Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Environmental and Social Determinants of Youth Physical Activity Intensity Levels at Neighborhood Parks in Las Vegas, NV

Parks can play an important role in youth activity. This study used observational data to evaluate the relationship of environmental and social determinants to youth physical activity intensity levels in Las Vegas neighborhood parks. System for observing play and leisure activity in youth was used to code activity levels as sedentary, walking, or vigorous in five low-income and five high-income parks. Environmental determinants included amenities, incivilities, size, high-speed streets, sidewalk condition, and temperature. Social determinants included percent minority and Hispanic, gender, and income. A multinomial logistic regression model was performed. We observed 1,421 youth, 59 % male, 41 % female; 21 % were sedentary, 38 % walking, and 41 % vigorous. Males were more likely to be observed walking (OR 1.42) and vigorous (OR 2.21) when compared to sedentary. High-speed streets (OR 0.76), sidewalks condition (OR 0.34), and low-income neighborhoods (OR 0.07) was associated with decreased odds of vigorous activity; incivilities (OR 1.34) and amenities (OR 1.27) were associated with greater odds of being vigorous. Environmental and social determinants are associated with physical activity intensity levels at parks. Stakeholders should ensure quality parks, as they relate to physical activity levels in youth. Understanding environmental and social determinants that influence physical activity at parks is critical to utilizing their full potential in an effort to combat childhood obesit

Evaluating the Impact of Environmental and Social Determinants of Physical Activity in Low Income Neighborhood Parks in Las Vegas, NV

Introduction: With rising rates of childhood obesity, the built environment has emerged as a contributing factor. Public parks provide an opportunity to increase physical activity levels in youth. This study used observational data to evaluate the relationship of environmental and social determinants with physical activity in 5 parks in low income areas of Las Vegas, NV. Methods: Five parks in geographically different neighborhoods which had median household incomes between $15,000 and$41,650 were chosen. SOPLAY was used for measurement during a 4 hour observation period. Physical activity was coded as sedentary, walking, or very active. Environmental correlates within 1/2 mile of the park included number of high speed streets, sidewalk availability and condition, size of park, condition of park grounds, and number of activity areas available in the park. Sociodemographic data included gender, age, and neighborhood % minority and % Hispanic from Census 2010. Multiple linear regression models will then be applied to determine the relationship of the predictor variables with physical activity behavior. Results: Final results will be presented. We anticipate that there will be a relationship between environmental and social determinants and category of physical activity. Conclusion: This work is important, as low income populations are more influenced by the built environment than those of higher income. Neighborhood parks provide an opportunity for physical activity. Understanding what environmental and social determinants are correlated with physical activity is valuable information for the planning of public health interventions

Monitoring Metastasis and Cachexia in a Patient with Breast Cancer: A Case Study

Cachexia, a wasting syndrome associated with advanced cancer and metastasis, is rarely documented in breast cancer patients. However, the incidence of cachexia in breast cancer is now thought to be largely underestimated. In our case report of a breast cancer patient with bone metastasis monitored during the course of her treatment, we document the development of cachexia by image analysis in relation to her metastatic burden. Elucidation of the link between metastatic burden and cachexia could unveil a highly specific screening process for metastasis, by assessing true muscle mass loss. Our patient was a 49-year-old premenopausal woman, with metastatic invasive ductal breast carcinoma in the vertebral and iliac bones on presentation, which progressed with new metastases to her hips, thigh bones, and vertebrae. In the two-year period, that is between her diagnosis and death, she lost >10% of her baseline weight. During these two years, we retrospectively identified a decrease in paraspinal muscle (PM) at the third lumbar vertebra followed by a sharp decline in weight. The increased tumor burden over time in metastatic sites was accompanied by a decrease in abdominal muscle and visceral and subcutaneous fat and was followed by the patient's demise. The increasing tumor burden in the patient was correlated with the mass of other tissues to determine the tissue that could best serve as a surrogate marker to cachexia and tumor burden. We noted a strong negative correlation between PM area and metastatic tumor area at the third lumbar vertebral level, with PM loss correlating to increasing tumor burden. The monitoring of PM wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and extent of metastatic disease, especially in breast cancer, where metastasis to bone is frequent. Based on our data and review of the literature in this case study, longitudinal monitoring of cachexia in the selected muscle groups can give clinicians early indications of the extent of cachexia in metastatic breast cancer patients