US emergency department visits for fireworks injuries, 2006-2010

7
US emergency department visits for fireworks injuries, 2006e2010 Joseph K. Canner, MHS,* Adil H. Haider, MD, MPH, Shalini Selvarajah, MD, MPH, Xuan Hui, MD, ScM, Han Wang, MD, MPH, David T. Efron, MD, Elliott R. Haut, MD, Catherine G. Velopulos, MD, Diane A. Schwartz, MD, Albert Chi, MD, and Eric B. Schneider, PhD Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland article info Article history: Received 3 January 2014 Received in revised form 11 March 2014 Accepted 21 March 2014 Available online xxx Keywords: Emergency department Fireworks NEDS Injury abstract Background: Most literature regarding fireworks injuries are from outside the United States, whereas US-based reports focus primarily on children and are based on datasets which cannot provide accurate estimates for subgroups of the US population. Methods: The 2006e2010 Nationwide Emergency Department Sample was used to identify patients with fireworks injury using International Classification of Diseases, Ninth Revision, Clinical Modification external cause of injury code E923.0. International Classification of Dis- eases, Ninth Revision, Clinical Modification diagnosis codes were examined to determine the mechanism, type, and location of injury. Sampling weights were applied during analysis to obtain US population estimates. Results: There were 25,691 emergency department visits for fireworks-related injuries be- tween 2006 and 2010. There was no consistent trend in annual injury rates during the 5-y period. The majority of visits (50.1%) were in patients aged <20 y. Most injuries were among males (76.4%) and were treated in hospitals in the Midwest and South (42.0% and 36.4%, respectively) than in the West and Northeast (13.3% and 8.3%, respectively) census regions. Fireworks-related injuries were most common in July (68.1%), followed by June (8.3%), January (6.6%), December (3.4%), and August (3.1%). The most common injuries (26.7%) were burns of the wrist, hand, and finger, followed by contusion or superficial injuries to the eye (10.3%), open wounds of the wrist, hand, and finger (6.5%), and burns of the eye (4.6%). Conclusions: Emergency department visits for fireworks injuries are concentrated around major national holidays and are more prevalent in certain parts of the country and among young males. This suggests that targeted interventions may be effective in combating this public health problem. ª 2014 Elsevier Inc. All rights reserved. 1. Introduction A number of researchers around the world have studied fire- works injuries relating to their respective national holidays where fireworks are commonly used, including China, Greece, India, Iran, and the United Kingdom [1e12]. In addition to looking at fireworks injuries in connection with public holi- days, most of these researchers also found that these injuries * Corresponding author. Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 618, Balti- more, MD 21287. Tel.: þ1 410 502 2673; fax: þ1 410 955 8101. E-mail address: [email protected] (J.K. Canner). Available online at www.sciencedirect.com ScienceDirect journal homepage: www.JournalofSurgicalResearch.com journal of surgical research xxx (2014) 1 e7 0022-4804/$ e see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2014.03.066

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journal homepage: www.JournalofSurgicalResearch.com

US emergency department visits for fireworksinjuries, 2006e2010

Joseph K. Canner, MHS,* Adil H. Haider, MD, MPH,Shalini Selvarajah, MD, MPH, Xuan Hui, MD, ScM, Han Wang, MD, MPH,David T. Efron, MD, Elliott R. Haut, MD, Catherine G. Velopulos, MD,Diane A. Schwartz, MD, Albert Chi, MD, and Eric B. Schneider, PhD

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland

a r t i c l e i n f o

Article history:

Received 3 January 2014

Received in revised form

11 March 2014

Accepted 21 March 2014

Available online xxx

Keywords:

Emergency department

Fireworks

NEDS

Injury

* Corresponding author. Department of Surgmore, MD 21287. Tel.: þ1 410 502 2673; fax:

E-mail address: [email protected] (J.K. C0022-4804/$ e see front matter ª 2014 Elsevhttp://dx.doi.org/10.1016/j.jss.2014.03.066

a b s t r a c t

Background: Most literature regarding fireworks injuries are from outside the United States,

whereas US-based reports focus primarily on children and are based on datasets which

cannot provide accurate estimates for subgroups of the US population.

Methods: The 2006e2010 Nationwide Emergency Department Sample was used to identify

patients with fireworks injury using International Classification of Diseases, Ninth Revision,

Clinical Modification external cause of injury code E923.0. International Classification of Dis-

eases, Ninth Revision, Clinical Modification diagnosis codes were examined to determine the

mechanism, type, and location of injury. Sampling weights were applied during analysis to

obtain US population estimates.

Results: There were 25,691 emergency department visits for fireworks-related injuries be-

tween 2006 and 2010. There was no consistent trend in annual injury rates during the 5-y

period. The majority of visits (50.1%) were in patients aged <20 y. Most injuries were among

males (76.4%) and were treated in hospitals in the Midwest and South (42.0% and 36.4%,

respectively) than in the West and Northeast (13.3% and 8.3%, respectively) census regions.

Fireworks-related injuriesweremost common in July (68.1%), followed by June (8.3%), January

(6.6%), December (3.4%), and August (3.1%). The most common injuries (26.7%) were burns of

the wrist, hand, and finger, followed by contusion or superficial injuries to the eye (10.3%),

open wounds of the wrist, hand, and finger (6.5%), and burns of the eye (4.6%).

Conclusions: Emergency department visits for fireworks injuries are concentrated around

major national holidays and are more prevalent in certain parts of the country and among

young males. This suggests that targeted interventions may be effective in combating this

public health problem.

ª 2014 Elsevier Inc. All rights reserved.

1. Introduction where fireworks are commonly used, including China, Greece,

A number of researchers around the world have studied fire-

works injuries relating to their respective national holidays

ery, Johns Hopkins Univeþ1 410 955 8101.anner).ier Inc. All rights reserved

India, Iran, and the United Kingdom [1e12]. In addition to

looking at fireworks injuries in connection with public holi-

days, most of these researchers also found that these injuries

rsity School of Medicine, 600 N. Wolfe Street, Blalock 618, Balti-

.

j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e72

were most prevalent among young males. However, little has

been written about the same phenomenon in the United

States, particularly with respect to Independence Day (July

4th) and New Year’s Eve (December 31st). The most recent

publications in the United States based on national data

concentrated on pediatric cases occurring between 1990 and

2003 [13,14]. Since that time, consumer fireworks consump-

tion has increased from 107e185.5 million pounds in 2012,

with a high of 255 million pounds in 2005, and several states

have relaxed their laws concerning fireworks [15e17]. In

addition, the Internet has created an environment where

firework procurement has become possible even in places

where they may not be legal.

We examined emergency department (ED) visits for

fireworks-related injuries from the Nationwide Emergency

Department Sample (NEDS), Healthcare Cost and Utilization

Project, and Agency for Healthcare Research and Quality. This

study aims to provide an update of national figures on

fireworks-related injury using a data set, which can provide

precise estimates for national totals and for descriptive fac-

tors. Findings from this study can help EDs to anticipate in-

creases in fireworks-related injuries during certain times of

the year and in certain parts of the country, as well as help

focus firework-related injury prevention efforts.

Table 1 e Demographic characteristics of emergencydepartment visits for injuries due to fireworks.

Characteristic n (%)

Age

Mean (SD) 22.8 (15.3)

Gender

Male 19,613 (76.4)

Female 6062 (23.6)

Region

Northeast 2124 (8.3)

Midwest 10,798 (42.0)

South 9363 (36.4)

West 3406 (13.3)

Income quartile

1 7915 (31.3)

2 7379 (29.2)

3 6013 (23.8)

4 3978 (15.7)

Total 25,691 (100)

2. Methods

The NEDS is an all-payer ED database containing approxi-

mately 28million ED visits per year and can beweighted to the

entire US population using weights provided by Healthcare

Cost and Utilization Project. For 2010, the NEDS included 961

hospitals in 29 states, representing a 20% stratified sample of

all hospital EDs in the US. The NEDS provides a variety of in-

formation relating to patient demographics, diagnosis, and

hospital course. The JohnsHopkins Institutional Review Board

approved this study.

NEDS data from 2006e2010 were queried to identify pa-

tients who were admitted with fireworks injuries to EDs at

hospitals across the United States. Patients with fireworks

injuries were identified using the International Classification

of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)

external cause of injury codes (“E-Codes”) for accidents caused

by explosive material, particularly fireworks: E923.0. The

NEDS includes up to four E-Codes for each visit, which were

searched for the indicated codes. TheNEDS also includes up to

15 ICD-9-CM diagnosis codes for each visit, which were

examined to determine additional details about the mecha-

nism of injury, type of injury, and location of injury. Type and

location of injury were determined using the International

Classification of Diseases Programs for Injury Categorization

written for Stata [18]. In particular, injuries were categorized

using the Barell Injury Diagnosis Matrix [19], which classifies

ICD-9-CM diagnosis codes according to body region and na-

ture of injury. If more than one diagnosis code was provided

for these patients, the code with the highest severity was

chosen, based on the Abbreviated Injury Scale as calculated by

the International Classification of Diseases Programs for

Injury Categorization program. If there was more than one

code with the highest severity for a particular patient, the first

of these codes was used.

As appropriate, the number of ED visits was divided by the

US census population to obtain population rates. ED charges

were adjusted for inflation and reported in 2010 dollars.

All analyses were performed using Stata version 12.1,

StataCorp, College Station, TX.

3. Results

A total of 625,166,156 ED visits between January 1, 2006 and

December 31, 2010 were examined, of which 25,691 (41.1 per

million ED visits) had an E-code indicating a fireworks injury.

Table 1 shows the demographic characteristics of these pa-

tients and Figure 1 gives a detailed age distribution. The age

distribution of ED visits involving a fireworks injury has two

peaks, one between ages 11 and 14 y and another between

ages 17 and 19 y. Starting at the age of 20 y, the number of

visits declines steadily and the oldest patients in the sample

were between the ages of 85 and 95 y. Therewere considerably

more visits for males than for females (76.4% versus 23.6%),

and there were more visits to hospitals in the Midwest and

South (42.0% and 36.4%, respectively) than in the West and

Northeast (13.3% and 8.3%, respectively). There were more

visits involving fireworks injuries in the lower two income

quartiles (31.3% and 29.2%), with the high-income quartile

being the lowest of all (15.7%).

Figure 2 shows the age distribution stratified by gender,

illustrating that the age patterns for males and females are

similar, but with the frequency of ED visits for females lower

than that of males for every age group except �75 y. There is

also much more of a peak during ages 10e19 y for males than

for females, for whom there is very little variation in fre-

quency of ED visits from age 0e30 y, except for a small peak at

ages 5e9 y.

Table 2 shows the temporal characteristics of the ED visits

for fireworks-related injuries, including year of visit, month of

Fig. 1 e Age distribution of fireworks-related injuries.

j o u rn a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e7 3

visit, and whether the visit occurred on weekday or weekend.

The number of visits per year varied between a low value of

4103 in 2009 and a high value of 5763 in 2006. When adjusted

for the US population, the annual rate of visits ranged from

1.34 per 100,000 in 2008 to 1.93 per 100,000 in 2006. All the 95%

confidence intervals (CIs) for these rates overlap, with the

exception of the 2009 rate, which is significantly lower than

the rates for 2006e2007. ED visits for fireworks-related injuries

were most common in July (68.1%), followed by June (8.3%),

January (6.6%), December (3.4%), and August (3.1%). The

Fig. 2 e Fireworks-related injurie

proportion of visits that occurred on the weekend was 38.1%.

In 2006 and 2007, years when Independence Day was on

Tuesday and Wednesday, respectively, weekend visits in July

were 18.7% over those 2 y. In 2008, Independence Daywas on a

Friday and 37.9% of visits were on a weekend. In 2009 and

2010, Independence Day was on Saturday and Sunday,

respectively, and weekend visits were 60.4% over those 2 y. A

similar pattern was observed in December and January, con-

necting a high proportion of weekend visits with years when

New Year’s Eve fell on a weekend.

s age distribution by gender.

Table 2 e Temporal characteristics of emergencydepartment visits for injuries due to fireworks.

Characteristic n (%)

Year of visit

2006 5763 (22.4)

2007 5222 (20.3)

2008 5727 (22.3)

2009 4103 (16.0)

2010 4877 (19.0)

Month of visit

January 1515 (6.6)

February 243 (1.1)

March 223 (1.0)

April 309 (1.3)

May 504 (2.2)

June 1890 (8.3)

July 15,554 (68.1)

August 701 (3.1)

September 378 (1.7)

October 350 (1.5)

November 381 (1.7)

December 776 (3.4)

Day of Week

Weekday 15,900 (61.9)

Weekend 9787 (38.1)

j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e74

Almost half (45.9%) of patients who visited an ED for a

fireworks injury had only one injury. About one-third (32.2%)

had two injuries, 10.7% had three injuries, and 4.4% had four

injuries. The highest number of injuries reported was 13. As

shown in Table 3, themost common body region of injury was

the wrist, hand, and finger (41.4%), followed by the eye (16.8%)

and the face (6.9%). The most common types of injuries,

regardless of body region, were burns (57.0%), contusions and

superficial injuries (16.2%), and open wounds (15.8%). The

most common injuries, accounting for 26.7% of all cases, were

burns of the wrist, hand, and finger. Other common injuries

included contusion or superficial injuries to the eye (10.3%),

open wounds of the wrist, hand, and finger (6.5%), and burns

of the eye (4.6%).

There were 879 patients with injuries that were not

covered by the Barell Injury Diagnosis Matrix. These included

foreign bodies in the eye (27%), ear symptoms (12%), and a

variety of other miscellaneous eye and limb symptoms.

In 6070 cases, there were one or more E-Codes, in addition

to the E-Code for fireworks-related injury, indicating the

Table 3 e Body region and injury type for injuries due tofireworks.

Barell matrix body region n (%)

Wrist, hand, or finger 10,271 (41.4)

Eye 4170 (16.8)

Face 1707 (6.9)

Head, face, or neck (specific location unspecified) 1505 (6.1)

Barell matrix injury type

Burn 14,141 (57.0)

Contusions and superficial injuries 4015 (16.2)

Open wound 3921 (15.8)

Fracture 1132 (4.6)

Total 24,803 (100)

specific place of occurrence of the fireworks injury. Of these,

the vastmajority (82.1%) occurred at home. A small number of

cases occurred in a “place for recreation and sport” (7.7%) or

on street or highway (7.5%).

Fireworks injuries did not generally result in death. Of the

25,435 ED visits withmortality information, the patient died in

the ED in fewer than 11 cases, and 18 (0.07%) died after being

admitted to the hospital. Most patients were either discharged

from the ED (86.2%), admitted as an inpatient at the same

hospital (6.3%), or transferred to another hospital (5.1%).

ED charges are available for 22,661 visits (88.2%). There was

a wide variety of charges relating to ED visits for fireworks

injuries, ranging from $27e$31,628. The mean charge was

$1256 (standard deviation, $2105), and the median charge was

$688 (Interquartile range, $420e$1234). Although the number

of ED visits for fireworks-related injuries was relatively stable

between 2006 and 2010, the total annual ED charges increased

significantly from $4.37 million (95% CI, $3.66 millione$5.08

million) in 2006 to $7.8 million (95% CI, $6.01 millione$9.55

million) in 2010.

4. Discussion

As with reports of fireworks-related injuries from other

countries, these injuries were most prevalent in the United

States around holiday times. The high number of injuries in

July is probably due to fireworks use on or around the Inde-

pendence Day (July 4th) holiday. Aside from the injury peak in

July, there is a smaller increase in injuries in the months of

June and August, with the higher prevalence in June probably

connected the Independence Day holiday. The higher preva-

lence of injuries in December and January is likely connected

to the New Year’s Eve (December 31st) holiday.

Overall, weekend injuries comprised 38% of all injuries,

considerably more than one would expect if the injuries were

equally distributed amongst all days of the week. Weekend

injuries were higher than expected for all months of the year

except for January. This is similar to other reports of ED uti-

lization [20] and may reflect increased injury risk on the

weekend. In addition, the year-to-year variation in the pro-

portion of weekend visits in July adds support to the conclu-

sion that the July injuries are related to the Independence Day

holiday. Similarly, the year-to-year variation in the proportion

of weekend visits in December and January supports the

conclusion that injuries in these months are related to the

New Year’s Eve holiday.

Most reports in the literature regarding fireworks-related

injuries are single-center studies from countries other than

the United States. The most recent report from the United

States was published by Witsaman et al. [14] in 2006 and per-

tained to pediatric injuries from 1990e2003. Focusing on the

pediatric population ignores a substantial proportion of

fireworks-related injuries; 49.9% of patients in the current

study were aged �20 y. Although fireworks-related injuries

decline with age, there are reportable numbers of patients

even in their eighties who experience these injuries.

The source of the data for the report byWitsaman et al. was

the National Electronic Injury Surveillance System (NEISS)

operated by the Consumer Product Safety Commission (CPSC)

Table 4 e Fireworks injury data from the NEISS, 2006e2010.

Year Deaths ED visits (95% CI) MidJuneemidJuly(% of total)

Sex ratio (M:F) % Age <15 y % Age <20 y Hand injury

2006 11 9200 (6900e11,700) 6400 (70) 3:1 36 47 2300

2007 11 9800 (7700e11,800) 6300 (64) 70:30 42 54 2000

2008 7 7000 (5200e9000) 5000 (71) 62:38 40 58 1400

2009 2 8800 (6800e10,800) 5900 (67) 73:27 39 54 1900

2010 3 8600 (6600e10,700) 6300 (73) 65:35 40 53 30%

F ¼ female; M ¼ male.

j o u rn a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e7 5

[21]. The CPSC publishes a series of annual reports on injuries

related to a variety of consumer products, including fireworks

[22]. The NEISS is a stratified sample of 98 US hospital EDs. In

comparison, the NEDS includes data from over 950 US Hos-

pital EDs. Consequently, the standard errors for estimates

from the NEISS are much larger than those for the NEDS.

Based on the 95% CIs provided in the CPSC reports, it appears

that the standard errors for the NEISS annual fireworks-

related injury estimates are usually at least 1000, whereas

the corresponding standard errors in the NEDS are around

300. As shown in Table 4, the NEISS data are highly variable

from year to year, and the estimates of total injuries per year

generally exceed those of the NEDS by several 1000 cases.

With respect to age and gender distributions and the type and

location of injury, however, the two sources are consistent.

One advantage that the NEDS has over the NEISS is that the

NEDS has a sufficient sample of hospitals to draw conclusions

about geographical variations in injury rates. When NEDS

injury estimates for each census region were adjusted for

population, we find significant differences between the re-

gions. The Midwest region has by far the highest rate, with

16.2 fireworks-related injuries per 100,000 population (95% CI,

14.3e18.2). The South has about half that rate: 8.4 per 100,000

(95% CI, 7.4e9.3). The rates in the Northeast andWest are half

as much again: 3.9 (95% CI, 3.3e4.4) and 4.8 (95% CI, 4.1e5.6)

per 100,000, respectively. Perhaps not coincidentally, some of

the states with the most liberal firework laws are in the Mid-

west (e.g., Indiana) and South (e.g., South Carolina and Ten-

nessee). In contrast, the four states that maintain a total

prohibition on all consumer fireworks (Delaware, Massachu-

setts, New Jersey, and New York) are all in the Northeast, the

area with the lowest injury rate [23]. Five states (Kentucky,

Table 5 e US states in the NEDS by census region.

Region States

Northeast Connecticut, Massachusetts, Maine (2006e2009),

New Hampshire (2006e2009), New Jersey, New

York (2007e2010), Rhode Island (2007e2010), and

Vermont

Midwest Iowa, Indiana, Illinois (2009e2010), Kansas,

Minnesota, Missouri, Nebraska, Ohio, South Dakota,

and Wisconsin

South Florida, Georgia, Kentucky (2008e2010), Maryland,

North Carolina (2007e2010), South Carolina,

and Tennessee

West Arizona, California, Hawaii, Nevada (2010 only),

and Utah

Utah, New Hampshire, Maine, and Michigan) significantly

liberalized their laws in 2011 or 2012, after the period of the

present study [16]. See Table 5 for a list of all states included in

the NEDS by census region.

The American Pyrotechnics Association (APA) contends,

using injury data from NEISS and firework import data from

the US International Trade Commission, that fireworks-

related injury as a function of fireworks consumption has

declined since 1976 [16,17]. Although the number of firework-

related injuries has fluctuated between 7000 and 12,500 during

that time, with some evidence of an increase between 1976

and 1994 and a slight decline thereafter, fireworks consump-

tion has increased from around 30 million pounds in 1976 to

>200 million pounds in 2012, peaking at 281 million pounds in

2005. Accordingly, the number of injuries per 100,000 pounds

has decreased from 38.3 in 1976 to 4.1 in 2012. However, as

Witsaman et al. point out, firework weight is probably not the

appropriate denominator, as it does not relate to the actual

number of fireworks used, but rather gives more significance

to heavier fireworks and less to lighter fireworks. Moreover,

although heavier fireworks may cause more severe injuries,

there is no reason to believe that heavier fireworks are more

likely to cause injuries than lighter fireworks.

The APA conclusions, moreover, fail to acknowledge a

recent reversal in the trends that they cite. Although the

number of injuries per 100,000 pounds did indeed decrease

sharply from 38.3 in 1976 to 4.4 in 2003, the rate has decreased

muchmore slowly since then, bottoming out at 3.3 in 2006 and

increasing to 4.1 starting in 2012.

4.1. Limitations

The primary limitation of this study is that it relies on

administrative data, in particular the use of ICD-9-CM codes,

which are used primarily for billing purposes. E-codes, which

are used in the present study to identify fireworks-related

injuries, are not typically required in billing for trauma, as

the mechanism of injury does not usually have implications

for billing. Also, as noted in the NEDS documentation, the

collection and reporting of E-codes vary greatly across states,

as some states require collection of E-codes and others do not

[24]. Accordingly, the total number of ED visits for fireworks

injuries may be underestimated. This may explain why injury

estimates in the NEISS are higher than those in the NEDS, as

NEISS hospitals are actively monitoring their ED cases for

injuries caused by consumer products. The possible under-

estimation of injuries in the NEDS is less likely to affect

the distributions of demographic, temporal, clinical, and

j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e76

economic characteristics related to fireworks injuries, as there

is no reason to believe that the ascertainment of mechanism

of injury is related to these characteristics. The similarity

between the NEDS and the NEISS with respect to these char-

acteristics supports this conclusion.

Another limitation of this study is that the NEDS does not

indicate the state or local area where the hospital is located.

Accordingly, it is difficult to correlate injury rates with the

strength of state laws or with local events that might involve

fireworks. In addition, fireworks consumption is only avail-

able on a national level, which means that fireworks con-

sumption cannot be correlated with injury rates even at the

level of a census region. Further, the tremendous variability in

state and local laws regarding the sale of fireworks, either

directly or over the Internet, may lead to local differences in

fireworks consumption and injury rates that we are unable to

assess at that granular level.

5. Conclusions

Notwithstanding claims by the APA that firework safety has

improved over time despite the liberalization of fireworks

laws in some states, firework-related injuries remain a public

health problem, particularly because they are concentrated

around certain times of the year, on weekends, and in certain

geographic regions. The fact that firework-related injuries

have remained steady over time, despite liberalized fireworks

laws and increases in firework consumption suggest that

public health measures have been moderately successful.

However, more data are needed on the effectiveness of spe-

cific public health measures. The results from this study

suggest that public health measures should be targeted by

time (Independence Day and New Year’s Eve holidays), by

location (Midwest and South), and toward thosewho purchase

fireworks for younger males.

The regional variation in fireworks injuries, the constantly

changing pattern of state laws concerning fireworks, and the

increased availability of fireworks over the Internet highlight

the need for more standardized regulation of fireworks across

the US. Continued monitoring of fireworks injury rates is

needed to ascertain the effect of the liberalization of fireworks

laws in some states; and consumption and injury data by state

are needed to more precisely estimate the relationship be-

tween state fireworks laws and injury rates.

Acknowledgment

J.K.C., E.B.S., and A.H.H. contributed for conception and

design; J.K.C. and E.B.S. for analysis and interpretation; J.K.C.,

E.B.S. and S.S. for writing the manuscript; X.H., H.W., D.T.E.,

E.R.H., C.G.V., D.A.S., and A.C. for revising themanuscript; and

A.H.H. for funding.

Disclosure

The authors reported no proprietary or commercial interest in

any product mentioned or concept discussed in this article.

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