Background: Zinc supplementation has been considered a potential therapy for coronavirus disease 2019 (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 who were 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 intensive care unit (ICU) admission ≤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. Results: 190 patients (40.4%) were ambulatory and 280 patients (59.6%) were hospitalized. Mortality at 30 days was 6.5% in the zinc group and 9.2% in the placebo group (OR: .68; 95% CI .34–1.35); ICU admission rates were, respectively, 5.2% and 11.3% (OR: .43; 95% CI .21–.87). Combined outcome was lower in the zinc group versus the placebo group (OR: .58; 95% CI .33–.99). Consistent results were observed in prespecified subgroups of patients aged <65 years, those with comorbidity, and those who needed oxygen therapy at baseline. Length of hospital stay was shorter in the zinc group versus the placebo group (difference: 3.5 days; 95% CI 2.76–4.23) in the inpatient group; duration of COVID-19 symptoms decreased with zinc treatment versus placebo in outpatients (difference: 1.9 days; 95% CI .62–2.6). No severe adverse events were observed during the study. Conclusions: Our results showed that, in COVID-19 patients, oral zinc can decrease 30-day death, ICU admission rate and can shorten symptom duration. Clinical Trials Registration. ClinicalTrials.gov, NCT05212480.

Background: Ultrasonographic B-lines have recently emerged as a bedside imaging tool for the differential diagnosis of acute dyspnea in the Emergency Department (ED). However, despite its simplicity, LUS has not fully penetrated emergency department. This study aimed to assess the accuracy and reproducibility of ultrasonographic B-lines performed by emergency medicine (EM) residents for the diagnosis of congestive heart failure (CHF) in patients admitted to ED for acute dyspnea. Patients and methods: This is a cross-sectional prospective study conducted between January 2016 and October 2017 including patients aged over 18 years admitted to ED for acute dyspnea. At admission, two consecutive bedside LUS study were performed by a pair of EM residents who received a 2-h course for recognition of sonographic B-lines to determine independently B-lines score and B-profile pattern. All participating sonographers were blinded to patients’ clinical data. B-lines score ≥ 15 or a B-profile pattern was considered as suggestive of CHF. The final leading diagnosis was assessed by two expert sonographers, who were blinded to the residents’ interpretations, based on clinical findings, chest X-ray, brain natriuretic peptide, cardiac and lung ultrasound testing. Accuracy and agreement of B-lines score and B-profile pattern were calculated. Results: We included 700 patients with a mean age of 68 ± 12.6 years and a sex ratio (M/F) of 1.43. The diagnosis of CHF was recorded in 371 patients (53%). The diagnostic performance of B-lines score at a cut-off 15 and B-profile pattern was, respectively, 88% and 82.5% for sensitivity, 75% and 84% for specificity, 80% and 85% for positive predictive value, 84% and 81% for negative predictive value. The area under receiver operating characteristic curve was 0.86 [0.83–0.89] and 0.83 [0.80–0.86], respectively, for B-lines score and B-profile pattern. There was an excellent agreement between residents for the diagnosis of CHF using both scores (kappa = 0.81 and 0.85, respectively, for ordinal scale B-lines score and B-profile pattern). Conclusion: Lung ultrasound B-lines assessment has a good accuracy and an excellent reproducibility in the diagnosis of CHF in the hand of EM residents following a short training program. Trial registration Name of the registry: clinicaltrials.gov; Trial registration number: NCT03717779; Date of registration: October 24, 2018 ‘Retrospectively registered’; URL of trial registry record: clinicaltrials.gov

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. 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). 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. 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.

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

Background: Little is known about the pattern and appropriateness of antibiotic prescriptions in patients with acute respiratory tract infections (ARTIs). Objective: Describe the antibiotics used to treat ARTIs in Tunisian primary care offices and emergency departments (EDs), and assess the appropriateness of their use. Methods: It was a prospective multicenter cross-sectional observational clinical study conducted at 63 primary care offices and 6 EDS during a period of 8 months. Appropriateness of antibiotic prescription was evaluated by trained physicians using the medication appropriateness index (MAI). The MAI ratings generated a weighted score of 0 to 18 with higher scores indicating low appropriateness. The study was conducted in accordance with the Declaration of Helsinki and national and institutional standards. The study was approved by the Ethics committee of Monastir Medical Faculty. Results: From the 12,880 patients screened we included 9886 patients. The mean age was 47.4, and 55.4% were men. The most frequent diagnosis of ARTI was were acute bronchitis (45.3%), COPD exacerbation (16.3%), tonsillitis (14.6%), rhinopharyngitis (12.2%) and sinusitis (11.5%). The most prescribed classes of antibiotics were penicillins (58.3%), fluoroquinolones (17.6%), and macrolides (16.9%). Antibiotic therapy was inappropriate in 75.5% of patients of whom 65.2% had bronchitis. 65% of patients had one or more antibiotic prescribing inappropriateness criteria as assessed by the MAI. The most frequently rated criteria were with expensiveness (75.8%) and indication (40%). Amoxicillin-clavulanic acid and levofloxacin were the most inappropriately prescribed antibiotics. History of cardiac ischemia ([OR] 3.66; 95% [CI] 2.17–10.26; p < 0.001), asthma ([OR] 3.29, 95% [CI] 1.77–6.13; p < 0.001), diabetes ([OR] 2.09, 95% [CI] 1.54–2.97; p = 0.003), history of COPD ([OR] 1.75, 95% [CI] 1.43–2.15; p < 0.001) and age > 65 years (Odds Ratio [OR] 1.35, 95% confidence interval [CI] 1.16–1.58; p < 0.001) were associated with a higher likelihood of inappropriate prescribing. Conclusion: Our findings indicate a high inappropriate use of antibiotics in ARTIs treated in in primary care and EDs. This was mostly related to antibiotic prescription in acute bronchitis and overuse of expensive broad spectrum antibiotics. Future interventions to improve antibiotic prescribing in primary care and EDs is needed. Trial registration: the trial is registered at Clinicaltrials.gov registry (NCT04482231).