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.

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OBJECTIVE -The purpose of this study was to generate normative values for periods of euglycemia as well as for daily patterns of glycemic excursions in patients with type 1 and type 2 diabetes monitored continuously for a maximum period of 21 days and blinded to glucose levels.RESEARCH DESIGN AND METHODS -This was a multicenter, prospective observational study in which 101 consecutive patients with type 1 (n ϭ 60) or type 2 (n ϭ 41) diabetes underwent blinded continuous glucose monitoring. Serial glucose measurements were divided into periods of euglycemia (70 -180 mg/dl), hyperglycemia (Ͼ180 mg/dl), and hypoglycemia (Ͻ70 mg/dl). The proportions of time patients were hypoglycemic, euglycemic, and hyperglycemic and the total areas under the curves (AUCs) were determined.RESULTS -During the observation period the 101 subjects contributed an average 287 Ϯ 132 h of continuous glucose values. Subjects remained in the euglycemic range for ϳ63% of the total day, were hypoglycemic 8%, and were hyperglycemic 29%. Hypoglycemia was more prevalent nocturnally (11 vs. 7%) and hyperglycemia diurnally (31 vs. 25%). Compared with subjects with type 2 diabetes, type 1 diabetic subjects had more frequent hypoglycemic episodes per day (2.1 vs. 1.0; P Ͻ 0.001) that were of longer duration (1.1 vs. 0.7 h; P Ͻ 0.0001), reflecting a greater number of hours per day in the hypoglycemic range (2.3 vs. 1.0 h; P Ͻ 0.0001). The mean hypoglycemic AUC values were Ͼ150% higher for type 1 compared with type 2 diabetic subjects (41 vs. 16, respectively; P Ͻ 0.0001).CONCLUSIONS -These normative data will assist in study and sample size planning for future investigations of continuous glucose monitoring and allow for qualitative comparisons with trials of therapeutic interventions aimed at reducing the occurrence of glycemic excursions.

A 1-year prospective study of risk factors for seropositivity to and contraction of Lyme disease among members of a small rural community (population, approximately 150) was conducted in northwestern California in 1988-1989. The initial rate of seropositivity for Borrelia burgdorferi for 119 current or former residents ranged from 15 to 20% among three laboratories, with statistically significant interlaboratory agreement. Questionnaires were completed by 93 current residents at entry and 80 residents a year later to evaluate the association of serologic status with 20 categorical and 47 continuous variables. Seropositive subjects had resided in the study area about 2 years longer, were bitten by unspecified biting flies more often, and were less likely to have engaged in hiking than seronegative subjects. One of 59 seronegative subjects seroconverted a year later (annual incidence = 1.7%). The cumulative frequency of seropositivity for Lyme disease in the study population was > or = 24%. Of 83 subjects examined physically, 13 were diagnosed as having definite and 18 as having probable Lyme disease. The seropositivity rate was significantly higher (38.7%) among individuals with definite/probable Lyme disease than in asymptomatic subjects (13.5%). Subjects who were seronegative or free of Lyme disease reported nearly as many tick bites as subjects who were seropositive or had a diagnosis of the disease. Age, time spent outdoors in the fall multiplied by a clothing index, and woodcutting were significantly associated with Lyme disease in logistic regression analyses.

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