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.

Aims To examine the effects of reduced nicotine cigarettes on smoking behavior, toxicant exposure, dependence and abstinence. Design Randomized, parallel arm, semi-blinded study. Setting University of Minnesota Tobacco Use Research Center. Interventions Six weeks of: (i) 0.05 mg nicotine yield cigarettes; (ii) 0.3 mg nicotine yield cigarettes; or (iii) 4 mg nicotine lozenge; 6 weeks of follow-up. Measurements Compensatory smoking behavior, biomarkers of exposure, tobacco dependence, tobacco withdrawal and abstinence rate. Findings Unlike the 0.3 mg cigarettes, 0.05 mg cigarettes were not associated with compensatory smoking behaviors. Furthermore, the 0.05 mg cigarettes and nicotine lozenge were associated with reduced carcinogen exposure, nicotine dependence and product withdrawal scores. The 0.05 mg cigarette was associated with greater relief of withdrawal from usual brand cigarettes than the nicotine lozenge. The 0.05 mg cigarette led to a significantly higher rate of cessation than the 0.3 mg cigarette and a similar rate as nicotine lozenge. Conclusion The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation; however, future research is clearly needed to support these preliminary findings.

clinicaltrials.gov Identifier: NCT02139930.

No abstract

Aims-To examine if menstrual phase affects relapse in women attempting to quit smoking.Design-An intent-to-treat randomized smoking cessation trial where women were assigned to quit smoking in either the follicular (F) or luteal (L) menstrual phase and were followed for up to 26 weeks. They were assessed for relapse by days to relapse and relapse phase to determine if those who begin a quit attempt during the F phase were more successful than those who begin during the L phase.Setting-Tobacco Use Research Center, University of Minnesota, Minneapolis, Minnesota. Participants-A total of 202 women.Measurements-Latency to relapse from continuous and prolonged abstinence, point prevalence, phase of relapse, first slip within the first 3 and 5 days post-quit date, subject completion rates and symptomatology (i.e. withdrawal and craving).Findings-The mean days to relapse from continuous abstinence and relapse from prolonged abstinence for the F group were 13.9 and 20.6 days, respectively, and 21.5 and 39.2 days, respectively, for the L group. Using point prevalence analysis at 14 days, 84% of the F group had relapsed compared with 65% of the L group [χ 2 = 10.024, P = 0.002; odds ratio (OR) = 2.871, 95% confidence interval (CI), 1. 474-5.590]. At 30 days, 86% of the F group relapsed, compared with 66% of the L group (χ 2 = 11.076, P = 0.001; OR = 3.178, 95% CI, 1.594-6.334).Conclusion-Women attempting to quit smoking in the F phase had less favorable outcomes than those attempting to quit in the L phase. This could relate to ovarian hormones, which may play a role in smoking cessation for women.

No abstract

The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects, or by subjects smoking during withdrawal. To reduce these occurrences, 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine (21 mg) or placebo transdermal patches. Subject attrition was low, with 80.5% of participants continuing through the 5-week study period. Abstinence rates were also high over this period (75% and 61% in active and placebo groups, respectively). In this multisite, double-blind trial, withdrawal severity was assessed using a nine-item daily self-report questionnaire, and abstinence was confirmed via CO monitoring. Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes, irritability, anxiety, appetite, sleep disruption, difficulty concentrating, restlessness, depression, and impatience. Treatment with transdermal nicotine reduced craving for cigarettes, anxiety, irritability, and appetite, as well as weight gain (1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups, respectively).

BACKGROUND. Weight gain after smoking cessation is often cited by women smokers as a primary reason for not attempting to quit smoking or for relapsing after a cessation attempt. METHODS. A randomized trial of 417 women smokers was conducted to test the addition of two weight control strategies to a smoking cessation program. Participants received the standard smoking cessation program, the program plus nicotine gum, the program plus behavioral weight control, or the program plus both nicotine gum and behavioral weight control. Weight and smoking status were measured at the end of treatment and at 6 and 12 months posttreatment. RESULTS. Smoking cessation rates were highest in the group receiving the smoking cessation program plus nicotine gum. Weight gain did not vary by treatment condition, so its effect on relapse could not be examined by group. There was no significant relationship between weight gained and relapse in individuals. CONCLUSIONS. The added behavioral weight control program was attractive to the participants and did not reduce smoking cessation rates. However, it did not produce the expected effect on weight, thereby restricting our ability to examine the effect of weight control on smoking cessation and relapse.