Understanding factors affecting length of hospital stay (LOS) in patients with severe influenza may improve their management.
Methods
A retrospective cohort study on laboratory-confirmed, adult influenza patients hospitalized in 2004 and 2005 was conducted. For all influenza cases during that period, immunofluorescence assay on nasopharyngeal aspirate was used for rapid diagnosis, and oseltamivir (75 mg twice daily for 5 days) prescribed if the patient presented within 2 days of symptom onset. Independent factors associated with time to discharge were identified using Cox proportional hazards models. An adjusted hazard ratio (aHR) >1 signifies a higher chance of early discharge. Viral shedding and influenza vaccination history were studied during one ‘flu’ season.
Results
A total of 356 patients (influenza A 93.5%) were studied. The majority of patients were old (70.2 ±8.4years), had ≥1 comorbid illness (69.1%) and developed respiratory or cardiovascular complications (69.4%). Oseltamivir initiated within 2 days of illness was associated with shorter total LOS (Kaplan-Meier estimated median 4 versus 6 days [-33%]; aHR for discharge 1.54, 95% confidence intervals [95% CI] 1.23–1.92, P<0.0001). Older age (≥70 years), comorbidities and complications were associated with prolonged LOS. Prolonged viral RNA detection >day 4 of illness (23 out of 99 consecutive patients) was also independently associated with longer LOS (aHR 0.36 [95% CI 0.19–0.71], P=0.003), whereas influenza vaccination within 6 months was associated with shorter LOS (aHR 2.14 [95% CI 1.18–3.85], P=0.012).
Conclusion
Our analyses suggest that timely oseltamivir treatment is independently associated with shorter LOS in patients hospitalized for severe influenza. Efforts to ensure early diagnosis and therapeutic intervention are warranted.
References
1.
HarperS.A., FukudaK., UyekiT.M., CoxN.J., BridgesC.B.Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP).MMWR Recomm Rep2005; 54: 1–40.
2.
ThompsonW.W., ShayD.K., WeintraubE.Influenza-associated hospitalizations in the United States.JAMA2004; 292: 1333–1340.
3.
ThompsonW.W., ShayD.K., WeintraubE.Mortality associated with influenza and respiratory syncytial virus in the United States.JAMA2003; 289: 179–186.
4.
SimonsenL., FukudaK., SchonbergerL.B.The impact of influenza epidemics on hospitalizations.J Infect Dis2000; 181: 831–837.
YapF.H., HoP.L., LamK.F., ChanP.K., ChengY.H., PeirisJ.S.Excess hospital admissions for pneumonia, chronic obstructive pulmonary disease, and heart failure during influenza seasons in Hong Kong.J Med Virol2004; 73: 617–623.
7.
WongC.M., ChanK.P., HedleyA.J., PeirisJ.S.M.Influenza-associated mortality in Hong Kong.Clin Infect Dis2004; 39: 1611–1617.
8.
KaiserL., & HaydenF.G.Hospitalizing influenza in adults. In Current Clinical Topics in Infectious Diseases, 1999; pp. 112–134. Edited by RemingtonJ.S., SwartzM.N.. Malden, MA, USA: Blackwell Science.
9.
WalshE.E., CoxC., FalseyA.R.Clinical features of influenza A virus infection in older hospitalized persons.J Am Geriatr Soc2002; 50: 1498–1503.
10.
IsonM.G., GnannJ.W.Jr., Nagy-AgrenS.NIAID Collaborative Antiviral Study Group. Safety and efficacy of nebulized zanamivir in hospitalized patients with serious influenza.Antivir Ther2003; 8: 183–190.
11.
OliveiraE.C., MarikP.E., ColiceG.Influenza pneumonia: a descriptive study.Chest2001; 119: 1717–1723.
12.
OliveiraE.C., LeeB., ColiceG.L.Influenza in the intensive care unit.J Intensive Care Med2003; 18: 80–91.
13.
MosconaA.Neuraminidase inhibitors for influenza.N Engl J Med2005; 353: 1363–1373.
14.
WardP., SmallI., SmithJ., SuterP., DutkowskiR.Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic.J Antimicrob Chemother2005; 55 (Suppl 1): i5–i21.
15.
LinJ.T., YuX.Z., CuiD.J.A multicentre, randomized, controlled trial of oseltamivir in the treatment of influenza in a high-risk Chinese population.Curr Med Res Opin2006; 22: 75–82.
16.
SinghS., BarghoornJ., BagdomasA.Clinical benefits with oseltamivir in treating influenza in adult populations.Clin Drug Invest2003; 23: 561–569.
17.
BeigelJ.H., FarrarJ., HanA.M.; Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian influenza A (H5N1) infection in humans.N Engl J Med2005; 353: 1374–1385.
pandemicflu.gov.Washington D.C: US Department of Health and Human Services [cited: 1 September 2006]. Available from http://www.pandemicflu.gov.
20.
Hospital Authority.Fact sheet on antiviral therapy against influenza, Dec 2005 and HA operational plan on laboratory testing for human influenza infection. Nov 2005. Hong Kong, SAR: Hospital Authority [cited 1 September 2006]. Available from: http://www3.ha.org.hk/idctc/default.asp.
21.
LeeN., HuiD., WuA.A major outbreak of severe acute respiratory syndrome in Hong Kong.N Engl J Med2003; 348: 1986–1994.
22.
TreanorJ.J., HaydenF.G., VroomanP.S.Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group.JAMA2000; 283: 1016–1024.
23.
SchmidM.L., KudesiaG., WakeS.Prospective comparative study of culture specimens and methods in diagnosing influenza in adults.BMJ1998; 316: 275.
24.
MurkofskyR.L., PhillipsR.S., McCarthyE.P., DavisR.B., HamelM.B.Length of stay in home care before and after the 1997 Balanced Budget Act.JAMA2003; 289: 2841–2848.
25.
BowlesS.K., LeeW., SimorA.E.; Oseltamivir Compassionate Use Program Group. Use of oseltamivir during influenza outbreaks in Ontario nursing homes, 1999–2000.J Am Geriatr Soc2002; 50: 608–616.
26.
NicholsonK.G., AokiF.Y., OsterhausA.D.Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group.Lancet2000; 355: 1845–1850.
27.
CooperN.J., SuttonA.J., AbramsK.R.Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials.BMJ2003; 326: 1235.
28.
KaiserL., WatC., MillsT.Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations.Arch Intern Med2003; 163: 1667–1672.
29.
AokiF.Y., MacleodM.D., PaggiaroP.; IMPACT Study Group. Early administration of oral oseltamivir increases the benefits of influenza treatment.J Antimicrob Chemother.2003; 51: 123–129.
30.
KawaiN., IkematsuH., IwakiN.Factors influencing the effectiveness of oseltamivir and amantadine for the treatment of influenza: a multicenter study from Japan of the 2002–2003 influenza season.Clin Infect Dis2005; 40: 1309–1316.
31.
SalgadoC.D., FarrB.M., HallK.K., HaydenF.G.Influenza in the acute hospital setting.Lancet Infect Dis2002; 2: 145–155.
32.
SintchenkoV., GilbertG.L., CoieraE., DwyerD.Treat or test first? Decision analysis of empirical antiviral treatment of influenza virus infection versus treatment based on rapid test results.J Clin Virol2002; 25: 15–21.
33.
PoehlingK.A., ZhuY., TangY.W., EdwardsK.Accuracy and impact of a point-of-care rapid influenza test in young children with respiratory illnesses.Arch Pediatr Adolesc Med2006; 160: 713–718.
34.
BoothS., BaleriolaC., RawlinsonW.D.Comparison of two rapid influenza A/B test kits with reference methods showing high specificity and sensitivity for influenza A infection.J Med Virol2006; 78: 619–622.
35.
KaiserL., FritzR.S., StrausS.E., GubarevaL., HaydenF.G.Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses.J Med Virol2001; 64: 262–268.
36.
GrossP.A., HermogenesA.W., SacksH.S., LauJ., LevandowskiR.A.The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature.Ann Intern Med1995; 123: 518–527.
37.
DeguchiY., TakasugiY., TataraK.Efficacy of influenza vaccine in the elderly in welfare nursing homes: reduction in risks of mortality and morbidity during an influenza A (H3N2) epidemic.J Med Microbiol2000; 49: 553–556.
38.
NordinJ., MulloolyJ., PobleteS.Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans.J Infect Dis2001; 184: 665–670.
39.
WangC.S., WangS.T., LaiC.T., LinL.J., LeeC.T., ChouP.Reducing major cause-specific hospitalization rates and shortening hospital stays after influenza vaccination.Clin Infect Dis2004; 39: 1604–1610.
HaydenF., KlimovA., TashiroM.Neuraminidase inhibitor susceptibility network position statement: antiviral resistance in influenza A/H5N1 viruses.Antivir Ther2005; 10: 873–877.
42.
HaydenF.G., BelsheR., VillanuevaC.Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis.J Infect Dis2004; 189: 440–449.
43.
ShijuboN., YamadaG., TakahashiM.Experience with oseltamivir in the control of nursing home influenza A outbreak.Intern Med2002; 41: 366–370.
44.
KawaiN., IkematsuH., IwakiN.A comparison of the effectiveness of oseltamivir for the treatment of influenza A and influenza B: a Japanese multicenter study of the 2003–2004 and 2004–2005 influenza seasons.Clin Infect Dis2006; 43: 439–444.
45.
RothbergM.B., BellantonioS., RoseD.N.Management of influenza in adults older than 65 years of age: cost-effectiveness of rapid testing and antiviral therapy.Ann Intern Med2003; 139: 321–329.
