Background: Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. Methods: This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50 mcg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID50) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. Results: From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907). Conclusions: Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines. Clinicaltrials.gov: NCT05289037

Objective We aimed to provide pain advice ('The treatment of pain is very important and be sure to tell the staff when you have pain') as an intervention and evaluate its effect upon patient satisfaction. The purpose of this pilot trial was to ensure the design and methods of a future trial are sound, practicable and feasible. Method We undertook a pilot, randomised, controlled, clinical intervention trial in a single ED. The control arm received standard care. The intervention arm received standard care plus pain advice from an independent investigator. All patients and treating ED staff were blinded to patient enrolment. Patient satisfaction with their pain management (six-point ordinal scale) was measured 48 h post-ED discharge, by a blinded researcher. The primary outcome was satisfaction with pain management. Results Of the 280 and 275 patients randomised to the control and intervention arms, respectively, 196 and 215 had complete data, respectively. 77.6% (152/196) and 88.8% (191/215) of patients reported being provided with pain advice, respectively (difference 11.3% (95% CI 3.6 to 19.0)). The intervention was associated with absolute and relative increases in patient satisfaction of 6.3% and 14.2%, respectively. 91.3% (179/196) and 76.3% (164/215) of patients who were/ were not very satisfied reported having received 'pain advice' (difference 15.0% (95% CI 7.6 to 22.5)). Conclusions The intervention to provide pain advice resulted in a non-significant increase in patient satisfaction. A larger multicentre trial is feasible and is recommended to further explore the effects of provision of pain advice. Trial registration number ACTRN12615000097549.

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037.

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AT use is common among paediatric ED patients. Parents who arrange AT have differing perceptions of AT usefulness and safety from those who do not.

Objective To determine the patient and clinical variables associated with administration of any analgesia, nurse-initiated analgesia (NIA, prescribed and administered by a nurse) and early analgesia (within 30 min of presentation). Methods We undertook a retrospective cohort study of patients who presented to a metropolitan ED in Melbourne, Australia, during July and August, 2013. The ED has an established NIA programme. Patients were included if they were aged 18 years or more and presented with a painful complaint. The study sample was randomly selected from a list of all eligible patients. Data were extracted electronically from the ED records and by explicit extraction from the medical record. Logistic regression models were constructed to assess associations with the three binary study end points. Results 1289 patients were enrolled. Patients were less likely to receive any analgesia if they presented 08:00-15:59 hours (OR 0.67, 95% CI 0.46 to 0.98) or 16:00-24:00 hours (OR 0.55, 95% CI 0.37 to 0.80) were triage category 5 (OR 0.20, 95% CI 0.08 to 0.49) or required an interpreter (OR 0.34, 95% CI 0.14 to 0.86). Patients were less likely to receive NIA or early analgesia if they were aged 56 years or more (OR 0.70 and 0.63; OR 0.57 and 0.21, respectively) or if they had received ambulance analgesia (OR 0.59, 95% CI 0.36 to 0.95; OR 0.38, 95% CI 0.20 to 0.74, respectively). Conclusions Patients who present during the daytime, have a triage category of 5 or require an interpreter are less likely to receive analgesia. Older patients and those who received ambulance analgesia are less likely to receive NIA or early analgesia.

Generally, the level of patient satisfaction is high. Greater satisfaction is associated with deeper sedation, sedation with propofol and non-orthopaedic procedures.

Introduction: To determine the association between both abnormal individual vital signs and abnormal vital sign groups in the emergency department, and undesirable patient outcomes: hospital admission, medical emergency team calls and death. Method: We undertook a prospective cohort study in a tertiary referral emergency department (February-May 2015). Vital signs were collected prospectively in the emergency department and undesirable outcomes from the medical records. The primary outcomes were undesirable outcomes for individual vital signs (multivariate logistic regression) and vital sign groups (univariate analyses). Results: Data from 1438 patients were analysed. Admission was associated with tachycardia, tachypnoea, fever, ≥1 abnormal vital sign on admission to the emergency department, ≥1 abnormal vital sign at any time in the emergency department, a persistently abnormal vital sign, and vital signs consistent with both sepsis (tachycardia/hypotension/abnormal temperature) and pneumonia (tachypnoea/fever) (p < 0.05). Medical emergency team calls were associated with tachycardia, tachypnoea, ≥1 abnormal vital sign on admission (odds ratio: 2.3, 95% confidence interval: 1.4-3.8), ≥2 abnormal vital signs at any time (odds ratio: 2.4, 95% confidence interval: 1.2-4.7), and a persistently abnormal vital sign (odds ratio: 2.7, 95% confidence interval: 1.6-4.6). Death was associated with Glasgow Coma Score ≤13 (odds ratio: 6.3, 95% confidence interval: 2.5-16.0), ≥1 abnormal vital sign on admission (odds ratio: 2.6, 95% confidence interval: 1.2-5.6), ≥2 abnormal vital signs at any time (odds ratio: 6.4, 95% confidence interval: 1.4-29.5), a persistently abnormal vital sign (odds ratio: 4.3, 95% confidence interval: 2.0-9.0), and vital signs consistent with pneumonia (odds ratio: 5.3, 95% confidence interval: 1.9-14.8). Conclusion: Abnormal vital sign groups are generally superior to individual vital signs in predicting undesirable outcomes. They could inform best practice management, emergency department disposition, and communication with the patient and family.