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The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. OBJECTIVE To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FIO 2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. INTERVENTIONS Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. MAIN OUTCOME AND MEASURES The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a PaO 2 /FIO 2 ratio less than 150 mm Hg, whichever came first. RESULTS A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. CONCLUSIONS AND RELEVANCE In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and PaO 2 /FIO 2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease.

A straightforward and unified approach is presented for the calculation of the population attributable risk per cent (etiologic fraction) in the general multivariate setting, with emphasis on using data from case-control studies. The summary attributable risk for multiple factors can be estimated, with or without adjustment for other (confounding) risk factors. The relation of this approach to procedures in the literature is discussed. Given values of the relative risks for various combinations of factors, all that is required is the distribution of these factors among the cases only. The required information can often be estimated solely from case-control data, and in some situations relative risk estimates from one population can be applied to calculation of attributable risk for another population. The authors emphasize the benefits to be obtained from logistic regression models, so that risks need not be estimated separately in a large number of strata, some of which may contain inadequate numbers of individuals. This approach allows incorporation of important interactions between factors, but does not require that all possible interactions be included. The approach is illustrated with data on four risk factors from a pair-matched case-control study of participants in a multicenter breast cancer screening project.

HE RISK OF SUDDEN DEATH IN PA-tients with hypertrophic cardiomyopathy (HCM) has been known for almost 50 years. [1][2][3][4][5][6] Indeed, this disease is the most common cause of sudden cardiac death in young people, 1-6 including trained athletes. 7 However, only in the last few years has the implantable cardioverterdefibrillator (ICD) been systematically used as a potentially life-saving For editorial comment see p 452.

In hypertrophic cardiomyopathy, the magnitude of hypertrophy is directly related to the risk of sudden death and is a strong and independent predictor of prognosis. Young patients with extreme hypertrophy, even those with few or no symptoms, appear to be at substantial long-term risk and deserve consideration for interventions to prevent sudden death. The majority of patients with mild hypertrophy are at low risk and can be reassured regarding their prognosis.

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One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n ‫؍‬ 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n ‫؍‬ 29) ; (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n ‫؍‬ 28) versus 15 mg/kg rabbit ATG (n ‫؍‬ 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P ‫؍‬ .8) in the first and in 50% versus 11% (P ‫؍‬ .001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P ‫؍‬ .02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%; P ‫؍‬ .04), as confirmed by multivariate analysis (P ‫؍‬ .03). Time to 50 ؋ 10 9 /L platelets was comparable in the first trial (21 vs 24 days; P ‫؍‬ .3) and delayed in the ATG arm in the second trial (23 vs 38 days; P ‫؍‬ .02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG. (Blood. 2001;98:2942-2947)

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