitis sufferers. To alleviate symptoms, patients turn to over-the-counter topical nasal decongestants, with imidazolines often being the active ingredient of choice, as they provide rapid and long-lasting symptom relief, via vasoconstriction within the nasal mucosa. When used correctly, nasal vasoconstrictors are considered safe. However, misuse and deviation away from the recommended frequency of dose or maximum length of treatment can result initially in acute rebound congestion and if continued, rhinitis medicamentosa (RM). The pathophysiology and mechanisms of RM have not been fully elucidated and are complicated by difficulties in determining where the underlying disease ends, and RM begins. RM is characterised by the presence of chronic nasal congestion which responds less effectively and for progressively shorter periods to nasal vasoconstrictor treatments. Consequently, patients try to relieve symptoms by taking the nasal vasoconstrictor more frequently or at higher doses, which ultimately exacerbates the congestion further and creates a dependency on the nasal vasoconstrictor. Why RM develops is unclear, hypothesised mechanisms include structural, functional and inflammatory changes in the nasal mucosa, changes in receptor sensitivity or innervation pathways. To which extent this is solely in response to the use of imidazoline derivates or related to the presence of preservatives in topical nasal treatments is yet to be determined. Although treatment options exist for RM, prevention may be the best medicine. Provision of better education around the use of nasal vasoconstrictions, coupled with preservative free formulations and lowest possible dose delivery, may help to reduce the likelihood of developing the disease from the outset, reducing the burden on both the patient and healthcare providers
Morphine for chronic breathlessness (MABEL) in the UK: a multi-site, parallel-group, dose titration, double-blind, randomised, placebo-controlled trial
Full text linkBackground: The effectiveness of opioids for breathlessness seen in laboratory-based studies has not been replicated in clinical trials. We aimed to assess the effectiveness of oral morphine for breathlessness in long-term conditions. Methods: This phase 3, parallel-group, double-blind, placebo-controlled trial across 11 centres randomly assigned consenting adults (1:1, stratified by site and causal disease) with a modified Medical Research Council breathlessness score of 3 or more due to cardiorespiratory conditions to receive 5–10 mg twice daily oral long-acting morphine or placebo (as well as a blinded laxative) for 56 days. The primary outcome was worst breathlessness score in the past 24 h at day 28, measured using a numerical rating scale (NRS; 0=not breathless at all; 10=worst imaginable breathlessness). Secondary outcomes included physical activity levels, worst cough NRS, quality of life, and morphine-related toxicities. Patients who received at least one dose of study drug were eligible for inclusion in efficacy and safety analyses. The trial was registered with ISRCTN (ISRCTN87329095) and the EU Clinical Trials Register (EudraCT 2019-002479-33). Findings: Between March 18, 2021, and Oct 26, 2023, 143 participants were randomly assigned to receive either morphine (73 participants) or placebo (67 participants) and were included in the analyses; three participants did not receive the allocated treatment. Participants had a mean age of 70·5 (SD 9·4) years, were mostly male (93 [66%]), and were mostly White (132 [94%]). By day 28, 64 (88%) participants in the morphine group versus 66 (99%) in the placebo group had 90% adherence or greater. We found no evidence of difference in worst breathlessness at day 28 (morphine 6·19 [95% CI 5·57 to 6·81] vs placebo 6·10 [5·44 to 6·76]; adjusted mean difference 0·09 [95% CI –0·57 to 0·75], p=0·78) or any secondary measure, except for improved cough seen at day 56 (adjusted mean difference –1·41 [–2·18 to –0·64]). Increased moderate to vigorous physical activity was seen at day 28 (adjusted mean difference 9·51 min/day [0·54–18·48]) but this was not significant after multiple-measures correction. The morphine group had more adverse events (251 vs 162), serious adverse events (15 vs three, of which three in the morphine group and zero in the placebo group were deemed to be related to the study), and study drug withdrawals (13 vs two). There were no treatment-related deaths. Interpretation: We found no evidence that morphine improves worst breathlessness intensity. Further research is needed to understand whether there is any role for morphine in chronic breathlessness, but our findings do not support its use in this setting. Funding: NIHR Health Technology Assessment programme (HTA Project 17/34/01
Which Patients with COPD Would Benefit from Cough Monitoring?
Full text linkBackground: Cough monitoring for exacerbation detection is optimally effective if used for the appropriate cohort of chronic obstructive pulmonary disease (COPD) patients, i.e., increased cough during exacerbation and prodrome is a prerequisite enabling (early) detection. Methods: A post hoc analysis of data from a validation study on an alert system for exacerbation detection based on nighttime cough was used to study if patient data were predictive for the increased cough during exacerbation and for cough count distribution. The quantitative effect on the performance of the alert system when using patient stratification was studied as well. Results: Patient data were not predictive for robust cough statistics: neither the nighttime cough count median nor the interquartile range were found to have statistically relevant correlation with the available patient data. Patients with and without increased cough during exacerbation did show differences in their characteristics. Using patient age and symptom questionnaire data, a classifier based on a logistic regression model was parametrised having an accuracy of 85% in predicting presence or absence of increased cough during exacerbation. Using the classifier for patient stratification, the performance of the exacerbation alert system increased with sensitivity going from 59 to 76%. Conclusions: The post hoc analysis suggests that patient data can be used to stratify COPD patients for cough monitoring
