Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.

OBJECTIVE: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies. DESIGN/PATIENTS: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study). MEASUREMENTS: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD). RESULTS: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores. CONCLUSIONS: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.

Pulmonary Rehabilitation for Adults with Chronic Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Despite the known benefits of pulmonary rehabilitation (PR) for patients with chronic respiratory disease, this treatment is underused. Evidence-based guidelines should lead to greater knowledge of the proven benefits of PR, highlight the role of PR in evidence-based health care, and in turn foster referrals to and more effective delivery of PR for people with chronic respiratory disease. Methods: The multidisciplinary panel formulated six research questions addressing PR for specific patient groups (chronic obstructive pulmonary disease [COPD], interstitial lung disease, and pulmonary hypertension) and models for PR delivery (telerehabilitation, maintenance PR). Treatment effects were quantified using systematic reviews. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel made the following judgments: strong recommendations for PR for adults with stable COPD (moderate-quality evidence) and after hospitalization for COPD exacerbation (moderate-quality evidence), strong recommendation for PR for adults with interstitial lung disease (moderate-quality evidence), conditional recommendation for PR for adults with pulmonary hypertension (low-quality evidence), strong recommendation for offering the choice of center-based PR or telerehabilitation for patients with chronic respiratory disease (moderate-quality evidence), and conditional recommendation for offering either supervised maintenance PR or usual care after initial PR for adults with COPD (low-quality evidence). Conclusions: These guidelines provide the basis for evidence-based delivery of PR for people with chronic respiratory disease.

Residual Lung Abnormalities after COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID-19 Study.

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP-COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83-155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05-1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00-1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07-1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6-9.5), rising to 11.7% (95% CrI, 10.3-13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19-related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.

The variation of anticoagulation prescribed in foot and ankle surgery in the UK - UK foot and ankle thrombo-embolism audit (UK-FATE).

INTRODUCTION: Venous thrombo-embolism (VTE) is a recognised complication of foot and ankle surgery. There are multiple possible anticoagulation treatments available in the UK to mitigate the risk of developing VTE. Our primary objective was to assess the variability of chemical anticoagulation prescribed in patients undergoing foot and ankle procedures. METHODS: This was a UK-based national, multicenter, prospective audit spanning a collection duration of 9 months on all foot and ankle procedures, carried out in 68 UK centers between 1st June 2022 and 30th November 2022, with a further 3-month follow up period. All patients who underwent a foot and ankle surgical procedure (including Achilles tendon rupture treatment) were included in this study. RESULTS: Data on a total of 13,569 patients was submitted. Following data cleansing, 11,363 patients were available for further analysis, with anticoagulation data available for 11,099 patients. There were eleven different chemical anticoagulation treatments recorded across the cohort. A total of 3630 (31.95 %) patients received no chemical anticoagulation. The patients receiving chemical anticoagulation medication could be split into 4 main groups. The most common chemical anticoagulation received was low molecular weight heparin (LMWH) (6303, 84.4 % of patients receiving chemical anticoagulation). Aspirin was given in 4.1 % (308 patients), a Factor Xa inhibitor in 10 % (744 patients) and other anticoagulants (e.g. Warfarin) in 1.5 % (114 patients). The overall VTE rate in this sub analysis of patients receiving chemical anticoagulation, was 1.1 % (83 cases out of 7469). There was no significant difference seen in incidence of VTE between types of anticoagulants, when confounding factors were considered. The duration of post-operative chemical prophylaxis used by participants for most chemical anticoagulants was 6 weeks (64.50 %). CONCLUSION: There was significant variability of chemical anticoagulants reported in the study, with five different categories of anticoagulants used (including no chemical anticoagulation), and none clearly superior/inferior. The duration of anticoagulation was consistent across types of thromboprophylaxis.

Joint patient and clinician priority setting to identify 10 key research questions regarding the long-term sequelae of COVID-19.

Given the large numbers of people infected and high rates of ongoing morbidity, research is clearly required to address the needs of adult survivors of COVID-19 living with ongoing symptoms (long COVID). To help direct resource and research efforts, we completed a research prioritisation process incorporating views from adults with ongoing symptoms of COVID-19, carers, clinicians and clinical researchers. The final top 10 research questions were agreed at an independently mediated workshop and included: identifying underlying mechanisms of long COVID, establishing diagnostic tools, understanding trajectory of recovery and evaluating the role of interventions both during the acute and persistent phases of the illness.

Whole-body and muscle responses to aerobic exercise training and withdrawal in ageing and COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients exhibit lower peak oxygen uptake (V'O2 peak), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle-level deconditioning (impacted by ventilatory constraints) and/or dysfunction in mitochondrial ATP production capacity is debated. By studying aerobic exercise training (AET) at a matched relative intensity and subsequent exercise withdrawal period we aimed to elucidate the whole-body and muscle mitochondrial responsiveness of healthy young (HY), healthy older (HO) and COPD volunteers to whole-body exercise. METHODS: HY (n=10), HO (n=10) and COPD (n=20) volunteers were studied before and after 8 weeks of AET (65% V'O2 peak) and after 4 weeks of exercise withdrawal. V'O2 peak, muscle maximal mitochondrial ATP production rate (MAPR), mitochondrial content, mitochondrial DNA (mtDNA) copy number and abundance of 59 targeted fuel metabolism mRNAs were determined at all time-points. RESULTS: Muscle MAPR (normalised for mitochondrial content) was not different for any substrate combination in HO, HY and COPD at baseline, but mtDNA copy number relative to a nuclear-encoded housekeeping gene (mean±sd) was greater in HY (804±67) than in HO (631±69; p=0.041). AET increased V'O2 peak in HO (17%; p=0.002) and HY (21%; p<0.001), but not COPD (p=0.603). Muscle MAPR for palmitate increased with training in HO (57%; p=0.041) and HY (56%; p=0.003), and decreased with exercise withdrawal in HO (-45%; p=0.036) and HY (-30%; p=0.016), but was unchanged in COPD (p=0.594). mtDNA copy number increased with AET in HY (66%; p=0.001), but not HO (p=0.081) or COPD (p=0.132). The observed changes in muscle mRNA abundance were similar in all groups after AET and exercise withdrawal. CONCLUSIONS: Intrinsic mitochondrial function was not impaired by ageing or COPD in the untrained state. Whole-body and muscle mitochondrial responses to AET were robust in HY, evident in HO, but deficient in COPD. All groups showed robust muscle mRNA responses. Higher relative exercise intensities during whole-body training may be needed to maximise whole-body and muscle mitochondrial adaptation in COPD.

Exploring the prevalence and impact of hip and knee pain in pulmonary rehabilitation: a propensity-matched cohort study.

BACKGROUND: Musculoskeletal pain is more common in individuals with chronic respiratory diseases than the aged-matched general population. This investigation aimed to understand the prevalence and impact of hip and knee pain on pulmonary rehabilitation outcomes and completion rates. METHODS: Participants who experienced hip/knee pain in the 4 weeks prior to pulmonary rehabilitation completed an Oxford Hip and/or Knee Score alongside a routine pulmonary rehabilitation assessment. Participants engaged in a twice-weekly, 6-week outpatient pulmonary rehabilitation programme. A 1:1 propensity score match for age, sex, BMI, sessions attended and MRC score was completed prior to group comparison for a pulmonary rehabilitation cohort without hip/knee pain. RESULTS: 6.5% (n = 97) of pulmonary rehabilitation participants reported pain: hip (n = 27), knee (n = 40) or hip and knee pain (n = 30). 75 participants with hip/knee pain provided sufficient data for pre pulmonary rehabilitation matching and were propensity matched with a pulmonary rehabilitation group without hip/knee pain. The average Oxford Score across all reported joints was 28.7 (8.5) indicating moderate/severe pain at baseline. Statistically significant improvements were made in Oxford Scores for the left hip, left knee and right knee (P < 0.01) but not the right hip following pulmonary rehabilitation. There was no statistically significant difference between groups for improvements in quadriceps strength, walking tests or depression scores, both groups achieved within group significance. There were no significant differences in pulmonary rehabilitation completion rates between groups. CONCLUSIONS: Prevalence of hip/knee pain in individuals presenting to pulmonary rehabilitation is 6.5%. Pain improved in the majority of joints following pulmonary rehabilitation and pain did not impact the effectiveness or completion of the programme. TRIAL REGISTRATION: This trial was an evaluation of a clinical service and has not been registered in a public domain.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

Unravelling the mystery of the 'minimum important difference' using practical outcome measures in chronic respiratory disease.

It is important for clinicians and researchers to understand the effects of treatments on their patients, both at an individual and group level. In clinical studies, treatment effects are often reported as a change in the outcome measure supported by a measure of variability; for example, the mean change with 95% confidence intervals and a probability ( p) value to indicate the level of statistical significance. However, a statistically significant change may not indicate a clinically meaningful or important change for clinicians or patients to interpret. The minimum clinically important difference (MCID) or minimally important difference (MID) has therefore been developed to add clinical relevance or patient experience to the reporting of an outcome measure. In this article, we consider the concept of the MID using the example of practical outcome measures in patients with CRD. We describe the various ways in which an MID can be calculated via anchor- and distribution-based methods, looking at practical examples and considering the importance of understanding how an MID was derived when seeking to apply it to a particular situation. The terms MID and MCID are challenging and often used interchangeably. However, we propose all MIDs are described as such, but they could be qualified by a suffix: MIDS (MID - Statistical), MID-C (MID - Clinical outcome), MID-P (MID - Patient determined). However, this type of classification would only work if accepted and adopted. In the meantime, we advise clinicians and researchers to use an MID where possible to aid their interpretation of functional outcome measures and effects of interventions, to add meaning above statistical significance alone.

Outcome measures in a combined exercise rehabilitation programme for adults with COPD and chronic heart failure: A preliminary stakeholder consensus event.

Combined exercise rehabilitation for chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) is potentially attractive. Uncertainty remains as to the baseline profiling assessments and outcome measures that should be collected within a programme. Current evidence surrounding outcome measures in cardiac and pulmonary rehabilitation were presented by experts at a stakeholder consensus event and all stakeholders (n = 18) were asked to (1) rank in order of importance a list of categories, (2) prioritise outcome measures and (3) prioritise baseline patient evaluation measures that should be assessed in a combined COPD and CHF rehabilitation programme. The tasks were completed anonymously and related to clinical rehabilitation programmes and associated research. Health-related quality of life, exercise capacity and symptom evaluation were voted as the most important categories to assess for clinical purposes (median rank: 1, 2 and 3 accordingly) and research purposes (median rank; 1, 3 and 4.5 accordingly) within combined exercise rehabilitation. All stakeholders agreed that profiling symptoms at baseline were 'moderately', 'very' or 'extremely' important to assess for clinical and research purposes in combined rehabilitation. Profiling of frailty was ranked of the same importance for clinical purposes in combined rehabilitation. Stakeholders identified a suite of multidisciplinary measures that may be important to assess in a combined COPD and CHF exercise rehabilitation programme.

Evaluating the interactive web-based program, activate your heart, for cardiac rehabilitation patients: a pilot study.

BACKGROUND: Conventional cardiac rehabilitation (CR) programs are traditionally based on time-constrained, structured, group-based programs, usually set in hospitals or leisure centers. Uptake for CR remains poor, despite the ongoing evidence demonstrating its benefits. Additional alternative forms of CR are needed. An Internet-based approach may offer an alternative mode of delivering CR that may improve overall uptake. Activate Your Heart (AYH) is a Web-based CR program that has been designed to support individuals with coronary heart disease (CHD). OBJECTIVE: The aim of this pilot study was to observe the outcome for participants following the AYH program. METHODS: We conducted a prospective observational trial, recruiting low-risk patients with CHD. Measures of exercise, exercise capacity, using the Incremental Shuttle Walk Test (ISWT), dietary habits, and psychosocial well-being were conducted by a CR specialist at baseline and at 8 weeks following the Web-based intervention. RESULTS: We recruited 41 participants; 33 completed the program. We documented significant improvements in the ISWT distance (mean change 49.69 meters, SD 68.8, P<.001), and Quality of Life (QOL) (mean change 0.28, SD 0.4, P<.001). Dietary habits improved with an increased proportion of patients consuming at least 5 portions of fruit and vegetables per day, (22 [71%] to 29 [94%] P=.01) and an increased proportion of patients consuming at least 2 portions of oily fish per week (14 [45%] to 21 [68%], P=.01). We did not detect changes in anxiety and depression scores or exercise behavior. CONCLUSIONS: We observed important improvements in exercise capacity, QOL, and dietary habits in a group of participants following a Web-based CR program. The program may offer an alternative approach to CR. A mobile version has been developed and we need to conduct further trials to establish its value compared to supervised CR.

Characteristics of Patients Not Receiving Chemical Thromboprophylaxis Following Foot and Ankle Surgery: Data From the Multicenter, Prospective UK Foot and Ankle Thrombo-Embolism Audit (UK-FATE).

BACKGROUND: Although the rate of venous thromboembolism (VTE) after foot and ankle surgery is low, multiple factors influence risk for individual patients. Furthermore, there are no clear guidelines on which patients may benefit from chemical thromboprophylaxis. Our aim was to assess patients not treated with chemical thromboprophylaxis after foot and ankle surgery, and to report on their specific patient and surgical risk factors for VTE. METHODS: This was a multicenter, prospective, national audit of patients undergoing foot and ankle surgery (including Achilles tendon ruptures) from 68 participating UK centers. The study was conducted between June 1, 2022, and November 30, 2022, with a further 3-month follow-up. Following data cleansing, 3309 patients were included who did not receive postoperative thromboprophylaxis. RESULTS: Most patients were elective cases (2589 patients, 78.24%) with ASA grade I or II (2679 patients, 80.96%), fully weightbearing postoperatively (2752 patients, 83.17%), and either without ankle splintage, or splinted in a plantigrade boot (2797 patients, 84.53%). The VTE rate was 0.30% overall (11 cases), with no VTE-related mortality. No single demographic, surgical, or postoperative factor was associated with reduced risk of VTE. However, patients who had elective or trauma surgery not involving the ankle, who were ASA grade I or II and who were weightbearing immediately postoperatively (without splinting or in a plantigrade boot) had a VTE rate of 0.05% (1 of 1819 patients), compared with 0.67% (10 of 1490 patients, P = .002). CONCLUSION: Patients not receiving chemical thromboprophylaxis had a low incidence of symptomatic VTE, although they do represent a curated group considered lower risk. Within this group we describe characteristics associated with a substantially lower risk of VTE. All patients should be assessed on an individual basis, and further work is required to substantiate our findings.

The Training to Improve Dyspnoea Study- Patient Experiences of Using a High Frequency Airway Oscillating Device.

Introduction: The High Frequency Airway Oscillating device (HFAO) was developed to help patients with COPD feel less breathless through flow resistive respiratory muscle training and fixed rate oscillations. Previous work has demonstrated that this device can improve inspiratory muscle strength over and above a sham device. Both groups improved their breathlessness and preserved clinical benefits though there were no statistically significant differences seen over and above the sham device. It is important to understand patient perceptions of using a device and how this may influence their treatment and therefore a qualitative analysis was conducted to understand participant experiences of a HFAO device. Methods: This was an exploratory qualitative analysis involving participants recruited to the Training to Improve Dyspnoea (TIDe) study. Participants completed a satisfaction survey and were invited to take part in a focus group. Focus groups were conducted by a researcher independent to the randomised controlled trial. Data was analysed independently by two researchers using inductive thematic analysis, and themes/sub-themes were agreed jointly. Data is presented in themes and sub themes and triangulated with survey response data. Results: Fourteen participants were recruited to two focus groups (71% male, mean [SD] age 64[9] years). The key themes were patient selection, device use, and investment. Patient selection explores the disease characteristics, emotional impact and management of care. Device use explores the device prescription and usage, routine and lifestyle and effectiveness. Investment covers accessibility, understanding, benefits vs participation and overall perceptions of the device. Conclusion: This research demonstrates the complexity of device interventions and that key considerations should be given to patient selection, the device use itself and, the time and cost investment required for participants to successfully implement the device into daily life.

Incidence, demographics, characteristics and management of acute Achilles tendon rupture: An epidemiological study.

BACKGROUND: Achilles tendon rupture (ATR) account for 10.7% of all tendon and ligament injuries and causes lasting muscular deficits and have a profound impact on patients' quality of life. The incidence, characteristics and management of ATR in the United Kingdom (UK) is poorly understood. This investigation aims to understand the incidence of ATR in the UK. METHODS: Prospective data collection of ATR incidence from a United Kingdom Emergency department. Retrospective review of management protocols and immobilisation duration from electronic medical records. RESULTS: ATR incidence is 8 per 100,000 people per annum. Participants were predominately male (79.2%) and primarily reported a sporting mechanism of injury (65.2%). Mean immobilisation duration was 63.1 days. 97.1% were non-surgically managed post ATR. 46.2% of participants had experienced a previous ATR or Achilles tendinopathy prior to their current ATR. CONCLUSION: The incidence of ATR found was 8. cases per 100,000 people per annum. Most ATR were managed non-surgically in this cohort. The majority of ruptures occurred during sporting activity. Almost one quarter (23.3%) of individuals report Achilles pain prior to ATR.

Effect of ankle versus thigh tourniquets on post-operative pain in foot and ankle surgery.

BACKGROUND: Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss, improve visualization in the surgical field, and to potentially reduce surgical time. There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure, placement site, and duration of use. There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery. AIM: To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery. METHODS: Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken. Intraoperative tourniquet duration, tourniquet pressure and site, and postoperative pain scores using Visual Analogue Score were collected in immediate recovery, at six hours and at 24 h post-op. Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure, duration, site, and pain scores using Pearson correlation coefficient. RESULTS: All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh. There was no correlation between the site of the tourniquet and pain scores in recovery, at six hours and after 24 h. There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op (r = 0.14, P = 0.04) but not at six or 24 h post-operatively. CONCLUSION: This study shows that there was no statistically significant correlation between tourniquet pressure, site and post-op pain in patients undergoing foot and ankle surgery. The choice of using a tourniquet is based on the surgeon's preference, with the goal of minimizing the duration of its application at the operative site.

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.

Long COVID and cardiovascular disease: a prospective cohort study.

BACKGROUND: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. OBJECTIVES: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. METHODS: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. RESULTS: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). CONCLUSION: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need. TRAIL REGISTRATION NUMBER: ISRCTN10980107.

Skeletal muscle molecular responses to resistance training and dietary supplementation in COPD.

BACKGROUND: Skeletal muscle dysfunction is a systemic feature of chronic obstructive pulmonary disease (COPD), contributing to morbidity and mortality. Physical training improves muscle mass and function in COPD, but the molecular regulation therein is poorly understood. METHODS: Candidate genes and proteins regulating muscle protein breakdown (ubiquitin proteasome pathway), muscle protein synthesis (phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin pathway), myogenesis (MyoD, myogenin and myostatin) and transcription (FOXO1, FOXO3 and RUNX1) were determined in quadriceps muscle samples taken at four time points over 8 weeks of knee extensor resistance training (RT) in patients with COPD and healthy controls (HCs). Patients with COPD were randomly allocated to receive protein/carbohydrate or placebo supplements during RT. RESULTS: 59 patients with COPD (mean (SD) age 68.0 (9.3) years, forced expiratory volume in 1 s (FEV1) 46.9 (17.8) % predicted) and 21 HCs (66.1 (4.8) years, 105.0 (21.6) % predicted) were enrolled. RT increased lean mass (~5%) and strength (~20%) in all groups. Absolute work done during RT was lower throughout in patients with COPD compared with HCs. RT resulted in increases (from basal) in catabolic, anabolic, myogenic and transcription factor protein expression at 24 h, 4 weeks and 8 weeks of exercise in HCs. This response was blunted in patients with COPD, except for myogenic signalling, which was similar. Nutritional supplementation did not augment functional or molecular responses to RT. CONCLUSIONS: The potential for muscle rehabilitation in response to RT is preserved in COPD. Except for markers of myogenesis, molecular responses to RT are not tightly coupled to lean mass gains but reflect the lower work done during RT, suggesting some caution when identifying molecular targets for intervention. Increasing post-exercise protein and carbohydrate intake is not a prerequisite for a normal training response in COPD.