High costs of influenza: Direct medical costs of influenza disease in young children

Vaccine 28 (2010) 4913–4919

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High costs of influenza: Direct medical costs of influenza disease in young children夽 Gerry Fairbrother a,∗ , Amy Cassedy b , Ismael R. Ortega-Sanchez c , Peter G. Szilagyi d , Kathryn M. Edwards e , Noelle-Angelique Molinari c , Stephanie Donauer b , Diana Henderson f , Sandra Ambrose d , Diane Kent e , Katherine Poehling g , Geoffrey A. Weinberg d , Marie R. Griffin e , Caroline B. Hall d , Lyn Finelli c , Carolyn Bridges c , Mary Allen Staat f , the New Vaccine Surveillance Network (NVSN)c a

Health Policy and Clinical Effectiveness, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, United States Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States c National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States d School of Medicine and Dentistry, University of Rochester, Rochester, NY, United States e School of Medicine, Vanderbilt University, Nashville, TN, United States f Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States g Pediatrics, Epidemiology and Prevention, Wake Forest University, Winston-Salem, NC, United States b

a r t i c l e

i n f o

Article history: Received 30 September 2009 Received in revised form 3 May 2010 Accepted 16 May 2010 Available online 31 May 2010 Keywords: Children Medical cost Influenza

a b s t r a c t This study determined direct medical costs for influenza-associated hospitalizations and emergency department (ED) visits. For 3 influenza seasons, children <5 years of age with laboratory-confirmed influenza were identified through population-based surveillance. The mean direct cost per hospitalized child was $5402, with annual cost burden estimated at $44 to $163 million. Factors associated with highcost hospitalizations included intensive care unit (ICU) admission and having an underlying high-risk condition. The mean medical cost per ED visit was $512, with annual ED cost burden estimated at $62 to $279 million. Implementation of the current vaccination policies will likely reduce the cost burden. © 2010 Elsevier Ltd. All rights reserved.

1. Introduction Disease burden attributed to the influenza virus is substantial and results in excess hospitalizations and emergency department (ED) visits for children [1–4]. Although robust estimates of the total hospitalization burden exist [5], reported mean influenzarelated hospitalization costs vary widely for both children alone [6–8] and children and adults [9]. The mean costs for influenza hospitalizations ranged from $3521 [9], to $13,446 [7]. The methods, populations studied, and the results differ greatly, with the lowest estimates using ICD-9-CM codes [9] for the diagnosis of influenza rather than laboratory-confirmed influenza, and the highest esti-

Abbreviations: ED, emergency department; ACIP, Advisory Committee on Immunization Practices; NVSN, New Vaccine Surveillance Network; ICU, intensive care unit; IQR, interquartile range; ARI, acute respiratory infection. 夽 The contents of the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the Center for Disease Control. ∗ Corresponding author. Tel.: +1 513 636 0189; fax: +1 513 636 0171. E-mail address: [email protected] (G. Fairbrother). 0264-410X/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2010.05.036

mates using laboratory-confirmed influenza cases from tertiary care centers that included greater proportions of children with complex medical conditions [7,8]. The cost of influenza-related ED visits has received less attention than the cost of hospitalized cases, and has not been assessed in population-based settings. One study reported an estimated mean cost of $142 for ED visits, however data were collected over a decade ago [9]. While the overall costs for ED visits are reported to be small compared to inpatient services, far more ED influenza visits occur, thus adding substantially to the total cost burden of influenza [4,9]. Moreover, major gaps in our knowledge about the factors associated with high costs remain. Studies have shown that a small number of children often account for a disproportionate share of medical care expenditures [10–12]. Mean influenza cost estimates may be influenced by children with complex conditions requiring high levels of care. Indeed, studies have noted higher costs in older children and in children with high risk conditions [6,8,9]. However, the specific factors associated with high influenza-related costs need additional study. A better understanding of the factors associated with the direct medical costs of influenza can support

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the current efforts toward more effective control of influenza and thereby reduce costs associated with influenza illness. We assessed influenza costs using a multi-site, populationbased New Vaccine Surveillance Network (NVSN). Active inpatient and ED surveillance for acute respiratory infections (ARI) identified children with laboratory-confirmed influenza at the 3 NVSN sites. We examined the direct medical costs in children less than 5 years of age hospitalized or evaluated in the ED during 3 consecutive influenza seasons. We also evaluated factors associated with high-cost hospitalizations.

2. Methods 2.1. Study design and population The design and methods of the NVSN active population-based surveillance project have been previously described [4,13–17]. For this study, 3 seasons of data from the inpatient and ED surveillance were analyzed (2003–2004, 2004–2005, and 2005–2006) from three counties in the US which contain the cities of Nashville, Rochester, and Cincinnati. The surveillance hospitals at each county cared for >95% of hospitalized children in their respective counties, while the surveillance EDs at each county cared for a variable proportion of the county’s pediatric ED visits: 30% in Nashville, 60% in Rochester, and 95% in Cincinnati. For hospital surveillance, children were enrolled within 48 h of admission, Sunday through Thursday. In the ED, children were systematically enrolled at each site: 3–4 days per week in Nashville and Rochester (rotating days) and every fourth day in Cincinnati. Children admitted to the hospital through the ED were categorized as hospitalized and all costs from both sources were combined. Children eligible for enrollment were <5 years of age, had symptoms of an acute respiratory infection or fever, and were residents of the active surveillance counties. Children were excluded if they had fever and neutropenia associated with chemotherapy, were hospitalized in the prior 4 days, were transferred from another surveillance hospital, or had symptoms for greater than 14 days. Demographic, medical, and social histories were obtained by standardized interviews of the parents or guardians. Clinical laboratory evaluations, hospital course, and discharge diagnoses were obtained from hospital and ED records. High-risk medical conditions for influenza complications were recorded and included asthma and reactive airways disease, chronic lung conditions, cardiac disease, long-term salicylate therapy, sickle cell disease, immunologic disorders, kidney disease and chronic renal dysfunction, genetic metabolic syndromes, diabetes, neurological disorders, and other chronic diseases [18]. Children were considered premature if their parents reported that the child had been born more than 4 weeks early. Nasal and throat swabs were collected from each enrolled child for influenza culture and reverse transcriptase polymerase chain reaction (RT-PCR) testing. A child was considered influenza positive if either the viral culture or two independent RT-PCR tests on the same specimen were positive [4]. During 2003–2005, respiratory syncytial virus (RSV) cultures and RT-PCR testing were also performed. Cost and physician fee charge data were gathered from the accounting databases at each participating hospital. Although the billing source for each site varied, each contained similar data elements. Detailed data on services, procedures and costs were collected for each child; a physician from each of the 3 sites (MAS, PS, KE) sorted costs into the following 5 general summary categories following the typology of an earlier study: diagnostics, therapeutics, room costs, medical supplies and physician services

[8]. Department-specific cost-to-charge ratios that were available from hospitals were used to adjust these medical costs. Cost-tocharge ratios were not available for physician fees. To avoid issues inherent to traditional hospital accounting data systems, total costs for physician services were estimated using gross physician fees [19,20]. For a sensitivity analysis and projections, physician fees were later adjusted using a generic cost-to-charge ratio [21]. The Medical component of the Consumer Price Index was used to adjust costs for inflation converted to constant 2006 dollars. Data obtained from the hospital accounting databases were merged with the NVSN database to develop a comprehensive dataset which included demographic, medical, and cost data. Data from all 3 years and all 3 sites were combined. To examine high cost hospitalizations, children were grouped into 2 categories. If direct medical costs were in the top 10th percentile, the hospitalization was considered to be high cost [11], while those hospitalizations with costs in the lower 90th percentile were considered non-high cost. Pediatricians who categorized expenditures for all hospitalizations (MAS, PS, KE) also reviewed the medical records of the high cost children to determine to what extent their costs could be attributed to influenza. 2.2. Institutional Review Board Approval Informed written consent was obtained from the parent/guardian of each child enrolled. The Institutional Review Boards at the Centers for Disease Control and Prevention (CDC) and at each site approved the study. Neither the treating clinicians nor parents/guardians were informed of the research virology results during the hospitalization or ED visit. 2.3. Statistical analyses We summarized direct medical costs using univariate analysis and calculated means, standard deviations, medians, and interquartile distributions. We used the Kruskal–Wallis test to determine group differences in the median total costs and length of hospital stays, and the Chi-square and Fisher’s Exact tests to analyze the relationships and characteristics associated with high cost and non-high cost children. A two-sided P-value of <0.05 indicated statistical significance. We conducted all statistical analyses in SAS 9.1 (SAS Institute Inc. Cary, NC). We estimated the total cost burden of medically attended influenza (hospitalizations and ED visits) using mean costs from this study, and rates of hospitalizations and ED visits from an earlier study reporting on rates from the same NVSN sites as in the present study [4]. This prior study reported rates of hospitalizations attributable to influenza for years 2000–2004 varying between 0.4 per 1000 children (95% confidence interval 0.2–0.6 per 1000) and 1.5 per 1000 children (95% confidence interval 1.2–1.9 per 1000) [4]. ED visit rates, which were available for 2 of the 4 years, were 6 per 1000 children (95% confidence interval 4–9 per 1000) for 2002–2003 and 27 per 1000 (95% confidence interval 22–33 per 1000) for 2003–2004. In calculations, in order to account for variations in burden across seasons, we used a range for hospitalization rate of 0.4–1.5 per 1000 children, with 95% confidence interval of 0.2–1.9 per 1000 children. We used a range for ED visit rates of 6–27 per 1000 children with 95% confidence interval from 4 to 33 per 1000 children [4]. These rates are consistent with those reported in other studies, and most published rates fall within these confidence bands [3,14,22–24]. To estimate the total national influenza burden, we multiplied the influenza attributed ED visit and hospitalization rates from the prior study [4] by the average number of children <5 years of age residing in the US according to the U.S. Census Bureau estimates for 2003 through 2006 [25]. To estimate cost burden for these children, we multiplied the influenza attributed

G. Fairbrother et al. / Vaccine 28 (2010) 4913–4919

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Table 1 Characteristics of hospitalized and emergency department influenza-positive children, 2003–2006. Hospitalized (n = 188)

P value*

Emergency department (n = 202)

n

(%)

n

(%)

107 81

(57) (43)

120 82

(59) (41)

.62

77 70 41

(41) (37) (22)

47 114 41

(23) (56) (20)

<.001

Insurance Private Public None

61 119 8

(32) (63) (4)

42 146 14

(21) (72) (7)

.01

Presence of risk factor for influenzaa Yes No

49 139

(26) (74)

47 155

(23) (77)

.52

97 91

(52) (48)

17 185

(8) (92)

<.001

Gender Male Female Ethnicity/race White/non-Hispanic Black Other

Age in months <6 months of age ≥6 months of age a *

According to ACIP Influenza Recommendations, April, 2003 [18]. Significance of differences between characteristics of hospitalized and ED only children.

ED visit and hospitalization rates calculated as described above by the mean cost per child with laboratory-confirmed influenza.

subsequently hospitalized) were more likely to be black, older, and have public insurance (Table 1).

3. Results NVSN surveillance during the 3 study years detected a total of 436 influenza-positive cases in the hospital and ED settings combined. Due to one hospital closing and another changing its billing policies, we were unable to obtain cost data for 35 patients (8%). Deviations from the enrollment protocol resulted in the exclusion of 11 cases (2.5%) from the Cincinnati site. These 11 cases did not differ from other enrolled children from Cincinnati with respect to race, gender, or insurance status, but were more likely to be >6 months of age (P = 0.02). Overall, results were similar with these children included and excluded. Of the 390 cases (89%) with laboratory-confirmed influenza and available cost data, 188 were hospitalized, while 202 were seen only in the ED. Compared to children who were hospitalized, children seen in the ED (and not

3.1. Influenza-related hospitalization and emergency department costs The mean direct medical cost per influenza-associated hospitalization was $5402, with a median of $3347 (Table 2). Of hospitalization costs, 60% of the total direct medical costs were due to room costs, including intensive care unit (ICU) and operating and recovery room costs, as well as facilities-related costs incurred in the ED visits. Physician fees accounted for another 20% of the total hospital costs (Table 2). The mean medical cost per patient seen in the ED was $512 with a median cost of $409. The largest components of ED costs were physician fees ($233, or 46% of the total costs) and ED room costs ($215, or 42% of the total costs).

Table 2 Direct medical cost for hospitalized and emergency department influenza-positive patients, 2003–2006. Hospitalizations (n = 188) Mean Diagnostics Radiology Labs Other diagnostics

%

Emergency department (n = 202) Median

(IQR)

$124 $284 $42

8 2 5 1

$65 $177 $0

(0–78) (33–303) (0–46)

Therapeutics Pharmaceutics Blood Other therapies

$276 $3 $187

9 5 <1 3

$136 $0 $1

(35–348) (0–0) (0–122)

Room costs and ED Emergency department ICU Operating and recovery Room

$371 $710 $19 $2126

60 7 13 <1 39

$274 $0 $0 $1615

(0–526) (0–0) (0–0) (716–2443)

Supplies Supplies

$186

3 3

$64

(0–332)

Physician services MD fees

$1074

20 20

Total average costs

$5402

100

Mean

Median

(IQR)

$14 $16 $14

9 3 3 3

$0 $0 $0

(0–0) (0–0) (0–14)

3 $5

1

$0

(0–2)

$13

3

$0

(0–0)

42

$182

(130–259)

<1 $2

<1

$0

(0–0)

$193

(117–255)

$409

(333–557)

42 $215

%

$644

(310–1026)

$233

46 46

$3347

(2354–4862)

$512

100

4916

Table 3 Hospital costs and total LOS for 188 hospitalized children with laboratory-confirmed influenza, 2003–2006. Hospital costs

Length of stay (total LOS)

Mean

Med

(IQR)

P value

Total cost

Percent of cost

Mean

Med

(IQR)

P valuea

Total bed days

Percent total bed days

ICU No Yes

171 17

$3668 $22,850

$3190 $16,561

(2306–4423) (8337–24,999)

<.001

$627,253 $388,448

62% 38%

2.1 6.1

2 4

(1–2) (3–7)

<.001

358 103

78% 22%

High risk condition No Yes

139 49

$4578 $7743

$3294 $3538

(2279–4846) (2665–5752)

.23

$636,275 $379,426

63% 37%

2.3 3.0

2 2

(1–2) (1–3)

.40

314 147

68% 32%

Prematurity No Yes

161 27

$5100 $7210

$3353 $3060

(2384–4896) (1970–4013)

.28

$821,033 $194,668

81% 19%

2.4 2.9

2 2

(1–2) (1–4)

.61

382 79

83% 17%

RSV co-infectionb No Yes

135 21

$5367 $6967

$3344 $3479

(2333–4830) (2368–4846)

.99

$724,537 $146,314

83% 17%

2.3 3.1

2 1

(1–2) (1–4)

1.00

311 66

82% 18%

Pneumonia No Yes

149 39

$4817 $7641

$3294 $3667

(2322–4794) (2670–6223)

.06

$717,701 $298,000

71% 29%

2.2 3.5

2 2

(1–2) (1–4)

.01

324 137

70% 30%

Gender Male Female

107 81

$6112 $4466

$3376 $3266

(2384–4896) (2322–4794)

.50

$653,966 $361,735

64% 36%

2.6 2.3

2 2

(1–2) (1–3)

.59

273 188

59% 41%

Race Non-White White

111 77

$5745 $4909

$3550 $3294

(2351–5004) (2372–4794)

.76

$637,671 $378,031

63% 37%

2.5 2.3

2 2

(1–3) (1–3)

.37

282 179

61% 39%

Private insurance No Yes

127 61

$5628 $4934

$3538 $3115

(2368–5004) (2309–4237)

.21

$714,755 $300,947

70% 30%

2.4 2.5

2 2

(1–2) (1–3)

.88

306 155

66% 34%

97 91

$4672 $6181

$3353 $3325

(2406–4838) (2267–5087)

.68

$453,210 $562,491

45% 55%

2.3 2.6

2 2

(1–2) (1–3)

.27

225 236

49% 51%

Age group <6 months 6–59 months a b

P-value refers to comparison of population medians (Kruskal–Wallis). RSV status is not known for 32 children. These children are not included in the cost for RSV co-infection.

G. Fairbrother et al. / Vaccine 28 (2010) 4913–4919

N

G. Fairbrother et al. / Vaccine 28 (2010) 4913–4919

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Table 4 Mean cost, rates, national burden, and national cost for influenza for children <5 years of age. Hospital

Emergency department C.I.

Mean cost per child (2003–2006) Rate per 1000a National burden (# per year) National cost (in millions) a

$5402 0.4–1.5 (8059–30,219) $43.53–163.25

C.I.

(0.2–1.9) (4029–38,278) ($21.77–206.78)

$512 6–27 120,878–543,951 $61.89–278.50

(4–33) (80,585–664,829) ($41.26–340.39)

2000–2004 for hospital; 2002–2004 for emergency department.

3.2. Factors associated with influenza-related hospitalization and ED costs Table 3 displays the factors associated with higher costs among the 188 hospitalized children. An ICU stay generated significantly greater costs than a non-ICU stay. No other factors were significant at the patient level. Despite the fact that the small number of children in the ICU had substantially higher individual costs, children not in the ICU accounted for 62% of the total population-wide medical costs and 78% of the total bed days. Moreover, while there were no significant differences in mean or median costs by age, children <6 months of age accounted for 52% (Table 1) of the influenzarelated hospitalizations and 45% of the total costs (Table 3). RSV co-infection was found in 17% of the children with influenza in the first 2 seasons (when testing was done), 18% in 2003–2004, and 9% in 2004–2005; there was no significant difference in the mean cost of children with and without RSV co-infection. 3.3. Characteristics of high-cost hospitalizations (top 10% of costs) Overall, there were 20 high-cost hospitalizations, ranging from $8337 to $95,524 (data not shown). Chart reviews revealed that 17 (85%) of the high-cost hospitalizations appeared to be clearly influenza related: 11 (55%) with influenza alone and 6 (30%) with influenza plus RSV co-infection. Five of the 20 children had neurological problems, 4 with first-time seizures associated with the admission illness, and 1 child had hydrocephalus. Three children with confirmed influenza had high-cost hospitalizations for which influenza did not clearly account for the majority of the costs. The primary causes of these 3 hospitalizations included supraventricular tachycardia with respiratory distress, Epstein-Barr Virus infection with fever and dehydration, and cervical adenitis requiring incision and drainage. After controlling for age, race, insurance type, and gender, only ICU use was significantly associated with high cost. Prematurity, RSV co-infection, high-risk status, and pneumonia were not significantly associated with high cost. In multivariable analyses of factors predicting ICU stay after adjusting for race, age, gender and insurance status, only high-risk status was significantly associated with ICU stay. RSV co-infection, prematurity, and pneumonia were not significantly associated with ICU stay (data not shown). 3.4. Projected national costs of influenza-related hospitalizations and ED visits Using rates of hospitalization for influenza from a previous study (0.4–1.5 per 1000 [CI: 0.2–1.9, Table 4]) [4] and the mean costs per hospitalization from this study ($5402, Table 2), and extrapolating to the US population of children younger than 5 years of age [25], we estimate annually between 8059 and 30,219 (CI: 4029–38,278) influenza-related hospitalizations in the US accounting for $43.53 and $163.25 million (CI: $21.77–$206.78 million) in direct medical costs annually. ED rates varied from 6 to 27 per 1000 children (CI: 4–33). Using the overall mean cost of an ED visit, as reported in Table 2 ($512),

and extrapolating to the US population of children younger than 5 years of age [25], we estimate between 120,878 and 543,951 (CI: 80,585–664,829) influenza-related ED visits accounting for $61.89 to $278.50 million (CI: $41.26–$340.39 million) in direct medical costs occur annually. 4. Discussion This is the first study of the cost burden of influenza on children that utilized population-based surveillance in different geographical sites over multiple influenza seasons, and involved costs for both hospitalized children and children cared for in the ED [6,8,9]. This study reported mean and median costs of influenza in children <5 years of age to be $5402 and $3347, respectively for hospitalized children, and $512 and $409, respectively for children cared for in the ED over 3 influenza seasons. Our average cost of hospitalization ($5402) was consistent, but slightly lower than costs reported in one prior study ($6124) [6], and considerably lower than costs reported in two other pediatric studies in Philadelphia ($13,159) [8] and Chicago ($13,446) [7]. These latter two studies included older children with a higher proportion of high-risk children and were conducted at major regional tertiary care centers. Although most attention has understandably focused on hospitalizations due to influenza, our findings highlight the important contribution of ED visit rates and costs to the overall annual economic burden of influenza in the US. National cost burden of influenza-related hospitalizations and ED visits were estimated at $43 to $163 million and $62 to $289 million, respectively. Thus, despite ED visits costing one-tenth of hospitalizations for influenza, their much greater frequency results in a considerable populationwide burden that is comparable to the cost of hospitalizations due to influenza. This study is also the first that retrospectively examined charts of high-cost children to determine whether hospitalizations or ED visits were clinically attributable to influenza and its complications or to other conditions unrelated to the influenza infection. Our findings that resource utilization rates and costs for 85% of the children with the high-cost care were due to influenza infection or complications directly related to influenza or co-infections of influenza and RSV highlight the unequivocal disease effect on this population. Children in this group often had complications of their underlying conditions, which were triggered by influenza. These findings, along with the fact that this study was population-based, provide greater confidence in our extrapolations of the cost burden of influenza nationwide. Our findings support the need for development of overall strategies to increase vaccination rates, as well as targeted preventive strategies toward selected at-risk children. With respect to the first point, our data show that ED visits and low-risk hospitalizations contribute substantially to the overall costs, as the number of ED visits is far larger than the number of hospitalizations, and far more hospitalizations occur among low-risk children than among high-risk children. Vaccination rates were low in this population (fewer than 30% of children aged 6–23 months and fewer than 20%

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of children 24–59 months were fully vaccinated in the 2006–07 season) [26]. Our findings suggest that the most important strategy for containing costs is to vaccinate all children, supporting the recent recommendations for routine influenza vaccination of children up through 18 years of age [27]. Furthermore, this research demonstrated that vaccinating children <6 months of age, if a vaccine could be licensed in this age group, could have a substantial impact on hospitalization costs. The need to vaccinate pregnant women and household and other contacts of young children is emphasized by 45% of the burden of influenza costs being from infants under 6 months of age. As a way to further protect vulnerable children the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) recommend vaccinating women who will be pregnant during the influenza season, and also all household contacts and out-of home caregivers of children <5 years old, as well as all children with chronic medical conditions [28]. However, current vaccination rates of pregnant women and of children are poor (13% and <40%, respectively in the 2006–07 season) [29], indicating the need for additional efforts and strategies to raise these rates. The increased proportion of influenza plus RSV co-infection cases among those with severe illness raises questions about the risk of more severe disease among co-infected children and risk for co-infection. However, the relatively small number of such cases precluded additional analyses. Other studies should be considered to better explore issues related to influenza and RSV co-infection. Our study was limited by the relatively small sample size despite surveillance across 3 seasons and 3 separate geographic settings (188 hospitalized patients and 202 patients seen in the ED) and included only children <5 years of age. Furthermore, since the 3 surveillance sites were in the Northeast, South, and Midwest, our findings may not be representative of other areas within in the US. Our study also used unadjusted physician fees, which may overestimate total medical costs by approximately 6% to 14% [21]. The lack of a hospital specific cost-to-charge ratio for physician services may indicate little flexibility of hospitals to depart from fees in service contracts with physicians for a variety of reasons including costshifting, uncompensated care, competition for physician services or other pecuniary, institutional, or idiosyncratic issues implicit in physician service contracts as analyzed elsewhere [20,30–32]. However, from a payer’s perspective we believe that our base case total medical cost estimates are close approximations to the true economic costs.

4.1. Conclusions Costs associated with influenza hospitalizations and ED visits among young children account for a significant economic burden in the US. Hospitalizations and ED visits by healthy infants and young children account for the largest share of cost, because of their large numbers. The single best way to prevent influenza and its associated costs is to vaccinate all children, as well as the household and other contacts of those children too young to be vaccinated.

Acknowledgements Author contributions: Dr Fairbrother 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: Fairbrother, Cassedy, Staat, OrtegaSanchez, Molinari. Acquisition of data: Cassedy, Henderson, Ambrose, Kent. Analysis and interpretation of data: Fairbrother, Cassedy, Staat, Ortega-Sanchez, Molinari. Drafting of the manuscript: Cassedy, Fairbrother, Staat.

Critical revision of the manuscript for important intellectual content: Cassedy, Fairbrother, Staat, Ortega-Sanchez, Edwards, Szilagyi, Molilnari, Poehling, Weinberg, Griffin, Molinari, Bridges, Donauer, Finelli, Hall. Statistical analysis: Cassedy. Obtained funding: Staat. Administrative, technical, or material support: Henderson, Ambrose, Kent. Study supervision: Fairbrother, Staat, Ortega-Sanchez. Financial Disclosures: The following authors have made disclosure: Marie Griffin has Marie R Griffin, MD, MPH has investigator initiated grant funding from MedImmune. Caroline Hall, MD has consulted for MedImmune. Mary Allen Staat, MD, MPH, has rotavirus research funding from Merck and Company and from GlaxoSmithKlien. Conflicts of interest: The other authors declare that they have no financial disclosures or conflicts of interest. Funding/Support: CDC provided funding through cooperative agreements with the 3 sites. Role of the Sponsor: CDC provided data management support for the NVSN surveillance data. The study had CDC co-author(s) and CDC staff reviewed. Clinical Centers: None. We thank all the practices who participated in this study. In addition, we thank the following members of the NVSN: Nashville: Carol Ann Clay, RN, Erin Keckley, RN, Diane Kent, RN, Nayleen Whitehead, Yuwei Zhu, MD, MS. Rochester: Christina Albertin, MPH, Geraldine Lofthus, PhD, Ken Schnabel, PhD. Cincinnati: Vanessa Florian, Michol Holloway, MPH, Linda Jamison, RN, Meredith E. Tabangin, MPH.

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