Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial.

BACKGROUND: Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine. METHODS: In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248. FINDINGS: Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebos -1·29%, 95% CI -14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, -6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (-12·9%, -34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, -13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, -5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, -11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected. INTERPRETATION: Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need. FUNDING: National Institute for Health Research Policy Research Programme.

Relationship of perioperative anaphylaxis to neuromuscular blocking agents, obesity, and pholcodine consumption: a case-control study.

BACKGROUND: The observation that patients presenting for bariatric surgery had a high incidence of neuromuscular blocking agent (NMBA) anaphylaxis prompted this restricted case-control study to test the hypothesis that obesity is a risk factor for NMBA anaphylaxis, independent of differences in pholcodine consumption. METHODS: We compared 145 patients diagnosed with intraoperative NMBA anaphylaxis in Western Australia between 2012 and 2020 with 61 patients with cefazolin anaphylaxis with respect to BMI grade, history of pholcodine consumption, sex, age, comorbid disease, and NMBA type and dose. Confounding was assessed by stratification and binomial logistic regression. RESULTS: Obesity (odds ratio [OR]=2.96, χ2=11.7, P=0.001), 'definite' pholcodine consumption (OR=14.0, χ2=2.6, P<0.001), and female sex (OR=2.70, χ2=9.61, P=0.002) were statistically significant risk factors for NMBA anaphylaxis on univariate analysis. The risk of NMBA anaphylaxis increased with BMI grade. Confounding analysis indicated that both obesity and pholcodine consumption remained important risk factors after correction for confounding, but that sex did not. The relative rate of rocuronium anaphylaxis was estimated to be 3.0 times that of vecuronium using controls as an estimate of market share, and the risk of NMBA anaphylaxis in patients presenting for bariatric surgery was 8.8 times the expected rate (74.9 vs 8.5 per 100 000 anaesthetic procedures). CONCLUSIONS: Obesity is a risk factor for NMBA anaphylaxis, the risk increasing with BMI grade. Pholcodine consumption is also a risk factor, and this is consistent with the pholcodine hypothesis. Rocuronium use is associated with an increased risk of anaphylaxis compared with vecuronium in this population.

Inaccuracies in calculating predicted body weight and its impact on safe ventilator settings.

In many centres, height is used as a determinant for calculating predicted body weight. This predicted body weight is then multiplied to generate the desired tidal volume. The approach exhibits some mathematical effects: (1) any errors in height measurement are multiplied by 5.5 when generating the tidal volume (assuming 6 ml/kg); (2) any errors in height measurement have a greater impact on shorter patients. The aim of this study was to: (1) establish the current practice of setting a tidal volume in England; (2) assess the implications of inaccurate height measurements on tidal volume settings using the most common practice; (3) identify the most accurate and precise method of determining height to aid accurate application of a lung protective strategy. The six extra corporeal membrane oxygenation centres in the UK, and the 34 intensive cares with the highest admission figures were identified from the intensive care national audit and research centre database. Most frequent practice was to use of a 1-m tape on the supine patient on admission. Inaccuracies in height estimation using a 1-m tape resulted in a standard deviation of 23 ml and a spread of over 120 ml tidal volume in individual patients.There are a number of methods of estimating height in a supine patient but the most accurate appeared to be simply using a 2-m tape.

Macroscopic barotrauma caused by stiff and soft-tipped airway exchange catheters: an in vitro case series.

BACKGROUND: Many airway management guidelines include the use of airway exchange catheters (AECs). There are reports, however, of harm from their use, from both malpositioning and in particular from the administration of oxygen via an AEC leading to barotrauma. METHODS: We used an in vitro pig lung model to investigate the safety of administering oxygen at 4 different flow rates from a high-pressure source via 2 different AECs: a standard catheter and a soft-tipped catheter. Experiments were performed with the catheters positioned either above the carina or below it at the first point of resistance to advancement (hold-up). The experiments were then repeated to produce a series of 32 cases. RESULTS: With an AEC positioned above the carina, we did not observe macroscopic lung damage after the administration of oxygen. The administration of oxygen through an AEC positioned below the carina resulted in macroscopic barotrauma regardless of the rate of oxygen delivery. Increasing speed of oxygen flow led to faster and more extensive damage. Use of an "injector" at 2.5 or 4 bar led to instantaneous macroscopic lung damage and advancement of the AEC through the lung tissue. Our observations were the same when both types of AECs were used. CONCLUSIONS: Our results are consistent with reports of harm during the use of AECs and demonstrate the risk of administering oxygen through these devices when they are positioned below the carina. An indicator, ideally made on an AEC at the time of manufacture and designed to lie at the same level as the teeth, may be useful in preventing the insertion of that AEC beyond the level of the carina and improve the safety of using such devices.