Incidence of Outpatient Visits and Hospitalizations Related to Influenza in Infants and Young Children
* Center for Child Health Care Studies
|| Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts
National Center for Infectious Diseases
National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia
¶ Department of Laboratory Medicine
# Division of General Pediatrics, Children’s Hospital, Boston, Massachusetts
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONREFERENCES |
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Objective. The Advisory Committee on Immunization Practices currently encourages influenza vaccination for all children aged 6 to 23 months when feasible, based on studies that have demonstrated that young children have high hospitalization rates attributable to influenza. The Advisory Committee on Immunization Practices recently voted to recommend influenza vaccination for all children beginning during the 2004–2005 influenza season; information on the rate of outpatient visits due to influenza is needed to better evaluate the potential health impact and cost-effectiveness of the recommendation. We estimated the incidence of outpatient visits as well as hospitalizations for specific acute respiratory illnesses and for influenza-associated outpatient-visit and hospitalization rates among healthy infants and children in a Massachusetts health maintenance organization.
Design/Methods. Surveillance data were used to identify when influenza viruses, respiratory syncytial viruses, and parainfluenza viruses were circulating in the greater Boston area during 1994–2000. Using computerized medical records, we identified outpatient visits and hospitalizations for selected respiratory illnesses. Outpatient-visit rates and hospitalizations attributed to influenza were calculated by subtracting the rate of visits during the periseasonal period from the rate of visits during the influenza period. Rates were stratified by age and risk for complications from influenza.
Results. Between 1994 and 2000, there were 188 139 outpatient visits and 885 hospitalizations for respiratory illnesses in the study population. Among healthy children aged 6 to 23 months, the rate per 100 person-months for outpatient visits during influenza periods was 14.5 (95% confidence interval [CI]: 13.9 to 15.1), and the excess rate that could be attributed to influenza compared with the periseasonal period was 1.8 (95% CI: 1.1 to 2.4). Among healthy children, the rate of hospitalizations for acute respiratory disease was 10.4 per 10 000 person-months (95% CI: 6.0 to 17.0), and the rate that could be attributed to influenza when compared with the periseasonal baseline period was 3.9 (95% CI: –2.0 to 0.0). Among children who were at high risk for complications from influenza, the rate of outpatient visits per 100 person-months was 28.7 (95% CI: 26.6 to 30.9) during influenza periods. The rate of hospitalizations among high-risk children was 44.6 per 10 000 person-months (95% CI: 19.0 to 17.0).
Conclusion. Influenza season is associated with a substantial increase in outpatient visits by healthy children. These estimates of outpatient visits for influenza will help quantify the potential health benefits and cost savings from influenza vaccination of healthy children aged 6 to 23 months.
Key Words: influenza • children • epidemiology • hospitalization • outpatient visit
Abbreviations: ACIP, Advisory Committee on Immunization Practices • HMO, health maintenance organization • HPHC, Harvard Pilgrim Health Care • HVMA, Harvard Vanguard Medical Associates • CDC, Centers for Disease Control and Prevention • ICD-9, International Classification of Diseases, Ninth Revision • RSV, respiratory syncytial virus • CI, confidence interval
Influenza is a leading cause of respiratory illness among children.1 The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics Committee on Infectious Diseases currently encourage influenza vaccination of healthy children aged 6 to 23 months, a group whose influenza-associated hospitalization rates are comparable to those of other high-risk groups including the elderly.2–5 In addition, the ACIP recently voted to recommend influenza vaccination for children in this age group for the 2004–2005 influenza season.6 The ACIP has requested more evidence about the safety and effectiveness of the vaccine in 6- to 23-month-old children. The severity of the current influenza season has illustrated the need for more information regarding the epidemiology of influenza as well as health care use related to influenza.
In addition to recommendations from national groups, a key component in the uptake of newly recommended childhood vaccines is financial support for the program.7 Clearer information on the potential impact of vaccinating children in this age group is needed for reimbursement decisions.5 Cost-effectiveness is an important consideration in decisions about financing new vaccination programs.8,9 Previous cost-effectiveness analyses have suggested that influenza vaccination of young children may result in cost savings, but these analyses have been based on limited empirical data about health care utilization rates due to influenza.10,11
Improving our understanding of the cost-effectiveness of influenza vaccination for children will require more data on the rates of outpatient visits attributable to influenza. Outpatient costs often are important determinants of the cost-effectiveness of vaccination programs.12,13 Outpatient visits may also represent a higher direct economic cost due to influenza than do hospitalizations; however, scant data currently exist about the rate of outpatient visits due to childhood influenza.3,14
This study’s primary purpose was to estimate the rate of outpatient visits attributable to influenza in healthy children in a large health maintenance organization (HMO). We also evaluated the influenza-attributable rates of outpatient visits among high-risk children and the influenza-attributable hospitalization rates among both healthy and high-risk children.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Study Population
Children aged 6 months through 17 years who were enrolled in Harvard Pilgrim Health Care (HPHC) and affiliated provider group Harvard Vanguard Medical Associates (HVMA) between October 1994 and September 2000 comprised the study population. HPHC is a group-model HMO, and HVMA is a large, multispecialty group practice with 14 health centers in the Boston, Massachusetts area. Subjects were eligible for inclusion in the study if they had been continuously enrolled for 1 year or since birth at the start of each influenza season. The average annual number of study subjects was 48 551, and a total of 82 170 children were included in the study population. Age was calculated at the beginning of each influenza season.
Outpatient Data
Data sets created for the Vaccine Safety Datalink study from electronic medical records were used to complete the outpatient analysis. The Vaccine Safety Datalink is a large, linked database project that is funded by the National Immunization Program, Centers for Disease Control and Prevention (CDC).2 HVMA data were analyzed on a total of 188 139 outpatient and emergency department visits during the study period. HVMA uses automated medical records, which are the sole source of clinical information regarding HVMA outpatient visits.
Because influenza is often not diagnosed specifically in children with respiratory illnesses, it is necessary to examine a broad range of International Classification of Diseases, Ninth Revision (ICD-9) codes when attempting to estimate illness associated with influenza. Influenza is also associated with a number of secondary infections that should be included when estimating health care utilization related to influenza. Outpatient visits for acute respiratory disease were defined by using the ICD-9 codes 460 to 466.99, 480.8, 480.9, 481.0, 482, 482.2, 482.3, 482.9, 483, 485, 485.0, 486, 486.0, 487 to 487.99, and 493 to 493.99 (Appendix 1).15 This list of ICD-9 codes includes influenza, acute respiratory diseases, and pneumonia. Codes that indicate a diagnosis of pneumonia but specify a cause of infection (such as mycoplasma or chlamydia) that is not related to influenza were excluded.
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Hospitalization Data
Hospitalizations for acute respiratory disease were defined by using 2 sets of ICD-9 codes. Data from HPHC claims files were used to analyze hospitalizations. The primary analysis included the codes previously listed for the outpatient analysis. The primary analysis included 731 hospitalizations. To compare the inpatient rates with other published data, we also conducted a secondary analysis by using an expanded set of ICD-9 codes that were used by Izurieta et al.4 The second set included a broader range of ICD-9 codes: 460 to 496 and 510 to 519 (Appendix 2). There were 885 hospitalizations identified for acute respiratory disease in the secondary analysis. We did not include hospitalizations for cardiovascular conditions, because we wanted to include conditions that were similar to the analysis that was completed by Izurieta et al.4
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High-Risk Status
To evaluate the rate of outpatient visits related to influenza among healthy children, we stratified the population into 2 groups: healthy children and those at high risk for complications from influenza. High-risk children have been shown to have a higher rate of hospitalizations and outpatient visits than healthy children.16,17 Children who had been diagnosed with any of a number of chronic or serious illnesses, including cardiopulmonary, autoimmune, or renal diseases and cancer (Appendix 3), in the 1 year before the start of each influenza season were identified as high risk.4 Children were considered healthy if they had not been hospitalized and did not have an outpatient or emergency department visit for any of these conditions during the year before the start of each influenza season.
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Viral Surveillance Data
Surveillance data from local laboratories were used to determine when influenza and respiratory syncytial viruses (RSVs) were circulating in the greater Boston area. Data were contributed by: the National Respiratory and Enteric Virus Surveillance System of the CDC; the Influenza Branch of the CDC; the Massachusetts Department of Public Health, State Laboratory Institute and the Department of Laboratory Medicine, Children’s Hospital, Boston. Surveillance data from the CDC were used as the primary source of information and combined with data from the Massachusetts Department of Public Health and Children’s Hospital for time periods for which CDC surveillance data were unavailable.
Study Periods
Five seasonal study periods were defined by using a method developed by Izurieta et al.4 This method allows for seasonal variation in influenza epidemics and takes into account the circulation of other respiratory viruses that may cause symptoms that are similar to those of influenza. The 5 periods were:
- Influenza virus period: any period of
2 consecutive weeks between October and May in which influenza accounted for 5% of the season’s total number of influenza virus isolates and <5% of the season’s total RSV isolates.
- Extended influenza virus period: any period of 2 consecutive weeks in which influenza accounted for 5% of the season’s total number of influenza virus isolates and the circulation of other viruses was not considered.
- RSV period: any period of 2 consecutive weeks between October and May in which each week accounted for 5% of the season’s total number of RSV isolates and <5% of the season’s total influenza virus isolates.
- Periseasonal baseline period: any period of 2 consecutive weeks between October and May in which each week accounted for <5% of total RSV isolates and <5% of influenza virus isolates and no parainfluenza 1 or 3.
- Summer baseline period: any period of 2 consecutive weeks between June and September in which no isolates of influenza virus, RSVs, or parainfluenza virus 1 or 3 were identified.4
Alternative Method to Define Seasonal Periods
We also considered using the methods for defining seasonal periods that were developed by Neuzil et al.3 This method defines influenza and RSV seasons by using different criteria than the method described previously. When our surveillance data were analyzed by using the alternative method, there was very little separation between the respiratory syncytial weeks and the influenza weeks. Because no influenza-predominant periods emerged, we were unable to calculate rates attributed to influenza and did not pursue this analytic approach further.
Statistical Analysis
Outpatient visits per 100 person-months during each of the seasonal periods were calculated, and hospitalizations were calculated by using 10 000 person-months as the denominator. Outpatient-visit rates and hospitalizations that could be attributed to influenza were calculated by subtracting the rate during the influenza periods from the rate during periseasonal and summer baseline periods from the influenza season rates. Exact 95% confidence intervals (CIs) were calculated by using the normal approximation to the binomial.18 All analyses were completed by using SAS (SAS Institute, Cary, NC), version 8.2. For the primary analysis, rates were stratified by age and risk status.
Race-adjusted rates and CIs for all 6- to 23- month-old children were calculated by using the direct standardization method for both outpatient visits and hospitalizations using race data from the US census that reflected the national race distributions during each of the study years.18,19 Race data for the study population were obtained from birth certificate data provided by the Massachusetts Department of Public Health. We could not adjust for race in the older age groups, because race data for children who migrated into the HMO are not consistently available.
A 2-level socioeconomic variable was constructed by linking data from the 2000 US census with a geocode variable provided by Mapping Analytics Inc (Rochester, NY) that was created based on the address information of each study subject.20 Subjects were identified by whether they lived in an impoverished census tract or not. An impoverished census tract was defined as any tract in which 20% of the population lived below the poverty level.21 The remaining census tracts, in which <20% of the population lived below the poverty level, were defined as not impoverished. Outpatient rates and hospitalizations were calculated by using the method described previously and were stratified by age, risk, and poverty status.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Surveillance Data
Between 1994 and 2000, a total of 2883 viruses were detected in 20 631 respiratory specimens in the Boston area. Of these viruses, 679 were influenza viruses and 2056 were RSVs. There was a total of 15 weeks during which influenza viruses predominated and a total of 20 weeks in which RSVs predominated. The period of extended influenza circulation accounted for a total of 48 weeks. The periseasonal baseline period consisted of 54 weeks, and the summer baseline period consisted of 47 weeks. Figure 1 shows the circulation of influenza viruses and RSVs during the 1996–1997 influenza season.
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Outpatient-Visit Rates
The rates of outpatient visits attributable to influenza among both healthy and high-risk 6- to 23-month-old children were significant. Among healthy children aged 6 to 23 months, the rate of outpatient visits for acute respiratory diseases during periods in which influenza predominated over other respiratory diseases was 14.5 per 100 person-months (95% CI: 13.9 to 15.1) (Table 1). The rate that could be attributed to influenza during these periods compared with the rate during the periseasonal baseline period was 1.8 per 100 person-months (95% CI: 1.1 to 2.4) (Table 2). The rate of outpatient visits among healthy 6- to 23-month-old children that could be attributed to influenza compared with the rate during the summer baseline period was 8.9 per 100 person-months (95% CI: 8.3 to 9.5) (Table 2).
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Among children aged 6 to 23 months who were at high risk for complications from influenza, the rate of outpatient visits for acute respiratory diseases during periods in which influenza predominated was 28.7 per 100 person-months (95% CI: 26.6 to 30.9) (Table 1). The rate that could be attributed to influenza compared with the rate during the periseasonal baseline period was 2.6 per 100 person-months (95% CI: 0.24 to 5.0) (Table 2). The rate of outpatient visits among high-risk 6- to 23-month-old children that could be attributed to influenza compared with the rate during the summer baseline period was 16.1 per 100 person-months (95% CI: 13.9 to 18.4) (Table 2).
Hospitalization Rates
In the primary analysis of hospitalization rates, which used the same codes for acute respiratory illness as the outpatient analysis, the rate of acute respiratory illness-associated hospitalizations among healthy 6- to 23-month-old children during periods in which influenza was circulating was 10.4 per 10 000 person-months (95% CI: 6.0 to 17.0) (Table 3). The rate of hospitalizations that was attributable to influenza compared with the periseasonal baseline period was 3.9 per 10 000 person-months (95% CI: –2.0 to 10.0) (Table 4). The hospitalization rate that could be attributed to influenza compared with the rate during the summer baseline period was 5.1 per 10 000 person-months (95% CI –1.0 to 11.0) (Table 4).
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When we used the primary definition of acute respiratory illness, the rate of hospitalizations among high-risk children aged 6 to 23 months was 44.6 per 10 000 person-months (95% CI: 19.0 to 88.0) during periods in which influenza predominated (Table 3). The rate of hospitalizations that could be attributed to influenza compared with the rate during the periseasonal baseline period was 6.1 per 10 000 person-months (95% CI: –28.0 to 41.0) (Table 4). The hospitalization rate that could be attributed to influenza compared with the rate during the summer baseline period was 21.3 per 10 000 person-months (95% CI: –12.0 to 55.0) (Table 4).
In the secondary analysis of hospitalization rates, in which the expanded definition of acute respiratory illness was used, the rates of hospitalizations during influenza-predominant periods were slightly different from the rates determined by using the more-limited definition. The rates of hospitalizations among healthy children aged 6 to 23 months that could be attributed to influenza when compared with the periseasonal baseline and summer baseline periods were both significant. Among high-risk children, the rates were slightly different from the high-risk results from the primary analysis, but none were significant.
Race and Poverty Adjustment
The race-adjusted rate of outpatient visits among healthy 6- to 23-month-old children during influenza periods was 16.2 per 100 person-months (95% CI: 15.6 to 16.9) (Table 1). The race-adjusted rate of outpatient visits during periods when influenza was circulating among high-risk 6- to 23-month-old children was 35.6 per 100 person-months (95% CI: 33.3 to 38.0) (Table 1). The results were similar for hospitalizations among healthy and high-risk children.
There were no significant differences between rates of outpatient visits or hospitalizations during influenza periods among healthy or high-risk 6- to 23-month old children when the rates were stratified by poverty status. The rate of outpatient visits among healthy 6- to 23- month-old children who lived in poor census tracts was 13.7 per 100 person-months (95% CI: 12.0 to 15.4), and the rate for 6- to 23-month-old children who did not live in poor census tracts was 14.7 per 100 person-months (95% CI: 14.0 to 15.4). The rate of outpatient visits among high-risk 6- to 23- month-old children who lived in poor census tracts was 29.6 per 100 person-months (95% CI: 24.6 to 34.7), and the rate for 6- to 23-month-old children who did not live in poor census tracts was 29.0 per 100 person-months (95% CI: 26.4 to 31.7) (table is available on request).
High-Risk Status
On average, 10.8% of children were identified annually as high risk, and each of these children had an average of 1.05 high-risk conditions. The most prevalent high-risk conditions included asthma, which accounted for an average of 79% of all high-risk conditions per year. Cardiovascular diseases accounted for an average of 8% of all high-risk conditions, and all other diseases accounted for 13% of high-risk conditions.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONREFERENCES |
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Circulation of influenza viruses was associated with a substantial elevation in outpatient visits as well as hospitalizations for healthy children of all ages, with the highest rates among 6- to 23-month-old children. These findings lend support to recent recommendations by ACIP and the American Academy of Pediatrics Committee on Infectious Diseases to vaccinate children in this age group against influenza when feasible.2 The observed rates of outpatient visits and hospitalizations are comparable with those in 2 previous studies.3,4 More extensive evaluations of influenza-vaccination programs tailored to different populations and health care settings are warranted to inform decisions regarding the universal recommendation of influenza vaccination for children 6 to 23 months of age.
Comparisons With Other Studies
There is a dearth of information in the literature about outpatient visits associated with influenza. To our knowledge, only 2 previous studies have evaluated outpatient-visit rates associated with influenza, 1 in a Tennessee Medicaid population3 and the other in Vanderbilt’s vaccine-research clinic.14 Our study is unique in that we were able to use specific diagnostic codes to identify outpatient visits for influenza and other respiratory conditions. The rate of outpatient visits attributable to influenza among 6- to 23-month-olds in the current study is 1.8 per 100 person-months. The average length of each influenza season was 4.7 months, which results in an annual rate of 8.5 outpatient visits attributable to influenza per 100 children. This is comparable with the rate in the Tennessee Medicaid study, which reported an annual rate of 6 to 15 per 100 children.3 The Vanderbilt vaccine-clinic study reported annual rates of 93 per 1000 among children aged <1 year and 110 per 1000 among 1- to 2- year olds.14 Although these rates are comparable, our study focused on different study years and used different seasonal definitions than the previous studies, thus the rates in these 2 populations may, in fact, be different.
Similar to a previous study in 2 west-coast HMOs,4 we found significantly increased rates of hospitalization attributable to influenza among the youngest age group compared with the periseasonal and summer baseline periods when using the expanded set of ICD-9 codes. The hospitalization rates among 6- to 23-month-old children in this study (3.9 per 10 000 person-months, using the primary definition and 6.4 per 10 000 person-months using the expanded set of ICD-9 codes) appear somewhat lower than those among 0- to 1-year-old children in the previous study, which reported rates of 112 and 86 per 100 000 person-months.4 This may be due to differences in the ages of the children included or to differences in inclusion criteria for hospitalizations. The hospitalization rates among the older children were comparable to those in the previous study.
Race and Poverty Adjustment
The rates of outpatient visits and hospitalizations during all seasonal periods in the race-adjusted analysis were slightly higher than the rates in the unadjusted analysis, but they were comparable. We found no difference in rates of outpatient visits or hospitalizations between children who were identified as poor and nonpoor. This implies that children of different socioeconomic status may use influenza-related services at the same rate when financial access to health care is equalized. These results suggest that the higher rates of influenza-associated hospitalizations observed in the study of Tennessee Medicaid patients relative to the study in the 2 west-coast HMOs may have stemmed at least in part from differences in health care system factors rather than income-associated factors alone.
Limitations
Disentangling the effects of influenza from those of RSV remains a challenge in epidemiologic studies that use an ecologic approach to assess the influence of these viruses on health care utilization.22 We adopted the methods of a previous study that used regional laboratory data to separate the effects of influenza from those of RSV.3,4 Because testing for influenza is uncommon in outpatient settings, scant data exist on the incidence of laboratory-confirmed influenza virus infections in pediatric outpatients. Therefore, we selected diagnostic codes to define "influenza-attributable illness" and virologic surveillance data to define when influenza viruses were predominant. However, this approach does not completely eliminate confounding by either RSV or other respiratory pathogens that may occur during the same time periods as influenza. Thus, rates of outpatient visits and hospitalizations reported here may overestimate the actual burden associated with influenza circulation. Conversely, there may have been visits during the periseasonal periods that could have been attributed to influenza and were not captured in our influenza-attributable rate. By choosing to focus on acute respiratory disease, we may also underestimate the true burden of influenza by not capturing all diagnoses for otitis media, febrile seizures, gastrointestinal presentations, sepsis, and encephalopathy.23,24
In addition, health care use represents only a portion of the morbidity and cost due to influenza. A prospective study of school-aged children in Seattle found that only one fourth of those with influenza episodes made a health care visit.25 The school days missed by children and work days missed by parents far outnumbered outpatient visits for this illness. Thus, our study’s results should be considered with those from other studies in any assessment of the total burden of influenza and the potential benefit of vaccination among children aged 6 to 23 months.
Conclusions and Policy Implications
This study confirms that influenza is associated with substantial increases in outpatient visits during the influenza season compared with the periinfluenza season. The results of this study are also in agreement with past studies that concluded that the rate of hospitalizations attributable to influenza among the youngest age group is greater than the rate of hospitalizations among older children and adolescents. Influenza-associated outpatient visit use in general populations is comparable with previous estimates, with the observed visit rates depending on length of influenza season and diagnostic inclusion criteria as well as the population and health care system under study.
These findings provide the basis for an updated evaluation of the cost-effectiveness of childhood influenza vaccination. Because outpatient visits are very common relative to hospitalizations, their costs and incidence are likely to be key determinants of the cost-effectiveness of influenza vaccines. Outpatient illness also is associated with work loss by parents of children with influenza, and this is another important driver of costs. Expanded influenza vaccination of young children might have a greater impact in reducing influenza-attributable visits and associated costs in outpatient settings compared with hospital settings.
On the basis of these results, updated evaluations of the risk-benefit tradeoffs and cost-effectiveness of childhood influenza vaccination are warranted. Studies such as the Virus Watch,26,27 which was conducted during the 1960s and 1970s, could provide data that would measure the health care utilization and societal burden of influenza more accurately. Improved rapid influenza diagnostic tests with higher sensitivities are also needed to test for influenza among children treated for respiratory illnesses during influenza season.28 Epidemiologic studies using these improved methods would provide better data for future cost-effectiveness estimates.
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ACKNOWLEDGMENTS |
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This study was supported by the Vaccine Safety Datalink Project, National Immunization Program, Centers for Disease Control and Prevention, via a contract with the American Association of Health Plans.
We gratefully acknowledge the contributions of Barbara Werner and Raimond Konomi of the Massachusetts Department of Public Health, State Laboratory Institute, who shared influenza surveillance data. We thank Charlene Gay for assistance with the manuscript.
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FOOTNOTES |
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Received for publication Aug 7, 2003; Accepted Nov 20, 2003.
Reprint requests to (M.A.O.) Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, 133 Brookline Ave, 6th Fl, Boston, MA 02215. E-mail: megan_Vobrien@hphc.org
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 L. Finelli, A. Fiore, R. Dhara, L. Brammer, D. K. Shay, L. Kamimoto, A. Fry, J. Hageman, R. Gorwitz, J. Bresee, et al. Influenza-Associated Pediatric Mortality in the United States: Increase of Staphylococcus aureus Coinfection Pediatrics, October 1, 2008; 122(4): 805 - 811. [Abstract] [Full Text] [PDF]
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Committee on Infectious Diseases Prevention of Influenza: Recommendations for Influenza Immunization of Children, 2007-2008 Pediatrics, April 1, 2008; 121(4): e1016 - e1031. [Abstract] [Full Text] [PDF]
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T. Nolan, D. I. Bernstein, S. L. Block, M. Hilty, H. L. Keyserling, C. Marchant, H. Marshall, P. Richmond, R. Yogev, J. Cordova, et al. Safety and Immunogenicity of Concurrent Administration of Live Attenuated Influenza Vaccine With Measles-Mumps-Rubella and Varicella Vaccines to Infants 12 to 15 Months of Age Pediatrics, March 1, 2008; 121(3): 508 - 516. [Abstract] [Full Text] [PDF]
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T. Vesikari, A. Karvonen, H. M. Smith, A. Dunning, A. Razmpour, M. K. Saville, W. C. Gruber, and B. D. Forrest Safety and Tolerability of Cold-Adapted Influenza Vaccine, Trivalent, in Infants Younger Than 6 Months of Age Pediatrics, March 1, 2008; 121(3): e568 - e573. [Abstract] [Full Text] [PDF]
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D. M. Zerr, J. A. Englund, A. S. Robertson, E. K. Marcuse, M. M. Garrison, and D. A. Christakis Hospital-Based Influenza Vaccination of Children: An Opportunity to Prevent Subsequent Hospitalization Pediatrics, February 1, 2008; 121(2): 345 - 348. [Abstract] [Full Text] [PDF]
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E. K. Miller, M. R. Griffin, K. M. Edwards, G. A. Weinberg, P. G. Szilagyi, M. A. Staat, M. K. Iwane, Y. Zhu, C. B. Hall, G. Fairbrother, et al. Influenza Burden for Children With Asthma Pediatrics, January 1, 2008; 121(1): 1 - 8. [Abstract] [Full Text] [PDF]
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 A. G. S. C. Jansen, E. A. M. Sanders, A. W. Hoes, A. M. van Loon, and E. Hak Influenza- and respiratory syncytial virus-associated mortality and hospitalisations Eur. Respir. J., December 1, 2007; 30(6): 1158 - 1166. [Abstract] [Full Text] [PDF]
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S. W. Roush, T. V. Murphy, and and the Vaccine-Preventable Disease Table Working Historical Comparisons of Morbidity and Mortality for Vaccine-Preventable Diseases in the United States JAMA, November 14, 2007; 298(18): 2155 - 2163. [Abstract] [Full Text] [PDF]
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M. C. Shinall Jr, E. J. Plosa, and K. A. Poehling Validity of Parental Report of Influenza Vaccination in Children 6 to 59 Months of Age Pediatrics, October 1, 2007; 120(4): e783 - e787. [Abstract] [Full Text] [PDF]
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E. N. Lewis, M. R. Griffin, P. G. Szilagyi, Y. Zhu, K. M. Edwards, and K. A. Poehling Childhood Influenza: Number Needed to Vaccinate to Prevent 1 Hospitalization or Outpatient Visit Pediatrics, September 1, 2007; 120(3): 467 - 472. [Abstract] [Full Text] [PDF]
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S. E. Coffin, T. E. Zaoutis, A. B. W. Rosenquist, K. Heydon, G. Herrera, C. B. Bridges, B. Watson, R. Localio, R. L. Hodinka, and R. Keren Incidence, Complications, and Risk Factors for Prolonged Stay in Children Hospitalized With Community-Acquired Influenza Pediatrics, April 1, 2007; 119(4): 740 - 748. [Abstract] [Full Text] [PDF]
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C. M. Shuler, M. Iwamoto, C. B. Bridges, M. Marin, R. Neeman, P. Gargiullo, T. A. Yoder, H. L. Keyserling, and P. D. Terebuh Vaccine Effectiveness Against Medically Attended, Laboratory-Confirmed Influenza Among Children Aged 6 to 59 Months, 2003-2004 Pediatrics, March 1, 2007; 119(3): e587 - e595. [Abstract] [Full Text] [PDF]
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 K. A. Spaude, E. Abrutyn, C. Kirchner, A. Kim, J. Daley, and D. N. Fisman Influenza Vaccination and Risk of Mortality Among Adults Hospitalized With Community-Acquired Pneumonia Arch Intern Med, January 8, 2007; 167(1): 53 - 59. [Abstract] [Full Text] [PDF]
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T. Vesikari, D. M. Fleming, J. F. Aristegui, A. Vertruyen, S. Ashkenazi, R. Rappaport, J. Skinner, M. K. Saville, W. C. Gruber, B. D. Forrest, et al. Safety, Efficacy, and Effectiveness of Cold-Adapted Influenza Vaccine-Trivalent Against Community-Acquired, Culture-Confirmed Influenza in Young Children Attending Day Care Pediatrics, December 1, 2006; 118(6): 2298 - 2312. [Abstract] [Full Text] [PDF]
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K. Ampofo, P. H. Gesteland, J. Bender, M. Mills, J. Daly, M. Samore, C. Byington, A. T. Pavia, and R. Srivastava Epidemiology, Complications, and Cost of Hospitalization in Children With Laboratory-Confirmed Influenza Infection Pediatrics, December 1, 2006; 118(6): 2409 - 2417. [Abstract] [Full Text] [PDF]
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 A. L. Naleway, W. J. Smith, and J. P. Mullooly Delivering Influenza Vaccine to Pregnant Women Epidemiol. Rev., August 1, 2006; 28(1): 47 - 53. [Abstract] [Full Text] [PDF]
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 K. A. Poehling, K. M. Edwards, G. A. Weinberg, P. Szilagyi, M. A. Staat, M. K. Iwane, C. B. Bridges, C. G. Grijalva, Y. Zhu, D. I. Bernstein, et al. The underrecognized burden of influenza in young children. N. Engl. J. Med., July 6, 2006; 355(1): 31 - 40. [Abstract] [Full Text] [PDF]
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F. T. Bourgeois, C. Valim, J. C. Wei, A. J. McAdam, and K. D. Mandl Influenza and Other Respiratory Virus-Related Emergency Department Visits Among Young Children Pediatrics, July 1, 2006; 118(1): e1 - e8. [Abstract] [Full Text] [PDF]
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J. C. van der Wouden, H. J. Bueving, S. Thomas, J. A. Linder, N. Bhat, D. K. Shay, and T. M. Uyeki Influenza-associated deaths among children. N. Engl. J. Med., March 23, 2006; 354(12): 1317 - 1318. [Full Text] [PDF]
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 J S Nguyen-Van-Tam Influenza related hospital admissions in children: evidence about the burden keeps growing but the route to policy change remains uncertain Arch. Dis. Child., January 1, 2006; 91(1): 5 - 7. [Full Text] [PDF]
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N. Bhat, J. G. Wright, K. R. Broder, E. L. Murray, M. E. Greenberg, M. J. Glover, A. M. Likos, D. L. Posey, A. Klimov, S. E. Lindstrom, et al. Influenza-Associated Deaths among Children in the United States, 2003-2004 N. Engl. J. Med., December 15, 2005; 353(24): 2559 - 2567. [Abstract] [Full Text] [PDF]
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K. M. Neuzil and M. R. Griffin Vaccine Safety--Achieving the Proper Balance JAMA, December 7, 2005; 294(21): 2763 - 2765. [Full Text] [PDF]
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R. Keren, T. E. Zaoutis, C. B. Bridges, G. Herrera, B. M. Watson, A. B. Wheeler, D. J. Licht, X. Q. Luan, and S. E. Coffin Neurological and Neuromuscular Disease as a Risk Factor for Respiratory Failure in Children Hospitalized With Influenza Infection JAMA, November 2, 2005; 294(17): 2188 - 2194. [Abstract] [Full Text] [PDF]
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 S. Goldberg, S. Schwartz, G. Izbicki, R. B. Hamami, and E. Picard Sensitivity of Exercise Testing for Asthma in Adolescents Is Halved in the Summer Chest, October 1, 2005; 128(4): 2408 - 2411. [Abstract] [Full Text] [PDF]
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 J. S. Brownstein, K. P. Kleinman, and K. D. Mandl Identifying Pediatric Age Groups for Influenza Vaccination Using a Real-Time Regional Surveillance System Am. J. Epidemiol., October 1, 2005; 162(7): 686 - 693. [Abstract] [Full Text] [PDF]
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G. De Marco, S. Mangani, A. Correra, S. Di Caro, L. Tarallo, A. De Franciscis, T. Jefferson, and A. Guarino Reduction of Inappropriate Hospital Admissions of Children With Influenza-Like Illness Through the Implementation of Specific Guidelines: A Case-Controlled Study Pediatrics, October 1, 2005; 116(4): e506 - e511. [Abstract] [Full Text] [PDF]
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D. P. Ritzwoller, C. B. Bridges, S. Shetterly, K. Yamasaki, M. Kolczak, and E. K. France Effectiveness of the 2003-2004 Influenza Vaccine Among Children 6 Months to 8 Years of Age, With 1 vs 2 Doses Pediatrics, July 1, 2005; 116(1): 153 - 159. [Abstract] [Full Text] [PDF]
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S S S Teo, J S Nguyen-Van-Tam, and R Booy Influenza burden of illness, diagnosis, treatment, and prevention: what is the evidence in children and where are the gaps? Arch. Dis. Child., May 1, 2005; 90(5): 532 - 536. [Abstract] [Full Text] [PDF]
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A. Kempe, M. F. Daley, J. Barrow, N. Allred, N. Hester, B. L. Beaty, L. A. Crane, K. Pearson, and S. Berman Implementation of Universal Influenza Immunization Recommendations for Healthy Young Children: Results of a Randomized, Controlled Trial With Registry-Based Recall Pediatrics, January 1, 2005; 115(1): 146 - 154. [Abstract] [Full Text] [PDF]
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