Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, ...multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity.
Prospective cohort study.
Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States.
Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics.
None.
Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes.
SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI.
Summary Background Administration of vaccines by needle-free technology such as jet injection might offer an alternative to needles and syringes that avoids the issue of needle phobia and the risk of ...needle-stick injury. We aimed to assess the immunogenicity and safety of trivalent influenza vaccine given by needle-free jet injector compared with needle and syringe. Methods For this randomised, comparator-controlled trial, we randomly assigned (1:1) healthy adults (aged 18–64 years) who attended one of four employee health clinics in the University of Colorado health system, with stratification by site, to receive one dose of the trivalent inactivated influenza vaccine Afluria given either intramuscularly with a needle-free jet injector (Stratis; PharmaJet, Golden, CO, USA) or with needle and syringe. Randomisation was done with a computer-generated randomisation schedule with a block size of 100. Because of the nature of the study, masking of participants was not possible. Immunogenicity was assessed by measurement of the hemagglutination inhibition antibody titres in serum for the three viral strains included in the vaccine. We included six coprimary endpoints: three strain-specific geometric mean titre ratios and the absolute differences in three strain-specific seroconversion rates. The immune response of the jet injector group was regarded as non-inferior to that of the needle and syringe group if both the upper bound of each of the three 95% CIs for the strain-specific geometric mean titre ratios was 1.5 or less, and the upper bound of the three 95% CIs for the strain-specific seroconversion rate differences was less than 10 percentage points. We used t test for group comparison. This study is registered with ClinicalTrials.gov , number NCT01688921. Findings During the 2012–13 influenza season of the northern hemisphere, we allocated 1250 participants to receive vaccination by needle-free jet injector (n=627) or needle and syringe (n=623). In the intention-to-treat immunogenicity population, all participants with two serum samples were included (575 in the jet injector group and 574 in the needle and syringe group). The immune response to Afluria when given by needle-free jet injector met the criteria for non-inferiority for all six coprimary endpoints. The jet injector group met the geometric mean titre criterion for non-inferiority for the A/H1N1, A/H3N2, and B strains (upper bound of the 95% CI for the geometric mean titre ratios were 1·10 for A/H1N1, 1·17 for A/H3N2, and 1·04 for B strains). The jet injector group met the seroconversion rate criterion for non-inferiority for the A/H1N1, A/H3N2, and B strains (upper bound of the 95% CI of the seroconversion rate differences were 6·0% for A/H1N1, 7·0% for A/H3N2, and 5·7% for B strains). We recorded serious adverse events in three participants, none of which were study related. Interpretation The immune response to influenza vaccine given with the jet injector device was non-inferior to the immune response to influenza vaccine given with needle and syringe. The device had a clinically acceptable safety profile, but was associated with a higher frequency of local injection site reactions than was the use of needle and syringe. The Stratis needle-free jet injector device could be used as an alternative method of administration of Afluria trivalent influenza vaccine. Funding Biomedical Advanced Research and Development Authority (BARDA), PATH, bioCSL, and PharmaJet.
Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. ...Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.
To assess the role of ANGPTL4 in COVID-19-related outcomes.
Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University.
Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4.
Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log
increase, 1.53; 95% CI, 1.17-2.00;
= 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (
for interaction = 8.1 × 10
). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19.
single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls.
ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.
Elevated blood pressure is a highly prevalent condition that is etiologically related to coronary heart disease and stroke, two of the leading causes of morbidity and mortality throughout the world. ...Excess salt (sodium chloride) intake is a major determinant of elevated blood pressure. In this article, we discuss the scientific rationale for population-wide salt reduction, the types and strength of available evidence, policy-making on dietary salt intake in the United States and other countries, and the role and impact of key stakeholders. We highlight a number of lessons learned, many of which are germane to policy development in other domains.
There is debate amongst surgeons regarding the use of antibiotics to prevent fistulae after palatoplasty. Prescribing should be evidence based, as antibiotic stewardship is integral to reducing ...antibiotic resistance. Our aim was to determine whether differing perioperative regimens affect the prevalence of postoperative fistulae.
The sample comprised participants from the Cleft Collective who had undergone palatoplasty. Participants were recruited across all 16 UK cleft centers between 2013 and 2021. The exposure was perioperative antibiotic regimen prescribed at the time of palatoplasty. The primary outcome was the presence of palatal fistula.
Fistula data were available for 167 participants when exploring antibiotic regimen and for 159 when exploring antibiotic agent. There was no evidence to suggest a difference in fistula rate between those receiving antibiotics on induction only versus as an inpatient or up to 7 days postoperatively (χ
= 4.57;
= 0.10). There was no evidence to suggest a difference in fistula rate between those who received co-amoxiclav and those who had an alternative antibiotic (χ
= 0.16;
= 0.69). Postoperative fistulae increased with the extent of the cleft (χ
= 20.39;
< 0.001). When adjusting for cleft type, no evidence of an association between antibiotic regimen and fistulae was found (inpatient antibiotics: OR 1.36; 95% confidence interval, 0.53-3.51; antibiotics up to 7 days postoperatively: OR 0.68; 95% confidence interval, 0.26-1.80).
The choice of antibiotic and dosing regimen does not influence the formation of postoperative fistulae. These results should be supported by interventional trials.
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