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.
BACKGROUND.The use of adjuvant chemotherapy to treat adults with localized resectable soft‐tissue sarcoma remains controversial. The objective of this systematic review was to update the 1997 meta‐analysis of randomized controlled trials (RCTs) to reassess the efficacy of doxorubicin‐based chemotherapy with respect to recurrence and survival.METHODS.A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft‐tissue sarcoma. Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were local, distant, and overall recurrence and survival calculated through the fixed effect or random effect model.RESULTS.Four new eligible trials were identified allowing for a total of 18 trials representing 1953 patients to be included in the analysis. The odds ratios (OR) for local recurrence was 0.73 (95% confidence interval [CI] 0.56‐0.94; P = .02) in favor of chemotherapy. For distant and overall recurrence the OR was 0.67 (95% CI 0.56‐0.82; P = .0001) in favor of chemotherapy. In terms of survival, doxorubicin alone had an OR of 0.84 (95% CI, 0.68‐1.03; P = .09), which as not statistically significant. However, the OR for doxorubicin combined with ifosfamide was 0.56 (95% CI, 0.36‐0.85; P = .01) in favor of chemotherapy.CONCLUSIONS.This updated meta‐analysis confirms the marginal efficacy of chemotherapy in localized resectable soft‐tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. These benefits are further improved with the addition of ifosfamide to doxorubicin‐based regimens, but must be weighed against associated toxicities. Cancer 2008. © 2008 American Cancer Society.
When making decisions regarding adjuvant chemotherapy, patients with early breast cancer who had been exposed to the Decision Board had better knowledge of the disease and treatment options and greater satisfaction with their decision making than those who received the standard consultation.
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