Epidemiology, treatment, costs, and long-term outcomes of patients with fireworks-related injuries (ROCKET); a multicenter prospective observational case series

Objective People in the Netherlands are legally allowed to celebrate New Year’s Eve with consumer fireworks. The aim of this study was to provide detailed information about the patient and injury characteristics, medical and societal costs, and clinical and functional outcome in patients with injuries resulting from this tradition. Methods A multicenter, prospective, observational case series performed in the Southwest Netherlands trauma region, which reflects 15% of the country and includes a level I trauma center, a specialized burn center, a specialized eye hospital, and 13 general hospitals. All patients with any injury caused by consumer fireworks, treated at a Dutch hospital between December 1, 2017 and January 31, 2018, were eligible for inclusion. Exclusion criteria were unknown contact information or insufficient understanding of Dutch or English language. The primary outcome measure was injury characteristics. Secondary outcome measures included treatment, direct medical and indirect societal costs, and clinical and functional outcome until one year after trauma. Results 54 out of 63 eligible patients agreed to participate in this study. The majority were males (N = 50; 93%), 50% were children below 16 years of age, and 46% were bystanders. Injuries were mainly located to the upper extremity or eyes, and were mostly burns (N = 38; 48%) of partial thickness (N = 32; 84%). Fifteen (28%) patients were admitted and 11 (20%) patients needed surgical treatment. The mean total costs per patient were €6,320 (95% CI €3,400 to €9,245). The most important cost category was hospital admission. Only few patients reported complaints in patient-reported quality of life and functional outcome after 12 months follow-up. Conclusion This study found that young males are most vulnerable for fireworks injuries and that most injuries consist of burns, located to the arm and hand, and eye injuries. On the long-term only few patients experienced reduced quality of life and functional limitations.

No other inconvenience associated with participation is expected. The risks associated with participation can be considered negligible and the burden can be considered minimal. The study could not be conducted without the participation of pediatric patients.

INTRODUCTION AND RATIONALE
Fireworks are used for celebrating all kinds of rituals and events worldwide. Despite their nice visible and audible effects, it has the potential to cause serious injuries.
Fireworks-related injuries occur frequent in both adults and children. It can be considered a public health problem as they often entail serious and avoidable injuries and often affect innocent bystanders (1-3).
In the USA, the Consumer Product Safety Commission (CPSC) presented a report stating that in 2015 approximately 12,000 fireworks-related injuries were treated in Emergency Departments (ED), reflecting an annual incidence rate of 3.7 per 100,000 individuals. Most patients were males (61%) and 42% were younger than 20 years of age (4). This is comparable with the results of several other studies (1-3, 5-9).
The percentages presented by the CPSC are comparable with the Netherlands with an incidence rate of 2.8 per 100.000 individuals per year treated at an ED with fireworks-related injuries (8). In 36% of the cases, victims were younger than 20 years of age and 76% were males. In the past ten years the number of fireworks-related injuries fluctuates between 400 and 1,000 cases annually. A clear up or downward trend is not observed in the past decade (8).
In two-thirds of all patients, the injuries are located at the hands, face and eyes, mostly Fireworks-related injuries are relatively easy to prevent and therefore a relevant public health problem. However, detailed knowledge is lacking on the treatment, functional impairment, and medical and societal costs on the long-term. This study aims to provide detailed information regarding patient, injury, and treatment characteristics, medical and societal costs, and patient-reported outcomes, with a follow-up of one year.

OBJECTIVES Primary Objective:
To determine the injury characteristics of fireworks-related injuries in patients reporting to a hospital for treatment.

1)
To determine the number and type of operations needed due to of fireworks-related injuries until one year after trauma 2) To determine the duration of hospital admission in these patients

3)
To determine the direct medical costs and the indirect societal costs (incl. work absence) in these patients

4)
To investigate the absence from school in these patients

5)
To investigate the patient-reported outcomes in these patients

Population (base)
All patients (no age limit) with fireworks-related injuries presenting to a hospital in the period between December 1, 2017 and January 31, 2018 in the Trauma Region Southwest Netherlands, will be eligible for inclusion. Patients will be recruited from every hospital in the Trauma Region Southwest Netherlands. In the Netherlands it is only permitted to lit fireworks as a consumer during the celebration of New Year's Eve and logically most fireworks-related injuries occur during that night or the period close before and after. Therefore, this specific time range was chosen.

Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1) Patients with any injury caused by fireworks treated* in a hospital in the Trauma Region Southwest Netherlands between December 1, 2017 and January 31, 2018 2) Provision of informed consent * Treatment is defined as any intervention for which ≥1 clinical follow-up visit is scheduled

Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study: 1) Patients who died within the first 24 hours due to other injuries than fireworks 2) Patients with incomplete or unknown contact information; 3) Insufficient understanding of Dutch or English to understand the study documents

TREATMENT OF SUBJECTS
Not applicable, this study is not an intervention study.

Investigational product/treatment
Not applicable, this study is not an intervention study.

Use of co-intervention (if applicable)
Not applicable, this study is not an intervention study.

Escape medication (if applicable)
Not applicable, this study is not an intervention study.

INVESTIGATIONAL PRODUCT
Not applicable, as this study does not involve an investigational product.

Name and description of investigational product(s)
Not applicable, as this study does not involve an investigational product.

Summary of findings from non-clinical studies
Not applicable, as this study does not involve an investigational product.

Summary of findings from clinical studies
Not applicable, as this study does not involve an investigational product.

Summary of known and potential risks and benefits
Not applicable, as this study does not involve an investigational product.

Description and justification of route of administration and dosage
Not applicable, as this study does not involve an investigational product.

Dosages, dosage modifications and method of administration
Not applicable, as this study does not involve an investigational product.

Preparation and labelling of Investigational Medicinal Product
Not applicable, as this study does not involve an investigational product.

Drug accountability
Not applicable, as this study does not involve an investigational product.

NON-INVESTIGATIONAL PRODUCT
Not applicable, as this study does not involve a non-investigational product.

Name and description of non-investigational product(s)
Not applicable, as this study does not involve a non-investigational product.

Summary of findings from non-clinical studies
Not applicable, as this study does not involve a non-investigational product.

Summary of findings from clinical studies
Not applicable, as this study does not involve a non-investigational product.

Summary of known and potential risks and benefits
Not applicable, as this study does not involve a non-investigational product.

Description and justification of route of administration and dosage
Not applicable, as this study does not involve a non-investigational product.

Dosages, dosage modifications and method of administration
Not applicable, as this study does not involve a non-investigational product.

Preparation and labelling of Non Investigational Medicinal Product
Not applicable, as this study does not involve a non-investigational product.

Drug accountability
Not applicable, as this study does not involve a non-investigational product.

Main study parameter/endpoint
The primary outcome measures are the injury characteristics. The following variables will be collected:

Secondary study parameters/endpoints (if applicable)
The following outcomes will serve as secondary outcome measures: The total duration of hospital admission will be calculated from the dates of admission and discharge from the hospital. Re-admission to a hospital during followup will be counted separately.
In order to determine the direct medical costs and indirect societal costs, patients will be asked to complete a custom-made questionnaire that contains detailed information on both items. Health care costs will include general practice care, medical specialist care, nursing care, physical therapy, hospitalization, medication, home care, and other costs directly associated with diagnosis, treatment and rehabilitation. The indirect societal costs will be calculated by the absence from paid work, production loss without absence from paid work and hindrance in the performance of paid and unpaid work.
School-going patients (and their parents) will be asked to complete a custom-made questionnaire regarding absence from school.
The EuroQol-5D-3L (EQ-5D-3L) is a validated questionnaire for measuring health- For specific injuries we will ask patients to complete additional questionnaires, in order to gain more insights in injury specific outcomes.
For patients with eye injuries: The Health Utilities Index Mark 3 (HUI-3), domain vision (consisting out of 2 questions, each with four possible answers), will be used to assess patients generic health status and health-related quality of life, regarding their eye injury. Patients aged ≥16 years will complete the HUI-3 themselves. Parents of a pediatric patient (<16 years) will complete the questionnaire, together with their child if possible.
Visual acuity is determined routinely and will be extracted from patient's medical file.
For patients with upper extremity injuries: The HUI-3, domain dexterity (one question with four possible answers) will assess the health-related quality of life regarding upper extremity injuries. Patients aged ≥16 Version 1.0 (September 11, 2017) 19 of 33 years will complete the HUI-3 themselves. Parents of a pediatric patient (<16 years) will complete the questionnaire, together with their child if possible.
The Quick-DASH is used in order to measure physical function and symptoms in people with any or multiple musculoskeletal disorders in the upper limb. It is scored in two components: the disability/symptom section (11 items, scored 1-5) and the optional high performance sport/music or work modules (each 4 items, scored 1-5).
A higher score indicates greater disability (14). Only patients aged ≥16 years will complete this questionnaire.
The Cold Intolerance Symptoms Severity (CISS) questionnaire is a 6-item questionnaire. The sum of all questions (range 4-100) defines the severity of cold intolerance, with a higher number representing more severe symptoms (15,16).
Only patients aged ≥16 year will complete this questionnaire.
For patients with lower extremity injury: The

Lower Extremity Functional Scale (LEFS) is a validated questionnaire
containing 20 items about a person's ability to perform everyday tasks. It can be used to evaluate the functional impairment of a patient with a disorder of one or both lower extremities. All items are scored so that a high score represents greater disability. The maximum score achievable is 80 points (17,18). Only patients aged ≥16 year will complete this questionnaire.

For patients with burn wounds
The Patient and Observer Scar Assessment Scale (POSAS v2.0; www.posas.org) (19) consists of two parts: a Patient Scale and an Observer Scale, which aim to provide a rating of several measured of scar quality (vascularity, pigmentation, relief/texture, thickness, pliability, surface area, pain, and itching/pruritus). Adult patients and parents of pediatric patients (<16 years) will complete the patient-reported part. A trained observer will complete the observerreported part.
Satisfaction level regarding function and cosmesis of the injured area will be determined using an 11-point numeric rating scale, ranging from 0 (extremely dissatisfied) to 10 (fully satisfied). Only patients aged ≥16 year will complete this questionnaire.
Version 1.0 (September 11, 2017) 20 of 33 Patients will also be asked to complete a custom-made questionnaire investigating their view on the use of consumer fireworks before and after trauma, and how the trauma influenced their opinion. Only patients aged ≥16 year will complete this questionnaire.

Other study parameters (if applicable)
In order to report characteristics of the study population and to determine treatment costs, patient characteristics, additional injury-related and outcomes-related variables will be collected. These will include: Patients characteristics to be collected:

Randomization, blinding and treatment allocation
Randomization and treatment allocation are not applicable, since this study is not an intervention study. Blinding of patients and surgeons also does not apply.

A: Patient selection
The local contact person in the participating hospital will provide details of each patient with fireworks-related injuries to the research team. A simple e-mail or phone call is sufficient for registration, the coordinating investigator (or a dedicated and trained research assistant) will take care of all further logistics and data collection. He/she will also call each hospital on a daily basis during the inclusion period in order to ask for any The study will not interfere with treatment or follow-up. Data concerning patient characteristics, injury characteristics, treatment details, and clinical outcome data will be extracted from the patient file as much as possible. These data will be collected from the patient's medical files as soon as possible after signing informed consent. For the purpose of the study, additional details concerning treatment and outcome (see paragraph 8) that are not mentioned in the patient's hospital files, will be registered on the case report forms directly. This will be done at the follow-up visits.
As soon as possible and within two weeks after inclusion patients will be asked to complete the questionnaire's, reflecting their pre-injury health status. For all participants this will be the EQ-5D-3L questionnaire. For patients with eye trauma the HUI-3 (domain vision), for patients with upper extremity trauma the HUI-3 (domain dexterity), the Quick-DASH, and CISS, for patients with lower extremity trauma the LEFS, and for patients with burn wounds the POSAS. At three, six and 12 months, treatment characteristics, health care consumption details and patient reported outcomes will be collected.  5 For patients with upper extremity injury, 6 For patients with lower extremity injury, 7 For patients with burn wounds. * Only at time of withdrawal For EQ-5D and HUI-3, pediatric versions are available for children <16 years. Parents of children <16 years complete the POSAS. Other questionnaires are completed by patients ≥16 years only.

Withdrawal of individual subjects
Participants can leave the study at any time for any reason if they wish to do so without having to give a reason. Their decision to withdraw will have no consequence for their medical treatment. The investigator can decide to withdraw a subject from the study for urgent medical reasons.

Replacement of individual subjects after withdrawal
Not applicable; no replacement will take place.

Follow-up of subjects withdrawn from treatment
Should a participant who is still under routine clinical follow-up decide to withdraw consent, they will receive the normal clinical follow-up as any other patient treated for fireworks-related injuries. As treatment are not part of this study, no additional controls are needed. Also, the research team will no longer contact patients after consent has been withdrawn.

SAFETY REPORTING
As this study is not subject to the Medical Research Involving Human Subjects Act (WMO), patients are not subjected to treatment in this study, and the study does not involve an investigational or non-investigational medicinal product, this paragraph does not apply.

Temporary halt for reasons of subject safety
As patients are not subjected to treatment in this study, this does not apply.

Adverse events (AEs)
As patients are not subjected to treatment in this study, this does not apply.

Serious adverse events (SAEs)
As patients are not subjected to treatment in this study, this does not apply.

Suspected unexpected serious adverse reactions (SUSARs)
As patients are not subjected to treatment in this study and the study does not involve an investigational medicinal product, this does not apply.

Annual safety report
As patients are not subjected to treatment in this study and the study does not involve an investigational medicinal product, this does not apply.

Follow-up of adverse events
As patients are not subjected to treatment in this study, this does not apply.

Data Safety Monitoring Board (DSMB) / Safety Committee
As patients are not subjected to treatment in this study and the study does not involve an investigational nor a non-investigational medicinal product, participants will have no larger risks than patients who are not participating in this study. Therefore, no DSMB will be installed.

STATISTICAL ANALYSIS
Data will be analyzed using the Statistical Package for the Social Sciences (SPSS) version 21.0 or higher (SPSS, Chicago, Ill., USA). Normality of continuous data will be tested with the Shapiro-Wilk test, and homogeneity of variances will be tested using the Levene's test. A p-value <0.05 will be taken as threshold of statistical significance in all statistical tests, and all tests will be two-sided. Missing values will not be replaced by imputation.

Primary study parameter(s)
Injury characteristics will be analyzed descriptively. They will be reported as mean with Standard Deviation (SD; parametric, continuous data) or median with quartiles (P 25 -P 75 ; non-parametric, continuous data), or as number with percentage (categorical data).
Data will be reported as a group as well separately for the groups of patients with eye injury, upper and lower extremity injury, hand injury, or burn wounds. Further subgroups will be determined based on the patients included. Relevant subgroups can be legal versus illegal fireworks, operator versus bystander.

Secondary study parameter(s)
Secondary outcome measures will be analyzed and reported the same as described for the primary outcome measures (paragraph 10.1). The only difference is that costs will be reported as mean with 95% confidence interval (95% CI). The 95% CI around the mean costs will be approximated by nonparametric bootstrapping.

Other study parameters
See section 10.2.
In order to check if the enrolled sample is a true representation of the total group of patients treated in a hospital for fireworks-related injuries. Gender and location of injuries of participants and non-participants will be compared using a Chi-squared test or Fisher's test. Differences in age between the two groups will be tested using a Student's T-test or Mann-Whitney U-test, as applicable.

Interim analysis (if applicable)
Not applicable, no interim analysis will be performed. However, in order to fuel the public debate, injury characteristics and specific treatment characteristics may be analyzed before follow-up is complete.

Regulation statement
The study will be conducted according to the principles of the Declaration of Helsinki (64 th World Medical Association General Assembly, Fortaleza, Brazil, October 2013). This study has been exempted by the medical research ethics committee (MREC); in Dutch: Medisch Ethische Toetsings Commissie (METC). Following review of the protocol, the MREC concluded that this study is not subject to the Medical Research Involving Human Subjects Act (WMO). They concluded that the study is a medical/scientific research, but no patients are subjected to procedures or are required to follow rules of behavior.

Recruitment and consent
Eligible persons with fireworks-related injuries (or the parents of pediatric patients) will be informed about the study as soon as possible after hospital presentation. They may receive the information at the ED/ward or at home. The local staff will ask permission to send contact details to the research team. Upon receipt of that permission, a local contact person in the participating hospital will provide details of the patient to the research team.
The coordinating investigator or research assistant will send the patient (or parents) the information brochure. The coordinating investigator or a research assistant will visit the patient at the ward/outpatient clinic or at home within two weeks after presentation, in order to further explain the study, answer any questions the patient (or parents) may have, and for signing informed consent. This gives patients up to two weeks to consider their participation. Should patients decline participation only due to the burden of the questionnaires, consent will be asked to only use the information registered in the medical files.
Participation in this study is on a voluntary basis. If persons do not wish to participate, they can do so without specifying why. Deciding not to participate in the study will not affect regular treatment and follow-up care. Participants are allowed to withdraw from the study at any time after they have given their written consent.
Participation in this study will not have any influence on treatment. The General Practitioner (GP) will be informed about the participation of his/her patient.

Objection by minors or incapacitated subjects (if applicable)
Pediatric patients are involved in this study. Should pediatric patients show any sign of objection, they will not undergo examination of scar tissue quality.
Adult patients will only be enrolled if they are able to provide informed consent themselves. They cannot be incapacitated.

Benefits and risks assessment,
Management (resuscitation, diagnostics, treatment, after-care, and follow-up visits) of study participants will not differ from those who do not participate. The study does not interfere with diagnostics, treatment, and follow-up at all. As part of this study, patients will be asked to complete questionnaires directly after inclusion (and within two weeks) and after three, six and after 12 months. Physical examination will be performed in patients with burn wounds to assess the scar quality at three, six and 12 months.
All clinical data will be collected during the follow-up visits as well as from the patients' medical files. Therefore, risks associated with participation can be considered negligible.
Participants should not expect any personal benefits from their participation in this study. Their participation may help future patients admitted with fireworks-related injuries.
There are no other known additional risks involved in this study, aside from the slight inconvenience of completing the questionnaires. This will take approximately 30 minutes each time, including regular follow-up. The total time investment per patient is thus 90 minutes for three follow-up moments.

Burden
Adult patients and parents of pediatric patients are asked to complete the EQ-5D-3L (adult, youth or youth-proxy version). Depending their trauma patients have to complete injury-specific questionnaires. Patients with burn wounds will be subjected to physical examination regarding scar quality. The burden of completing the questionnaires and the physical examination can be considered as minimal.

Group relatedness
This study is group-related and cannot be conducted without the participation of pediatric patients. Gaining inside into the epidemiology of fireworks-related injuries, treatment, and outcome in pediatric patients can only be studied by enrolling those pediatric patients.

Compensation for injury
As the study is not subject to the Medical Research Involving Human Subjects Act (WMO), the statutory obligation to provide insurance for subjects participating in medical research (article 7 of the WMO) also does not apply.

Incentives (if applicable)
There is no incentive for patients to participate in this study. There are no costs involved for study participants. The motivation for the study is a potential benefit to all future patients admitted with fireworks-related injuries, as the results of this study will increase our knowledge on the epidemiology, costs and outcomes of fireworks-related injuries.

Handling and storage of data and documents
Research data will be stored in a database (e.g., OpenClinica Clinical Trial Software for Electronic Data Capture or a similar platform that meets GCP standards and has an audit trail), and will be handled confidentially and anonymously. Research data that can be Research data will be stored under a code number that relates to individual persons.
In order to trace data to an individual subject, a subject identification code list will be made to link the data to the subject. This code consists of the study acronym, three letters for the admitting hospital and three numbers for patient's study ID (e.g., ROCKET-EMC-001 for the first patient at Erasmus MC). Only the code number will be used for study documentation, annual progress reports and research publications. The principal investigator and research assistant are the only persons with the information linking individual persons to study code numbers. This data will be stored during the investigation and will be disposed of 15 years after completion of the study.

Monitoring and Quality Assurance
Any information on paper collected during this study will be placed in a research folder, which will be filed in locked cabinets in the research offices at Erasmus MC. Any electronic information collected during this study will be saved in a password-protected area. Only the study staff will have access to these data.
Patients will be asked for permission to store the informed consent, contact details, and CRFs at Erasmus MC, as the coordinating investigator or research assistant will contact patients during the study and will collect their follow-up data.
One of the project leaders or an independent person will monitor quality of the data by checking entry of data into the database. Data entry of injury details for a random selection of 25% of patients will be checked. In addition, data entry of questionnaires will be checked for 10% of all enrolled patients.
The questionnaires that patients and the coordinating investigator or research assistant complete during follow-up will be considered as source documents. With Version 1.0 (September 11, 2017) 30 of 33 respect to the clinical data such as surgical details, adverse events and interventions, the (electronic) patients files and case report forms will serve as source data.

Amendments
Amendments are changes made to the research after a favorable opinion by the accredited MREC has been given. All amendments will be notified to the MREC that gave a favorable opinion.
Non-substantial amendments will not be notified to the accredited MREC, but will be recorded and filed by the sponsor. Examples of non-substantial amendments are typing errors and administrative changes like changes in names, telephone numbers and other contact details of involved persons mentioned in the submitted study documentation.

Annual progress report
Not applicable, as this study will not be subject to the Medical Research Involving Human Subjects Act (WMO).

Temporary halt and (prematurely) end of study report
No applicable, as this is not an intervention study.
Within one year after the end of the study (i.e., completing data collection), the investigator will submit a final study report with the results of the study, including any publications/abstracts of the study, to the accredited MREC.

Public disclosure and publication policy
Research data will be reported following the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines.
Research data can be presented or publicized in agreement with the principal investigator and project leaders only. Radiographs, CT images, and digital photographs will not be used for publication or teaching purposes without given consent by the patient.
No research data that can be traced to individual persons will be presented or published.
The primary publication will be made by the principle investigator. Each participating hospital will provide one co-author for a collaborator group authorship (or full authorship if the journal allows it). This way, hospitals will be acknowledged for their participation.
This study will be registered at The Netherlands National Trial Register (NTR) (in Dutch; Nederlands Trial Register; www.trialregister.nl).