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Baloxavir vs Oseltamivir: reduced Utilization and fees in Influenza | A00-280 Free PDF and exam dumps

summary

goals: To assess no matter if baloxavir use is linked to decrease fitness care useful resource utilization (HCRU) and fees for secondary influenza complications post treatment compared with oseltamivir.

study Design: Retrospective cohort study.

methods: patients filling a prescription for baloxavir or oseltamivir inside forty eight hours following an influenza-linked outpatient seek advice from have been recognized within the 2018-2019 influenza season from the united states Truven MarketScan research Databases and propensity matched 1:2 (baloxavir:oseltamivir). consequences have been assessed 15 and 30 days after antiviral medicine and protected all-cause, all respiratory-related, and select respiratory-related (influenza, asthma, persistent obstructive pulmonary disorder, or an infection) HCRU and charges.

outcomes: The analyze included 5080 baloxavir-handled and 10,one hundred sixty matched oseltamivir-handled sufferers. All-cause emergency branch (ED) visits and inpatient hospitalizations had been lessen in baloxavir-treated patients, with a statistically significant difference in the percentage hospitalized at 30 days (0.three% vs 0.5%; P = .04). ED visits for all or select respiratory-connected conditions have been drastically reduced with baloxavir (P < .01 for all comparisons). mean per-affected person cost discounts at day 30 for all-cause, all respiratory-related, and choose respiratory-related situations have been $seventy nine, $50, and $51, respectively, regardless of a little better prescription expenses for baloxavir. In high-risk patients (baloxavir: n = 1958; oseltamivir: n = 3949), the incidence of ED visits was significantly lower for all respiratory-connected and choose respiratory-related circumstances (P < .01); charge mark downs with baloxavir within the excessive-chance cohort have been radically more advantageous than within the ordinary cohort.

Conclusions: medicine of sufferers with influenza with single-dose baloxavir changed into generally associated with reduce HCRU and charges publish remedy compared with oseltamivir, exceptionally in excessive-possibility sufferers.

Am J Manag Care. 2022;28(3):In Press

_____

Takeaway points

We used assurance claims facts to examine health care useful resource utilization (HCRU) and costs between baloxavir- and oseltamivir-handled patients with influenza 15 and 30 days put up outpatient medicine.

  • After adjusting for differences in the handled businesses, baloxavir, in comparison with oseltamivir, became linked to lower HCRU and charges from secondary complications in sufferers with influenza.
  • The incidence of hospitalization, emergency department visits, and outpatient visits for any trigger become commonly lower following medication with baloxavir compared with oseltamivir, primarily among the many high-risk subgroup of patients with influenza.
  • Per-affected person health care charges in most classes were decrease with baloxavir than with oseltamivir, exceptionally among high-possibility sufferers.
  • _____

    Influenza is a contagious respiratory affliction of various severity, estimated to affect 3% to eleven% of individuals within the u.s. every year1 and leading to a substantial burden to the fitness care equipment. The CDC estimated that influenza has resulted in 9.3 million to 45 million symptomatic illnesses, 4.three million to 21 million scientific visits, 140,000 to 810,000 hospitalizations, and 12,000 to 61,000 deaths yearly considering that 2010, with preliminary estimates of 490,000 hospitalizations and 34,000 deaths for the 2018-2019 season.2 In 2015, the estimated regular annual economic burden of influenza to the fitness care gadget changed into $11.2 billion, with $3.2 billion and $8.0 billion attributed to direct and oblique costs, respectively.three

    although most people with influenza Excellerate within 2 weeks, the infection can trigger issues that latitude from reasonable (sinus and ear infections) to serious (pneumonia, myocarditis, encephalitis, myositis, and multiorgan failure), and the an infection can worsen continual scientific conditions corresponding to asthma, persistent obstructive pulmonary disorder (COPD), and heart disease.4 Airway irritation triggered by the influenza virus can harm tissue and compromise pulmonary feature, resulting in lower respiratory infections and different respiratory situations.5 Populations at increased chance for severe influenza-linked problems encompass adults 65 years or older, residents of lengthy-term care facilities, men and women with definite persistent scientific situations, and children younger than 2 years, among others.6,7

    Antiviral remedy is a advantageous adjunct to influenza immunization for managing indicators and cutting back the possibility of secondary complications, together with bacterial infections.eight professional guidelines suggest initiation of antiviral therapy inside 48 hours for patients with more severe disorder or who are at larger risk for complications.9,10 Early treatment with neuraminidase inhibitors (eg, oseltamivir), the latest standard of care, relieves influenza indicators, reduces the chance of issues, lowers health care resource utilization (HCRU), and decreases mortality in hospitalized patients.11-sixteen

    Baloxavir marboxil (“baloxavir”) is an oral single-dose treatment for influenza that became FDA permitted in October 2018; it has a mechanism of motion diverse from that of neuraminidase inhibitors. Baloxavir is a cap-based endonuclease inhibitor that interferes with viral RNA transcription and blocks viral replication.17 In a part three medical analyze in outpatients with influenza-like illness, baloxavir vastly shortened the time to alleviation of influenza indicators compared with placebo (fifty three.7 hours vs eighty.2 hours; P < .0001) and turned into as constructive as twice-daily oseltamivir given for 5 days.18 in a similar way, in a 2d section 3 analyze in outpatients at high chance for influenza complications (mainly sufferers with asthma, persistent lung ailment, and endocrine issues, including diabetes), baloxavir medication turned into linked to a enormously shorter time to improvement of influenza indicators in comparison with placebo (73.2 hours vs 102.three hours; P < .0001) and a numerically shorter time in comparison with oseltamivir (81.0 hours; P = .8347).19 In high-possibility sufferers, baloxavir medicine resulted in vastly fewer issues in comparison with placebo treatment (2.eight% vs 10.4%; P < .0001), with discount of sinusitis and bronchitis being the main drivers of the difference.19

    however scientific trials were not powered to accurately check charges of influenza issues put up baloxavir compared with put up oseltamivir, higher records sets may be more suitable ideal to determine this understudied element of therapeutic effectiveness. in this look at they leveraged the significant inhabitants afforded by using an aggregated coverage claims database to extra elucidate the have an effect on of baloxavir on influenza-related complications. They compared the consequences of baloxavir and oseltamivir on HCRU and charges, together with those related to respiratory conditions, in sufferers with influenza over the 2018-2019 season.

    strategies

    information source

    information were extracted from the MarketScan industrial Claims and Encounters Database and the MarketScan Medicare Supplemental and Coordination of merits Database (IBM Watson fitness). The databases include suggestions on health insurance claims of employees, dependents, and retirees insured by company-sponsored business and Medicare insurance. The claims catch inpatient and outpatient care, use of facilities and capabilities, prescription fills, and price assistance from about 350 payers. The study used deidentified information and become exempt from institutional evaluate board review. The analysis become compliant with the medical health insurance Portability and Accountability Act.

    look at Design

    This retrospective cohort analyze in comparison HCRU and price outcomes in patients who filled a prescription for baloxavir or oseltamivir between November 2018 and can 2019 (eAppendix figure [eAppendix available at ajmc.com]). sufferers 12 years and older with a prescription for baloxavir or oseltamivir had been recognized and had been required to have continuous enrollment facts for as a minimum 6 months preceding and 1 month following the index date of antiviral prescription fill. The prescription had to be crammed within 2 days after an influenza-linked outpatient discuss with. For any affected person, simplest the primary illustration of an influenza-related outpatient visit adopted by way of a imperative antiviral prescription within 2 days become protected in the look at. moreover, patients could not have obtained the comparator antiviral within 1 month of the index prescription and could not have had any prophylactic fills (≥ 10-day supply) for both antiviral agent.

    To modify for potential confounders, baloxavir-handled patients were propensity score matched at a 1:2 ratio to oseltamivir-handled patients the use of “nearest neighbor” matching (caliper = 0.1) for the following demographic and clinical variables: age, intercourse, geographic region, type of health plan, month of index experience, preindex Charlson Comorbidity Index (CCI) ranking, preindex HCRU (emergency branch [ED] visit or hospitalization), and days between outpatient seek advice from and prescription fill.

    A subgroup of sufferers at high chance of developing issues from influenza (excessive-chance subgroup) was described in response to age 65 years or older or presence of an inpatient or outpatient declare for any of here situations in the 6-month preindex duration: obesity; pregnancy; neurological, chronic lung, cardiovascular, hematologic, endocrine, kidney, liver, or metabolic ailment; or immune-related sickness. Propensity ranking matching become no longer repeated for this selected subgroup.

    consequences

    Cumulative outcomes have been assessed at 15 and 30 days after index prescription fill (excluding date of prescription). These blanketed all-cause and respiratory-linked HCRU and costs. the two styles of respiratory-related HCRU have been (1) HCRU for all respiratory-linked situations, which included a extensive latitude of conditions (international Classification of ailments, Tenth Revision [ICD-10] codes J00-J99) and (2) HCRU that concentrated on choose respiratory-linked conditions that included infection (J09-J16, J18, J20-21, J67), bronchial asthma (J45), and COPD (J40-J44) (eAppendix table 1). HCRU and charges have been assessed via fitness care environment (inpatient, outpatient, ED, pharmacy). All-trigger pharmacy encounters were recorded because the complete variety of prescription fills and charges in the designated length. fees had been according to genuine 2018 and 2019 costs. A sensitivity evaluation become performed to verify HCRU and fees starting from the day of the outpatient influenza analysis. This accounted for the can charge of the antiviral in addition to for the variable time frame of 0 to forty eight hours after the outpatient talk over with all through which any HCRU could have happened.

    Statistical analysis

    The propensity-matched cohorts have been in comparison with the χ2 verify and Fisher’s genuine verify (for frequency ≤ 5) for categorical measures and the Wilcoxon signed-rank examine for counts and fees. Analyses were carried out the use of SAS edition 9.four utility (SAS Institute Inc).

    outcomes

    analyze population

    Of 647,152 patients who filled a prescription for baloxavir or oseltamivir all through the 2018-2019 influenza season, 200,837 patients (baloxavir: n = 5080; oseltamivir: n = 195,757) fulfilled the inclusion criteria (figure 1). The 5080 baloxavir-handled sufferers have been propensity matched with 10,a hundred and sixty oseltamivir-treated patients. Following matching, there have been no statistically colossal adjustments between cohort baseline qualities (table 1).

    Most sufferers (fifty six%) were aged between 18 and 49 years, 1% had been 65 years or older, and fifty five% have been feminine. Most patients lived in the southern united states (75%). only 15% of sufferers had a comorbidity (CCI score ≥ 1), and 10% had been hospitalized or visited the ED within the preceding 6 months.

    HCRU

    In commonplace, the cumulative incidence of all-cause ED visits and hospitalization became lessen for baloxavir than for oseltamivir, regardless of a bit of better all-cause prescription fills in both the 15- and 30-day comply with-up durations and outpatient visits within the 30-day comply with-up length (desk 2). The cumulative incidence of all-trigger, all respiratory-connected, and select respiratory-connected hospitalization in baloxavir-handled sufferers was lower than that in oseltamivir-handled patients over both periods. The cumulative incidence of all respiratory-linked and choose respiratory-linked 15- and 30-day ED visits in the baloxavir-treated community was below half that in the oseltamivir community (P < .01 for all comparisons). however the incidence of all respiratory-linked outpatient visits became similar in both groups, opt for respiratory-related outpatient visits have been significantly lower over each the 15- and 30-day result durations (P < .01 for both comparisons).

    prices

    consistent with HCRU, charges had been generally decrease for baloxavir-handled patients. normal imply all-trigger per-affected person costs had been lower with baloxavir medication than with oseltamivir medicine by using $seventy four (23% discount) through day 15 and $79 (13% discount) through day 30, regardless of just a little higher all-trigger prescription fees with baloxavir at day 30 (determine 2). mean 30-day all-cause hospitalization costs per affected person were tremendously lower for baloxavir-handled sufferers ($47 vs $119; P = .03). suggest per-affected person charge savings (% reduction) with baloxavir for all respiratory-related and choose respiratory-related expenses were $forty two (44%) and $forty three (64%), respectively, at day 15, and $50 (forty one%) and $51 (66%), respectively, at day 30. expenses for ED visits for all respiratory-connected and select respiratory-connected circumstances and for opt for respiratory-related outpatient visits were enormously lower at both days 15 and 30 within the baloxavir cohort (P < .01 for all comparisons).

    high-chance Subgroup analysis

    HCRU and costs were additionally analyzed for the subgroup of patients regarded to be at excessive chance for influenza issues, which covered 1958 sufferers (38%) in the baloxavir cohort and 3949 patients (39%) in the oseltamivir cohort (eAppendix desk 2). In this subgroup, the main ICD-10 code situations reported within the baloxavir and oseltamivir cohorts had been neurological sickness (38% vs 35%; P = .025), amino acid–linked metabolic illnesses (35% vs 34%; P = .379), endocrine illnesses (33% vs 31%; P = .051), and persistent lung disorder (19% vs 19%; P = .711).

    Propensity score matching become no longer repeated in the excessive-chance subgroup; however, no colossal alterations in baseline features have been followed between the 2 cohorts (eAppendix desk 3). Most sufferers had been aged between 18 and 49 years (53%), fifty nine% were female, and 3% have been 65 years or older; 38% had a CCI rating of as a minimum 1 and 17% had been hospitalized or had visited the ED within the preceding 6 months.

    In established, all-cause, all respiratory-connected, and select respiratory-related HCRU in all classes was larger within the excessive-possibility subgroup than in the total cohort. The 15- and 30-day cumulative incidence of ED visits for baloxavir-treated patients became less than half that of oseltamivir-treated patients for all respiratory-connected and choose respiratory-related situations (P < .01 for all comparisons) (eAppendix desk 4).

    remedy with baloxavir changed into associated with enhanced can charge reductions at both 15 and 30 days in the high-chance group than within the typical neighborhood. within the excessive-possibility neighborhood, suggest per-person cost rate reductions (percent discount) with baloxavir at days 15 and 30 were $177 (29%) and $204 (18%), $sixty five (42%) and $eighty two (39%), and $67 (67%) and $90 (73%) for all-trigger, all respiratory-linked, and select respiratory-linked circumstances, respectively (determine 3). charge discounts with baloxavir medicine gathered in all utilization classes, aside from 30-day prescription fill charges.

    Sensitivity evaluation

    The sensitivity analysis by which HCRU and charges had been decided from the day of the outpatient influenza analysis (as adverse to the day following prescription antiviral fill) confirmed a decrease 15- and 30-day cumulative incidence of all-cause, all respiratory-connected, and select respiratory-related ED visits and hospitalizations. effects had been statistically big for all comparisons, apart from 15-day all-cause and all respiratory-related hospitalizations and 30-day all respiratory-related hospitalizations (eAppendix desk 5). At each 15 and 30 days, baloxavir remedy changed into linked to monstrous per-patient can charge rate reductions for all circumstances, regardless of higher prescription fees (eAppendix table 6). universal cost savings per affected person with baloxavir had been increased 2- to 3-fold within the sensitivity evaluation in comparison with the bottom-case analysis.

    dialogue

    We compared influenza-linked issues, HCRU, and charges in more than 15,000 commercially insured patients with acute influenza handled with baloxavir or oseltamivir. The wholesale acquisition can charge for baloxavir marboxil is $a hundred and fifty, whereas that for a established oseltamivir routine degrees from $19 to $102 for 10 tablets. This examine illustrates other essential features of HCRU and health care costs that should be regarded, despite larger prescription charges, when managing influenza affliction.

    To make sure that the two cohorts in this examine had been related, they propensity rating matched sufferers in accordance with variables that could impact the consequences. They did not chiefly regulate for respiratory comorbidities in the propensity scoring mannequin because they had been already included within the CCI rating, and they additionally did not want to overadjust, which would doubtlessly bias outcomes; despite the fact, submit matching, there were no statistically significant differences between cohorts in regard to continual lung ailment. consequences have been assessed following prescription fill to be sure that they may be influenced temporally most effective by means of the antiviral selected.

    effects confirmed that, compared with oseltamivir-handled patients, people who received baloxavir had reduce HCRU and fees over the primary 15 days and up to 30 days after prescription fill for most HCRU classes. variations in HCRU and fees between baloxavir and oseltamivir were amplified in the high-possibility subgroup of sufferers with influenza. In their sensitivity analysis in which they decided consequences from the day of the influenza-connected outpatient analysis, they found identical effects despite greater prescription prices.

    Our evaluation gives insight into typical true-world HCRU and costs for influenza patients following antiviral remedy. Their assessment of extra particular respiratory-connected results and the use of a shorter 15-day time horizon show the have an impact on of antiviral alternative on conditions that can also greater probably be related to the influenza episode. as an instance, hospitalizations for conditions equivalent to asthma or COPD inside 15 days may also more confidently be linked to the influenza episode. Importantly, they accompanied reduce HCRU and charges in baloxavir-handled patients despite time horizon or results assessed.

    this is the primary real-world look at that compared HCRU and costs linked to baloxavir and oseltamivir. old precise-world studies in patients with influenza have compared HCRU and charges linked to oseltamivir vs no treatment. In an identical look at the use of MarketScan claims facts from the 2000 to 2005 influenza seasons for sufferers of any age, oseltamivir reduced the chance of 14-day all-cause hospitalization and respiratory-connected hospitalization by means of 38% and fifty seven%, respectively, in comparison without a treatment.20 They discovered that baloxavir decreased 15-day all-trigger and respiratory-related hospitalizations by means of 38% (calculated as 1 – [0.22% / 0.34%]) and 36% (calculated as 1 – [0.14% / 0.22%]), respectively, in comparison with oseltamivir, youngsters the ameliorations had been no longer tremendous. The all-trigger 30-day per-patient charge of $968 linked to oseltamivir remedy in their sensitivity analysis (calculated from the day of outpatient influenza talk over with) changed into corresponding to the 2019 US$–adjusted21 $820 can charge reported in the old look at,20 providing validity to their effects. although, in that examine, all-trigger fitness care charges were an identical among oseltamivir-treated and untreated sufferers, whereas they identified decrease costs with baloxavir (suggest costs, $877 [9.4% reduction]). one more evaluation the use of PharMetrics data identified 30-day all-cause hospitalization prices of 0.9% in oseltamivir-handled adult sufferers with influenza in comparison with 1.2% in untreated patients.22 The 2019 US$–adjusted charges for complete health care and hospitalization have been approximately $740 and $one hundred sixty in oseltamivir-treated sufferers, respectively, and approximately $760 and $200 in untreated sufferers, respectively. They found the same statistically significant discount within the 30-day all-cause hospitalization cost in their analysis (baloxavir, 0.3%; oseltamivir, 0.5%) and a reduction in all-cause complete and hospitalization-linked costs with baloxavir (figure 2). A greater contemporary claims analysis of greater than 1.5 million influenza cases between 2006 and 2010 discovered that antivirals (> 90% oseltamivir) reduced the hazards of 30-day hospitalization and ED use by 29% and 24%, respectively, compared and not using a antiviral medicine.14 In their look at, chance of 30-day hospitalization and ED use for baloxavir-treated patients turned into lower by forty five% (1 – [0.30% / 0.54%]) and sixteen% (1 – [2.19% / 2.60%]), respectively, in comparison with oseltamivir.

    The need to in the reduction of influenza-linked complications is primarily pressing in vulnerable populations at elevated possibility of deleterious results. in the existing study, all-cause, all respiratory-related, and select respiratory-related HCRU in all categories became improved in the excessive-possibility community than within the normal group for both medication cohorts. youngsters, variations between baloxavir and oseltamivir in decreased HCRU and fees were more suggested in excessive-possibility patients. All-trigger per-patient can charge savings with baloxavir were better in the excessive-possibility group than in the overall inhabitants at both day 15 ($177 vs $seventy four) and day 30 ($204 vs $79); for all respiratory-connected and choose respiratory-linked situations, per-patient can charge reductions with baloxavir ranged between $65 and $ninety within the high-risk neighborhood and between $forty two and $fifty one in the common patient inhabitants.

    in addition to the direct clinical and economic advantages to sufferers, providers, and payers from discount rates in influenza complications, HCRU, and fees for individual sufferers, the basic fitness care equipment additionally reaps benefits. In durations of restricted fitness care resources, such as throughout the COVID-19 global pandemic, a discount in influenza-connected ED visits and hospitalizations would raise the capacity to provide health care to other sufferers and could mitigate skill-stylish deaths. Atkins et al calculated that 8000 to 13,000 hospitalizations, representing four% to five% of total pandemic-related hospitalizations, were averted all the way through the 2009-2010 influenza pandemic on account of oseltamivir and zanamivir medication alone.23

    limitations

    This examine has barriers. First, however propensity score matching become used to steadiness populations in this retrospective look at, some variables comparable to earnings, influenza vaccination fame, and abilities ameliorations in company prescribing practices for baloxavir vs oseltamivir could not be measured reliably. youngsters, they haven't any purpose to suspect enormous transformations in profits, vaccination status, or other maybe unmeasured predictors of HCRU or costs. 2nd, because patients were selected in keeping with analysis codes in the claims database, the analysis of influenza become no longer always laboratory validated. youngsters, in contrast to some prior to now conducted analyses, they compared 2 active remedy palms. hence, they might expect fewer systematic variations comparable to changes in severity or “true” diagnoses between handled and untreated populations to bias their analysis. Third, the database represents individuals enrolled in industrial fitness plans and some supplemental Medicare plans and might hence not be representative of the total US inhabitants; the population changed into skewed to the southern u.s.. additionally, only 3% of their study population were older than 65 years as a result of their statistics source essentially lined commercially insured sufferers, most of whom were younger than 65 years. The results can also hence now not be generalizable to the population older than sixty five years, in whom the burden of influenza is appreciably larger: 50% to 70% of influenza-connected hospitalizations and 70% to 85% of influenza-linked deaths take place in individuals older than sixty five years.24 Fourth, physicians’ prescribing preferences may additionally latest a confounder in assessing variations between the remedy businesses, however this should still be offset with the aid of matching of the cohorts according to age, area, and baseline comorbidities. finally, because of the rarity of certain effects (eg, hospitalization), the pattern size during this analyze confers low statistical power. youngsters most results numerically appreciated baloxavir treatment, lots of the comparisons have been now not statistically large, particularly among the many greater generic all-trigger consequences.

    CONCLUSIONS

    Claims statistics for the 2018-2019 influenza season confirmed that patients who crammed a prescription for single-dose baloxavir following an outpatient talk over with for influenza had decrease HCRU and fees than patients who stuffed a prescription for oseltamivir. In specific, ED visits and outpatient visits for all respiratory-linked and select respiratory-linked problems had been greatly lower in the baloxavir cohort. charges for baloxavir-treated sufferers had been reduce than for oseltamivir-handled patients across distinct health care settings, regardless of greater prescription fills and charges. The reduction in HCRU and value capabilities with baloxavir compared with oseltamivir was even stronger in high-risk patients. These data suggest that baloxavir is associated with fewer secondary problems and decreased HCRU and costs in comparison with oseltamivir.

    Acknowledgments

    clinical writing and modifying services have been provided through Meher M. Dustoor, PhD, and Esther Tazartes, MS, of world effects community; these services had been funded by using Genentech Inc.

    author Affiliations: Genentech Inc (EN, CW, DC, RdCC), South San Francisco, CA.

    source of Funding: Genentech Inc.

    author Disclosures: Drs Neuberger, Wallick, Chawla, and de Cassia Castro are personnel of and stockholders in Genentech, which markets and distributes items mentioned listed here. Dr Wallick has additionally attended conferences as an employee of Genentech.

    Authorship counsel: thought and design (EN, CW); analysis and interpretation of records (EN, CW, DC, RdCC); drafting of the manuscript (EN, CW, DC); critical revision of the manuscript for critical intellectual content (EN, CW, DC, RdCC); statistical evaluation (EN, CW); provision of sufferers or look at substances (CW); administrative, technical, or logistic support (CW); and supervision (CW, RdCC).

    address Correspondence to: Edward Neuberger, PharmD, MS, MBA, Genentech Inc, 1 DNA way, South San Francisco, CA 94080. e-mail: edward.neuberger@gmail.com.

    REFERENCES

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    2. disease burden of influenza. CDC. 2020. Accessed June 15, 2020. https://www.cdc.gov/flu/about/burden/index.html

    three. Putri WCWS, Muscatello DJ, Stockwell MS, Newall AT. economic burden of seasonal influenza within the u.s.. Vaccine. 2018;36(27):3960-3966. doi:10.1016/j.vaccine.2018.05.057

    4. Flu indicators and issues. CDC. Accessed June 15, 2020. https://www.cdc.gov/flu/signs/symptoms.htm

    5. Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus–caused lung injury: pathogenesis and implications for medicine. Eur Respir J. 2015;45(5):1463-1478. doi:10.1183/09031936.00186214

    6. people at greater risk of setting up serious flu-linked problems. CDC. up to date August 27, 2021. Accessed August 30, 2021. https://www.cdc.gov/flu/about/sickness/high_risk.htm

    7. Mertz D, Kim TH, Johnstone J, et al. Populations in danger for severe or complicated influenza disease: systematic review and meta-analysis. BMJ. 2013;347:f5061. doi:10.1136/bmj.f5061

    8. MacIntyre CR, Chughtai AA, Barnes M, et al. The function of pneumonia and secondary bacterial infection in fatal and severe consequences of pandemic influenza a(H1N1)pdm09. BMC Infect Dis. 2018;18(1):637. doi:10.1186/s12879-018-3548-0

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    19. Ison MG, Portsmouth S, Yoshida Y, et al. Early treatment with baloxavir marboxil in high-risk adolescent and grownup outpatients with simple influenza (CAPSTONE-2): a randomised, placebo-managed, phase three trial. Lancet Infect Dis. 2020;20(10):1204-1214. doi:10.1016/S1473-3099(20)30004-9

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    23. Atkins CY, Patel A, Taylor TH Jr, et al. Estimating effect of antiviral drug use all through pandemic (H1N1) 2009 outbreak, u.s.. Emerg Infect Dis. 2011;17(9):1591-1598. doi:10.3201/eid1709.110295

    24. Flu & people 65 years and older. CDC. up to date August 26, 2021. Accessed August 30, 2021. https://www.cdc.gov/flu/highrisk/65over.htm




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