University Hospital Llandough (Welsh: Ysbyty Llandochau Prifysgol) is a district general hospital in Llandough, Penarth, Wales. It is managed by the Cardiff and Vale University Health Board.
Long COVID affects a substantial proportion of survivors of acute infection with severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), who suffer a variety of symptoms that limit their quality of life and economic activity. Although the aetiology of long COVID is obscure, it appears to be a chronic inflammatory condition. Complement dysregulation is a prevalent feature of long COVID. Specifically, markers of classical, alternative, and terminal pathway activation are often elevated in patients with this condition. Here, we used a sensitive assay for mannan-binding lectin-associated serine protease-2 (MASP-2)/C1Inh complexes to analyse lectin pathway activation in a previously characterised cohort of patients with long COVID (n = 159) and healthy convalescent individuals with no persistent symptoms after infection with SARS-CoV-2 (n = 76). The data were combined with those from the most predictive complement analytes identified previously to delineate potential biomarkers of long COVID. MASP-2/C1Inh complexes were significantly elevated in patients with long COVID (p = 0.0003). Generalised linear modelling further identified an optimal set of four markers, namely iC3b (alternative pathway), TCC (terminal pathway), MASP-2/C1Inh (lectin pathway), and the complement regulator properdin, which had a receiver operating characteristic predictive power of 0.796 (95% confidence interval = 0.664-0.905). Combinations of the classical pathway markers C4, C1q, and C1s/C1Inh were poorly predictive of long COVID. These findings demonstrate that activation of the lectin complement pathway, which occurs upstream of the alternative and terminal pathways and can be inhibited therapeutically, is a salient feature of long COVID.
Aims Cardiovascular-kidney-metabolic (CKM) syndrome has developed into a global public health crisis. Although integrated care is increasingly used to treat patients with CKM, current health economic models fail to capture the value of considering the CKM syndrome as a unified condition. We present a conceptual framework to guide development of a new health economic model that captures value holistically across interconnected CKM domains.Materials and Methods Following best-practice guidelines, we undertook a review of published literature to identify and connect the key biological drivers of the CKM syndrome. These insights were synthesised into a biological framework, which was simplified into a streamlined influence diagram of sufficient complexity to guide model development. Both framework and diagram were iteratively reviewed and developed based on feedback from clinicians, health economists and modelling specialists.Results A biological framework and influence diagram were developed to illustrate how the CKM syndrome's biological drivers interconnect and link to key clinical outcomes. We detail the components of these diagrams, explaining the rationale behind connections. We discuss how the proposed framework could inform a model for future health economic evaluation.Conclusion There is a clear unmet need for comprehensive modelling of the CKM syndrome to support evidence-based decision-making and guide management of this highly prevalent, far-reaching disease. As more evidence has become available, the mathematical development, in the near future, of a long-term, holistic and flexible health economic model has become feasible, despite some gaps. This work seeks to shape a shared understanding of the challenges and opportunities in this developing field.
Cystic fibrosis-related diabetes (CFrD) is a common complication of cystic fibrosis (CF). Many people with CFrD struggle to keep glucose within target range leading to poorer clinical outcomes and reduced life expectancy. Hybrid closed-loop (HCL) systems are an exciting innovation which may help people with CFrD improve their glucose management and experience a better quality-of-life. We explored the experiences of adults with CFrD who used the CamAPS FX HCL to: understand the benefits and challenges to using HCL in people with CFrD; and, help inform decision-making about HCL use in CFrD populations in routine clinical care. We interviewed 19 individuals who used the CamAPS FX HCL for ≥ 3 months during the CL4P-CF clinical trial. Data were analysed thematically. Participants reported multiple clinical and quality-of-life benefits to using HCL. Many described treatment burnout before using the system and, hence, benefitting from automated glucose regulation and an increased capacity to take on new activities. Participants also shared historical difficulties gaining/maintaining weight as a result of their CF and described how using the system helped them achieve weight/muscle gain, improved their bodily confidence and enabled to them to enjoy a greater diversity of foods. Participants also observed CF-related benefits, including a (perceived) reduced susceptibility to infections, improved mood/energy to take on CF management-tasks, and increased confidence and ability to undertake physical activity due to a reduced risk of hypoglycaemia. In addition, participants reported medical trauma arising from hospital admissions in childhood and exposure to medically-invasive procedures for their CF, and highlighted benefits to using a system which mitigated the need to use injections. Due to their earlier traumatic experiences, some expressed a preference for using tubeless pumps and cannulas that require less frequent replacement. Participants reported improved glucose management, CF-related benefits and wide-ranging quality-of-life gains resulting from HCL use. Given their earlier experiences of treatment burnout and medically-related trauma, and taking account of the distinctive challenges involved in managing CFrD, our findings suggest that people with CFrD are a uniquely deserving group for access to HCL technology if shown to be clinically and cost effective in this population. ClinicalTrials.gov: NCT05562492, registration date 28th September 2022.
