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AbstractObjectives:To determine the association between after-hours consultations and the likelihood of antibiotic prescribing for self-limiting upper respiratory tract infections (URTIs) in primary care practices.Design:A cross-sectional analysis using Australian national primary-care practice data (MedicineInsight) between February 1, 2016 and January 31, 2019.Setting:Nationwide primary-care practices across Australia.Participants:Adult and pediatric patients who visited primary care practices for first-time URTIs.Methods:We estimated the proportion of first-time URTI episodes for which antibiotic prescribing occurred on the same day (immediate prescribing) using diagnoses and prescription records in the electronic primary-care database. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the likelihood of antibiotic prescribing by the time of primary care visits were calculated using generalized estimating equations.Results:Among 357,287 URTI episodes, antibiotics were prescribed in 172,605 episodes (48.3%). After adjusting for patients’ demographics, practice characteristics, and seasons, we detected a higher likelihood of antibiotic prescribing on weekends compared to weekdays (OR, 1.42; 95% CI, 1.39–1.45) and on national public holidays compared to nonholidays (OR, 1.23; 95% CI, 1.17–1.29). When we controlled for patient presentation and diagnosis, the association between antibiotic prescribing and after-hours consultations remained significant: weekend versus weekdays (OR, 1.37; 95% CI, 1.33–1.41) and holidays versus nonholidays (OR, 1.10; 95% CI, 1.03–1.18).Conclusions:Primary-care consultations on weekends and public holidays were associated with a higher likelihood of immediate antibiotic prescribing for self-limiting URTIs in primary care. This finding might be attributed to lower resourcing in after-hours health care.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.