Conventional oxygen therapy versus CPAP as a ceiling of care in ward-based patients with COVID-19: a multi-centre cohort evaluation.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is commonly used for respiratory failure due to severe COVID-19 pneumonitis, including in patients deemed not likely to benefit from invasive mechanical ventilation (nIMV). Little evidence exists demonstrating superiority over conventional oxygen therapy, whilst ward-level delivery of CPAP presents practical challenges. We sought to compare clinical outcomes of oxygen therapy versus CPAP therapy in patients with COVID-19 who were nIMV. METHODS: This retrospective multi-centre cohort evaluation included patients diagnosed with COVID-19 who were nIMV, had a treatment escalation plan of ward-level care and clinical frailty scale ≤ 6. Recruitment occurred during the first two waves of the UK COVID-19 pandemic in 2020; from 1st March to May 31st, and from 1st September to 31st December. Patients given CPAP were compared to patients receiving oxygen therapy that required FiO2 ≥0.4 for more than 12 hours at hospitals not providing ward-level CPAP. Logistic regression modelling was performed to compare 30-day mortality between treatment groups, accounting for important confounders and within-hospital clustering. FINDINGS: Seven hospitals provided data for 479 patients during the UK COVID-19 pandemic in 2020. Overall 30-day mortality was 75.6% in the oxygen group (186/246 patients) and 77.7% in the CPAP group (181/233 patients). A lack of evidence for a treatment effect persisted in the adjusted model (adjusted odds ratio 0.84 95% CI 0.57-1.23, p=0.37). 49.8% of patients receiving CPAP-therapy (118/237) chose to discontinue it. INTERPRETATION: No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the current treatment guidance and widespread application of CPAP in this setting. FUNDING: L Pearmain is supported by the MRC (MR/R00191X/1). TW Felton is supported by the NIHR Manchester Biomedical Research Centre.

Risk factors and prognostic indicators for medial tibial stress syndrome.

The objective of the study was to examine the risk factors and prognostic indicators for medial tibial stress syndrome (MTSS). In total, 35 subjects were included in the study. For the risk factor analysis, the following parameters were investigated: hip internal and external ranges of motion, knee flexion and extension, dorsal and plantar ankle flexion, hallux flexion and extension, subtalar eversion and inversion, maximal calf girth, lean calf girth, standing foot angle and navicular drop test. After multivariate regression decreased hip internal range of motion, increased ankle plantar flexion and positive navicular drop were associated with MTSS. A higher body mass index was associated with a longer duration to full recovery. For other prognostic indicators, no relationship was found.

The additional value of a pneumatic leg brace in the treatment of recruits with medial tibial stress syndrome; a randomized study.

OBJECTIVE: To study the additional effect of a pneumatic leg brace with standard rehabilitation for the treatment of medial tibial stress syndrome (MTSS) in recruits. METHODS: In a single blinded randomized study, 15 recruits (age 17-22) followed a rehabilitation programme consisting of leg exercises and a graded running programme. Recruits performed daily exercises and ran three times a week. The running programme consisted of 6 consecutive phases. One group was, after randomization, additionally provided with a pneumatic leg brace. Follow-up was provided every other week. Days to completing the running programme was the primary outcome measure, the Sports Activity Rating Scale (SARS) score and satisfaction with the treatment were secondary outcome measures. RESULTS: In total 14 recruits completed the rehabilitation programme. No differences were found in the number of days until phase six of the running schedule was finished between the brace and the control group (Brace 58.8 +/- 27.7 (mean +/- SD) vs Non-Brace 57.9 +/- 26.2 (mean +/- SD, p = 0.57). Also no differences were found in the SARS scores between the groups. Overall satisfaction with the treatment was 6.4 +/- 1.1 (mean +/- SD) on a 1-10 scale for the brace group and 7.1 +/- 0.7 (mean +/- SD) for the control group (p = 0.06). Comfort of the brace was assessed as 4.8 +/- 1.3 (mean +/- SD) on a 1-10 scale. CONCLUSIONS: No additional large effect of the pneumatic leg brace could be found in recruits and wearing of the brace was not feasible, since the wearing comfort was low.

Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients.

ADAMTS13 may play a role in arterial thrombosis by cleaving the highly active and thrombogenic ultralarge Von Willebrand Factor (VWF) multimers into less active VWF multimers. The aim was to investigate the relationship between plasma levels of ADAMTS13, VWF and genetic variation in the ADAMTS13 gene with cardiovascular disease. We performed a case-control study in 374 patients with a first-ever arterial thrombosis before the age of 45 years in males and 55 years in women. We included 218 patients with coronary heart disease (CHD), 109 patients with ischemic stroke (IS) and 47 patients with peripheral arterial disease (PAD) and 332 healthy population-based controls. ADAMTS13 and VWF levels were measured 1-3 months after the event. ADAMTS13 levels were associated with cardiovascular disease (OR antigen 5.1 (95% CI 3.1-8.5, p<0.001) and OR activity 4.4 (95% CI 2.5-7.5, p<0.001), in the lowest quartiles). VWF levels were associated with cardiovascular disease (OR antigen 2.1 (95% CI 1.3-3.3, p=0.001) and OR activity 2.0 (95% CI 1.3-3.1, p=0.003), in the highest quartile). Patients with combined low ADAMTS13 levels and high VWF levels had an odds ratio of 7.7 (95% CI 3.3-17.7) (p for trend <0.0001). No association was found between genetic variation in the ADAMTS13 gene with levels of ADAMTS13 or with risk of cardiovascular disease. In conclusion, levels of ADAMTS13 and VWF are strongly associated with the risk of cardiovascular disease.

Elevated core and muscle temperature to levels comparable to exercise do not increase heat shock protein content of skeletal muscle of physically active men.

AIM: Exercise-associated hyperthermia is routinely cited as the signal responsible for inducing an increased production of heat shock proteins (HSPs) following exercise. This hypothesis, however, has not been tested in human skeletal muscle. The aim of the present study was to therefore investigate the role of increased muscle and core temperature in contributing to the exercise-induced production of the major HSP families in human skeletal muscle. METHODS: Seven physically active males underwent a passive heating protocol of 1 h duration during which the temperature of the core and vastus lateralis muscle were increased to similar levels to those typically occurring during moderately demanding aerobic exercise protocols. One limb was immersed in a tank containing water maintained at approximately 45 degrees C whilst the contra-lateral limb remained outside the tank and was not exposed to heat stress. Muscle biopsies were obtained from the vastus lateralis of both legs immediately prior to and at 48 h and 7 days post-heating. RESULTS: The heating protocol induced significant increases (P < 0.05) in rectal (1.5 +/- 0.2 degrees C) and muscle temperature of the heated leg (3.6 +/- 0.5 degrees C). Muscle temperature of the non-heated limb showed no significant change (P > 0.05) following heating (pre: 36.1 +/- 0.5, post: 35.7 +/- 0.2 degrees C). Heating failed to induce a significant increase (P > 0.05) in muscle content of HSP70, HSC70, HSP60, HSP27, alphaB-crystallin, MnSOD protein content or in the activity of superoxide dismutase and catalase. CONCLUSIONS: These data demonstrate that increases in both systemic and local muscle temperature per se do not appear to mediate the exercise-induced production of HSPs in human skeletal muscle and suggest that non-heat stress factors associated with contractile activity are of more importance in mediating this response.

Nutrition support for patients in the intensive care unit.

Enteral nutrition (EN) is the mainstay of nutrition delivery within intensive care seeking to capitalise on its benefits for the gastrointestinal tract and associated immune system, but this has brought new challenges in delivery to the sick. The hoped for benefit has led to the mistaken belief by some that parenteral nutrition (PN) is no longer required. However, a greater appreciation of the risks of EN delivery in the sick patient combined with improvements in PN formulation and use help explain why PN is not as risky as some have believed. Real outcome benefits have been described with the new glutamine containing PN formulations. PN remains important in the presence of gastrointestinal feed intolerance or failure.

Acute sensitivity of nematode taxa to CuSO4 and relationships with feeding-type and life-history classification.

The acute sensitivity to CuSO4 of a broad range of nematode taxa was analyzed in order to assess the potential of changes to nematode community structure to serve as a practical tool for the bioindication of heavy-metal pollution. An easy-to-use experimental set-up was developed along with an appropriate mathematical response model in order to quantify the response characteristics of nematodes to CuSO4 pressure. Three similar experiments were conducted using water, dune sand, and sandy soil as media, each of which was subjected to 12 increasing concentrations of CuSO4. In total, 130 response curves representing 70 nematode taxa were produced and analyzed. CuSO4 concentrations were normalized for differences in efficiency among media due to different adsorption. At low CuSO4 concentrations, many taxa exhibited stimulation rather than inhibition regarding recovery efficiency. At higher concentrations, the concentration level at which 50% of the nematode population was recovered after a 24-h incubation (recovery concentration 50% [RC50]) varied widely among taxa and ranged from 0.01 to 4 mM/L CuSO4 (normalized to water). Stimulation of recovery efficiency and RC50 were negatively correlated with the colonizer-persister (C-P) classification of taxa, which discriminates nematodes according to their reproductive potential. The maturity index, which relates to a nematode community's state of disturbance and eutrophication, was negatively correlated with CuSO4 concentration. The properties of the applied test method are discussed as are the relationships between the investigated short-term toxicity effects and long-term toxicity processes in the field. From the large range of observed RC50 values, it is concluded that a meaningful sensitivity classification of nematodes should be possible and thus would allow for a sensitive bioindication of heavy-metal pollution. From the correlation between RC50 and C-P classification, the authors further conclude that the maturity index will, in addition to enrichment and disturbance, respond to heavy-metal pollution and thus may serve as a general indicator of soil health.

Nematode community structure as a bioindicator in environmental monitoring.

Four of every five multicellular animals on the planet are nematodes. They occupy any niche that provides an available source of organic carbon in marine, freshwater and terrestrial environments. Nematodes vary in sensitivity to pollutants and environmental disturbance. Recent development of indices that integrate the responses of different taxa and trophic groups to perturbation provides a powerful basis for analysis of faunal assemblages in soil as in situ environmental assessment systems.

Feeding habits in soil nematode families and genera-an outline for soil ecologists.

Because research on nematode involvement in trophic interactions, foodweb structure, and biodiversity is constrained by lack of an overview of nematode feeding habits, this outline presents a consensus of current thought on nematode feeding habits. The source of food is fundamental to trophic interactions and provides the basis for our definitions of the essential feeding types: 1) plant feeder, 2) hyphal feeder, 3) bacterial feeder, 4) substrate ingester, 5) predator of animals, 6) unicellular eucaryote feeder, 7) dispersal or infective stage of parasites, and 8) omnivore. Lists of families and genera with their presumed feeding types are given. Major gaps in knowledge of feeding in the smaller tylenchids and many dorylaims are noted.