 |
|
Influenza-Associated Hospitalizations in the United States
William W. Thompson, PhD;
David K. Shay, MD, MPH;
Eric Weintraub, MPH;
Lynnette Brammer, MPH;
Carolyn B. Bridges, MD, MPH;
Nancy J. Cox, PhD;
Keiji Fukuda, MD, MPH
JAMA. 2004;292:1333-1340.
ABSTRACT
| |
Context Respiratory viral infections are responsible for a large number of hospitalizations in the United States each year.
Objective To estimate annual influenza-associated hospitalizations in the United States by hospital discharge category, discharge type, and age group.
Design, Setting, and Participants National Hospital Discharge Survey (NHDS) data and World Health Organization Collaborating Laboratories influenza surveillance data were used to estimate annual average numbers of hospitalizations associated with the circulation of influenza viruses from the 1979-1980 through the 2000-2001 seasons in the United States using age-specific Poisson regression models.
Main Outcome Measures We estimated influenza-associated hospitalizations for primary and any listed pneumonia and influenza and respiratory and circulatory hospitalizations.
Results Annual averages of 94 735 (range, 18 908-193 561) primary and 133 900 (range, 30 757-271 529) any listed pneumonia and influenza hospitalizations were associated with influenza virus infections. Annual averages of 226 054 (range, 54 523-430 960) primary and 294 128 (range, 86 494-544 909) any listed respiratory and circulatory hospitalizations were associated with influenza virus infections. Persons 85 years or older had the highest rates of influenza-associated primary respiratory and circulatory hospitalizations (1194.9 per 100 000 persons). Children younger than 5 years (107.9 primary respiratory and circulatory hospitalizations per 100 000 persons) had rates similar to persons aged 50 through 64 years. Estimated rates of influenza-associated hospitalizations were highest during seasons in which A(H3N2) viruses predominated, followed by B and A(H1N1) seasons. After adjusting for the length of each influenza season, influenza-associated primary pneumonia and influenza hospitalizations increased over time among the elderly. There were no significant increases in influenza-associated primary respiratory and circulatory hospitalizations after adjusting for the length of the influenza season.
Conclusions Significant numbers of influenza-associated hospitalizations in the United States occur among the elderly, and the numbers of these hospitalizations have increased substantially over the last 2 decades due in part to the aging of the population. Children younger than 5 years had rates of influenza-associated hospitalizations similar to those among individuals aged 50 through 64 years. These findings highlight the need for improved influenza prevention efforts for both young and older US residents.
INTRODUCTION
National estimates of influenza-associated mortality have been important for understanding the epidemiology of influenza over time and for resource planning for influenza epidemics and future influenza pandemics.1-4 However, mortality incompletely reflects the severity of influenza infections because many severe illnesses do not result in death. In addition, influenza types and subtypes have differential effects on morbidity and mortality. For example, during some seasons, influenza A(H1N1) and B viruses are associated with substantial numbers of hospitalizations and outpatient visits but small increases in mortality.5-7 Furthermore, influenza-associated hospitalizations contribute an important proportion of the total health burden and economic costs of influenza epidemics and pandemics.2, 8-10
Previous studies have estimated numbers and rates of influenza-associated hospitalizations by age group, risk status, influenza type and subtype, and vaccine status.11-20 However, only 2 studies, both using National Hospital Discharge Survey (NHDS) data, have provided national estimates of influenza-associated hospitalizations in the United States.11, 13 Barker11 estimated influenza-associated hospitalizations from 1970 through 1978 in 3 age groups using 3 mutually exclusive hospital outcomes: all-cause pneumonia and influenza, respiratory disease excluding all-cause pneumonia and influenza, and acute cardiac failure. The assessment of influenza-associated hospitalizations was limited to seasons in which influenza A(H3N2) viruses predominated and the assessment used winter seasons in which influenza A(H1N1) and B viruses predominated as the baseline period from which to estimate A(H3N2) excess hospitalizations. In the second study, Simonsen and colleagues13 estimated annual numbers of influenza-associated hospitalizations by virus type and subtype from the 1969-1970 through 1994-1995 seasons for primary pneumonia and influenza hospitalizations for 2 age groups (<64 years and  65 years). In most seasons, November hospitalizations were used as the baseline for estimating influenza-associated hospitalizations. In 6 seasons when the influenza circulation began late, a December baseline was used to estimate such hospitalizations.
We estimated annual numbers of influenza-associated hospitalizations from the 1979-1980 through the 2000-2001 respiratory seasons, a 22-year period for which national influenza laboratory surveillance data were available. We modified Poisson regression methods previously used to estimate influenza-associated mortality in the United States21 to estimate numbers and rates of influenza-associated hospitalizations.
METHODS
Definition of Respiratory Season
Influenza viruses typically circulate during winter months and across calendar years. Therefore, we defined July 1 through June 30 of the following year as a respiratory season so that an entire influenza season was studied.
National Viral Surveillance Data
In the United States, laboratory-based surveillance for influenza viruses is conducted from October through mid May (calendar week 40 through week 20). For the influenza virus surveillance periods from the 1979-1980 through 2000-2001 seasons, we obtained numbers of respiratory specimens that tested positive for influenza. Specimens are reported weekly by 50 to 75 US-based World Health Organization (WHO) collaborating virology laboratories to the Centers for Disease Control and Prevention. The laboratories provide numbers of total respiratory specimens tested for influenza and positive influenza tests by virus type and subtype.22 The monthly percentages of specimens that tested positive for influenza viruses were used in estimating the effect of influenza circulation on monthly hospitalizations in the United States. For summary purposes, we defined a predominant influenza virus type or subtype for each season based on whether the influenza type or subtype constituted more than 20% of the total influenza specimens that had tested positive in a given season.
NHDS Hospital Discharge Diagnoses
Hospital discharge diagnosis records were obtained from the NHDS23-28 for the 1979-1980 through 2000-2001 seasons. National Hospital Discharge Survey hospital discharge data are collected and reported by month for approximately 270 000 inpatient records sampled from approximately 500 hospitals. These records represent approximately 1% of all inpatient hospitalizations in the United States.29-30 The sampling design assigns a discharge weight to each hospital record. The discharge weight is the number of hospitalizations that the hospital record represents, and use of these weights permits calculations of nationally representative numbers of hospitalizations. We summed the corresponding discharge weights by month to obtain nationally representative numbers of hospitalizations.
International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes31 were used to categorize hospitalizations. Monthly hospitalizations were summarized by both first-listed and any-listed ICD-9-CM discharge codes. We considered the first-listed discharge code as the primary discharge diagnosis. We examined 2 diagnostic categories: pneumonia and influenza hospitalizations (ICD-9-CM codes 480-487) and respiratory and circulatory hospitalizations (ICD-9-CM codes 390-519). Thus, pneumonia and influenza hospitalizations were a subset of respiratory and circulatory hospitalizations.
Statistical Analyses
We modified methods developed for estimating US influenza-associated mortality21 to estimate influenza-associated hospitalizations with NHDS data. One advantage of this method is that it permitted the effect of influenza circulation to vary by month, and therefore hospitalization estimates could also fluctuate with influenza activity. Poisson regression models were fit to 8 age groups: younger than 5 years, 5 through 49 years, 50 through 64 years, 65 through 69 years, 70 through 74 years, 75 through 79 years, 80 through 84 years, and 85 years or older. Influenza virus circulation terms representing the percentages of specimens testing positive for influenza A(H1N1), A(H3N2), and B viruses during each month in the study period were included in all models.
The age-specific Poisson regression models we used can be written as
Y =  exp( 0 + 1[t] + 2[t2] + 3[t3]
+ 4[sin(2t /12)] + 5[cos(2t/12)]
+ 6[A(H1N1)] + 7[A(H3N2)]
+ 8[B]
where Y represents the number of hospitalizations during a particular month for a specific age group. The term was the population offset. The term t was the number of months in a time series from July 1979 through June 2001. We estimated the following coefficients: 0was the intercept, 1accounted for the linear time trend in months, 2and 3accounted for nonlinear time trends, 4and 5 accounted for seasonal changes in hospitalizations, and 6through 8were coefficients associated with the percentages of specimens testing positive for specific influenza viruses in a given month. Estimates of monthly US age-specific populations were used to account for changes in population trends over time and were obtained from the Census Bureau.32 Attempts to include a term for respiratory syncytial virus in these models were unsuccessful because of the high correlation between the cosine term and the respiratory syncytial virus term (r = 0.90) when the data were modeled on a monthly rather than on a weekly basis as was done in our recent mortality analyses.21 All analyses were performed using SAS statistical software version 8.2 (PROC GENMOD, SAS Institute Inc, Cary, NC). Because NHDS data sets are deidentified public-use data sets, their use does not require formal institutional review board approval.
We determined the number of weeks during each respiratory season for which at least 10% of specimens tested positive for influenza. We used these numbers in analyses to control for the length of the influenza season when examining trends in influenza hospitalization rates.
RESULTS
Annual Influenza Laboratory Surveillance
For the 1979-1980 through 2000-2001 seasons, an annual average of 30 936 specimens (range, 14 804-53 427) were tested for influenza. During months in which specimens were tested for influenza, an average of 13.3% of specimens tested positive for influenza. Influenza A(H1N1), A(H3N2), and B viruses were detected in 2.1%, 7.9%, and 3.3% of the total specimens tested, respectively. During the 22 respiratory seasons included in this study, A(H1N1), A(H3N2), and B viruses predominated in 7, 15, and 11 respiratory seasons, respectively. There were 11 seasons in which more than 1 virus type or subtype predominated. The average number of months in which at least 10% of specimens tested positive for influenza during each respiratory season was 2.8 months (range, 0-4 months).
Annual Trends in Primary Hospital Discharge Diagnoses
During the study period, there were annual averages of 1 097 564 primary and 1 681 449 any listed pneumonia and influenza hospitalizations (Table 1). There were annual averages of 8 843 498 primary and 14 722 488 any listed respiratory and circulatory hospitalizations. Primary pneumonia and influenza hospitalizations represented 12.4% of the primary respiratory and circulatory hospitalizations. The total numbers of primary pneumonia and influenza hospitalizations increased in a linear fashion from the 1979-1980 through the 2000-2001 respiratory seasons (Figure 1). The total numbers of primary respiratory and circulatory hospitalizations decreased from the 1982-1983 through 1990-1991 respiratory seasons but increased from the 1991-1992 through 1999-2000 respiratory seasons.
|
|
|
|
Table 1. Annual Numbers of Hospitalizations*
|
|
|
|
|
|
|
Figure. Monthly Numbers of Hospitalizations by Primary Discharge Type From the 1979-1980 Through 2000-2001 Respiratory Seasons
The curve plotting the respiratory and circulation data is a fourth-order polynomial curve, and the pneumonia and influenza curve represents a straight linear regression line.
|
|
|
Annual Estimates of Influenza-Associated Hospitalizations
We estimated annual averages of 94 735 (range, 18 908-193 561) primary and 133 900 (range, 30 757-271 529) any listed pneumonia and influenza hospitalizations were associated with influenza viruses in the United States during the 1979-1980 through 2000-2001 respiratory seasons (Table 2). These influenza-associated hospitalization estimates represented 8.6% of all primary and 8.0% of any listed pneumonia and influenza hospitalizations. Similarly, we estimated annual averages of 226 054 (range, 54 523-430 960) primary and 294 128 (range, 86 494-544 909) any listed respiratory and circulatory hospitalizations were associated with influenza viruses. For the respiratory and circulatory hospitalizations, these estimates represented 2.6% of all primary and 2.0% of any listed hospitalizations during the study period.
|
|
|
|
Table 2. Annual Numbers and Rates of Influenza-Associated Hospitalizations*
|
|
|
When we examined the year-to-year variability in influenza-associated hospitalizations, we noted a substantial increase in hospitalizations during the 1996-1997 through 1999-2000 influenza seasons, a period when A(H3N2) viruses predominated. Influenza-associated hospitalizations in the 2000-2001 season were the lowest since the 1995-1996 influenza season, and this corresponded with circulation of A(H1N1) viruses.
A summary of the numbers and rates of influenza-associated hospitalizations by discharge diagnosis and age group are presented in Table 3. Among children younger than 5 years, we estimated annual averages of 3454 (18.5 hospitalizations per 100 000 person-years) primary and 4916 (26.3 hospitalizations per 100 000 person-years) any listed pneumonia and influenza hospitalizations. For the same age group, we estimated 20 031 (107.9 hospitalizations per 100 000 person-years) primary and 21 156 (113.9 hospitalizations per 100 000 person-years) any listed respiratory and circulatory hospitalizations. Persons aged 5 through 49 years had the lowest rates of influenza-associated hospitalizations. Influenza-associated hospitalization rates increased dramatically with age. For example, among persons aged 85 years and older, we estimated annual averages of 21 788 (628.6 hospitalizations per 100 000 person-years) primary and 26 988 (777.3 hospitalizations per 100 000 person-years) any listed pneumonia and influenza hospitalizations. In this age group, we estimated annual averages of 40 813 (1194.9 hospitalizations per 100 000 person-years) primary and 57 350 (1669.2 hospitalizations per 100 000 person-years) any listed respiratory and circulatory influenza-associated hospitalizations.
|
|
|
|
Table 3. Age-Specific Annual Average Numbers and Rates of Influenza-Associated Hospitalizations*
|
|
|
Influenza-Associated Hospitalizations by Predominant Influenza Type and Subtype
In seasons during which A(H1N1) viruses predominated, 22.6 primary pneumonia and influenza and 55.9 primary respiratory and circulatory hospitalizations per 100 000 person-years were associated with influenza virus circulation. For B viruses, we estimated 37.7 and 81.4 influenza-associated hospitalizations per 100 000 person-years for primary pneumonia and influenza and primary respiratory and circulatory hospitalizations, respectively. A(H3N2) viruses were associated with the highest annual rates of influenza-associated hospitalizations. During seasons in which A(H3N2) viruses predominated, there were 43.5 primary pneumonia and influenza and 99.0 primary respiratory and circulatory hospitalizations per 100 000 person-years associated with influenza viruses.
Age-Specific Trends in Influenza-Associated Hospitalization Rates
Influenza-associated hospitalization rates increased annually during the study period among persons aged 50 through 64 years, 65 through 69 years, 70 through 74 years, 75 through 79 years, 80 through 84 years, and 85 years and older (P<.01 for each trend). After controlling for the length of the influenza season, a significant increase in the rates over time was still found among persons aged 65 through 69 years, 70 through 74 years, 75 through 79 years, 80 through 84 years, and 85 years and older (P<.05 for each trend).
Significant increases in influenza-associated hospitalization rates for respiratory and circulatory hospitalizations were found among persons younger than 5 years and those aged 65 through 69 years, 70 through 74 years, 75 through 79 years, 80 through 84 years, and 85 years and older (P<.05 for each trend). However, after controlling for the length of the influenza season, there were no significant increases in trends over time.
Length of Hospital Stay by Age Group and Diagnosis
Length of hospital stay varied by diagnosis and age group (Table 4). The median length of stay for primary pneumonia and influenza hospitalizations increased with age. The median length of stay was 3 days for those younger than 5 years; 4 days for those aged 5 through 49 years; 6 days for those aged 50 through 64, 65 through 69, and 70 through 74 years; and 7 days for those aged 75 through 79, 80 through 84, and 85 years and older. The median length of stay for primary respiratory and circulatory hospitalizations was 3 days for those younger than 5 years and those aged 5 through 49 years; 4 days for those aged 50 through 64 years; 5 days for those aged 65 through 69, 70 through 74, and 75 through 79 years; 6 days for those aged 80 through 84 years and those 85 years and older.
|
|
|
|
Table 4. Descriptive Statistics for Length of Stay
|
|
|
COMMENT
We used monthly influenza surveillance data and nationally representative hospital discharge data to estimate influenza-associated hospitalizations in the United States by discharge category, discharge type, and age group. We found that the numbers and rates of influenza-associated hospitalizations generally increased during the study period.
Our results are consistent with our recent mortality analyses, which found substantial increases in influenza-associated mortality among persons 65 years and older during the 1990s.21 We postulate that these increases in influenza-associated hospitalizations and deaths were due to several factors, including the aging of the population, the predominance of A(H3N2) viruses in many recent seasons, and the general trend for influenza viruses to circulate or to be detected for longer periods in respiratory seasons during the 1990s.
Using the nationally representative estimates of influenza-associated hospitalizations from this study and of deaths from our mortality study,21 we can estimate relative risks (RRs) describing the risk of an influenza-associated hospitalization compared with the risk of an influenza-associated death. For example, among children younger than 5 years, the RR for an influenza-associated hospitalization relative to death is 270; while among persons aged 50 through 64 years, the RR is 11. Young children are at much greater risk for an influenza-associated hospitalization compared with an influenza-associated death; this difference greatly diminishes with increasing age. These results will be useful for national cost-effectiveness and policy analyses which assess the pros and cons of alternative vaccination strategies to reduce the morbidity and mortality from influenza, including vaccinating all children or universal immunization.
An important implication of our results is that the use of primary pneumonia and influenza discharges to estimate influenza-associated hospitalizations does not fully capture the total effect of influenza virus activity on morbidity in the United States. Our estimates of any listed respiratory and circulatory hospitalizations were about 3 times as high as our estimates of primary pneumonia and influenza hospitalizations. Other studies also suggest that influenza virus activity is associated with an increase in hospitalizations for a broad range of cardiopulmonary diagnoses, and not just primary pneumonia and influenza discharges.11, 19
Generally, our estimated annual numbers and rates of influenza-associated hospitalizations are similar to previous national estimates made using NHDS data. Barker11 estimated 370 influenza-associated pneumonia and influenza hospitalizations per 100 000 persons who were at least 65 years during 5 A(H3N2) seasons in the 1970s while we estimated 281 any listed pneumonia and influenza hospitalizations per 100 000 persons during the 1979-1980 through 2000-2001 respiratory seasons for this age group. Barker's estimate for the sum of influenza-associated hospitalizations for respiratory disease and acute cardiac failure was an annual average of 419 hospitalizations per 100 000 persons who were at least 65 years. We estimated 581 any listed respiratory and circulatory hospitalizations per 100 000 annually, which was slightly higher but would be expected given the continued aging of this age group.
In the other study that used NHDS data, Simonsen and colleagues13 estimated 49 influenza-associated primary pneumonia and influenza hospitalizations per 100 000 persons for all ages, while we estimated 37 hospitalizations per 100 000 person-years for the same outcome. Comparing the results from these 2 studies during overlapping seasons (1979-1980 through 1994-1995), the annual estimates of influenza-associated pneumonia and influenza hospitalizations were highly correlated (r = 0.73, P<.01). Across the entire study period, Simonsen and colleagues13 estimated higher rates of primary pneumonia and influenza hospitalizations among persons younger than 65 years relative to our study (33 vs 13 hospitalizations per 100 000 persons, respectively). Conversely, we estimated higher rates of primary pneumonia and influenza hospitalizations among persons who were aged at least 65 years (174 vs 205 per 100 000 persons, respectively). The difference in rates among those younger than 65 years in the study by Simonsen et al most likely reflect the increased influenza morbidity found among younger individuals during the 1968-1969 pandemic period.
The results of this study are also consistent with several studies of influenza-associated hospitalizations restricted to young children. These studies found high rates of hospitalizations among both high-risk and healthy young children.16, 33-35 Although none of these previous studies were nationally representative, the estimated rates are in general quite similar. For example, for all children younger than 5 years, Mullooly and Barker12 estimated 1.2 hospitalizations per 1000 person-years, Neuzil and colleagues16 estimated 2.6 hospitalizations per 1000 person-years among healthy children, and Izurieta and colleagues35 estimated 0.9 hospitalizations per 1000 person-years among healthy children. In our study, we estimated an annual average of 1.1 hospitalizations per 1000 person-years among all children younger than 5 years, which also compares favorably with a recent study that found a laboratory-confirmed influenza hospitalization rate of 0.6 per 1000 among children younger than 5 years during a single mild influenza season.36
This study has several limitations. Because NHDS data do not include previous health information, it was not possible to determine which individuals were at risk for influenza complications due to underlying conditions (eg, asthma, heart disease, etc) or to control for changes in the prevalence of these conditions over time. Nor was it possible to identify individuals who had received influenza vaccine prior to the respiratory season in which the individual was hospitalized in order to assess vaccine effectiveness. Although our influenza mortality estimates were made using similar methods and weekly death data, in this study we were limited to making hospitalization estimates using monthly hospital discharge data. Use of weekly hospitalization and influenza circulation information would have permitted fluctuations in both data sources to be more closely associated and would have provided more precise estimates of influenza-associated hospitalizations. We were also not able to control for the circulation of respiratory syncytial virus, which is known to circulate at similar times as influenza viruses and is often associated with significant morbidity and mortality. Finally, we were unable to stratify data further for children younger than 5 years due to the few numbers of hospitalizations that occurred for children aged 2 to 4 years. Despite these limitations, our use of NHDS data provided nationally representative annual estimates of influenza-associated hospitalizations that can be compared over 2 decades. Smaller data sources often used to assess influenza vaccine effectiveness cannot offer these advantages.
Currently, we estimate that more than 200 000 respiratory and circulatory hospitalizations are associated with influenza each year in the United States, substantially more than estimates of pneumonia and influenza hospitalizations.13 As noted in our report describing influenza-associated mortality, the aging of the US population is an important contributor to the increasing numbers of influenza-associated hospitalizations and deaths.21 For example, between 1976 and 2001 the number of US citizens aged 85 and older had more than doubled.32, 37 Based on US census estimates, the numbers of very elderly people in the United States will continue to increase and thus we expect that the numbers of influenza-associated hospitalizations and deaths will likely increase over time. Additional efforts are needed to ensure that current recommendations for influenza vaccination for all high-risk individuals, household contacts of high-risk individuals, healthcare workers, and young children are fully implemented. Recent observational studies have suggested that influenza vaccination may reduce respiratory and circulatory hospitalizations substantially, particularly among the elderly.19, 38-39 Efforts to vaccinate older Americans and their contacts annually must continue to be a priority for immunization programs. Consideration should also be given to other influenza prevention methods for older Americans given the potential for decreased immune responsiveness to vaccines in the very elderly.40-41
After the elderly, the second highest rates of influenza-associated hospitalizations are found in young children. This point was highlighted during the 2003-2004 A(H3N2)–influenza season, which may have been particularly severe among children. Through July 2004, data on 152 deaths among children with laboratory-confirmed influenza virus infection during the last influenza season has been collected nationally.42 The Council of State and Territorial Epidemiologists voted in June 2004 to add deaths of children with evidence of influenza virus infection to its list of nationally reportable conditions. Clearly, new measures to prevent influenza-associated morbidity and mortality among young children are needed.
AUTHOR INFORMATION
| |
Corresponding Author: William W. Thompson, PhD, Immunization Safety Branch, National Immunization Program, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, MS E61, Atlanta, GA 30333 (wct2{at}cdc.gov).
Author Contributions: Dr Thompson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Thompson, Shay, Weintraub, Cox, Fukuda.
Acquisition of data: Weintraub, Brammer, Cox.
Analysis and interpretation of data: Thompson, Shay, Weintraub, Brammer, Bridges, Cox, Fukuda.
Drafting of the manuscript: Thompson, Shay.
Critical revision of the manuscript for important intellectual content: Thompson, Shay. Weintraub, Brammer, Bridges, Cox, Fukuda.
Statistical analysis: Thompson, Weintraub, Brammer.
Administrative, technical, or material support: Thompson, Weintraub, Bridges.
Study supervision: Thompson, Shay, Cox, Fukuda.
Funding/Support: This project did not receive any dedicated funding.
Acknowledgments: We thank Ericka Sinclair, Erin Murray, and Alicia Postema for assistance in organizing the WHO influenza isolate data.
Author Affiliations: Epidemiology and Surveillance Division, National Immunization Program (Drs Thompson, Shay, and Bridges and Mr Weintraub) and Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases (Ms Brammer and Drs Cox and Fukuda), Centers for Disease Control and Prevention, Atlanta, Ga.
Dr Shay is now with Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases.
REFERENCES
1. Harper SA, Fukuda K, Uyeki TM, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2004;53:1-40.
PUBMED
2. Meltzer MI, Cox NJ, Fukuda K. The economic impact of pandemic influenza in the United States: priorities for intervention. Emerg Infect Dis. 1999;5:659-671.
ISI
| PUBMED
3. Fukuda K. Are we ready for emerging strains of pandemic influenza? Int J Clin Pract Suppl. 2000;115:37-43.
PUBMED
4. Gensheimer KF, Fukuda K, Brammer L, et al. Preparing for pandemic influenza: the need for enhanced surveillance. Vaccine. 2002;(suppl 20):S63-S65.
FULL TEXT
| PUBMED
5. Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev. 1982;4:25-44.
FREE FULL TEXT
6. Glezen WP, Couch RB, Taber LH, et al. Epidemiologic observations of influenza B virus infections in Houston, Texas, 1976-1977. Am J Epidemiol. 1980;111:13-22.
FREE FULL TEXT
7. Frank AL, Taber LH, Glezen WP, et al. Influenza B virus infections in the community and the family: the epidemics of 1976-1977 and 1979-1980 in Houston, Texas. Am J Epidemiol. 1983;118:313-325.
FREE FULL TEXT
8. McBean AM, Babish JD, Warren JL. The impact and cost of influenza in the elderly. Arch Intern Med. 1993;153:2105-2111.
FREE FULL TEXT
9. Nichol KL, Wuorenma J, von Sternberg T. Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens. Arch Intern Med. 1998;158:1769-1776.
FREE FULL TEXT
10. Nichol KL. Complications of influenza and benefits of vaccination. Vaccine. 1999;17(suppl 1):S47-S52.
PUBMED
11. Barker WH. Excess pneumonia and influenza associated hospitalization during influenza epidemics in the United States, 1970-78. Am J Public Health. 1986;76:761-765.
FREE FULL TEXT
12. Mullooly JP, Barker WH. Impact of type A influenza on children: a retrospective study. Am J Public Health. 1982;72:1008-1016.
FREE FULL TEXT
13. Simonsen L, Fukuda K, Schonberger LB, Cox NJ. The impact of influenza epidemics on hospitalizations. J Infect Dis. 2000;181:831-837.
FULL TEXT
|
ISI
| PUBMED
14. Barker WH, Mullooly JP. Impact of epidemic type A influenza in a defined adult population. Am J Epidemiol. 1980;112:798-811.
FREE FULL TEXT
15. Glezen WP. Influenza and hospitalizations in children. N Engl J Med. 2000;342:1752-1753.
FREE FULL TEXT
16. Neuzil KM, Mellen BG, Wright PF, et al. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000;342:225-231.
FREE FULL TEXT
17. Nichol KL, Baken L, Nelson A. Relation between influenza vaccination and outpatient visits, hospitalization, and mortality in elderly persons with chronic lung disease. Ann Intern Med. 1999;130:397-403.
FREE FULL TEXT
18. Nordin J, Mullooly J, Poblete S, et al. 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 Dis. 2001;184:665-670.
FULL TEXT
|
ISI
| PUBMED
19. Nichol KL, Nordin J, Mullooly J, et al. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med. 2003;348:1322-1332.
FREE FULL TEXT
20. McBean AM, Hebert PL. New estimates of influenza-related pneumonia and influenza hospitalizations among the elderly. Int J Infect Dis. 2004;8:227-235.
FULL TEXT
|
ISI
| PUBMED
21. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179-186.
FREE FULL TEXT
22. Brammer TL, Izurieta HS, Fukuda K, et al. Surveillance for influenza—United States, 1994-95, 1995-96, and 1996-97 seasons. MMWR CDC Surveill Summ. 2000;49:13-28.
PUBMED
23. Graves EJ, Gillum BS. National hospital discharge survey: annual summary, 1994. Vital Health Stat 13. 1997;(128):i-v, 1-50.
PUBMED
24. Gillum BS, Graves EJ, Wood E. National hospital discharge survey. Vital Health Stat 13. 1998;(133):i-v, 1-51.
PUBMED
25. Lawrence L, Hall MJ. 1997 Summary: National Hospital Discharge Survey. Adv Data. 1999;(308):1-16.
PUBMED
26. Dennison C, Pokras R. Design and operation of the National Hospital Discharge Survey: 1988 redesign. Vital Health Stat 1. 2000;(39):1-42.
PUBMED
27. Hall MJ, Owings MF. 2000 National Hospital Discharge Survey. Adv Data. 2002;(329):1-18.
PUBMED
28. Kozak LJ, Hall MJ, Owings MF. National Hospital Discharge Survey: 2000 annual summary with detailed diagnosis and procedure data. Vital Health Stat 13. 2002;(153):1-194.
PUBMED
29. Haupt BJ, Kozak LJ. Estimates from two survey designs: national hospital discharge survey. Vital Health Stat 13. 1992;(111):1-75.
PUBMED
30. Dennison C, Pokras R. Design and operation of the National Hospital Discharge Survey: 1988 redesign. Vital Health Stat 1. 2000;(39):1-42.
PUBMED
31. The International Classification of Diseases 9th Revision Clinical Modification. Vol 1 Diseases: Tabular List. Ann Arbor, Mich: Edwards Brothers; 1978.
32. Intercensal Estimates of the Population By Age, Sex, And Race. Washington DC: US Bureau of the Census; 1990.
33. Neuzil KM, Zhu Y, Griffin MR, et al. Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. J Infect Dis. 2002;185:147-152.
FULL TEXT
|
ISI
| PUBMED
34. Neuzil KM, Wright PF, Mitchel EF Jr, Griffin MR. The burden of influenza illness in children with asthma and other chronic medical conditions. J Pediatr. 2000;137:856-864.
FULL TEXT
|
ISI
| PUBMED
35. Izurieta HS, Thompson WW, Kramarz P, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med. 2000;342:232-239.
FREE FULL TEXT
36. Iwane MK, Edwards KM, Szilagyi PG, et al. Population-based surveillance for hospitalizations associated with respiratory syncytial virus, influenza virus, and parainfluenza viruses among young children. Pediatrics. 2004;113:1758-1764.
FREE FULL TEXT
37. Health, United States, 1999: With Health and Aging Chartbooks. Hyattsville, Md: US Dept of Health and Human Services, National Center for Health Statistics; 1999. PHS No. 99-1232.
38. Nichol KL. The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Vaccine. 2003;21:1769-1775.
FULL TEXT
|
ISI
| PUBMED
39. Vu T, Farish S, Jenkins M, Kelly H. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community. Vaccine. 2002;20:1831-1836.
FULL TEXT
|
ISI
| PUBMED
40. Meyer KC. The role of immunity in susceptibility to respiratory infection in the aging lung. Respir Physiol. 2001;128:23-31.
FULL TEXT
|
ISI
| PUBMED
41. Miller RA. The aging immune system: primer and prospectus. Science. 1996;273:70-74.
ABSTRACT
42. Update: influenza activity—United States and Worldwide, 2003-04 season, and composition of the 2004-05 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2004;53:547-552.
PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Influenza Exerts Continued Pressure in an Era of Modern Medicine
Noah et al.
Am. J. Respir. Cell Mol. Bio. 2009;41:3-7.
FULL TEXT
Update: Novel Influenza A (H1N1) Virus Infections--Worldwide, May 6, 2009
JAMA 2009;301:2319-2321.
FULL TEXT
The public health impact of avian influenza viruses
Katz et al.
Poult. Sci. 2009;88:872-879.
ABSTRACT
| FULL TEXT
Variability in the Diagnostic Labeling of Nonbacterial Lower Respiratory Tract Infections: A Multicenter Study of Children Who Presented to the Emergency Department
Mansbach et al.
Pediatrics 2009;123:e573-e581.
ABSTRACT
| FULL TEXT
Cost-effectiveness of treating influenzalike illness with oseltamivir in the United States
Talbird et al.
Am J Health Syst Pharm 2009;66:469-480.
ABSTRACT
| FULL TEXT
Comparison of Viral Isolation and Multiplex Real-Time Reverse Transcription-PCR for Confirmation of Respiratory Syncytial Virus and Influenza Virus Detection by Antigen Immunoassays
Liao et al.
J. Clin. Microbiol. 2009;47:527-532.
ABSTRACT
| FULL TEXT
Impact of the 2004-2005 Influenza Vaccine Shortage on Pediatric Practice: A National Survey
McQuillan et al.
Pediatrics 2009;123:e186-e192.
ABSTRACT
| FULL TEXT
Prevention and Treatment of Seasonal Influenza
Glezen
NEJM 2008;359:2579-2585.
FULL TEXT
Additional Visit Burden for Universal Influenza Vaccination of US School-Aged Children and Adolescents
Rand et al.
Arch Pediatr Adolesc Med 2008;162:1048-1055.
ABSTRACT
| FULL TEXT
Detection of Respiratory Viruses by Molecular Methods
Mahony
Clin. Microbiol. Rev. 2008;21:716-747.
ABSTRACT
| FULL TEXT
High-Throughput Screening of a 100,000-Compound Library for Inhibitors of Influenza A Virus (H3N2)
Severson et al.
J Biomol Screen 2008;13:879-887.
ABSTRACT
Influenza-Associated Pediatric Mortality in the United States: Increase of Staphylococcus aureus Coinfection
Finelli et al.
Pediatrics 2008;122:805-811.
ABSTRACT
| FULL TEXT
A Novel Role for Non-Neutralizing Antibodies against Nucleoprotein in Facilitating Resistance to Influenza Virus
Carragher et al.
J. Immunol. 2008;181:4168-4176.
ABSTRACT
| FULL TEXT
Mortality Reduction with Influenza Vaccine in Patients with Pneumonia Outside "Flu" Season: Pleiotropic Benefits or Residual Confounding?
Eurich et al.
Am. J. Respir. Crit. Care Med. 2008;178:527-533.
ABSTRACT
| FULL TEXT
Protecting residential care facilities from pandemic influenza
Nuno et al.
Proc. Natl. Acad. Sci. USA 2008;105:10625-10630.
ABSTRACT
| FULL TEXT
Interim Within-Season Estimate of the Effectiveness of Trivalent Inactivated Influenza Vaccine--Marshfield, Wisconsin, 2007-08 Influenza Season
JAMA 2008;299:2381-2384.
FULL TEXT
Repeated Commit-or-Defer Decisions with a Deadline: The Influenza Vaccine Composition
Kornish and Keeney
Operations Research 2008;56:527-541.
ABSTRACT
Time Lines of Infection and Disease in Human Influenza: A Review of Volunteer Challenge Studies
Carrat et al.
Am J Epidemiol 2008;167:775-785.
ABSTRACT
| FULL TEXT
Prevention of Influenza: Recommendations for Influenza Immunization of Children, 2007-2008
Committee on Infectious Diseases
Pediatrics 2008;121:e1016-e1031.
ABSTRACT
| FULL TEXT
Influenza-Testing and Antiviral-Agent Prescribing Practices--Connecticut, Minnesota, New Mexico, and New York, 2006-07 Influenza Season
JAMA 2008;299:1127-1129.
FULL TEXT
Influenza- and respiratory syncytial virus-associated mortality and hospitalisations
Jansen et al.
Eur Respir J 2007;30:1158-1166.
ABSTRACT
| FULL TEXT
Effectiveness of Influenza Vaccine in the Community-Dwelling Elderly
Nichol et al.
NEJM 2007;357:1373-1381.
ABSTRACT
| FULL TEXT
Influenza Vaccination: An Unmet Need in Patients With Diabetes
Schaffner et al.
Clin. Diabetes 2007;25:145-149.
ABSTRACT
| FULL TEXT
Validity of Parental Report of Influenza Vaccination in Children 6 to 59 Months of Age
Shinall et al.
Pediatrics 2007;120:e783-e787.
ABSTRACT
| FULL TEXT
Viral Etiology of Acute Exacerbations of COPD in Hong Kong
Ko et al.
Chest 2007;132:900-908.
ABSTRACT
| FULL TEXT
Childhood Influenza: Number Needed to Vaccinate to Prevent 1 Hospitalization or Outpatient Visit
Lewis et al.
Pediatrics 2007;120:467-472.
ABSTRACT
| FULL TEXT
Trivalent Live Attenuated Intranasal Influenza Vaccine Administered During the 2003 2004 Influenza Type A (H3N2) Outbreak Provided Immediate, Direct, and Indirect Protection in Children
Piedra et al.
Pediatrics 2007;120:e553-e564.
ABSTRACT
| FULL TEXT
Use of implantable cardioverter defibrillators in Canadian and US survivors of out-of-hospital cardiac arrest
Birnie et al.
CMAJ 2007;177:41-46.
ABSTRACT
| FULL TEXT
Mass Distribution of Free, Intranasally Administered Influenza Vaccine in a Public School System
Carpenter et al.
Pediatrics 2007;120:e172-e178.
ABSTRACT
| FULL TEXT
Assessing the role of basic control measures, antivirals and vaccine in curtailing pandemic influenza: scenarios for the US, UK and the Netherlands
Nuno et al.
J R Soc Interface 2007;4:505-521.
ABSTRACT
| FULL TEXT
Influenza vaccination among the elderly Spanish population: trend from 1993 to 2003 and vaccination-related factors*
de Andres et al.
Eur J Public Health 2007;17:272-277.
ABSTRACT
| FULL TEXT
Incidence, Complications, and Risk Factors for Prolonged Stay in Children Hospitalized With Community-Acquired Influenza
Coffin et al.
Pediatrics 2007;119:740-748.
ABSTRACT
| FULL TEXT
Influenza vaccination as model for testing immune modulation induced by anti-TNF and methotrexate therapy in rheumatoid arthritis patients
Kapetanovic et al.
Rheumatology (Oxford) 2007;46:608-611.
ABSTRACT
| FULL TEXT
Influenza Vaccination and Risk of Mortality Among Adults Hospitalized With Community-Acquired Pneumonia
Spaude et al.
Arch Intern Med 2007;167:53-59.
ABSTRACT
| FULL TEXT
Comparison of the Influenza Virus-Specific Effector and Memory B-Cell Responses to Immunization of Children and Adults with Live Attenuated or Inactivated Influenza Virus Vaccines
Sasaki et al.
J. Virol. 2007;81:215-228.
ABSTRACT
| FULL TEXT
Epidemiology, Complications, and Cost of Hospitalization in Children With Laboratory-Confirmed Influenza Infection
Ampofo et al.
Pediatrics 2006;118:2409-2417.
ABSTRACT
| FULL TEXT
Direct Medical Costs of Bronchiolitis Hospitalizations in the United States
Pelletier et al.
Pediatrics 2006;118:2418-2423.
ABSTRACT
| FULL TEXT
FluSurge--A Tool to Estimate Demand for Hospital Services during the Next Pandemic Influenza
Zhang et al.
Med Decis Making 2006;26:617-623.
ABSTRACT
Direct Medical Cost of Influenza-Related Hospitalizations in Children
Keren et al.
Pediatrics 2006;118:e1321-e1327.
ABSTRACT
| FULL TEXT
Influenza Vaccination as Secondary Prevention for Cardiovascular Disease: A Science Advisory From the American Heart Association/American College of Cardiology
Davis et al.
J Am Coll Cardiol 2006;48:1498-1502.
ABSTRACT
| FULL TEXT
Influenza Vaccination as Secondary Prevention for Cardiovascular Disease: A Science Advisory From the American Heart Association/American College of Cardiology: Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Association of Critical Care Nurses, the American Association of Heart Failure Nurses, the American Diabetes Association, the Association of Black Cardiologists, Inc., the Heart Failure Society of America, and the Preventive Cardiovascular Nurses Association.: The American Academy of Nurse Practitioners supports the recommendations of this scientific advisory.: This science advisory is consistent with the recommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices.
Davis et al.
Circulation 2006;114:1549-1553.
ABSTRACT
| FULL TEXT
Incorporating Vaccine-Preventable Disease Surveillance Into the National Health Information Network: Leveraging Children's Hospitals
Fine et al.
Pediatrics 2006;118:1431-1438.
ABSTRACT
| FULL TEXT
National Impact of Universal Childhood Immunization With Pneumococcal Conjugate Vaccine on Outpatient Medical Care Visits in the United States
Grijalva et al.
Pediatrics 2006;118:865-873.
ABSTRACT
| FULL TEXT
Influenza Vaccination Coverage of Children Aged 6 to 23 Months: The 2002-2003 and 2003-2004 Influenza Seasons
Santibanez et al.
Pediatrics 2006;118:1167-1175.
ABSTRACT
| FULL TEXT
Surveillance for Influenza Admissions Among Children Hospitalized in Canadian Immunization Monitoring Program Active Centers, 2003-2004
Moore et al.
Pediatrics 2006;118:e610-e619.
ABSTRACT
| FULL TEXT
Distribution of Influenza Vaccine to High-Risk Groups
Ompad et al.
Epidemiol Rev 2006;28:54-70.
ABSTRACT
| FULL TEXT
Delivering Influenza Vaccine to Pregnant Women
Naleway et al.
Epidemiol Rev 2006;28:47-53.
ABSTRACT
| FULL TEXT
The underrecognized burden of influenza in young children.
Poehling et al.
NEJM 2006;355:31-40.
ABSTRACT
| FULL TEXT
Influenza control.
Glezen
NEJM 2006;355:79-81.
FULL TEXT
Influenza and Other Respiratory Virus-Related Emergency Department Visits Among Young Children
Bourgeois et al.
Pediatrics 2006;118:e1-e8.
ABSTRACT
| FULL TEXT
The guinea pig as a transmission model for human influenza viruses
Lowen et al.
Proc. Natl. Acad. Sci. USA 2006;103:9988-9992.
ABSTRACT
| FULL TEXT
The Epidemiology of Sepsis in Patients With Malignancy
Danai et al.
Chest 2006;129:1432-1440.
ABSTRACT
| FULL TEXT
Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons.
Keitel et al.
Arch Intern Med 2006;166:1121-1127.
ABSTRACT
| FULL TEXT
T Cell Responses Are Better Correlates of Vaccine Protection in the Elderly
McElhaney et al.
J. Immunol. 2006;176:6333-6339.
ABSTRACT
| FULL TEXT
Commentary: Benefits of influenza vaccine in US elderly--new studies raise questions
Glezen and Simonsen
Int J Epidemiol 2006;35:352-353.
FULL TEXT
Severe Pediatric Influenza in California, 2003-2005: Implications for Immunization Recommendations
Louie et al.
Pediatrics 2006;117:e610-e618.
ABSTRACT
| FULL TEXT
Influenza-associated deaths among children.
van der Wouden et al.
NEJM 2006;354:1317-1318.
FULL TEXT
Lessons Learned From Inpatient Vaccination in Michigan
Winston et al.
American Journal of Medical Quality 2006;21:125-133.
ABSTRACT
COPD exacerbations {middle dot} 2: Aetiology.
Sapey and Stockley
Thorax 2006;61:250-258.
ABSTRACT
| FULL TEXT
High Levels of Adamantane Resistance Among Influenza A (H3N2) Viruses and Interim Guidelines for Use of Antiviral Agents--United States, 2005-06 Influenza Season
JAMA 2006;295:881-882.
FULL TEXT
Efficacy of Quinolones against Secondary Pneumococcal Pneumonia after Influenza Virus Infection in Mice
Hayashi et al.
Antimicrob. Agents Chemother. 2006;50:748-751.
ABSTRACT
| FULL TEXT
Influenza Among Healthy Young Children: Changes in Parental Attitudes and Predictors of Immunization During the 2003 to 2004 Influenza Season
Daley et al.
Pediatrics 2006;117:e268-e277.
ABSTRACT
| FULL TEXT
Influenza -- Interpandemic as Well as Pandemic Disease
Dolin
NEJM 2005;353:2535-2537.
FULL TEXT
Influenza-Associated Deaths among Children in the United States, 2003-2004
Bhat et al.
NEJM 2005;353:2559-2567.
ABSTRACT
| FULL TEXT
Trends in Hospitalizations for Pneumonia Among Persons Aged 65 Years or Older in the United States, 1988-2002
Fry et al.
JAMA 2005;294:2712-2719.
ABSTRACT
| FULL TEXT
A Pilot Study of the Effectiveness of a School-Based Influenza Vaccination Program
King et al.
Pediatrics 2005;116:e868-e873.
ABSTRACT
| FULL TEXT
Neurological and Neuromuscular Disease as a Risk Factor for Respiratory Failure in Children Hospitalized With Influenza Infection
Keren et al.
JAMA 2005;294:2188-2194.
ABSTRACT
| FULL TEXT
Influenza Vaccine Confusion: A Call for an Alternative Evidence-Based Approach
Yogev
Pediatrics 2005;116:1214-1215.
FULL TEXT
Explaining Trends in Hospitalizations for Pneumonia and Influenza in the Elderly
Hebert et al.
Med Care Res Rev 2005;62:560-582.
ABSTRACT
Missed Opportunities for Influenza Vaccination in Children With Chronic Medical Conditions
Daley et al.
Arch Pediatr Adolesc Med 2005;159:986-991.
ABSTRACT
| FULL TEXT
Identifying Pediatric Age Groups for Influenza Vaccination Using a Real-Time Regional Surveillance System
Brownstein et al.
Am J Epidemiol 2005;162:686-693.
ABSTRACT
| FULL TEXT
Reduction of Inappropriate Hospital Admissions of Children With Influenza-Like Illness Through the Implementation of Specific Guidelines: A Case-Controlled Study
De Marco et al.
Pediatrics 2005;116:e506-e511.
ABSTRACT
| FULL TEXT
Influenza Vaccination Trends Among Adults 65 Years or Older in the United States, 1989-2002
Lu et al.
Arch Intern Med 2005;165:1849-1856.
ABSTRACT
| FULL TEXT
Enhanced Expression of an {alpha}2,6-Linked Sialic Acid on MDCK Cells Improves Isolation of Human Influenza Viruses and Evaluation of Their Sensitivity to a Neuraminidase Inhibitor
Hatakeyama et al.
J. Clin. Microbiol. 2005;43:4139-4146.
ABSTRACT
| FULL TEXT
Novel mechanism of immunosuppression by influenza virus haemagglutinin: selective suppression of interleukin 12 p35 transcription in murine bone marrow-derived dendritic cells
Noone et al.
J. Gen. Virol. 2005;86:1885-1890.
ABSTRACT
| FULL TEXT
Diesel Exhaust Enhances Influenza Virus Infections in Respiratory Epithelial Cells
Jaspers et al.
Toxicol Sci 2005;85:990-1002.
ABSTRACT
| FULL TEXT
Does This Patient Have Influenza?
Call et al.
JAMA 2005;293:987-997.
ABSTRACT
| FULL TEXT
The real impact of influenza?
Rohde
Thorax 2004;59:1073-1073.
FULL TEXT
Weathering the Influenza Vaccine Crisis
Treanor
NEJM 2004;351:2037-2040.
FULL TEXT
Childhood Influenza-Vaccination Coverage--United States, 2002-03 Influenza Season
JAMA 2004;292:2074-2075.
FULL TEXT
|
