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.

In 1991, a novel robot, MIT-MANUS, was introduced to study the potential that robots might assist in and quantify the neuro-rehabilitation of motor function. MIT-MANUS proved an excellent tool for shoulder and elbow rehabilitation in stroke patients, showing in clinical trials a reduction of impairment in movements confined to the exercised joints. This successful proof of principle as to additional targeted and intensive movement treatment prompted a test of robot training examining other limb segments. This paper focuses on a robot for wrist rehabilitation designed to provide three rotational degrees-of-freedom. The first clinical trial of the device will enroll 200 stroke survivors. Ultimately 160 stroke survivors will train with both the proximal shoulder and elbow MIT-MANUS robot, as well as with the novel distal wrist robot, in addition to 40 stroke survivor controls. So far 52 stroke patients have completed the robot training (ongoing protocol). Here, we report on the initial

Abstract-Robotics and related technologies have begun to realize their promise to improve the delivery of rehabilitation therapy. However, the mechanism by which they enhance recovery remains unclear. Ultimately, recovery depends on biology, yet the details of the recovery process remain largely unknown; a deeper understanding is important to accelerate refinements of robotic therapy or suggest new approaches. Fortunately, robots provide an excellent instrument platform from which to study recovery at the behavioral level. This article reviews some initial insights about the process of upper-limb behavioral recovery that have emerged from our work. Evidence to date suggests that the form of therapy may be more important than its intensity: muscle strengthening offers no advantage over movement training. Passive movement is insufficient; active participation is required. Progressive training based on measures of movement coordination yields substantially improved outcomes. Together these results indicate that movement coordination rather than muscle activation may be the most appropriate focus for robotic therapy.

Investigators have demonstrated that a variety of intensive movement training protocols for persistent upper limb paralysis in patients with chronic stroke (6 months or more after stroke) improve motor outcome. This randomized controlled study determined in patients with upper limb motor impairment after chronic stroke whether movement therapy delivered by a robot or by a therapist using an intensive training protocol was superior. Robotic training (n = 11) and an intensive movement protocol (n = 10) improved the impairment measures of motor outcome significantly and comparably; there were no significant changes in disability measures. Motor gains were maintained at the 3-month evaluation after training. These data contribute to the growing awareness that persistent impairments in those with chronic stroke may not reflect exhausted capacity for improvement. These new protocols, rendered by either therapist or robot, can be standardized, tested, and replicated, and potentially will contribute to rational activity-based programs.Key Words: Stroke-Recovery of function-Rehabilitation. S troke causes permanent disability that is dependent in large part on motor impairment, and although most patients walk independently, often with a device or orthosis, recovery of arm and hand function occurs less often.1-3 Despite the tendency to focus restorative treatments in the weeks soon after the stroke inasmuch as motor improvements, in general, plateau 3 to 6 months later, 4,5 a new convergence of animal and human studies has focused on the treatment efficacy of repetitive exercise of the paralyzed upper limb to alter motor performance in patients with chronic stroke.5-13 These emerging data have stimulated the clinical development of activity-based techniques based on a combination of the control of guidance and speed of the movements and intensive practice.14-19 In patients with chronic stroke referred to an outpatient clinic, we have attempted to establish a standard therapistdelivered intensive physical therapy program, and then to compare it to a treatment with a robotic-driven protocol that has been demonstrated to alter motor performance significantly in patients with chronic stroke. 15 METHODS Study Population and DesignWe screened 55 patients with stroke referred to the outpatient clinic and who had impaired arm and hand mobility for at least 6 months. Twenty-one patients who met the inclusion criteria were randomized to robotic training that was identical to a past robotic trial 15 or to an intensive upper extremity movement-based treatment from a therapist. The therapist's protocol was designed by a group of senior therapists working in the stroke recovery program, and represented a combination of common practice treatments that, for the purpose of this experiment, matched the session duration, number, and timing of robot treatments. Patients were measured monthly for 3 months to test whether there was spontaneous improvement. Measurements of motor impairment were also obtained at the mid-point and the end of trai...