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Blood loss is a potential cause of morbidity and mortality in craniosynostosis surgery. Recent reports have suggested that the use of tranexamic acid (TXA), an antifibrinolytic agent, mitigates this blood loss. A retrospective cohort study of patients undergoing craniosynostosis surgery at a tertiary craniofacial hospital in Sydney was undertaken. Primary outcomes were blood loss and transfusion requirements. Two groups were compared: those who received intravenous prophylactic TXA and those who underwent surgery without TXA. Statistical analysis was performed with Student t test and the Mann-Whitney U test for nonparametric results. We identified 206 patients who underwent craniosynostosis surgery over an 8 year period; 78 control patients and 128 patients that received TXA. Tranexamic acid was found to result in a weight-adjusted calculated blood loss mean difference of 9.6 ml/kg across all procedures (P = 0.0332 95% confidence interval 0.7734-18.4266). The actual blood loss reduction achieved with TXA was 6.7 ml/kg in spring cranioplasties, compared to 15.2 ml/kg in fronto-orbital remodeling procedures. There was a statistically and clinically significant reduction in postoperative transfusion incidence, with transfusions required in 27% of controls and 6% of TXA patients (P

Introduction There is relatively little published on the effects of COVID-19 on respiratory physiology, particularly breathing patterns. We sought to determine if there were lasting detrimental effect following hospital discharge and if these related to the severity of COVID-19. Methods We reviewed lung function and breathing patterns in COVID-19 survivors > 3 months after discharge, comparing patients who had been admitted to the intensive therapy unit (ITU) (n = 47) to those who just received ward treatments (n = 45). Lung function included spirometry and gas transfer and breathing patterns were measured with structured light plethysmography. Continuous data were compared with an independent t-test or Mann Whitney-U test (depending on distribution) and nominal data were compared using a Fisher’s exact test (for 2 categories in 2 groups) or a chi-squared test (for > 2 categories in 2 groups). A p-value of Results We found evidence of pulmonary restriction (reduced vital capacity and/or alveolar volume) in 65.4% of all patients. 36.1% of all patients has a reduced transfer factor (TLCO) but the majority of these (78.1%) had a preserved/increased transfer coefficient (KCO), suggesting an extrapulmonary cause. There were no major differences between ITU and ward lung function, although KCO alone was higher in the ITU patients (p = 0.03). This could be explained partly by obesity, respiratory muscle fatigue, localised microvascular changes, or haemosiderosis from lung damage. Abnormal breathing patterns were observed in 18.8% of subjects, although no consistent pattern of breathing pattern abnormalities was evident. Conclusions An “extrapulmonary restrictive” like pattern appears to be a common phenomenon in previously admitted COVID-19 survivors. Whilst the cause of this is not clear, the effects seem to be similar on patients whether or not they received mechanical ventilation or had ward based respiratory support/supplemental oxygen.

Tidal breathing measurements can be used to identify changes in respiratory status. Structured light plethysmography (SLP) is a non-contact tidal breathing measurement technique. Lack of reference equations for SLP parameters makes clinical decision-making difficult. We have developed a set of growth-adjusted reference equations for seven clinically pertinent parameters of respiratory rate (fR), inspiratory time (tI), expiratory time (tE), duty cycle (tI/total breath time), phase (thoraco-abdominal asynchrony (TAA)), relative thoracic contribution (RTC) and tidal inspiratory/expiratory flow at 50% volume (IE50). Reference equations were developed based on a cohort of 198 seated healthy subjects (age 2–75 years, height 82–194 cm, 108 males). We adopted the same methodological approach as the Global Lung Function Initiative (GLI) report on spirometric reference equations. 5 min of tidal breathing was recorded per subject. Parameters were summarised with their medians. The supplementary material provided is an integral part of this work and a reference range calculator is provided therein. We found predicted fR to decrease with age and height rapidly in the first 20 years and slowly thereafter. Expected tI, tE and RTC followed the opposite trend. RTC was 6.7% higher in females. Duty cycle increased with age, peaked at 13 years and decreased thereafter. TAA was high and variable in early life and declined rapidly with age. Predicted IE50 was constant, as it did not correlate with growth. These reference ranges for seven key measures ensure that clinicians and researchers can identify tidal breathing patterns in disease and better understand and interpret SLP and tidal breathing data., A set of reference equations for seven key tidal breathing parameters measured using structured light plethysmography (SLP) to help clinicians better understand and interpret SLP data and the value of tidal breathing patterns https://bit.ly/2Og2H3h

Background Obstructive sleep apnoea (OSA) is very common in patients with type 2 diabetes (T2D). We and others have shown that OSA was associated with diabetes-related microvascular complications in patients with T2D in cross-sectional and longitudinal studies and that compliance with continuous positive airway pressure (CPAP) reduced the progression of microvascular complications. Hence, we hypothesised that adequate CPAP reduces the development of microvascular complication in patients with T2D. Methods SLEEP T2D is a cohort study with embedded feasibility, open-label, parallel-arm, randomised control trial (RCT) over 2 years. The primary aim is the feasibility of conducting a definitive RCT assessing the impact of CPAP on chronic kidney disease and other microvascular complications in patients with T2D. The main parameters are to assess willingness of participants to be randomised, follow-up rates, CPAP adherence/compliance, to optimise the choice of outcome measures for a substantive trial, and to identify the parameters for sample size calculations. The secondary aims of the study are related to the impact of CPAP, sleep-related disorders, and sleep chronotype on a variety of diabetes-related end points. The study participants were recruited from the T2D services in multiple NHS trusts across England. The main exclusion criteria for the cohort study are as follows: T1D, eGFR 2, known OSA, active malignancy or chronic kidney disease from reasons other than diabetes, pregnancy, professional drivers, and a history of falling asleep whilst driving within last 2 years. The main exclusion criteria from the RCT were as follows: Apnoea-Hypopnoea Index TM, Resmed). Discussion The feasibility RCT will help us design the future RCT to assess the impact of CPAP on diabetes-related microvascular complications. The cohort study will generate preliminary data regarding the impact of sleep quality, duration, and chronotype on diabetes-related outcomes which could lead to further mechanistic and interventional studies. Trial registration ISRCTN, ISRCTN12361838. Registered 04 April 2018, Protocol version: v5.0 02.12.19.

Background Pediatric airway models currently available for use in education or simulation do not replicate anatomy or tissue responses to procedures. Emphasis on mass production with sturdy but homogeneous materials and low-fidelity casting techniques diminishes these models' abilities to realistically represent the unique characteristics of the pediatric airway, particularly in the infant and younger age ranges. Newer fabrication technologies, including 3-dimensional (3D) printing and castable tissue-like silicones, open new approaches to the simulation of pediatric airways with greater anatomical fidelity and utility for procedure training. Methods After ethics approval, available/archived computerized tomography data sets of patients under the age of 2 years were reviewed to identify those suitable for designing new models. A single 21-month-old subject was selected for 3D reconstruction. Manual thresholding was then performed to produce 3D models of selected regions and tissue types within the dataset, which were either directly 3D-printed or later cast in 3D-printed molds with a variety of tissue-like silicones. A series of testing mannequins derived using this multimodal approach were then further refined following direct clinician feedback to develop a series of pediatric airway model prototypes. Results The initial prototype consisted of separate skeletal (skull, mandible, vertebrae) and soft-tissue (nasal mucosa, pharynx, larynx, gingivae, tongue, functional temporomandibular joint [TMJ] "sleeve," skin) modules. The first iterations of these modules were generated using both single-material and multimaterial 3D printing techniques to achieve the haptic properties of real human tissues. After direct clinical feedback, subsequent prototypes relied on a combination of 3D printing for osseous elements and casting of soft-tissue components from 3D-printed molds, which refined the haptic properties of the nasal, oropharyngeal, laryngeal, and airway tissues, and improved the range of movement required for airway management procedures. This approach of modification based on clinical feedback resulted in superior functional performance. Conclusions Our hybrid manufacturing approach, merging 3D-printed components and 3D-printed molds for silicone casting, allows a more accurate representation of both the anatomy and functional characteristics of the pediatric airway for model production. Further, it allows for the direct translation of anatomy derived from real patient medical imaging into a functional airway management simulator, and our modular design allows for modification of individual elements to easily vary anatomical configurations, haptic qualities of components or exchange components to replicate pathology.

An example of the East–Freeman Automatic Vent from Oxford was found in the early anaesthesia equipment collection at St George Hospital, Sydney. It weighs less than 200 g and is representative of a group of miniature ventilators that were described in the 1960s, including the Minivent from South Africa and the Microvent from Canada. All relied on a pressure-operated inflating valve that was described in 1966 by Mitchell and Epstein from Oxford. The ventilators were compact, portable and were powered by the gas supply from the anaesthesia machine or other driving source that distended a reservoir bag. The main problem was that they could stick in the inspiratory phase. This led to pressure in the lungs rising towards the driving pressure. There was a risk of barotrauma to the patient if the system was not promptly disconnected. While theyhad provided an alternative to hand bagging, they were superseded, as more sophisticated and safer ventilators became widely available.

Objective The 2019 Coronavirus (COVID-19) results in a wide range of clinical severity and there remains a need for prognostic tools which identify patients at risk of rapid deterioration and who require critical care. Chest radiography (CXR) is routinely obtained at admission of COVID-19 patients. However, little is known regarding correlates between CXR severity and time to intubation. We hypothesize that the degree of opacification on CXR at time of admission independently predicts need and time to intubation. Methods In this retrospective cohort study, we reviewed COVID-19 patients who were admitted to an urban medical center during March 2020 that had a CXR performed on the day of admission. CXRs were divided into 12 lung zones and were assessed by two blinded thoracic radiologists. A COVID-19 opacification rating score (CORS) was generated by assigning one point for each lung zone in which an opacity was observed. Underlying comorbidities were abstracted and assessed for association. Results One hundred forty patients were included in this study and 47 (34%) patients required intubation during the admission. Patients with CORS ≥ 6 demonstrated significantly higher rates of early intubation within 48 h of admission and during the hospital stay (ORs 24 h, 19.8, p < 0.001; 48 h, 28.1, p < 0.001; intubation during hospital stay, 6.1, p < 0.0001). There was no significant correlation between CORS ≥ 6 and age, sex, BMI, or any underlying cardiac or pulmonary comorbidities. Conclusions CORS ≥ 6 at the time of admission predicts need for intubation, with significant increases in intubation at 24 and 48 h, independent of comorbidities. Key Points • Chest radiography at the time of admission independently predicts time to intubation within 48 h and during the hospital stay in COVID-19 patients. • More opacities on chest radiography are associated with several fold increases in early mechanical ventilation among COVID-19 patients. • Chest radiography is useful in identifying COVID-19 patients whom may rapidly deteriorate and help inform clinical management as well as hospital bed and ventilation allocation. Electronic supplementary material The online version of this article (10.1007/s00330-020-07354-y) contains supplementary material, which is available to authorized users.

Background: Despite chronic obstructive pulmonary disease (COPD) being the commonest non-communicable disease in Nepal, there is limited research evidence estimating the spirometry-based burden of ...

Background It is not clear if point-of-care (POC) testing for hemoglobin A1c (HbA1c) is associated with glycemic control in type 2 diabetes. Methods In this cross-sectional study, we linked general practitioner (GP) data on 22,778 Norwegian type 2 diabetes patients to data from the Norwegian Organization for Quality Improvement of Laboratory Examinations. We used general and generalized linear mixed models to investigate if GP offices’ availability (yes/no) and analytical quality of HbA1c POC testing (average yearly “trueness score”, 0–4), as well as frequency of participation in HbA1c external quality assurance (EQA) surveys, were associated with patients’ HbA1c levels during 2014–2017. Results Twenty-eight out of 393 GP offices (7%) did not perform HbA1c POC testing. After adjusting for confounders, their patients had on average 0.15% higher HbA1c levels (95% confidence interval (0.04–0.27) (1.7 mmol/mol [0.5–2.9]). GP offices participating in one or two yearly HbA1c EQA surveys, rather than the maximum of four, had patients with on average 0.17% higher HbA1c levels (0.06, 0.28) (1.8 mmol/mol [0.6, 3.1]). For each unit increase in the GP offices’ HbA1c POC analytical trueness score, the patients’ HbA1c levels were lower by 0.04% HbA1c (−0.09, −0.001) (−0.5 mmol/mol [−1.0, −0.01]). Conclusions Novel use of validated patient data in combination with laboratory EQA data showed that patients consulting GPs in offices that perform HbA1c POC testing, participate in HbA1c EQA surveys, and maintain good analytical quality have lower HbA1c levels. Accurate HbA1c POC results, available during consultations, may improve diabetes care.

Gliosis and fibrosis after spinal cord injury (SCI) lead to formation of a scar that is thought to present both molecular and mechanical barriers to neuronal regeneration. The scar consists of a meshwork of reactive glia and deposited, cross-linked, extracellular matrix (ECM) that has long been assumed to present a mechanically “stiff” blockade. However, remarkably little quantitative information is available about the rheological properties of chronically injured spinal tissue. In this study we utilize atomic force microscopy microindentation to provide quantitative evidence of chronic mechanical stiffening after SCI. Using the results of this tissue characterization, we assessed the sensitivity of both mouse and human astrocytes in vitro and determined that they are exquisitely mechanosensitive within the relevant range of substrate stiffness observed in the injured/uninjured spinal cord. We then utilized a novel immune modifying nanoparticle (IMP) treatment as a tool to reveal fibrotic scarring as one of the key drivers of mechanical stiffening after SCI in vivo. We also demonstrate that glial scar-forming astrocytes form a highly aligned, anisotropic network of glial fibers after SCI, and that IMP treatment mitigates this pathological alignment. Taken together, our results identify chronic mechanical stiffening as a critically important aspect of the complex lesion milieu after SCI that must be considered when assessing and developing potential clinical interventions for SCI.

Objective There are currently no definitive disease-modifying therapies for traumatic brain injury (TBI). In this study, we present a strong therapeutic candidate for TBI, immunomodulatory nanoparticles (IMPs), which ablate a specific subset of hematogenous monocytes (hMos). We hypothesized that prevention of infiltration of these cells into brain acutely after TBI would attenuate secondary damage and preserve anatomic and neurologic function. Methods IMPs, composed of US Food and Drug Administration-approved 500nm carboxylated-poly(lactic-co-glycolic) acid, were infused intravenously into wild-type C57BL/6 mice following 2 different models of experimental TBI, controlled cortical impact (CCI), and closed head injury (CHI). Results IMP administration resulted in remarkable preservation of both tissue and neurological function in both CCI and CHI TBI models in mice. After acute treatment, there was a reduction in the number of immune cells infiltrating into the brain, mitigation of the inflammatory status of the infiltrating cells, improved electrophysiologic visual function, improved long-term motor behavior, reduced edema formation as assessed by magnetic resonance imaging, and reduced lesion volumes on anatomic examination. Interpretation Our findings suggest that IMPs are a clinically translatable acute intervention for TBI with a well-defined mechanism of action and beneficial anatomic and physiologic preservation and recovery. Ann Neurol 2020;87:442-455.

Background: Chronic cough is a common respiratory complaint among the general population, causing substantial physical, social, and psychological burden. This study aims to estimate the prevalence of chronic cough and its risk factors among Nepalese adults.Methods: It is a community-based cross-sectional study among 1438 adults aged >=40 years from a semi-urban area of the Pokhara Metropolitan City of Western Nepal. Chronic cough was defined as daily coughing for at least three months duration during the preceding two years. We assessed the prevalence and associated risk factors of chronic cough.Results: Majority (54 were female and the average age (SD) was 56(10) years. The prevalence of chronic cough was 5%. Logistic regression analysis resulted in higher odds of chronic cough among aged gt;60 years (OR: 4.7; 95 2.5 textendash 8.9), COPD patients (OR:18.5; 95 11.2 textendash 30.6), biomass fuel smoke exposure (OR: 1.7; 95 1.1 textendash 2.7), and absence of kitchen chimney (OR: 2.9; 95 1.5 textendash 5.6). Similarly, chronic coughing is associated with among those who exposed to secondhand smoke (OR: 3.1; 95 1.9 textendash 4.9), former smokers (OR: 3.0; 95 1.6 textendash 5.4), current smokers (OR: 5.8; 95 3.2 textendash 10.3) and history of childhood lung infection (OR: 2.5; 95 1.3 textendash 5.0). However, there was no statistically significant association observed with sex, cardiovascular comorbidities, and tuberculosis history.Conclusions: Considering the significant impact of chronic cough on quality of life, it is important to design and implement programs and strategies to reduce modifiable risk factors like smoking, biomass fuel exposure, and preventing childhood lung infection.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3510.This abstract was presented at the 2021 ERS International Congress, in session textquotedblleftPrediction of exacerbations in patients with COPDtextquotedblright.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

Introduction: Arteriovenous fistulas are the preferred method of vascular access for haemodialysis. Data suggests patency rates can be low and may be related to vessel diameters prior to creation. We use specific size criteria for fistula selection. We aimed to establish patency rates in relation to vessel size and whether other factors affect fistula patency. Methods: Consecutive patients undergoing radiocephalic (RCF) or brachiocephalic (BCF) creation between 2016 and 2018 were analysed. Preoperative arterial and venous diameters were collected. Six-week and six-month primary and secondary patency rates were analysed to establish any impact of vessel size on patency and re-intervention rates between groups. A univariate analysis was performed. Results: Ninety four RCFs and 101 BCFs were created. Median artery and vein size for RCF were 2.7 and 3.0 mm respectively. For BCF, they were 4.6 and 4.3 mm respectively. At 6-weeks, overall satisfactory patency for RCF and BCF combined was 91.8%. 89.7% demonstrated primary patency; 2.1% secondary patency. At 6-months, overall patency was 78.7%; 58.5% demonstrated primary patency, 20.2% secondary patency. A univariate analysis, for both groups, revealed vein size was a significant predictor of overall satisfactory patency at 6-weeks, with larger veins more likely to remain patent ( p = 0.025 RCF, p = 0.007 BCF). However, artery size was not predictive ( p = 0.1 RCF, p = 0.5 BCF). At 6-months, neither artery nor vein diameter were predictive in either group. When comparing size of vessel based on fistula type, vessels used to create RCFs were smaller than those for BCFs ( p < 0.001). RCFs were more likely to receive endovascular intervention or occlude when compared to BCFs ( p = 0.014). Discussion: Excellent patency and maturation rates can be achieved using fairly strict vessel size criteria. Vein size might be the more important predictor of early success. RCFs can be challenging due to smaller vessels, but maturation rates can be optimised by close surveillance and aggressive re-intervention.

Background Chronic obstructive pulmonary disease is a major contributor to morbidity, mortality and health service costs but is vastly underdiagnosed. Evidence on screening and how best to approach this is not clear. There are also uncertainties around the natural history (prognosis) of chronic obstructive pulmonary disease and how it impacts on work performance. Objectives Work package 1: to evaluate alternative methods of screening for undiagnosed chronic obstructive pulmonary disease in primary care, with clinical effectiveness and cost-effectiveness analyses and an economic model of a routine screening programme. Work package 2: to recruit a primary care chronic obstructive pulmonary disease cohort, develop a prognostic model [Birmingham Lung Improvement StudieS (BLISS)] to predict risk of respiratory hospital admissions, validate an existing model to predict mortality risk, address some uncertainties about natural history and explore the potential for a home exercise intervention. Work package 3: to identify which factors are associated with employment, absenteeism, presenteeism (working while unwell) and evaluate the feasibility of offering formal occupational health assessment to improve work performance. Design Work package 1: a cluster randomised controlled trial with household-level randomised comparison of two alternative case-finding approaches in the intervention arm. Work package 2: cohort study – focus groups. Work package 3: subcohort – feasibility study. Setting Primary care settings in West Midlands, UK. Participants Work package 1: 74,818 people who have smoked aged 40–79 years without a previous chronic obstructive pulmonary disease diagnosis from 54 general practices. Work package 2: 741 patients with previously diagnosed chronic obstructive pulmonary disease from 71 practices and participants from the work package 1 randomised controlled trial. Twenty-six patients took part in focus groups. Work package 3: occupational subcohort with 248 patients in paid employment at baseline. Thirty-five patients took part in an occupational health intervention feasibility study. Interventions Work package 1: targeted case-finding – symptom screening questionnaire, administered opportunistically or additionally by post, followed by diagnostic post-bronchodilator spirometry. The comparator was routine care. Work package 2: twenty-three candidate variables selected from literature and expert reviews. Work package 3: sociodemographic, clinical and occupational characteristics; occupational health assessment and recommendations. Main outcome measures Work package 1: yield (screen-detected chronic obstructive pulmonary disease) and cost-effectiveness of case-finding; effectiveness of screening on respiratory hospitalisation and mortality after approximately 4 years. Work package 2: respiratory hospitalisation within 2 years, and barriers to and facilitators of physical activity. Work package 3: work performance – feasibility and acceptability of the occupational health intervention and study processes. Results Work package 1: targeted case-finding resulted in greater yield of previously undiagnosed chronic obstructive pulmonary disease than routine care at 1 year [n = 1278 (4%) vs. n = 337 (1%), respectively; adjusted odds ratio 7.45, 95% confidence interval 4.80 to 11.55], and a model-based estimate of a regular screening programme suggested an incremental cost-effectiveness ratio of £16,596 per additional quality-adjusted life-year gained. However, long-term follow-up of the trial showed that at ≈4 years there was no clear evidence that case-finding, compared with routine practice, was effective in reducing respiratory admissions (adjusted hazard ratio 1.04, 95% confidence interval 0.73 to1.47) or mortality (hazard ratio 1.15, 95% confidence interval 0.82 to 1.61). Work package 2: 2305 patients, comprising 1564 with previously diagnosed chronic obstructive pulmonary disease and 741 work package 1 participants (330 with and 411 without obstruction), were recruited. The BLISS prognostic model among cohort participants with confirmed airflow obstruction (n = 1894) included 6 of 23 candidate variables (i.e. age, Chronic Obstructive Pulmonary Disease Assessment Test score, 12-month respiratory admissions, body mass index, diabetes and forced expiratory volume in 1 second percentage predicted). After internal validation and adjustment (uniform shrinkage factor 0.87, 95% confidence interval 0.72 to 1.02), the model discriminated well in predicting 2-year respiratory hospital admissions (c-statistic 0.75, 95% confidence interval 0.72 to 0.79). In focus groups, physical activity engagement was related to self-efficacy and symptom severity. Work package 3: in the occupational subcohort, increasing dyspnoea and exposure to inhaled irritants were associated with lower work productivity at baseline. Longitudinally, increasing exacerbations and worsening symptoms, but not a decline in airflow obstruction, were associated with absenteeism and presenteeism. The acceptability of the occupational health intervention was low, leading to low uptake and low implementation of recommendations and making a full trial unfeasible. Limitations Work package 1: even with the most intensive approach, only 38% of patients responded to the case-finding invitation. Management of case-found patients with chronic obstructive pulmonary disease in primary care was generally poor, limiting interpretation of the long-term effectiveness of case-finding on clinical outcomes. Work package 2: the components of the BLISS model may not always be routinely available and calculation of the score requires a computerised system. Work package 3: relatively few cohort participants were in paid employment at baseline, limiting the interpretation of predictors of lower work productivity. Conclusions This programme has addressed some of the major uncertainties around screening for undiagnosed chronic obstructive pulmonary disease and has resulted in the development of a novel, accurate model for predicting respiratory hospitalisation in people with chronic obstructive pulmonary disease and the inception of a primary care chronic obstructive pulmonary disease cohort for longer-term follow-up. We have also identified factors that may affect work productivity in people with chronic obstructive pulmonary disease as potential targets for future intervention. Future work We plan to obtain data for longer-term follow-up of trial participants at 10 years. The BLISS model needs to be externally validated. Our primary care chronic obstructive pulmonary disease cohort is a unique resource for addressing further questions to better understand the prognosis of chronic obstructive pulmonary disease. Trial registration Current Controlled Trials ISRCTN14930255. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 13. See the NIHR Journals Library website for further project information.

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research.

The high frequency of aberrant PI3K pathway activation in hormone receptor-positive (HR+) breast cancer has led to the development, clinical testing, and approval of the p110α-selective PI3K inhibitor alpelisib. The limited clinical efficacy of alpelisib and other PI3K inhibitors is partially attributed to the functional antagonism between PI3K and estrogen receptor (ER) signaling, which is mitigated via combined PI3K inhibition and endocrine therapy. We and others have previously demonstrated a chromatin-associated mechanism by which PI3K supports cancer development and antagonizes ER signaling through the modulation of H3K4 methylation. Here we show that inhibition of the H3K4 histone methyltransferase MLL1 in combination with PI3K inhibition impairs HR+ breast cancer clonogenicity and cell proliferation. While combined PI3K/MLL1 inhibition reduces AKT effector signaling and H3K4 methylation, MLL1 inhibition increases PI3K effector signaling and upregulates the expression of receptor tyrosine kinase signaling cascades upstream of and including AKT. These data reveal a feedback loop between MLL1 and AKT in which MLL1 inhibition reactivates AKT. We additionally show that combined PI3K and MLL1 inhibition synergizes to cause cell death in in vitro and in vivo models of HR+ breast cancer, which is enhanced by the additional genetic ablation of the H3K4 methyltransferase and AKT target MLL4. Together, our data provide evidence of a feedback mechanism connecting histone methylation with AKT and may support the preclinical development and testing of pan-MLL inhibitors.Significance StatementPharmacological inhibition of PI3K provides limited efficacy in PIK3CA-mutated, HR+ breast cancers. Here the authors leverage PI3K/AKT-driven chromatin modification to identify MLL histone methyltransferases as a therapeutic target. Dual PI3K and MLL inhibition synergize to reduce clonogenicity and cell proliferation while enhancing apoptosis in in vitro models, and induces tumor regression in xenograft models of PI3K-activated, HR+ breast cancer. Furthermore, MLL1 inhibition reveals a feedback loop leading to AKT hyperactivation, which is relieved with combined PI3K/MLL inhibition. These findings demonstrate the utility of MLL inhibitors for the treatment of some solid cancers, as patients with HR+ breast cancer characterized by PIK3CA mutation may derive clinical benefit from combined PI3K/MLL inhibition.

Background: Undiagnosed COPD is a major problem in China but the optimal screening strategy to identify new cases is unclear. Aims and objectives: To evaluate the accuracy and cost-effectiveness of COPD screening tests and strategies amongst primary care patients in China Methods: Test accuracy study in four municipalities. Participants completed six index tests (CDQ, CAPTURE, Chinese Symptom-based questionnaire [C-SBQ], COPD-SQ, microspirometry [COPD-6], peak flow [USPE]) and the reference test (post-bronchodilator ndd Easy On-PC). Cases were those with FEV1/FVC below the lower limit of normal (LLN) on the reference test. Performance of individual screening tests and strategies was analysed, with cost-effectiveness analyses providing cost per additional true case detected. Results: 2445 participants (mean age 59.8 years, 39.1% [n=956] male) completed the study, 68.9% (n=1684) were never-smokers and 9.7% (n=237) had an existing COPD diagnosis. 13.6% (n=333) had spirometry-confirmed airflow obstruction. Airflow measurement devices (sensitivities 64.9% and 67.3%, specificities 89.7% and 82.6% for microspirometry and peak flow respectively) generally performed better than questionnaires, the most accurate of which was C-SBQ (sensitivity 63.1%, specificity 74.2%). The combination of C-SBQ and microspirometry used in parallel, maximised sensitivity (81.4%) and had specificity of 68%, with an incremental cost-effectiveness ratio of £64.20 (CNY385) per additional case detected compared with peak flow. Conclusions: Simple screening tests to identify undiagnosed COPD within the primary care setting in China are possible, and a combination of C-SBQ and microspirometry is the most sensitive.

Preeclampsia (PE), a multisystem hypertensive disorder of pregnancy is characterized by intrauterine growth restriction (IUGR), inflammation, and vascular dysfunction. NLRP3 inflammasome is a cytoplasmic complex that mediates inflammation and is implicated in CVD. Clinical studies show an association between PE and increased placental NLRP3 expression. We hypothesized that inhibition of NLRP3 using (1) a specific NLRP3 small molecule inhibitor, MCC950 (M9, 20 mg/kg/d, i.p.) or (2) esomeprazole (ESO, 3.5 mg/kg/d, oral), a therapeutic that is safe in pregnancy, would improve MAP, inflammation, IUGR, and vascular dysfunction in the reduced uterine perfusion pressure (RUPP) rat model of placental ischemia. Sham (S) or RUPP surgery was performed in pregnant Sprague Dawley rats on gestation day (GD) 14. A subset of rats from both groups received either vehicle, M9, or ESO on GD14-19 (n=9/group). On GD18, Uterine Artery Resistance Index (UARI) was measured via Doppler Ultrasound. MAP, fetal, and placental weight were measured, and blood and tissues were processed for additional analyses on GD19. MAP (mmHg) was elevated in RUPP (133±1) vs S (108±2; p

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in Nepal. It is a progressive lung disease and has a significant impact on the quality of life of patients. Health‐related quality of life (HRQOL) reflects the health‐ and disease‐related facets of quality of life. Limited studies have assessed the impact of COPD on HRQOL and associated factors in Nepal. This study is based on a cross-sectional household survey data from a semiurban area of Western Nepal. A validated Nepali version of St George’s Respiratory Questionnaire (SGRQ) was used to measure the HRQOL. COPD was defined together with post-bronchodilator airflow obstruction and the presence of respiratory symptoms. Post-bronchodilator airflow obstruction was defined as Forced Expiratory Volume in 1st second (FEV1) to Forced Vital Capacity (FVC) ratio < 0.70. COPD was diagnosed in 122 participants, and their median (IQR) total score of HRQOL was 40 (26 − 69); the score of symptoms, activity, and impact area were 53 (37 − 74), 57 (36 − 86), and 26 (13 − 62), respectively. The overall HRQOL was significantly different in terms of age, occupational status, physical activity, and comorbidities. Disease severity and the presence of respiratory symptoms had a significant difference in HRQOL (p = 0.0001). Appropriate measures to improve conditions and addressing the associated factors like respiratory symptoms and enhancing physical activity are necessary and important.

Until we have more comprehensive data from all regions in the world, we must be careful not to apply GLI equations indiscriminatelyhttps://bit.ly/3g1r9Q5

AIMS To use data from the Norwegian Diabetes Registry for Adults and Statistics Norway to assess factors associated with glycaemic control in type 1 diabetes. METHODS The analyses included all individuals aged ≥18 years who had a type 1 diabetes duration of >2 years and a recorded value in the registry between 2013 and 2015 (n=7601). Predicted mean HbA1c levels for subgroups of participants were assessed using linear regression analysis. RESULTS Young age (18-25 years), low education levels, smoking, living alone, exercising infrequently, monitoring glucose infrequently, high insulin requirements, low frequency of symptomatic hypoglycaemia, history of ketoacidosis and a BMI

Objectives To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. Methods Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren’s syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. Results IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. Conclusion We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

This bibliography records the 88 papers published by Australian and New Zealand authors in the Proceedings of the first nine International Symposia on the History of Anaesthesia (ISHA). Each ISHA has produced a published Proceedings of each symposium and these form an extremely valuable medical history research resource of over 850 papers. These have been published by a variety of anaesthesia societies, medical publishers and other bodies from around the world. Nearly all of these Proceedings had one small print run and most are now out of print and often unavailable. There is a definite need for all ISHA Proceedings to date to be available at one online site for ease of access for future historians studying the history of anaesthesia, intensive care, pain medicine, resuscitation and related fields. Scanning of early Proceedings with appropriate publisher, author and editorial approval would facilitate this.

A poly(7-oxanorbornene-2-carboxylate) polymer containing pendent triethyleneglycol (TEG) chains of 2.8 MDa (“2.8M TEG”) was synthesized and evaluated for long-term lubrication and wear reduction of ex vivo bovine cartilage as well as for synovitis in rats and dogs after intra-articular administration. Bovine cartilage surfaces were tested under torsional friction for 10,080 rotations while immersed in either saline, bovine synovial fluid (BSF), or 2.8M TEG. For each solution, coefficient of friction (μ), changes in surface roughness, and lost cartilage glycosaminoglycan were compared. To directly compare 2.8M TEG and BSF, additional samples were tested sequentially in BSF, BSF, 2.8M TEG, and then BSF. Finally, another set of samples were tested twice in saline to induce surface roughness and then tested in BSF, Synvisc, or 2.8M TEG to determine each treatment’s effect on worn cartilage. Next, male Lewis rats were injected in one knee with 2.8M TEG or saline and evaluated for effects on gait, and female beagles were injected with either 2.8M TEG or saline in one knee, and their synovial tissues analyzed for inflammation by H&E staining. Treatment with 2.8M TEG lowers μ, lessens surface roughness, and minimizes glycosaminoglycan loss compared to saline. The 2.8M TEG also reduces μ compared to BSF in pairwise testing and on worn cartilage surfaces. Injection of 2.8M TEG in rat or beagle knees gives comparable effects to treatment with saline, and does not cause significant synovitis.

Obstructive sleep apnoea (OSA) is a common disorder that is associated with serious comorbidities with a negative impact on quality of life, life expectancy and health costs. As OSA is related to obesity and is associated with sleep disruption, increased inflammation and oxidative stress, it is not surprising that OSA has an impact on the secretion of multiple hormones and is implicated in the development of many endocrine conditions. On the other hand, many endocrine conditions that can affect obesity and/or upper airways anatomy and stability have been implicated in the development or worsening of OSA. This bidirectional relationship between OSA and the endocrine system has been increasingly recognised in experimental and epidemiological studies and there are an increasing number of studies examining the effects of OSA treatment on endocrine conditions and vice versa. In this review article, we will critically appraise and describe the impact of OSA on the endocrine system including obesity, dysglycaemia, the pituitary, the thyroid, the adrenals, the reproductive system and the bones. In each section, we will assess whether a bidirectional relationship exists, and we will describe the potential underlying mechanisms. We have focused more on recent studies and randomised controlled trials where available and attempted to provide the information within clinical context and relevance.

Floor type management is an important factor in turkey production in hot climates exceeding 30°C. In this study, a total of 360 turkeys aged 4 wk were randomly distributed to investigate growth performance, carcass characteristics, certain health aspects (breast blisters score, footpad burns, hock discoloration, and plumage condition), and airborne conditions. Birds in the first group were raised on a littered floor (control; C), whereas birds in the other groups (T1, T2, T3, T4, and T5) were raised on cement, wire net, rubber mat, plastic and wooden slatted floors, respectively. The results indicated that growth performance and meat quality were improved, with increases in body weight, daily body weight gain, feed conversion ratio, and tenderness and juiciness values, when plastic and wooden slatted floors were used. Moreover, the use of plastic and wooden slatted floors attenuated body temperature, airborne dust particulates, and ammonia concentrations. In conclusion, placing plastic, wooden slatted, or wire floors reduced the incidence of health disorders and alleviated heat stress effects by decreasing body temperature and the heterophil to lymphocyte ratio. Thus, plastic and wooden slatted floors are suitable for growing turkeys under the conditions of this study.

Study objective To determine whether risk stratification in the out-of-hospital setting could identify patients with chest pain who are at low and high risk to avoid admission or aid direct transfer to cardiac centers. Methods Paramedics prospectively enrolled patients with suspected acute coronary syndrome without diagnostic ST-segment elevation on the ECG. The History, ECG, Age and Risk Factors (HEAR) score was recorded contemporaneously, and out-of-hospital samples were obtained to measure cardiac Troponin I (cTnI) level on a point-of-care device, to allow calculation of the History, ECG, Age, Risk Factors, and Troponin (HEART) score. HEAR and HEART scores less than or equal to 3 and greater than or equal to 7 were defined as low and high risk for major adverse cardiac events at 30 days. Results Of 1,054 patients (64 years [SD 15 years]; 42% women), 284 (27%) experienced a major adverse cardiac event at 30 days. The HEAR score was calculated in all patients, with point-of-care cTnI testing available in 357 (34%). A HEAR score less than or equal to 3 identified 32% of patients (334/1,054) as low risk, with a sensitivity of 84.9% (95% confidence interval [CI] 80.7% to 89%), whereas a score greater than or equal to 7 identified just 3% of patients (30/1,054) as high risk, with a specificity of 98.7% (95% CI 97.9% to 99.5%). A point-of-care HEART score less than or equal to 3 identified a similar proportion as low risk (30%), with a sensitivity of 87.0% (95% CI 80.7% to 93.4%), whereas a score greater than or equal to 7 identified 14% as high risk, with a specificity of 94.8% (95% CI 92.0% to 97.5%). Conclusion Paramedics can use the HEAR score to discriminate risk, but even when used in combination with out-of-hospital point-of-care cTnI testing, the HEART score does not safely rule out major adverse cardiac events, and only a small proportion of patients are identified as high risk.

Aims: The objectives of this study are to identify the proportion and characteristics of people with type 1 and 2 diabetes treated in primary, specialist and shared care and to identify the proportion of persons with type 2 diabetes reaching HbA1c treatment targets and the clinical risk factors and general practitioner and practice characteristics associated with treatment in specialist care. Methods: Population-based cross-sectional study including all adults ≥18 years diagnosed with diabetes in primary and specialist care in Salten, Norway. We used multivariable mixed-effects logistic regression models with level of care as outcome variable and population, general practitioner, and practice characteristics as exposure variables. Results: Of 2704 people with type 2 diabetes, 13.5% were treated in shared care and 2.1% in specialist care only. Of 305 people with type 1 diabetes, 14.4% received treatment in primary care only. The HbA1c treatment target of 53 mmol/mol (7.0%) was reached by 67.3% of people with type 2 diabetes in primary care versus 30.4% in specialist care. HbA1c, use of insulin, coronary heart disease, retinopathy and urban practice location were positively associated with treatment in specialist care. General practitioners’ use of a structured form and a diabetes nurse were negatively associated with specialist care. Conclusions: Of people with type 2 diabetes, 16% were treated in specialist care. They had higher HbA1c and more vascular complications, as expected from priority guidelines. The use of a structured diabetes form and diabetes nurses seem to support type 2 diabetes follow-up in primary care.

Objective Long term surveillance after endovascular aneurysm repair (EVAR) is essential to detect late complications, but there is variation in practice. The European Society for Vascular Surgery (ESVS) made a recommendation for a new surveillance protocol; one element involves risk stratifying patients depending on sac size reduction and presence of endoleak at their 30 day computed tomography angiogram into low risk groups (delayed imaging to five years) or higher risk groups (continue with the current protocol). The aim was to test this suggested protocol retrospectively within an EVAR patient cohort. Methods Data on EVARs performed from October 2009 to October 2019 were collected. Information gathered from an existing surveillance programme was used to assess the proposed ESVS protocol. All patients who underwent re-intervention were reviewed to see whether adopting the proposed ESVS protocol would have detected these events. Results In total, 309 procedures were included. Altogether, 219 of these patients had no endoleak (70.9%) and 86 had a type II (27.8%) endoleak. Only four developed a type I or III endoleak. No patient in the low risk cohort (no initial endoleak or sac shrinkage > 1 cm) required secondary intervention. Five year follow up data were available for 103 patients. In the type II endoleak group, there were 28 secondary interventions in 22 patients. No patient experienced a ruptured aneurysm within five years post-operatively. Had the proposed ESVS protocol been followed, all patients requiring a secondary intervention or with increasing sac size would have been detected/captured. Further, adherence to the ESVS guidelines would have resulted in 103 patients with a five year follow up history qualifying for reduced surveillance. A further 120 patients who had reached the three and four year follow up timepoints could have qualified for a reduced surveillance, reducing imaging cost further. Conclusion Adopting the proposed ESVS EVAR surveillance protocol safely identified “low risk” patients who did not go on to require a secondary intervention. These patients could benefit from reduced surveillance scanning.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition and the most common cause of sudden cardiac death (SCD) in patients below the age of 35. Genetic testing is a vital part of HCM diagnostics, yet correlation with clinical phenotypes remains complex. Identifying clinical predictors of informative genetic testing may prevent unnecessary investigations and improve cost-effectiveness of services. This article reviews the current literature pertinent to identifying such predictors.METHODS: Five literature databases were screened using a suitably designed search strategy. Studies investigating the correlation between having a positive genetic test for HCM and a range of clinical and radiological parameters were included in the systematic review.RESULTS: Twenty-nine observational studies of a total of 9,486 patients were included. The main predictors of informative genetic testing were younger age, higher septal thickness, reverse septal curvature, family history of HCM and SCD and the absence of hypertension. Two externally validated scoring systems have also been developed: the Mayo and Toronto scores. Novel imaging markers and complex algorithmic models are emerging predictors.CONCLUSION: Using clinical predictors to decide whom to test is a feasible alternative to investigating all comers. Nonetheless, currently there is not enough evidence to unequivocally recommend for or against this strategy. Further validation of current predictors and identification of new ones remain open research avenues.

Background The medium- and long-term effects of severe acute respiratory syndrome coronavirus 2 infection on survivors are unknown. In the current study, we assessed the medium-term effects of coronavirus disease 2019 (COVID-19) on survivors of severe disease. Methods This is a retrospective, case series of 200 patients hospitalized across 3 large Birmingham hospitals with severe-to-critical COVID-19 infection 4–7 months from disease onset. Patients underwent comprehensive clinical, laboratory, imaging, lung function tests (LFTs), and quality of life and cognitive assessments. Results At 4–7 months after disease onset, 63.2% of patients reported persistent breathlessness; 53.5%, significant fatigue; 37.5%, reduced mobility; and 36.8% pain. Serum markers of inflammation and organ injuries that persisted at hospital discharge had normalized on follow-up, indicating no sustained immune response causing chronic maladaptive inflammation. Chest radiographs showed complete resolution in 82.8%, and significant improvement or no change in 17.2%. LFTs revealed gas transfer abnormalities in 80.0% and abnormal spirometric values in 37.6% of patients. Compared with patients who did not experience breathlessness, those who did had significantly higher incidences of comorbid conditions and residual chest radiographic and LFT abnormalities (P Conclusions A significant proportion of severely ill patients with COVID-19 still experience symptoms of breathlessness, fatigue, pain, reduced mobility, depression and reduced quality of life 4–7 months after disease onset. Symptomatic patients tend to have more residual chest radiographic and LFT abnormalities.

Gln3 activates Nitrogen Catabolite Repression, NCR-sensitive expression of the genes required for Saccharomyces cerevisiae to scavenge poor nitrogen sources from its environment. The global TorC1 kinase complex negatively regulates nuclear Gln3 localization, interacting with an α-helix in the C-terminal region of Gln3, Gln3656–666. In nitrogen replete conditions, Gln3 is sequestered in the cytoplasm, whereas when TorC1 is down-regulated, in nitrogen restrictive conditions, Gln3 migrates into the nucleus. In this work, we show that the C-terminal Gln3–Tor1 interaction site is required for wild type, rapamycin-elicited, Sit4-dependent nuclear Gln3 localization, but not for its dephosphorylation. In fact, truncated Gln31-384 can enter the nucleus in the absence of Sit4 in both repressive and derepressive growth conditions. However, Gln31-384 can only enter the nucleus if a newly discovered second positively-acting Gln3–Tor1 interaction site remains intact. Importantly, the N- and C-terminal Gln3–Tor1 interaction sites function both autonomously and collaboratively. The N-terminal Gln3–Tor1 interaction site, previously designated Gln3URS contains a predicted α-helix situated within an unstructured coiled-coil region. Eight of the thirteen serine/threonine residues in the Gln3URS are dephosphorylated 3–15-fold with three of them by 10–15-fold. Substituting phosphomimetic aspartate for serine/threonine residues in the Gln3 URS abolishes the N-terminal Gln3–Tor1 interaction, rapamycin-elicited nuclear Gln3 localization, and ½ of the derepressed levels of nuclear Gln3 localization. Cytoplasmic Gln3 sequestration in repressive conditions, however, remains intact. These findings further deconvolve the mechanisms that achieve nitrogen-responsive transcription factor regulation downstream of TorC1.

Chlorisondamine (CSD) has been used to assess the neurogenic contribution to blood pressure (BP) and vasomotor sympathetic tone in animal models. It is assumed that the reduction in BP following CSD administration is associated to decreases in cardiac output (CO) and peripheral resistance, reflecting cardiac and vasomotor sympathetic tone, respectively. Surprisingly, this has not been characterized experimentally in mice, despite the extensive use of this animal model in cardiovascular research. We hypothesize that a specific dose of CSD can selectively block the sympathetic vasomotor tone. To test this hypothesis, we evaluated the effects of different doses of CSD (intraperitoneal) on BP and heart rate (HR) using telemetry, and on CO using echocardiography. BP and HR in normotensive C57Bl/6J mice reduced to a similar extent by all CSD doses tested (1–6 mg/kg). CSD at 6 mg/kg also reduced CO without affecting left ventricular stroke volume or fractional shortening. On the other hand, lower doses of CSD (1 and 2 mg/kg) produced significantly larger BP and HR reductions in DOCA‐salt–induced hypertensive mice, indicating a greater neurogenic BP response. In addition, all doses of CSD reduced CO in hypertensive mice. Our data suggest that the BP response to CSD in mice likely reflects reduced CO and vasomotor sympathetic tone. We conclude that CSD can be used to assess the neurogenic contribution to BP in mice but may not be appropriate for specifically estimating vasomotor sympathetic tone., Ganglionic blocker, chlorisondamine, can be used to assess the neurogenic contribution to BP in mice, but may not be appropriate to specifically estimate the vasomotor sympathetic tone.

Background Asthma and chronic obstructive pulmonary disease (COPD) are the most prevalent respiratory diseases, yet the lack of accessible standardised diagnostics in primary care often lead to erroneous or delayed diagnosis. In-community standardised respiratory diagnostic hubs (RDH) may improve patient access and diagnosis quality of asthma and COPD. Aim To evaluate the effectiveness of a RDH in primary care in establishing diagnosis in patients with suspected asthma and COPD. Methods A pilot multidisciplinary RDH was set up in inner city cosmopolitan Birmingham, to provide diagnostic services to the local population. Referred patients with suspected asthma, COPD had structured review inclusive of lung function and fraction exhaled nitric oxide ‘FeNO’ measurement. The interim diagnostic outcomes of this RDH are presented. Results Of 100 referred cases, 61 were for suspected asthma and 39 for suspected COPD. In the suspected asthma group, there were 12 (20%) cases on the asthma quality outcome framework ‘QOF’ register. Following RDH assessment, asthma was confirmed in 3/12(25%), excluded in 8/12 (67%), and remained suspected in 1/12 (8%), whilst in the 49/61 (80%) suspected asthma not on QOF register, asthma was confirmed in 18/49 (37%), remained suspected in 7/49 (14%) and an alternative diagnosis was established in 24/49 cases (49%). In the overall suspected asthma group, asthma was confirmed in 21/61 (34%) of cases, excluded in 32/61 (53%) and remained suspected in 8/61 (13%), demonstrating a diagnostic outcome in 53/61 (87%) cases. In suspected COPD, only 4 patients were on the COPD QOF register but the diagnosis was excluded in 3 of these cases following RDH assessment. In not-QOF registered suspected COPD, 11/35 (31%) had COPD confirmation, 22/35 (63%) had an alternative diagnosis and 2/35 (6%) remained suspected for COPD. RDH provided a diagnostic outcome in 37/39 (95%). Conclusion This pilot primary care RDH achieved a diagnostic outcome in the vast majority of referred cases, with asthma and COPD diagnoses excluded in over half of all referred cases. Additionally, asthma and COPD diagnoses were excluded in more than half of cases on the QOF register, prompting the need for applying this model of service at wider scale in the NHS.

Introduction Structured Light Plethysmography (SLP) is a novel non-invasive, contactless technique utilising only a grid of white light and cameras to track, measure, capture Throraco-Abdominal (TA) displacement and record quiet tidal breathing. Repeatability is used to assess the measurements from two devices for the same test subject when recorded simultaneously. Spirometry is considered to be the gold standard for measuring lung function but requires the application of forceful manoeuvres which might not be attainable by patients, and so SLP could provide an opportunity to evaluate these patients if successfully benchmarked to spirometry data. Aim To assess the correlation between SLP recordings with simultaneous spirometry measurement of quiet tidal breathing. Methods Quiet breathing in 14 healthy volunteers was simultaneously recorded via SLP ( Thora3Di, Pneumacare Ltd) and by spirometry (Power lab 4/20, AD Instruments Ltd). Statistical analysis using Wilcoxon paired signed-rank test to assess correlation and agreement of these techniques was assessed under three different breathing conditions: Normal, Deep & Shallow. Respiratory rate (RR), inspired, expired and total breathing times were analysed (Ti, Te, Ttot) and duty cycle (Ti/Ttot) was calculated under the three different breathing conditions. There was a good correlation between the techniques under normal and deep breathing conditions. Ethical Approval for the study was approved by Science, Technology, Engineering and Mathematics Ethical Review Committee at the University of Birmingham. Results There were only significant differences in shallow breathing measurements (Ti P=0.0015, Ti/Ttot P=0.0400) (see figure 1 A-E). Conclusions SLP shows good correlation with spirometry for all timing indices both under normal quiet breathing as well as deep breathing but showed a significant difference in shallow breathing indicating that it is a reliable technique during normal and deep breathing. However, during shallow breathing probably due to fast breathing the movement detection was disturbed as a result of the high frequency (50–60 bpm) or could be attributed to the effects of the mouthpiece and nose clip.