BACKGROUND Zinc supplementation has been considered one of the potential therapies for coronavirus disease-19 (COVID-19). We aimed to examine zinc efficacy in adult patients with COVID-19 infection. METHODS We conducted a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Patients tested positive for COVID-19 without end organ failure were randomized to oral zinc (n = 231) or matching placebo (n = 239) for 15 days. The primary combined outcome was death due to COVID-19 or ICU admission within 30 days after randomization. Secondary outcomes included length of hospital stay for inpatients and duration of COVID-19 symptoms with COVID-19 related hospitalization for outpatients. FINDINGS One hundred ninety patients (40.4%) were ambulatory and 280 patients (59.6%) were hospitalized. Mortality at 30-day was 6.5% in Zinc group and 9.2% in Placebo group [odds ratio (OR) 0.70 (0.37-1.32)]; ICU admission rate was respectively 5.2% and 11.3% [OR 0.46 (0.23-0.88)]. Combined outcome was lower in zinc group compared to placebo group [OR 0.62 (0.38-0.99)]. Consistent results were observed in prespecified subgroups of patients with age < 65 years, those with comorbidity, and those who needed oxygen therapy at baseline. Length of hospital stay was shorter in zinc group compared to placebo group [difference 3.5 days, 95% CI (2.76-4.23)] in inpatients group; duration of COVID-19 symptoms decreased with zinc treatment compared to placebo in outpatients [difference 1.9 days, 95% CI (0.62-2.6)]. No severe adverse events were observed during the study. INTERPRETATION Our results showed that in COVID-19 patients, oral zinc can decrease 30-day death and ICU admission rate and can shorten symptoms duration.

Introduction: Duration of antibiotic treatment in acute exacerbation of COPD (AECOPD) is most commonly based on expert opinion. Typical administration periods range from 5 to 7 days. A 2-day course with levofloxacin was not previously assessed. We performed a randomized clinical trial to evaluate the efficacy of 2-day versus 7-day treatment with levofloxacin in patients with AECOPD. Methods and analysis: Patients with AECOPD were randomized to receive levofloxacin for 2 days and 5 days placebo ( n = 155) or levofloxacin for 7 days ( n = 155). All patients received a common dose of intravenous prednisone daily for 5 days. The primary outcome measure was cure rate, and secondary outcomes included need for additional antibiotics, ICU admission rate, re-exacerbation rate, death rate, and exacerbation-free interval (EFI) within 1-year follow-up. The study protocol has been prepared in accordance with the revised Helsinki Declaration for Biomedical Research Involving Human Subjects and Guidelines for Good Clinical Practice. The study was approved by ethics committees of all participating centers prior to implementation (Monastir and Sousse Universities). Results: 310 patients were randomized to receive 2-day course of levofloxacin ( n = 155) or 7-day course ( n = 155). Cure rate was 79.3% ( n = 123) and 74.2% ( n = 115), respectively, in 2-day and 7-day groups [OR 1.3; 95% CI 0.78–2.2 ( p = 0.28)]. Need for additional antibiotics rate was 3.2% and 1.9% in the 2-day group and 7-day group, respectively; ( p = 0.43). ICU admission rate was not significantly different between both groups. One-year re-exacerbation rate was 34.8% ( n = 54) in 2-day group versus 29% ( n = 45) in 7-day group ( p = 0.19); the EFI was 121 days (interquartile range, 99–149) versus 110 days (interquartile range, 89–132) in 2-day and 7-day treatment groups, respectively; ( p = 0.73). One-year death rate was not significantly different between the 2 groups, 5.2% versus 7.1% in the 2-day group and 7-day group, respectively; ( p = 0.26). No difference in adverse effects was detected. Conclusion: Levofloxacin once daily for 2 days is not inferior to 7 days with respect to cure rate, need for additional antibiotics and hospital readmission in AECOPD. Our findings would improve patient compliance and reduce the incidence of bacterial resistance and adverse effects.

Introduction Duration of antibiotic treatment in acute exacerbation of COPD (AECOPD) is most commonly based on expert opinion. Biomarker guided strategy is increasingly recommended to limit unnecessary antibiotic use. We performed a randomized controlled study to evaluate the efficacy of 2-day versus C-reactive protein (CRP)-guided treatment with levofloxacin in patients with AECOPD. Methods Patients with AECOPD were randomized to receive oral levofloxacin daily for 7 days unless the serum CRP level decreased by at least 50% from the baseline value or levofloxacin for two days; thereafter, oral placebo tablet was prescribed according to the CRP. The primary outcome measure was cure rate, and secondary outcome included need for additional antibiotics, intensive care unit (ICU) admission, exacerbation rates and exacerbation free interval (EFI) within one-year follow-up. Results In intention to treat (ITT) analysis, cure rate was 76.1% (n = 118) and 79.3% (n = 123) respectively in 2-day and CRP-guided groups. In per protocol (PP) analysis, cure rate was 73% (n = 92) and 70.4% (n = 88) respectively in 2-day and CRP-guided groups. The difference between the two groups was not significant. The need for additional antibiotics and ICU admission rates were not significantly different between the two groups. One-year exacerbation rate was 27% (n = 42) in 2-day group versus 30.3% (n = 47) in CRP-guided group (p = 0.53); the EFI was 125 days (interquartile range, 100–151) versus 100 days (interquartile range, 78–123) in 2-day and CRP-guided groups respectively (p = 0.45). No difference in adverse effects was detected. Conclusion Levofloxacin once daily for 2 days had similar efficacy compared to CRP-guided in AECOPD. This short course treatment decreased antibiotic consumption which would improve patient compliance and reduce adverse effects.

Objectives: To evaluate the efficacy and safety of early administration of low-dose intranasal ketamine on reducing the need for opioid and nonopioid analgesic agents in emergency department (ED) patients with acute moderate to severe acute limbs’ trauma pain. Patients and Methods: This is a double-blind, randomized, prospective, controlled study conducted in the ED. The included patients were randomly assigned to intranasal pulverization of ketamine or placebo. Protocol treatment was given at the triage. The primary outcome is the need for opioids during ED stay. Secondary outcome included the requirement of nonopioid analgesic agents and the percentage of patients discharged from the ED with a visual analog scale (VAS) <30. A combined outcome score including the 3 outcome items was constructed. Results: The authors included 1102 patients, 550 patients in the placebo group, and 552 in the intranasal ketamine group. The groups were similar regarding demographics, clinical characteristics, and baseline VAS. The need for opioids was decreased in the intranasal ketamine group compared with the placebo group (17.2% vs. 26.5%; P<0.001). The need for nonopioid analgesics was significantly lower in the intranasal ketamine group compared with the placebo group (31.1% vs. 39.6%; P=0.003). The percentage of patients discharged with a VAS score <30 was significantly higher in the intranasal ketamine group (P<0.001). The mean combined outcome score was 0.97 in the placebo group and 0.67 in the intranasal ketamine group (P<0.001). Conclusion: Intranasal ketamine administered early in the triage was associated with a decrease in opioids and nonopioid analgesics need in patients with acute limb trauma-related pain.