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.

Patients who accumulate multiple emergency department visits and hospital admissions, known as super-utilizers, have become the focus of policy initiatives aimed at preventing such costly use of the health care system through less expensive community- and primary care-based interventions. We conducted cross-sectional and longitudinal analyses of 4,774 publicly insured or uninsured super-utilizers in an urban safety-net integrated delivery system for the period May 1, 2011-April 30, 2013. Our analysis found that consistently 3 percent of adult patients met super-utilizer criteria and accounted for 30 percent of adult charges. Fewer than half of super-utilizers identified as such on May 1, 2011, remained in the category seven months later, and only 28 percent remained at the end of a year. This finding has important implications for program design and for policy makers because previous studies may have obscured this instability at the individual level. Our study also identified clinically relevant subgroups amenable to different interventions, along with their per capita utilization and costs before and after being identified as super-utilizers. Future solutions include improving predictive modeling to identify individuals likely to experience sustained levels of avoidable utilization, better classifying subgroups for whom interventions are needed, and implementing stronger program evaluation designs.

Detailed laboratory measurements have been made on the frictional characteristics ofWesterly granite with ground surfaces and to normal stresses of 1 kb. These measurements show that for this type of surface there are three types of sliding: continuously stable, episodic stable, and stick-slip. All three of these modes have also beer• observed on the San Andreas fault in central California. In our .laboratory experiments, there is a transition from the first to third mode at from 5 to 15 bars normal stress, above which stick-slip predominates. Stick-slip, however, is always preceded by a small amount of stable slip. If this occurs on a large scale on faults, it may be a promising premonitory effect for earthquake prediction.Loading rate is found to influence the frictional strength inversely, which may be an explanation for stick-slip. Stress drops were found to increase with shear stress, but not linearly, suggesting that radiation efficiency may increase with stress drop.• Lamont-Doherty Geological Observatory contribution 1889.Potentially, however, laboratory experiments can provide much more information than this. Seismologists can now estimate many of the source parameters of earthquakes: energy release, moment, stress drop, particle motion, rupture velocity, and source size. At present, however, the meaning of these parameters in terms of the physics of the seismic source is quite uncertain. Furthermore, different estimations of many of these parameters are obtained from different source theories.In order to extend the usefulness of laboratory information to these problems, we have attempted to make more detailed measurements of frictional sliding of rock than had been attempted previously. This has resulted in the observation of several new phenomena that are described and discussed below. EXPERIMENTAL TECHNIQUE Most testing machines in common usefor frictional studies have serious design drawbacks 6392 Fa•cT•o•A•, S•,m•o oF GaA•TE 6393