Heterologous vaccine regimen: stakeholder acceptance and implementation considerations

Heterologous vaccine regimens deliver antigens through different vaccine components or vector types at sequential time points. Clinical development shows promising results and several candidates may be progressing to licensure in the coming years. This study aimed at exploring future acceptance and uptake of such regimens (also called heterologous prime-boost) and to identify implementation-associated benefits and challenges. Survey tools were developed based on findings from a previous literature search shared with the study team, and exploratory interviews with global stakeholders. An online survey and key informant interviews in six countries were conducted with stakeholders at national and sub-national level, including policy-makers, regulators and implementers. The interview guide and the online survey covered: (a) awareness of, and knowledge about, heterologous vaccine regimens; (b) rating of regimenassociated perceived benefits and challenges; (c) anticipation of possible challenges in relation to four hypothetical introduction scenarios; (d) potential acceptance benefits and challenges at the policy, health facility and recipient level. Sixty-two interviews were conducted at national level. The online survey was completed by 50 participants. Across the four introduction scenarios, respondents considered the highest potential for the introduction of heterologous regimens for immunoprophylaxis was among adolescents/ adults for diseases against which no vaccines are currently available. Most reservations were related to logistics, record keeping, and recipient compliance. Adding a new heterologous vaccine regimen to the routine immunization calendar for children was considered feasible if it could generate an increased and longer-term immune response. Introduction in preparation of or following a disease outbreak was considered less favourably, with respondents stressing the difficulty of logistics in emergency situations, and the potential lag in the onset of protection. The recent approval of the first heterologous vaccine regimen for the prevention of Ebola Virus Disease will soon bring new light to the topic

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients from 29 Countries

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events - in particular cardiovascular instability - were observed frequently

Efficacy and adverse events profile of videolaryngoscopy in critically ill patients: subanalysis of the INTUBE study

Background: Tracheal intubation is a high-risk procedure in the critically ill, with increased intubation failure rates and a high risk of other adverse events. Videolaryngoscopy might improve intubation outcomes in this population, but evidence remains conflicting, and its impact on adverse event rates is debated.Methods: This is a subanalysis of a large international prospective cohort of critically ill patients (INTUBE Study) performed from 1 October 2018 to 31 July 2019 and involving 197 sites from 29 countries across five continents. Our primary aim was to determine the first-pass intubation success rates of videolaryngoscopy. Secondary aims were characterising (a) videolaryngoscopy use in the critically ill patient population and (b) the incidence of severe adverse effects compared with direct laryngoscopy.Results: Of 2916 patients, videolaryngoscopy was used in 500 patients (17.2%) and direct laryngoscopy in 2416 (82.8%). First-pass intubation success was higher with videolaryngoscopy compared with direct laryngoscopy (84% vs 79%, P1/40.02). Patients undergoing videolaryngoscopy had a higher frequency of difficult airway predictors (60% vs 40%, P<0.001). In adjusted analyses, videolaryngoscopy increased the probability of first-pass intubation success, with an OR of 1.40 (95% confidence interval [CI] 1.05-1.87). Videolaryngoscopy was not significantly associated with risk of major adverse events (odds ratio 1.24, 95% CI 0.95-1.62) or cardiovascular events (odds ratio 0.78, 95% CI 0.60-1.02).Conclusions: In critically ill patients, videolaryngoscopy was associated with higher first-pass intubation success rates, despite being used in a population at higher risk of difficult airway management. Videolaryngoscopy was not associated with overall risk of major adverse events

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries

Key PointsQuestionAmong critically ill patients undergoing tracheal intubation worldwide, how common are major adverse events during the peri-intubation period? FindingsIn this prospective observational study that included 2964 patients from 197 sites across 29 countries from October 2018 to July 2019, at least one major clinical event occurred after intubation in 45.2% of patients, including cardiovascular instability in 42.6%, severe hypoxemia in 9.3%, and cardiac arrest in 3.1%. MeaningAmong an international sample of critically ill patients undergoing tracheal intubation, major cardiopulmonary events occurred frequently.ImportanceTracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. ObjectiveTo evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and ParticipantsThe International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. ExposuresTracheal intubation. Main Outcomes and MeasuresThe primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. ResultsOf 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and RelevanceIn this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events-in particular cardiovascular instability-were observed frequently.This international cohort study describes the incidence and nature of cardiovascular instability, severe hypoxemia, and cardiac arrest surrounding endotracheal intubation