Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov , NCT04327388 ; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 1...

Antibiotic use is a modifiable driver of antibiotic resistance. In many circumstances, antibiotic use is overly broad or unnecessary. We systematically assessed factors associated with antibiotic prescribing for respiratory tract infections (RTI). Studies were included if they used actual (not self-reported or intended) prescribing data, assessed factors associated with antibiotic prescribing for RTIs, and performed multivariable analysis of associations. We searched Medline, Embase, and International Pharmaceutical Abstracts using keyword and MeSH (medical subject headings) search terms. Two authors reviewed each abstract and independently appraised all included texts. Data on factors affecting antibiotic prescribing were extracted. Our searches retrieved a total of 2,848 abstracts, with 97 included in full-text review and 28 meeting full inclusion criteria. Compared to other factors, diagnosis of acute bronchitis was associated with increased antibiotic prescribing (range of adjusted odds ratios [aOR], 1.56 to 15.9). Features on physical exam, such as fever, purulent sputum, abnormal respiratory exam, and tonsillar exudate, were also associated with higher odds of antibiotic prescribing. Patient desire for an antibiotic was not associated or was modestly associated with prescription (range of aORs, 0.61 to 9.87), in contrast to physician perception of patient desire for antibiotics, which showed a stronger association (range of aORs, 2.11 to 23.3). Physician's perception of patient desire for antibiotics was strongly associated with antibiotic prescribing. Antimicrobial stewardship programs should continue to expand in the outpatient setting and should emphasize clear and direct communication between patients and physicians, as well as signs and symptoms that do and do not predict bacterial etiology of upper respiratory tract infections.T he rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases (1, 2). It is well established that antibiotic use is a significant, and modifiable, driver of antibiotic resistance (3-5), and that antibiotics are often misused (6). In settings where a prescription is required to access antibiotics, the prescriber-patient encounter is a logical target for improving appropriate use.Despite the importance of the topic, there is no existing systematic review to identify drivers of antibiotic prescribing from real prescription data. A narrative review of factors influencing antibiotic prescribing highlighted the multiple sources of influence affecting a potential prescribing encounter, including factors related to the prescribing physician (e.g., fear of failure, diagnostic uncertainty, or inadequate training), the patient (e.g., a high-risk or vulnerable patient history), and the environment (e.g., regulation of pharmaceutical prescribing and dispensing and lack of resources for etiological diagnosis) (7). Another study systematically reviewed reasons for inappropriate antibiotic prescriptions, f...

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Background Knowledge of hepatitis C virus (HCV) is believed to be important in altering risk behaviour, improving engagement in care, and promoting willingness to initiate HCV treatment. We assessed factors associated with HCV knowledge and treatment willingness amongst people who inject drugs (PWID) in an era of direct acting antivirals. Methods Data were derived from three prospective cohort studies of PWID in Vancouver, Canada, between June 2014 and May 2015. HCV knowledge and treatment willingness were assessed using a Likert scale. Multivariable linear regression identified factors associated with higher HCV knowledge and treatment willingness. Results Amongst 630 participants, mean scores for HCV knowledge and treatment willingness were 25.41 (standard deviation [SD]: 2.52) out of 30, and 6.83 (SD: 1.83) out of 10, respectively. In multivariable analyses, Caucasian ancestry (adjusted linear regression model estimate [β] 0.50; 95% confidence interval [CI] 0.17, 0.82), employment (β 0.76; 95% CI: 0.38, 1.13), diagnosed mental health disorder (β 0.44; 95% CI: 0.11, 0.78) and previous HCV treatment (β 0.94; 95% CI: 0.46, 1.43) were independently associated with higher knowledge. Downtown Eastside (DTES) residence (i.e., epicenter of Vancouver’s drug scene) was independently associated with lower knowledge (β −0.48; 95% CI: −0.81, −0.15). Greater HCV knowledge (β 0.12; 95% CI: 0.07, 0.17) was independently associated with higher HCV treatment willingness. DTES residence (β −0.31; 95% CI: −0.56, −0.06) and daily crack cocaine smoking (β −0.52; 95% CI: −0.92, −0.13) were independently associated with lower treatment willingness. Conclusion Socioeconomic factors, such as neighborhood residence and employment, were associated with HCV knowledge. Higher HCV knowledge was associated with more HCV treatment willingness. Our findings suggest that increasing HCV knowledge amongst PWID may be an integral component of the HCV cascade of care and that efforts might be best targeted to individuals with greater socioeconomic disadvantage.