Epidemiology of Exertional Heat Illnesses in Youth, High School, and College Football : Medicine & Science in Sports & Exercise

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EPIDEMIOLOGY

Epidemiology of Exertional Heat Illnesses in Youth, High School, and College Football

YEARGIN, SUSAN W.; KERR, ZACHARY Y.; CASA, DOUGLAS J.; DJOKO, ARISTARQUE; HAYDEN, ROSS; PARSONS, JOHN T.; DOMPIER, THOMAS P.

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Medicine & Science in Sports & Exercise 48(8):p 1523-1529, August 2016. | DOI: 10.1249/MSS.0000000000000934
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Abstract

Introduction 

Data on exertional heat illness (EHI) in youth football are limited and have not been compared across competition levels.

Purpose 

This study describes the epidemiology of EHI events in youth, high school (HS), and college football in the 2012–2014 seasons.

Methods 

One hundred and eighteen youth teams (players age 5–14 yr), 96 HS programs (~14–18 yr), and 34 college programs (~18–23 yr) participated. During games and practices, athletic trainers recorded EHI events and athlete exposures (AE), defined as one athlete participating in one game/practice. We calculated the number of reported EHI by time in season, game/practice, and need for emergency transportation. EHI rates, risk, included rate ratios (IRR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated in 2015.

Results 

EHI rates for youth, HS, and college football were 1.82, 0.57, and 1.67/10,000 AE, respectively. Rates were highest during the preseason (youth: 2.76; HS: 1.47; college: 3.66/10,000 AE). Game rates were higher than practice rates in youth (4.04 vs 1.22/10,000 AE; IRR = 3.31; 95% CI, 1.75–6.26) and college (4.42 vs 1.38/10,000 AE; IRR = 3.21; 95% CI, 2.00–5.16); the practice rate was higher than the game rate in HS (0.63 vs 0.27/10,000 AE; IRR = 2.33; 95% CI, 1.01–5.38). The EHI risk was higher in college (0.9%) than in youth (0.6%; RR = 1.59; 95% CI, 1.06–2.37) and HS (0.5%; RR = 2.01; 95% CI, 1.43–2.81). Common EHI events included heat cramps (youth: 15.8%; HS: 28.6%; college: 45.6%), heat exhaustion (youth: 42.1%; HS: 32.9%; college: 20.0%), and dehydration (youth: 31.6%; HS: 28.6%; college: 28.9%).

Conclusions 

EHI risk was low. Higher preseason football EHI rates across levels emphasize developing and continually modifying preseason heat acclimatization policies. Lower EHI rates in HS games and youth practices may be attributable to night events, suggesting the importance of modifying/canceling events based on environmental conditions.

Exertional heat illnesses (EHI) develop in warm to hot environmental conditions when active individuals engage in sport or physical activity. Time lost from sport, morbidity, and mortality are concerns associated with EHI. Exertional heat stroke (EHS) is potentially fatal and accounts for ~2% of all sport-related deaths (25) and ~15% of all football deaths annually (5). Specifically, a total of 35 football players died from EHS from 1995 to 2010, of which 2005–2009 had the greatest amount of deaths than any other 5-yr period for over three decades (29). Understanding EHI incidence is desirable for health care providers because emergency rooms reported a 133% increase in EHI cases over a decade without a significant change in average temperatures (33).

Patients under 20 yr of age comprise the largest proportion of EHI cases documented in emergency rooms. Of those, 48% were youth and adolescent male athletes participating in American football at the time of incident (33). Football participation also accounted for 8% of EHI in 20- to 39-yr-old male athletes (33). Recent epidemiological data indicate that the rate of EHI in high school (HS) football is 10–11 times that of all other sports (18,19,39).

To address EHI incidence and predisposing factors, the National Collegiate Athletic Association (NCAA) mandated heat acclimatization guidelines starting in 2003 with successful results (40). Secondary school heat acclimatization guidelines exist but are not mandated (7,35). There are no such national guidelines for youth sports. In addition, the majority of EHI research to date has focused primarily on football players 15 yr and older, leaving a knowledge gap about EHI prevalence in youth sports. The youth football population, estimated at three million, is larger than that of HS and collegiate levels (31).

Data on EHI in youth football are limited and evidence is needed to support the development of prevention guidelines. Furthermore, no studies have compared the epidemiology of EHI among the three most common competition levels (i.e., youth, high school, and college). Therefore, the purpose of the current study was to describe the epidemiology of EHI events in football across the youth, HS, and college levels in the 2012–2014 seasons.

METHODS

Data collection

A descriptive epidemiology design was used to report EHI that occurred in football at three primary playing levels. This observational cohort employs data that were collected as part of three larger independent injury surveillance programs (ISP). These programs, operated by the Datalys Center for Sports Injury Research and Prevention, include the Youth Football Surveillance System (YFSS), the National Athletic Treatment, Injury and Outcomes Network (NATION), and the NCAA ISP. All three programs used the same common data elements with slight variations accommodating for the setting and level of competition.

Athletes age approximately 5–14 yr (YFSS), 14–18 yr (NATION), and 18–23 yr (NCAA ISP) old were included within the respective surveillance programs. Each competition level was distinct and included their own individual teams, guidelines, and rules. During the 2012–2014 seasons, the YFSS included a total of 118 teams providing 310 team seasons (some participating in multiple years of the study). The NATION program included 96 secondary school football programs providing 184 team seasons, and the NCAA ISP included 34 institutions providing 71 team seasons. During the study period, an average of 20 players were on each youth football team; although specific squad size information was not available for all football teams at the high school and collegiate levels, national participation data from the 2013/2014 academic year indicate average squad sizes of 76 and 107 in high school (32) and collegiate football (36), respectively.

Methodologies for each surveillance program have been previously described but are summarized below (15,20,23). De-identified injury and exposure information were reported by athletic trainers (ATs) using an export application that extracts common data elements from the surveillance systems (20). These electronic injury documentation applications are commonly used by ATs in sports medicine settings including the Athletic Trainer System (Keffer Development, Grove City, PA), Injury Surveillance Tool (Datalys Center, Indianapolis, IN), and the Sports Injury Monitoring System (SIMS; FlanTech, Iowa City, IA). The YFSS was limited to the Datalys Center Injury Surveillance Tool.

Procedures

Participating ATs from each level of competition attended each practice and game for each team during the 2012–2014 seasons, collecting data on athlete exposures (AE) and injuries. AE was defined as one athlete participating in one game or practice. A reportable injury was an injury that occurred as a result of participation in an organized practice/game and required attention from an AT or physician. When EHI events occurred, ATs could categorize them as 1) dehydration, 2) heat cramps, 3) heat syncope, 4) hyponatremia, 5) exertional heat exhaustion (EHE), or 6) EHS. We relied upon the expertise of the ATs to appropriately select the correct diagnosis.

For each EHI event, ATs recorded the time of season (i.e., preseason, regular season, postseason), event type (i.e., practice, competition), participation restriction time, and if emergency transportation was needed. Injuries requiring at least 24 h of participation restriction time were considered time loss (TL) injuries. Environmental conditions were not included for all three databases and therefore were not included in analysis. Data were reviewed through both automated and manual quality control processes before inclusion in the research database (20). De-identified data were exported to the research database at least once per day.

Statistical analysis

Data were analyzed in 2015 using SAS-Enterprise Guide software (version 4.3; SAS Institute Inc., Cary, NC). Descriptive analyses included the injury frequencies, proportions, rates per 1000 AE, and pooled 1-yr risks. Comparative analyses across competition levels included rate ratios (IRR), risk ratios (RR), and injury proportion ratios (IPR). An IRR examines how the occurrence of new events per unit of person time (in this study, AE) may differ between two groups. An RR examines how the risk of the event occurring to an individual may differ between two groups. An IPR examines how the distribution of the occurrences in total may differ between two groups.

The following is an example of an IRR of the rates of EHI events in games versus practices:

The following is an example of an RR of the risk of EHI events in college versus youth players:

An athlete season was defined as one athlete’s participation in one season. Youth athlete seasons were determined by the number of players on the preseason roster at the beginning of each season; high school and collegiate athlete seasons were determined by squad size estimates from participation data from the National Federation of State High School Associations (32) and the NCAA (36), respectively.

The following is an example of an IPR comparing the proportion of EHI events that were TL injuries in college versus high school:

IRR and IPR with 95% confidence intervals (CI) not including 1.00 were considered significant. The YFSS and NATION protocols were reviewed and approved by the Western Institutional Review Board (Puyallup, WA); the NCAA ISP protocol was reviewed and approved by the NCAA Research Review Board (Indianapolis, IN).

RESULTS

Frequencies

During the 2012–2014 seasons, 198 EHI events were reported. These included 38 (19.2%) sustained by 36 youth players, 70 (35.4%) sustained by 65 HS players, and 90 (45.5%) sustained by 70 college players (Table 1). Most EHI events at all three levels occurred in practices (youth: 52.6%; HS: 91.4%; college: 74.4%). Whereas 42.1% of EHI events occurred in the preseason in youth football, larger proportions occurred in the preseason at the HS and college levels (82.9% and 65.6%, respectively).

T1-12
TABLE 1:
Injury rates by season in youth, high school, and collegiate football.

Injury rates

Rates varied by level of competition, event type, and time in season (Table 1). The game EHI rate was higher than the practice rate in youth football (4.04 vs 1.22/10,000 AE; IRR = 3.31; 95% CI, 1.75–6.26) and college football (4.42 vs 1.38/10,000 AE; IRR = 3.21; 95% CI, 2.00–5.16). However, the practice EHI rate was higher than the game rate in HS football (0.63 vs 0.27/10,000 AE; IRR = 2.33; 95% CI, 1.01–5.38). The preseason EHI rate was higher than that of the regular season at the youth (2.47 vs 0.63/10,000 AE; IRR = 3.92; 95% CI, 1.50–10.19), HS (1.47 vs 0.15/10,000 AE; IRR = 9.51; 95% CI, 5.11–17.70), and college level (3.66 vs 0.85/10,000 AE; IRR = 4.28; 95% CI, 2.76–6.64).

Compared with the HS level, the EHI rate in games was higher in youth (IRR = 14.88; 95% CI, 5.91–37.48) and college (IRR = 16.29; 95% CI, 6.63–40.02). No difference was found between youth and college EHI rates in games (IRR = 0.91; 95% CI, 0.49–1.69). Compared with the HS level, the EHI rate in practices were higher in youth (IRR = 1.93; 95% CI, 1.17–3.19) and college (IRR = 2.18; 95% CI, 1.54–3.07). No difference was found between youth and college EHI rates in practices (IRR = 0.89; 95% CI, 0.54–1.46).

Compared with the HS level, the EHI rate in the preseason was higher in youth (IRR = 1.88; 95% CI, 1.08–3.27) and college (IRR = 2.49; 95% CI, 1.73–3.57). No difference was found between youth and college EHI rates in the preseason (IRR = 0.76; 95% CI, 0.43–1.31). Compared with the HS level, the EHI rate in the regular season was higher in youth (IRR = 10.69; 95% CI, 5.29–21.60) and college (IRR = 5.52; 95% CI, 2.83–10.79). In addition, the regular season EHI rate in youth was higher than college (IRR = 1.94; 95% CI, 1.12–3.36).

Injury risk

The EHI risk was highest in college (0.9%), followed by youth (0.6%) and HS (0.5%; Table 2). The EHI risk in college was higher than those in HS (0.5%; RR = 2.01; 95% CI, 1.43–2.81) and youth (RR = 1.59; 95% CI, 1.06–2.37).

T2-12
TABLE 2:
Pooled 1-yr risks of heat injury in youth, high school, and collegiate football, 2012–2014 seasons.a

Types of EHI events

The most common EHI events were heat cramps (youth: 15.8%; HS: 28.6%; college: 45.6%), heat exhaustion (youth: 42.1%; HS: 32.9%; college: 20.0%), and dehydration (youth: 31.6%; HS: 28.6%; college: 28.9%; Table 3). Only one case of EHS (at the college level) was reported. The proportion of EHI events resulting in TL increased with the level of competition (youth: 31.6%; HS: 44.3%; college: 68.9%; Table 4). College had a larger proportion of TL injuries than HS (IPR = 1.56; 95% CI, 1.16–2.09) and youth (IPR = 2.18; 95% CI, 1.34–3.55); however, no difference was found between HS and youth (IPR = 1.40; 95% CI, 0.82–2.40).

T3-12
TABLE 3:
Types of EHI in youth, high school, and collegiate football.
T4-12
TABLE 4:
Proportion of EHI resulting in TL in youth, high school, and collegiate football.

Emergency transport

Emergency transport was required for few EHI events. Only one EHI event required emergency transport in youth (2.6%). At the HS and college levels, four (5.7%) and two (2.2%) EHI events required emergency transport.

DISCUSSION

This is the first study to examine and compare the epidemiology of EHI in youth, HS, and college football. Through using similar methodologies within each level of competition, we assessed potential disparities in EHI incidence. EHI events were reported at all levels of competition, with the highest rates found in youth, but the highest risk found in college. Our findings emphasize the need for EHI prevention across all three levels, with specific attention paid to youth football.

Our injury rates were typically higher than that of previous research (9,18,19,33,39), although this may be attributable to our inclusion of non-time-loss injuries. Nevertheless, the larger EHI rate among youth football was surprising when compared with orthopedic injury rates, which typically increase by age and level (30). In fact, the characterization of EHI rates across levels was similar to that of a study of concussions with the same datasets (14). As with concussions, the similar EHI rate in youth could have been a result of focused media and sports medicine attention upon heat-related events. In addition, our settings had ATs present at every event and thus were more apt to detect and diagnose these ailments. Also, because youth football typically has smaller rosters, players may play both sides of the ball, leading to increased exposure time and, consequently, increases in cumulative metabolic heat gain, core body temperature, and sweat rate (11,17,41).

Behavioral variations across levels may exist as well. Older populations may not disclose EHI symptoms or attribute them to general exhaustion or fatigue. Youth anecdotally manifests CNS dysfunction associated with both EHI and concussions more openly (complaining, grumpiness, etc.) and earlier than their older counterparts, thus aiding in the diagnosis of EHI events. Additional research is needed to better explore the biological and behavioral differences of players at each level as regards EHI events. At the same time, the distribution of football site locations at each level varied. Resulting differences in environmental conditions may confound the association between EHI cases and playing level. Future research should match levels by location to better assess competition differences.

Differences in game and practice rates

Game rates were lower in HS football compared with youth and college football. Traditional Friday night football games during the regular season that begin in the evening hours (~7:00 p.m.) correspond with significantly lower ambient temperatures and lower EHI risk (2,10,13,38). Specifically, ambient and black globe (solar radiation) temperatures drop after sunset. Hosting games in the evening hours therefore reduces convective and radiative heat gain by players. Consequently, sweat and sodium losses lessen, diminishing these primary EHI risk factors (2,5). Dissimilarly, start times at the college level may be dependent upon TV scheduling, which leads to game times that occur in the daytime and cannot be easily modified. At the youth level, games may be scheduled back to back because of field and referee fees, thus stretching exposure time into the afternoon hours when environmental conditions provide the highest thermal load (2,10,13,38). Follow-up interviews with participating ATs reveal that many EHI events occurred during mid-day games and players had been at the fields most of the morning before their game time (e.g., brother played in an earlier game, etc.). Thus, EHI risk may be mitigated by avoiding early arrival to games and prior heat exposure (2,38). If parents’ schedules require players to arrive earlier, youth players should avoid direct sunlight, stay hydrated, and avoid playing sandlot football and participating in other physical activities before their game.

Practice rates were lower than game rates at the youth and college levels. At the youth level, practice may occur in the evening to accommodate parents’ work schedules. At the college level, the length of time and number of practices within a day are controlled by the NCAA and institution-specific compliance officers (40). However, no policies exist related to modifying practice times if environmental conditions are too dangerous. Cooper et al. (10) recorded environmental measurements and reported that the majority of collegiate Southeastern Conference football practices held during August preseason were conducted in extreme-risk or high-risk categories. At the HS level, practice rates were higher than game rates and exceeded those previously reported in the HS football population (18,19,39). Guidelines and recommendations related to the prevention of heat-related events are abundant (2–4,7,16,34,35), but implementation occurs at the district level rather than the national level. For example, Georgia is the only state with financial penalties associated with practicing in hot conditions (16). A recent study found that only 2.5% of all surveyed ATs noted that their HSs complied with National Athletic Trainers Association–led Inter-Association Task Force released preseason heat acclimatization guidelines (22). It is important to better understand the barriers and facilitators of proper compliance with recommended guidelines to ensure the protection of the health and well-being of football players.

Our study found the differences in rates by level of competition, which may illustrate how each level of competition varies in aspects related to the settings in which both games and practices occur. However, it is also important to note that although rates may account for variations in at-risk exposure time across and within the levels of competition, they may be biased by limitations. First, our exposure measure, AE, was unit based as opposed to time based. The use of AE was necessary to reduce reporter burden; however, we were unable to report injury rates by the minutes or hours in which each athlete was active in each game and practice. Thus, all athletes participating in a game, whether it was for one play or for all four quarters, were logged as contributing one AE. At the same time, potential variations in participation may also be associated with squad size, because the average squad size in our youth football teams were 20, compared with national averages of 76 and 107 during the 2013/2014 academic year in high school and collegiate football, respectively (32,36). Future research should consider manners to better account for possible variations in individual participation and squad size.

Time in-season

As in numerous previous research (10,18,19,24,30,33,39), injury rates were the highest during the preseason across all levels of competition. In addition, several studies have noted that the majority of EHI events occur after 1–2 h of practicing (18,19,39). Among a sample of HS ATs, the National Athletic Trainers Association–Inter-Association Task Force guideline that had the least compliance was “Single-practice days consisted of practice no more than three hours in length” (39.7%) (22). These findings may underline the need for reform (i.e., time and length) of preseason football practices for college and the development of national standards for HS and youth. Timing of preseason practices before 10 a.m. or after 4 p.m., or the modification of practice start time based on the environmental conditions, may be important steps in reducing EHI risk. Currently, these preventive practices are only encouraged and not mandated; it is estimated that only 8% of HS football programs reported making such practice changes (24).

Higher preseason rates also stress the need for mandatory heat acclimatization protocols. Heat acclimatization provides a multitude of thermoregulatory benefits during the preseason period such as conservation of sodium and lower core body temperatures (1). Adult populations typically take 14 d to fully achieve these adaptations based on the environment they are experiencing; youth may take longer (1). The NCAA has a mandated heat acclimatization period during preseason, but HSs and youth organizations lack national rules. Research indicates that HSs with ATs institute some heat acclimatization and EHI prevention guidelines (22), but not all HSs, let alone youth organizations, can afford an AT.

Risk of EHI

Very few epidemiological studies examine the risk of injury, even though such a measure may be more intuitive to stakeholders (e.g., coaches, players, and parents) within a sports organization such as a football program. The EHI risk among youth, HS, and college football was relatively low, with less than 1% of all players sustaining an EHI. However, the EHI risk was higher in college football than in HS and youth football. With exercise intensity as the primary mechanism of EHS and predisposing factor of heat cramps (8), it could be that the EHI risk in college was higher because of engaging in and sustaining higher intensities during sport-related activities (40). Our risk estimates are based upon preseason roster sizes in youth football and squad size estimates in high school and college. Because players may leave throughout the course of the season because of other injuries, our risk estimates may be underestimates. Thus, future surveillance studies should continue refining methods to better estimate risks.

Types of EHI

Heat cramps comprised 15.8%–45.6% of EHI across competition levels. Fatigue is considered a primary factor (28) of heat cramps, which may explain why they frequently occurred during practice as players engaged in repetitive drills, conditioning, and plays. Dehydration and sodium losses are additional contributing heat cramp factors and are directly related to the length of practices and games (28). Heat cramps may be dependent on the player’s sensitivity to these predisposing factors, possibly explaining why there was not a consistent trend for when heat cramps occurred across competition levels.

EHE and dehydration each comprised large proportions of reported EHI events (20.0%–42.1%). Dehydration can technically be an isolated condition; however, it is not possible to have EHE without the presence of dehydration (1). Therefore, ATs may have had difficulty choosing a diagnosis to best fit their assessment. Collegiate and military investigations have also noted that the majority of EHI events were heat cramps or heat exhaustion (6,10). Our findings may be explained by previous research that established 50%–75% of athletes arrive dehydrated to games and practices (12,27,37). Ensuring athletes are appropriately euhydrated before participation is essential to reduce risk of EHI.

Severity

Previous research has found that fatalities occur more often in college football than youth and high school football (5,29). Our data mirrored such data, finding the more severe cases occurring in college football; college football had the only reported EHS case as well as the largest proportion of EHI events that were TL. This, coupled with college football having the highest 1-yr risk of EHI, may highlight the need for concern for this population despite existing heat acclimatization guidelines (40).

Approximately 3.5% of EHI in our study needed emergency transport, highlighting the substantial burden on the medical community with possible morbidities and treatments (18). ATs may not always call emergency medical services in EHI, giving the possibility of more cases in which EMS may have been necessary (21). Even though only one EHS case was reported, it is possible that those EHI instances transported by EMS were heat stroke cases based on the severity of symptoms typically needed to enact the emergency action plan. Such severe cases of EHI are rare but have life-altering implications. For example, a third of HS football players required up to 21 d of recovery, and 3% did not return to play, after sustaining an EHI event (39). In addition, cases of EHI have been reported in two emergency room epidemiology studies, with rates that were significantly lower than our own across football levels (0.002 to 0.02/1000 cases) (9,33). However, this may be because these studies did not include field-of-play assessments.

With proper prevention strategies, EHI events should be avoidable in most cases. In addition, proper identification and management of EHI events should minimize severe cases. Past research at the high school level found that in 66% of cases, a medical professional was not on-site at the start of the EHI event (19). Our findings, coupled with the previous research, warrant future prospective research within the football population. Practically though, parents and coaches need to be prepared to respond to EHI, and ATs are needed at all levels of football competition.

Limitations

Our study did not include wet bulb globe temperature, nor heat index recordings across competition levels, limiting the ability to provide further insight into results. EHS was hard to examine because it was minimally reported. EHI diagnoses were based on AT opinion and not standardized criteria, making it difficult to verify the type of EHI treated. Our dataset was dependent upon the professional opinion of the AT or physician assessing the case. Previous research has identified obstacles to health care providers accurately recognizing EHS in the field (26). Even emergency room health care providers struggle to diagnose EHI, as proven by Nelson et al. (33) who reported that 48% of EHI events were never given an exact descriptor. Future research with standardized EHI diagnosis criteria is needed. Last, our exposure measure, AE, was unit based as opposed to time based. Thus, we were unable to report injury rates by the minutes or hours in which each athlete was active in each game and practice. However, this limitation was necessary to reduce reporter burden. The pooled 1-yr risks were limited because the squad sizes were not tracked throughout the season and the high school and collegiate denominators were based on the average number of players and not the actual roster sizes. Also, we could not censor the denominator based on the dropout or attrition over the course of the season. Future research could benefit by reporting specific team squad sizes when the season begins and ends, as well as the length of the team’s season by days in order to calculate more accurate EHI risk estimates.

CONCLUSIONS

The overall risk of EHI events was low. However, EHI risk was the highest in college, meriting concern for this population despite existing heat acclimatization guidelines. Higher preseason EHI rates across all competition levels may emphasize the need for continued modifications in preseason practices for college football and the development of national standards for HS and youth sports. The lower injury rates rate in HS football games and youth football practices may be attributable to traditional night starting times decreasing extrinsic thermal load. Thus, EHI prevention guidelines may need to consider game and practice modifications based on environmental conditions that are specific to competition level. With proper prevention strategies, EHI events should be avoidable in most cases.

Funding for this study was provided by USA Football, the National Athletic Trainers’ Association Research and Education Foundation, BioCrossroads in partnership with the Central Indiana Corporate Partnership Foundation, and the National Collegiate Athletic Association. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the programs’ sponsors, nor does it constitute endorsement by the American College of Sports Medicine. John Parsons is the Director of the National Collegiate Athletic Association Sport Science Institute, which partially funded this study. No other conflict or financial disclosures were reported by the remaining authors of this article.

We thank the many athletic trainers who have volunteered their time and efforts to submit data to the National Collegiate Athletic Association Injury Surveillance Program, National Athletic Treatment, Injury and Outcomes Network, and Youth Football Surveillance System programs. Their efforts are greatly appreciated and have had a tremendously positive effect on the safety of athletes.

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Keywords:

PEDIATRIC; HEAT EXHAUSTION; HEAT CRAMPS; EMERGENCY; HIGH SCHOOL

© 2016 American College of Sports Medicine