The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases

Background There are a lack of reliable data on the epidemiology and associated burden and costs of asthma. We sought to provide the first UK-wide estimates of the epidemiology, healthcare utilisation and costs of asthma. Methods We obtained and analysed asthma-relevant data from 27 datasets: these comprised national health surveys for 2010–11, and routine administrative, health and social care datasets for 2011–12; 2011–12 costs were estimated in pounds sterling using economic modelling. Results The prevalence of asthma depended on the definition and data source used. The UK lifetime prevalence of patient-reported symptoms suggestive of asthma was 29.5 % (95 % CI, 27.7–31.3; n = 18.5 million (m) people) and 15.6 % (14.3–16.9, n = 9.8 m) for patient-reported clinician-diagnosed asthma. The annual prevalence of patient-reported clinician-diagnosed-and-treated asthma was 9.6 % (8.9–10.3, n = 6.0 m) and of clinician-reported, diagnosed-and-treated asthma 5.7 % (5.7–5.7; n = 3.6 m). Asthma resulted in at least 6.3 m primary care consultations, 93,000 hospital in-patient episodes, 1800 intensive-care unit episodes and 36,800 disability living allowance claims. The costs of asthma were estimated at least £1.1 billion: 74 % of these costs were for provision of primary care services (60 % prescribing, 14 % consultations), 13 % for disability claims, and 12 % for hospital care. There were 1160 asthma deaths. Conclusions Asthma is very common and is responsible for considerable morbidity, healthcare utilisation and financial costs to the UK public sector. Greater policy focus on primary care provision is needed to reduce the risk of asthma exacerbations, hospitalisations and deaths, and reduce costs

Aerobic Function and Muscle Deoxygenation Dynamics during Ramp Exercise in Children

PURPOSE:To characterise changes in deoxyhemoglobin ([HHb]) response dynamics in boys and girls during ramp incremental exercise to investigate whether the reduced peak oxygen uptake (peakV˙O2) in girls is associated with a poorer matching of muscle O2 delivery to muscle O2 utilisation, as evidenced by a more rapid increase in [HHb].METHODS:52 children (31 boys, 9.9 ± 0.6 years, 1.38 ± 0.07 m, 31.70 ± 5.78 kg) completed ramp incremental exercise on a cycle ergometer during which pulmonary gas exchange and muscle oxygenation parameters were measured.RESULTS:When muscle [HHb] was expressed against absolute work rate and V˙O2, girls had an earlier change in [HHb] as evidenced by the lower c/d parameter (Girls: 54 ± 20 W vs Boys: 67 ± 19 W, P=0.023; Girls: 0.82 ± 0.28 L·min vs. Boys: 0.95 ± 0.19 L·min, P=0.055) and plateau (Girls: 85 ± 12 W vs. Boys: 99 ± 18 W, P=0.031; Girls: 1.02 ± 0.25 L·min vs. Boys: 1.22 ± 0.28 L·min, P=0.014). However, when expressed against relative work-rate or V˙O2, there were no sex differences in [HHb] response dynamics (all P>0.20). Significant correlations were observed between absolute and fat-free mass normalised peak V˙O2 and the HHb c/d and plateau parameters when expressed against absolute work-rate or V˙O2. Furthermore, when entered into a multiple regression model, the [HHb] plateau against absolute V˙O2 contributed 12% of the variance in peak V˙O2 after adjusting for fat-free mass, gas exchange threshold, and body fatness (model R =0.81, P<0.001).CONCLUSION:The sex-difference in peak V˙O2 in 9-10 year old children is, in part, related to sex-specific changes in muscle O2 extraction dynamics during incremental exercise

Urban public space initiatives and health in Africa: A mixed-methods systematic review

Public space initiatives (PSIs) in African cities can significantly promote health and social well-being, yet their implementation and impact are unknown across the continent. There is a substantial gap in literature on PSIs in African countries, with most studies concentrated in wealthier cities and lacking comprehensive assessments of long-term health impacts. The objective of this study was to synthesise evidence on the typology, location, features, and outcomes of these initiatives as well as the guiding principles that underlie their design and implementation. Employing a mixed-methods model, the study systematically reviews peer-reviewed and grey literature articles, focusing on the types, settings, and outcomes of PSIs. Data is analyzed using the CASP appraisal tool and thematic analysis. We analysed 47 studies, 15 of which were mixed methods, 22 qualitative and 10 quantitative. Sports accounted for 50% of initiatives. 30 of the 47 papers originated from South Africa. Communities viewed initiatives’ wellbeing impacts through social, economic, and ecological lenses, with health being but one dimension. The sustainability of initiatives was often limited by funding, historical marginalization, and competing land uses. Findings underscore the need for more comprehensive, long-term evaluations and cross-sector collaborations to sustain and enhance health-promoting public spaces in African cities

A Multi-disciplinary Commentary on Preclinical Research to investigate Vascular Contributions to Dementia

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder.</p

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder

Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)

The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease (AD) and associated socio-economic burdens. Abnormal metabolism of amyloidâ β (Aβ) has been proposed as a signiï¬ cant pathomechanism in AD, supported by results of recent clinical trials using antiâ Aβ antibodies. Nonetheless, the cognitive beneï¬ ts of the current treatments are limited. The etiology of AD is multifactorial, encompassing Aβ and tau accumulation, neuroinï¬ ammation, demyelination, vascular dysfunction, and comorbidities, which collectively lead to widespread neurodegeneration in the brain and cognitive impairment. Hence, solely removing Aβ from the brain may be insufï¬ cient to combat neurodegeneration and preserve cognition. To attain effective treatment for AD, it is necessary to (1) conduct extensive research on various mechanisms that cause neurodegeneration, including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level; (2) identify neuroprotective intervention targets against different neurodegeneration mechanisms; and (3) discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients. The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated, multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD. The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD, with the goal of halting or even reversing cognitive decline

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Synaptic interactome mining reveals p140Cap as a new hub for PSD proteins involved in psychiatric and neurological disorders

Altered synaptic function has been associated with neurological and psychiatric conditions including intellectual disability, schizophrenia and autism spectrum disorder (ASD). Amongst the recently discovered synaptic proteins is p140Cap, an adaptor that localizes at dendritic spines and regulates their maturation and physiology. We recently showed that p140Cap knockout mice have cognitive deficits, impaired long-term potentiation (LTP) and long-term depression (LTD), and immature, filopodia-like dendritic spines. Only a few p140Cap interacting proteins have been identified in the brain and the molecular complexes and pathways underlying p140Cap synaptic function are largely unknown. Here, we isolated and characterized the p140Cap synaptic interactome by co-immunoprecipitation from crude mouse synaptosomes, followed by mass spectrometry-based proteomics. We identified 351 p140Cap interactors and found that they cluster to sub complexes mostly located in the postsynaptic density (PSD). p140Cap interactors converge on key synaptic processes, including transmission across chemical synapses, actin cytoskeleton remodeling and cell-cell junction organization. Gene co-expression data further support convergent functions: the p140Cap interactors are tightly co-expressed with each other and with p140Cap. Importantly, the p140Cap interactome and its co-expression network show strong enrichment in genes associated with schizophrenia, autism, bipolar disorder, intellectual disability and epilepsy, supporting synaptic dysfunction as a shared biological feature in brain diseases. Overall, our data provide novel insights into the molecular organization of the synapse and indicate that p140Cap acts as a hub for postsynaptic complexes relevant to psychiatric and neurological disorders