Purification and use of crude green glycerol from the transesterification of triglycerides in the formulation of an alcohol gel hand sanitizer.

The aim of this study was to produce an alcohol gel hand sanitizer containing green glycerol. Crude glycerol was purified using chemical and physical treatments. The sanitizer was prepared using 71.100 g of 99.3° GL ethanol, 28.0 g H2O, 0.5 g of Carboxypolymethylene [Carbopol 940® or Carbomer], 5 drops of triethanolamine (pH 5-7), and glycerol (1.5% w/w). The thermal behavior of the ethanol, carbopol, triethanolamine, glycerol, and alcohol gels were evaluated using Thermogravimetry and Differential Thermal Analysis. The apparent viscosity was obtained using a rotary viscometer. The determination of in vitro spreadability was achieved by an adaptation of the Knorst method. The ethanol content was measured by headspace gas chromatography using a flame ionization detector. The thermal behavior of the gels was influenced by the presence of glycerol, which confirms the possible network interactions formed. The relative densities of the samples were between 0.887 and 0.890 g/cm3. No alteration of the pH of the formulation resulted from the incorporation of glycerol. The apparent viscosities of the alcohol gels were greater than 20,000 cP. No alteration in the in vitro spreadability of the gel alcohol (530.6 mm2) resulted from the addition of glycerol. Hand sanitizer was produced using glycerol from a transesterification reaction. It represents an alternative use for the glycerol being produced in biodiesel processes. The product satisfied the requirements of WHO that preconize a formulation containing 1.45% glycerol as an humectant to protect skin against dryness and dermatitis.

Effectiveness of mRNA COVID-19 Monovalent and Bivalent Vaccine Booster Doses Against Omicron Severe Outcomes Among Adults Aged ≥50 Years in Ontario, Canada: A Canadian Immunization Research Network Study.

We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada. Monovalent and bivalent mRNA COVID-19 booster doses provided similar strong initial protection against severe outcomes. Uncertainty remains around waning of protection from these vaccines.

Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults.

INTRODUCTION: We assessed protection from COVID-19 vaccines and/or prior SARS-CoV-2 infection against Omicron-associated severe outcomes during successive sublineage-predominant periods. METHODS: We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, PCR-tested adults aged ≥50 years in Ontario, Canada between January 2, 2022 and June 30, 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection. RESULTS: We included 18,526 cases with Omicron-associated severe outcomes and 90,778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance, but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95%CI 63%-72%; fourth-dose, 6-month: 80%, 95%CI 77%-83%), but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95%CI 48%-67%; 12-month: 49%, 95%CI 41%-56%; fourth-dose, 6-month: 62%, 95%CI 56%-68%, 12-months: 51%, 95%CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance, but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95%CI 36%-75%; fourth-dose, 6-month: 63%, 95%CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95%CI 79%-96%). Prior infection alone did not confer lasting protection. CONCLUSION: Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.

Essential Oil and Plant Extracts as Preservatives and Natural Antioxidants Applied to Meat and Meat Products: A Review.

The meat and meat product industry has evolved according to the needs of the market. Consumers are increasingly seeking quality in food. Thus, the concern regarding the excessive use of additives such as preservatives and antioxidants has driven research towards natural, healthy and safe substitutes. Essential oils and plant extracts have been shown to be a good option for resolving this problem. They are completely natural with biological activity, which mainly includes prevention of oxidation and the proliferation of microorganisms, thus arousing the interest of the industry and consumers. This review will present studies published in the last five years regarding the potential of essential oils and plant extracts to act as preservatives and antioxidants in meat and meat products. The forms of application, innovations in the area, alternatives to the incorporation of essential oils and extracts in meat products, effects caused in food, and limitations of applications will be detailed and discussed.

In vitro and in vivo efficacy of poly(lactic acid) nanofiber packaging containing essential oils from Ocimum basilicum L. and Ocimum gratissimum L. against Aspergillus carbonarius and Aspergillus niger in table grapes.

Apergillus carbonarius and Aspergillus niger are the principal fungi that attack table grapes, and they are responsible for producing and contaminating these fruits with ochratoxin A. Packaging containing essential oils from Ocimum gratissimum L. and Ocimum basilicum L. encapsulated in poly(lactic acid) (PLA) nanofibers were produced, the antifungal and antiocratoxigenic activities against A. carbonarius and A. niger were evaluated in vitro and in vivo, and the effect of these packages on the quality of table grapes was determined. The nanofibers were produced by the Solution Blow Spinning technique and characterized by Scanning Electron Microscopy and Thermogravimetric Analysis. Fungal contamination and ochratoxin A production were significantly controlled by PLA nanofibers containing the essential oils and the physicochemical parameters of the grapes were preserved, preserving the quality and the shelf life of the fruit. Therefore, the active packaging developed herein has potential and may be suitable for application in fruits.

Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial.

BACKGROUND: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir. METHODS: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed. RESULTS: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation. INTERPRETATION: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation. STUDY REGISTRATION: ClinicalTrials. gov, no. NCT04330690.

RSV-associated hospitalization in adults in the USA: A retrospective chart review investigating burden, management strategies, and outcomes.

Background and Aims: The burden of respiratory syncytial virus (RSV) infection in adults is of growing concern. This study was designed to quantify disease burden, treatment approaches, and outcomes associated with RSV infections in adult subpopulations, from prehospitalization to hospital discharge. Methods: A retrospective chart analysis was conducted to collect patient-case data from hospitalized US adults (aged >18 years) with RSV infection during two RSV seasons. Patients were categorized into risk groups: comorbid lung disease, immunocompromised, older adults (aged ≥65 years), and other adults (aged <65 years). Physicians reported diagnosis, treatment choices including respiratory supportive therapy (oxygen and fluid supplementation), and outcome variables using a standardized online case form. Results: The majority (277/379; 73%) of patients presented to the emergency room, with a mean age of 60 years. Once hospitalized, the median length of stay was 6.0 days (3.0-9.0), with disease severity having the greatest impact on duration of stay. No significant between-group differences in rates of patients requiring management in intensive care units were found (comorbid lung disease, 28%; immunocompromised, 36%; older adults, 26%; and other adults, 23%). Overall, respiratory supportive therapy was the most commonly used form of treatment. Antibiotics were administered in over half of all risk groups (comorbid lung disease, 61%; immunocompromised, 59%; older adults, 59%; and other adults, 51%). Patients usually required follow-up visits following discharge, with 10%-16% requiring skilled nursing care and approximately 25% requiring assistance from a social worker. Conclusion: RSV in adult subpopulations, irrespective of age, is a significant burden to healthcare systems.

Influenza: clinical aspects, diagnosis, and treatment.

PURPOSE OF REVIEW: To review the clinico-epidemiological aspects of influenza in the context of the Coronavirus Disease 2019 (COVID-19) pandemic; the recent advances in point-of-care molecular diagnostics and co-detection of influenza and coronaviruses, and the development of new influenza therapeutics. RECENT FINDINGS: Rates of influenza have declined globally since the 2020-2021 season; waning population immunity and uncertainty in vaccine strains could pose a risk in its significant resurgence, especially where pandemic public health interventions start being lifted. As symptoms are similar for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, accurate, rapid diagnostics are needed to guide management. In addition to neuraminidase inhibitors, newer class of antivirals including polymerase inhibitors show promise in treating influenza infections in adults, children, and high-risk individuals. SUMMARY: This review summarizes the most recent data on rapid molecular diagnostics, including point-of-care tests and co-detection of influenza and SARS-CoV-2 viruses. The implications to inform clinical and infection control practices, and detection of antiviral resistance are discussed. The latest clinical trial data on neuraminidase inhibitors and polymerase inhibitors, their efficacy, limitations, and resistance concerns are reviewed.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Combining baloxavir marboxil with standard-of-care neuraminidase inhibitor in patients hospitalised with severe influenza (FLAGSTONE): a randomised, parallel-group, double-blind, placebo-controlled, superiority trial.

BACKGROUND: Neuraminidase inhibitors (NAIs) are considered the standard of care for hospitalised patients with influenza. We aimed to test whether combining the cap-dependent endonuclease inhibitor baloxavir marboxil (hereafter baloxavir) with standard-of-care NAIs would result in improved clinical outcomes compared with NAI monotherapy in hospitalised patients with severe influenza. METHODS: We did a randomised, parallel-group, double-blind, placebo-controlled, superiority trial. Patients aged 12 years or older who were hospitalised with laboratory-confirmed influenza (by RT-PCR or a rapid test) and had a National Early Warning Score 2 (NEWS2) of 4 or greater were included. Recruitment took place in 124 centres across 25 countries. Using a permuted-block method and an interactive response system, patients were randomly assigned (2:1) to receive either baloxavir plus NAIs (hereafter the baloxavir group) or placebo plus NAIs (hereafter the control group). Participants, investigators, and those assessing outcomes were masked to group assignment. Baloxavir was administered orally on day 1 and day 4 (40 mg for bodyweight <80 kg, or 80 mg for ≥80 kg), and on day 7 if no clinical improvement had occurred by day 5. The NAIs included in this study were oseltamivir, zanamivir, and peramivir, which were selected and administered according to local standard practice. The primary endpoint was time to clinical improvement, defined as time to a NEWS2 of 2 or lower for 24 h or hospital discharge, whichever came first, based on daily assessments over the study duration of 35 days. Secondary endpoints included safety analyses. The modified intention-to-treat infected (mITTI) population (ie, all patients who were randomly assigned to treatment, received a dose of study drug, and were RT-PCR-positive for influenza at any timepoint according to the treatment assigned at randomisation) was used in all efficacy analyses. The safety population (ie, all patients who received at least one dose of study treatment, according to the treatment received) was used in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03684044. FINDINGS: Overall, 366 patients were enrolled between Jan 8, 2019, and March 16, 2020, of whom 241 were assigned to the baloxavir group and 125 to the control group. The mITTI population comprised 322 patients, 208 in the baloxivir group and 114 in the control group. In total, 280 (87%) of these patients had influenza A infections. Median time to clinical improvement was 97·5 h (95% CI 75·9 to 117·2) in the baloxavir group and 100·2 h (75·9 to 144·4) in the control group (median difference -2·7 h [95% CI -53·4 to 25·9], p=0·467). Baloxavir plus NAI was well tolerated, and no new safety signals were observed; serious adverse events occurred in 29 (12%) of 239 patients in the baloxavir group versus 19 (15%) of 124 patients in the control group, of which one was considered related to treatment (orthostatic hypotension in a patient in the control group). Overall, four deaths (2%) occurred in the baloxavir group and seven (6%) in the control group; none were considered related to treatment. INTERPRETATION: Combining baloxavir with NAIs did not result in superior clinical outcomes compared with NAIs alone. The combination of baloxavir plus NAI was well tolerated. The findings suggest that combination antivirals would not be routinely indicated in clinical practice for hospitalised patients with severe influenza. FUNDING: F Hoffmann-La Roche and the Biomedical Advanced Research and Development Authority.

Decline of Influenza and Respiratory Viruses With COVID-19 Public Health Measures: Alberta, Canada.

OBJECTIVE: To determine the incidence of influenza and noninfluenza respiratory viruses (NIRVs) pre-/post-implementation of public health measures aimed to decrease coronavirus disease 2019 (COVID-19) transmission using population-based surveillance data. We hypothesized that such measures could reduce the burden of respiratory viruses (RVs) transmitting via the same routes. PATIENTS AND METHODS: An interrupted time-series analysis of RV surveillance data in Alberta, Canada, from May 2017 to July 2020 was conducted. The burden of influenza and NIRVs before and after intervention initiation at week 11 was compared. The analysis was adjusted for seasonality, overdispersion, and autocorrelation. RESULTS: During the study period, an average of 708 and 4056 weekly respiratory multiplex molecular panels were conducted pre-/post-intervention, respectively. We found significant reductions in test positivity rates in the postintervention period for influenza (-94.3%; 95% CI, -93.8 to 97.4%; P<.001) and all NIRVs (-76.5%; 95% CI, -77.3 to -75.8%; P<.001) in the crude model, and -86.2% (95% CI, -91.5 to -77.4%: P<.001) and -75% (95% CI, -79.7 to -69.3%; P<.001), respectively, in the adjusted models. Subanalyses for individual viruses showed significant decreases in respiratory syncytial virus, human metapneumovirus, enterovirus/rhinovirus, and parainfluenza. For non-severe acute respiratory coronavirus 2 human coronaviruses, the decline was not statistically significant after adjustment (-22.3%; 95% CI, -49.3 to +19%, P=.246). CONCLUSION: The implementation of COVID-19 public health measures likely resulted in reduced transmission of common RVs. Although drastic lockdowns are unlikely to be required given widespread COVID-19 vaccination, targeted implementation of such measures can lower RV disease burden. Studies to evaluate relative contributions of individual interventions are warranted.

Pre-Vaccine Positivity of SARS-CoV-2 Antibodies in Alberta, Canada during the First Two Waves of the COVID-19 Pandemic.

We systematically evaluated SARS-CoV-2 IgG positivity in a provincial cohort to understand the local epidemiology of COVID-19 and support evidence-based public health decisions. Residual blood samples were collected for serology testing over 5-day periods monthly from June 2020 to January 2021 from six clinical laboratories across the province of Alberta, Canada. A total of 93,993 individual patient samples were tested with a SARS-CoV-2 nucleocapsid antibody assay with positives confirmed using a spike antibody assay. Population-adjusted SARS-CoV-2 IgG seropositivity was 0.92% (95% confidence interval [CI]: 0.91 to 0.93%) shortly after the first COVID-19 wave in June 2020, increasing to 4.63% (95% CI: 4.61 to 4.65%) amid the second wave in January 2021. There was no significant difference in seropositivity between males and females (1.39% versus 1.27%; P = 0.11). Ages with highest seropositivity were 0 to 9 years (2.71%, 95% CI: 1.64 to 3.78%) followed by 20 to 29 years (1.58%, 95% CI: 1.12 to 2.04%), with the lowest rates seen in those aged 70 to 79 (0.79%, 95% CI: 0.65 to 0.93%) and >80 (0.78%, 95% CI: 0.60 to 0.97%). Compared to the seronegative group, seropositive patients inhabited geographic areas with lower household income ($87,500 versus $97,500; P < 0.001), larger household sizes, and higher proportions of people with education levels of secondary school or lower, as well as immigrants and visible minority groups (all P < 0.05). A total of 53.7% of seropositive individuals were potentially undetected cases with no prior positive COVID-19 nucleic acid test (NAAT). Antibodies were detectable in some patients up to 9 months post positive NAAT result. This seroprevalence study will continue to inform public health decisions by identifying at-risk demographics and geographical areas. IMPORTANCE Using SARS-CoV-2 serology testing, we assessed the proportion of people in Alberta, Canada (population 4.4 million) positive for COVID-19 antibodies, indicating previous infection, during the first two waves of the COVID-19 pandemic (prior to vaccination programs). Linking these results with sociodemographic population data provides valuable information as to which groups of the population are more likely to have been infected with the SARS-CoV-2 virus to help facilitate public health decision-making and interventions. We also compared seropositivity data with previous COVID-19 molecular testing results. Absence of antibody and molecular testing were highly correlated (95% negative concordance). Positive antibody correlation with a previous positive molecular test was low, suggesting the possibility of mild/asymptomatic infection or other reasons leading individuals from seeking medical attention. Our data highlight that the true estimate of population prevalence of COVID-19 is likely best informed by combining data from both serology and molecular testing.

Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres.

BACKGROUND: Data on the outcomes of noninfluenza respiratory virus (NIRV) infections among hospitalized adults are lacking. We aimed to study the burden, severity and outcomes of NIRV infections in this population. METHODS: We analyzed pooled patient data from 2 hospital-based respiratory virus surveillance cohorts in 2 regions of Canada during 3 consecutive seasons (2015/16, 2016/17, 2017/18; n = 2119). We included patients aged ≥ 18 years who developed influenza-like illness or pneumonia and were hospitalized for management. We included patients confirmed positive for ≥ 1 virus by multiplex polymerase chain reaction assays (respiratory syncytial virus [RSV], human rhinovirus/enterovirus (hRV), human coronavirus (hCoV), metapneumovirus, parainfluenza virus, adenovirus, influenza viruses). We compared patient characteristics, clinical severity conventional outcomes (e.g., hospital length-of stay, 30-day mortality) and ordinal outcomes (5 levels: discharged, receiving convalescent care, acute ward or intensive care unit [ICU] care and death) for patients with NIRV infections and those with influenza. RESULTS: Among 2119 adults who were admitted to hospital, 1156 patients (54.6%) had NIRV infections (hRV 14.9%, RSV 12.9%, hCoV 8.2%) and 963 patients (45.4%) had influenza (n = 963). Patients with NIRVs were younger (mean 66.4 [standard deviation 20.4] yr), and more commonly had immunocompromising conditions (30.3%) and delay in diagnosis (median 4.0 [interquartile range (IQR) 2.0-7.0] days). Overall, 14.6% (12.4%-19.5%) of NIRV infections were acquired in hospital. Admission to ICU (18.2%, median 6.0 [IQR 3.0-13.0] d), hospital length-of-stay (median 5.0 [IQR 2.0-10.0] d) and 30-day mortality (8.4%; RSV 9.5%, hRV 6.6%, hCoV 9.2%) and the ordinal outcomes were similar for patients with NIRV infection and those with influenza. Age > 60 years, immunocompromised state and hospital-acquired viral infection were associated with worse outcomes. The estimated median cost per acute care admission was $6000 (IQR $2000-$16 000). INTERPRETATION: The burden of NIRV infection is substantial in adults admitted to hospital and associated outcomes may be as severe as for influenza, suggesting a need to prioritize therapeutics and vaccines for at-risk people.

Outcomes among critically ill adults with influenza infection.

Background: Influenza infection is a major cause of mortality in critical care units. Methods: ata on critically ill adult patients with influenza infection from 2014 to 2019 were retrospectively collected, including mortality and critical care resource utilization. Independent predictors of mortality were identified using Cox regression. Results: ne hundred thirty patients with confirmed influenza infection had a mean age of 56 (SD 16) years; 72 (55%) were male. Mean Acute Physiology and Chronic Health Evaluation (APACHE II) score was 22 (SD 9). One hundred eight (83%) patients had influenza A (46% H1N1pdm09, 33% H3N2); 21 (16%) had influenza B. Fifty-five (42%) patients had bacterial co-infection. Only 5 (4%) had fungal co-infection. One hundred eight (83%) patients required mechanical ventilation; 94 (72%), vasopressor support; 26 (20%), continuous renal replacement therapy (CRRT); and 11 (9%), extracorporeal membrane oxygenation. One hundred twenty one (93%) patients received antiviral therapy (median 5 d). Thirty-day mortality was 23%. Patients who received antiviral treatment were more likely to survive with an adjusted hazard ratio (aHR) of 0.15 (95% CI 0.04 to 0.51, p = 0.003). Other independent predictors of mortality were the need for CRRT (aHR 2.48, 95% CI 1.14 to 5.43, p = 0.023), higher APACHE II score (aHR 1.08, 95% CI 1.02 to 1.14, p = 0.011), and influenza A (aHR 7.10, 95% CI 1.37 to 36.8, p = 0.020) compared with influenza B infection. Conclusions: mong critically ill influenza patients, antiviral therapy was independently associated with survival. CRRT, higher severity of illness, and influenza A infection were associated with mortality.

Historique: L'infection par l'influenza est une cause majeure de décès en soins intensifs. Méthodologie: Les chercheurs ont procédé à la collecte rétrospective des données sur des patients adultes gravement malades à cause d'une infection par l'influenza entre 2014 et 2019, y compris la mortalité et l'utilisation des ressources en soins intensifs. Ils ont établi les prédicteurs indépendants de mortalité au moyen de la régression de Cox. Résultats: Les 130 patients atteints d'une infection confirmée par l'influenza avaient un âge moyen de 56 ans (±16), et 72 (55 %) étaient de sexe masculin. Le score APACHE II (acronyme anglais d'évaluation de la physiologie aiguë et de la santé chronique) s'élevait à 22 (±9). Au total, 108 patients (83 %) étaient atteints de la grippe de type A (46 % H1N1pdm09, 33 % H3N2) et 21 (16 %), de la grippe de type B. De plus, 55 patients (42 %) étaient atteints d'une co-infection bactérienne, et seulement cinq (4 %), d'une co-infection fongique. Par ailleurs, 108 patients (83 %) ont eu besoin de ventilation mécanique, 94 (72 %), d'un soutien vasopresseur; 26 (20 %), d'une thérapie continue de remplacement rénal (TCRR) et 11 (9 %), d'une oxygénation extracorporelle. Au total, 121 patients (93 %) ont reçu une antivirothérapie (pendant une période médiane de cinq jours). La mortalité au bout de 30 jours s'élevait à 23 %. Les patients qui avaient reçu une antivirothérapie étaient plus susceptibles de survivre, selon un risque relatif ajusté (RRa) de 0,15 (IC à 95 % : 0,04 à 0,51, p = 0,003). Il y avait d'autres prédicteurs indépendants de mortalité : la nécessité de recourir à une TCRR (RRa 2,48, IC à 95 % : 1,14 à 5,43, p = 0,023), un score APACHE II élevé (RRa 1,08, IC à 95 % : 1,02 à 1,14, p = 0,011) et l'infection par l'influenza de type A (RRa 7,10, IC à 95 % : 1,37 à 36,8, p = 0,020) plutôt que par l'influenza de type B. Conclusions: Chez les patients gravement malades atteints de l'influenza, l'antivirothérapie était associée de manière indépendante à la survie. La TCRR, la plus grande gravité de la maladie et l'infection par l'influenza de type A étaient liées à la mortalité.

Development of an Ordinal Scale Treatment Endpoint for Adults Hospitalized With Influenza.

BACKGROUND: An obstacle in influenza therapeutics development is the lack of clinical endpoints, especially in hospitalized patients. A single time-point binary outcome measure is limited by patients' diverse clinical trajectories and low event rates. METHODS: A 6-point ordinal scale with ascending clinical status severity (scoring: discharged; subacute care; acute care without/with respiratory failure; intensive care unit [ICU]; death) was proposed to study outcomes of adults hospitalized with influenza. Individual patient data from 2 active surveillance cohorts' datasets (2015/2016-2017/2018; Edmonton, Hong Kong) was used for evaluation. The impact of neuraminidase inhibitor (NAI) treatment on longitudinal ordinal outcome changes over 30 days was analyzed using mixed-effects ordinal logistic regression and group-based trajectory models. RESULTS: Patient (n = 1226) baseline characteristics included age (mean 68.0 years), virus-type (A 78.1%, B 21.9%), respiratory failure (57.2%), ICU admittance (14.4%), and NAI treatment within 5 days of illness (69.2%). Outcomes at 30 days included discharged (75.2%), subacute care (13.7%), acute care (4.5%), and death (6.6%). Two main clinical trajectories were identified, predictive by baseline scoring (mean ±â€…SD, 4.3 ±â€…0.6 vs 3.5 ±â€…0.6, P < .001). Improved outcomes with NAI treatment within 5 days were indicated by significantly lower clinical status scores over time (unadjusted odds ratio [OR], 0.53; 95% confidence interval [CI], .41-.69; P < .001; adjusted OR, 0.62; 95% CI, .50-.77; P < .001, for baseline score, age, and within-patient correlations). In subanalysis, influenza vaccination was also associated with lower scores (adjusted OR, 0.67; 95% CI, .50-.90; P = .007). Analyses of binary endpoints showed insignificant results. CONCLUSIONS: The ordinal outcome scale is a potentially useful clinical endpoint for influenza therapeutic trials, which could account for the diverse clinical trajectories of hospitalized patients, warranting further development.

Burden of influenza B virus infection and considerations for clinical management.

Influenza B viruses cause significant morbidity and mortality, particularly in children, but the awareness of their impact is often less than influenza A viruses partly due to their lack of pandemic potential. Here, we summarise the biology, epidemiology and disease burden of influenza B, and review existing data on available antivirals for its management. There has long been uncertainty surrounding the clinical efficacy of neuraminidase inhibitors (NAIs) for influenza B treatment. In this article, we bring together the existing data on NAIs and discuss these alongside recent large randomised controlled trial data for the new polymerase inhibitor baloxavir in high-risk influenza B patients. Finally, we offer considerations for the clinical management of influenza B, with a focus on children and high-risk patients where disease burden is highest.

Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts.

BACKGROUND: Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed. RESULTS: A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out. CONCLUSIONS: Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.).