Study design
The CRWs represents an exhaustive retrospective and prospective cohort study aimed at evaluating the impact of occupational radiation exposure on chronic non-communicable diseases within the cohort of interventional radiology and nuclear medicine radiation workers in Chongqing. The project's protocol was developed through collaborative endeavors between the Chongqing Center for Disease Control and Prevention and the Radiation Medicine Institute of the Chinese Academy of Medical Sciences. The implementation phase of this study will be executed in close collaboration with diverse local disease prevention and control centers in Chongqing. The initiation of this project occurred in 2022, with the slated completion of baseline data collection in 2024. Commencing in 2025, data collection for follow-up and physical examinations will be conducted on a biennial basis.
Study population
A survey was undertaken among workers in interventional radiology, nuclear medicine, and diagnostic radiology in Chongqing, employing cluster sampling based on predetermined inclusion criteria. A subset of interventional radiology workers, possessing a valid practicing physician's certificate, demonstrating proficiency in surgical interventional procedures with a surgical volume of at least 10 procedures weekly, will undergo a dose reconstruction study of the intraocular lens. In the case of nuclear medicine workers, individuals operating radioactive nuclides will be subject to a skin dose reconstruction study.
All participants or their respective relatives were informed of the utilization of data in this study, and the outcomes of all examinations and tests were succinctly communicated to each study participant. Participants retaining the option to discontinue their involvement may withdraw from the study at any point in time.
Inclusion and exclusion criteria
Inclusion criteria encompass formal hospital employees with radiation worker certificates, engaged full time in relevant departments, and holding professional titles such as doctor, nurse, technician, among others. Full-time nuclear medicine cleaning personnel are also included.
Exclusion criteria pertain to regular trainees, informal employees, and those in temporary positions in the departments not involved in related work.
Rejection criteria dictate that cohort members who have transferred and are no longer occupied in the aforementioned positions will be excluded from subsequent research; however, their preliminary data will be retained.
Study procedure
Figure 1 illustrates the procedural details of the CRWs follow-up. Upon participants' endorsement of the informed-consent form, they will receive a personal profile and be assigned a digit code for identification. During the initial follow-up, participants will be required to complete a baseline questionnaire, encompassing details on educational background, lifestyle, and personal and family disease history. Subsequently, the collection of occupational health examination data and blood samples will take place. The follow-up schedule and procedure of this study will adhere to the Chinese follow-up guidelines for the Medical Research Registration and Filing Information System. In the cross-sectional study, biennial follow-ups will ensue, during which participants will complete a follow-up questionnaire covering occupational exposure doses, health, and psychological status. Simultaneously, occupational health examination data for participants will be collected. Certain interventional radiology and nuclear medicine participants will engage in dose monitoring and data collection for dose reconstruction. Statistical analyses will then be conducted, revealing that participants with higher doses will undergo studies on biological dose-response curves and biomarkers. Biennial follow-ups will be sustained for a period of 20–30 years, culminating in a comprehensive cohort analysis.
Study size
In 2023, a comprehensive annual survey was conducted on the number of radiation workers in Chongqing, revealing 2,416 radiodiagnosis and radiotherapy institutions employing a total of 12,986 professionals. These individuals were distributed across various specialties, encompassing X-ray imaging diagnosis (9,260), nuclear medicine (342), and interventional radiology (2,543), as detailed in Table 1. Within this context, there were 107 interventional radiology departments, housing 235 interventional doctors performing a minimum of 10 surgeries weekly, constituting 9.24% of the interventional radiology workforce. The research team intends to enlist these 235 interventional doctors for the reconstruction of radiation-sensitive organ doses. Furthermore, there were 342 members engaged in nuclear medicine, with an additional 115 radiation workers directly involved in tasks like packaging and injection of radioactive isotopes. This subset, accounting for 34.23% of the total nuclear medicine radiation workers, will also be recruited for the reconstruction of radiation-sensitive organ doses. To serve as the control group for the study, 3,000 individuals will be randomly selected from the pool of radiology diagnostic workers.
Table 1
Distribution of radiation workers in different levels of radiodiagnosis and radiotherapy units
Hospital level | radiodiagnosis and radiotherapy institutions n% | Occupational Category n% |
radiological diagnosis | radiation therapy | nuclear medicine | interventional medicine |
Level 3 Level 2 Level 1 Total | 87(3.6) 240(9.93) 2089(86.47) 2416 | 3018(32.60) 2023(21.85) 4219(45.56) 9260 | 655(77.88) 172(20.45) 14(1.66) 841 | 280(81.87) 38(11.11) 24(7.02) 342 | 1848(72.67) 631(24.81) 64(2.52) 2543 |
Data collection
Demographic characteristics
A demographic characteristics questionnaire has been specifically devised for the CRWs study. Guidelines and requirements for completing this questionnaire have been developed to ensure that cohort participants satisfactorily fill out the CRWs Health Questionnaire, encompassing queries related to demographic characteristics such as name, identity card, age, etc. The questionnaire format is illustrated in Table 2. Investigators from the Center for Disease Control and Prevention will visit all hospitals, distribute questionnaires to cohort participants, and oversee the completion and collection of the questionnaires. Subsequent to questionnaire completion, reviews are conducted by investigators to identify any missing items. In the event of omissions, the questionnaire is promptly returned to the respective radiation worker for completion. Following the collection phase, data entry and summarization are carried out using Epidata and exported to Excel. These data are then stored in a comprehensive database.
Table 2
Summary of the CRWs Health Questionnaire
Variable Category | Variable Name |
Basic information | Gender Age (calculated according to ID number) The highest educational level Marital status Monthly total household income Residential situation (living alone or together) Height Weight Occupational Exposure Types (1 Interventional Radiology; 2 Nuclear Medicine; 3 Other) Number of X-ray/CT examinations received |
Occupational history of radiation work | Current occupational history in radiation work Previous occupational history in radiation work |
131I Operation Status | Current 131I operation status |
Medical history (with or without) | Cardiovascular system: hypertension, coronary heart disease, stroke; Endocrine system: thyroid disease, diabetes; Neurosystem: neurasthenia; Digestive system: gallbladder disease, fatty liver, hepatitis, cirrhosis, gastric ulcer; Respiratory system: chronic obstructive pulmonary disease; Urinary system: Kidney disease; Immune system: Gout; Hematology: Aplastic anemia, abnormal white blood cells; Other: cataracts, depression, malignant tumors, etc. |
History of infectious diseases (with or without) | Hepatitis A Hepatitis B Hepatitis C Helicobacter pylori infection, others. |
Family history of disease (with or without) | Hypertension Senile dementia Diabetes Heart disease/coronary heart disease Cerebral apoplexy Aplastic anemia History of mental illness Sudden unexplained death Cancer Other |
Recent symptoms (with or without) | Non-specific symptoms: headache, dizziness, nausea, sleep disorders, fatigue, decreased memory, tinnitus, drowsiness, difficulty concentrating, and others; Skin and mucosal symptoms: gingival bleeding, subcutaneous ecchymosis, nosebleeds, bruising, and others. |
Contact history (with or without) | Toxic exposure Contact history in epidemic area (except for novel coronavirus pneumonia) |
Health related behaviors | Sleep condition Smoking situation Alcohol consumption situation Tea drinking situation Physical activity Emotional status eating habits |
Note: SDS, Self- Rating Depression Scale; CPSS, Chinese Perceived Stress Scale. |
Lifestyle
The lifestyle questionnaire constitutes an integral component of the CRWs Health Questionnaire, encompassing dietary habits, smoking, drinking, and other relevant information (Table 2). Serving as foundational data, akin to the demographic characteristics questionnaire, it is not frequently required during subsequent follow-ups. During the baseline establishment, investigators employ face-to-face or telephonic communication with cohort participants to ensure the accuracy and authenticity of the data. The questionnaire is administered in a dedicated space, with one investigator posing inquiries and another recording the responses. Data entry into the database involves the collaboration of two individuals for heightened accuracy.
Working history
A questionnaire has been designed for the collection of work history information, encompassing details such as occupational exposure work history, types of occupational exposure, and duration of exposure (Table 2). Participants will be invited to engage in face-to-face meetings or phone contacts in dedicated rooms to enhance the clarity and accuracy of their recollections regarding work history. The obtained data are stored systematically in the database, and updates on the occupational history of radiation work (Table 3) will be accumulated and expanded with each subsequent follow-up in the future.
Table 3
Summary of the CRWs Follow-up Questionnaire
Variable Category | Variable Name |
Basic information | Work unit name Gender Age (calculated according to ID number) Residence (9 districts and counties in the main city) Start working time Working experience (calculated based on start of work and submission of questionnaires) |
Occupational history of radiation work | Occupational history of interventional radiology work Occupational history in nuclear medicine work Occupational history of diagnostic radiology work |
Health related information | Smoking situation Alcohol consumption situation Disease situation |
Health survey
The cohort participants will undergo a health survey based on principles of economics and effectiveness. The baseline questionnaire, encompassing medical history, family history of disease, current symptoms, etc. (Table 2), will be completed and entered under the supervision of investigators during the initial survey. Subsequent follow-ups will update and record any newly developed diseases among the participants.
In accordance with the Technical Specification for Occupational Health Monitoring of Radiological Workers (GBZ 235–2011), required occupational health examinations will be conducted on the cohort participants by designated occupational health examination institutions. Investigators will gather occupational health examination data and pertinent information for interventional, nuclear medicine, and diagnostic radiology personnel, consolidating them in a designated Excel database named the Occupational Health Examination Form (Table 4). This process will be conducted biennially for continuous collection of occupational health examination data from the participants during follow-ups.
Table 4
Summary of Occupational Health Examination Form
Variable Category | Variable Name |
Basic information | Medical examination institutions Category: Pre employment, On duty, Off duty name Work unit Gender Birth year ID card Irradiation source Occupational exposure types |
Testing items | Height, weight, blood pressure Internal medicine and surgical examination Blood routine |
| Thyroid function Liver function Kidney function Chromosome aberration analysis |
Adaptive Opinion | Micronucleus Examination of ocular fundus Electrocardiogram Abdominal ultrasound Can continue with the original radiation work Temporarily disconnected from radiation work Not suitable for continuing to engage in radiation work |
Dose reconstruction
Interventional surgeons conducting a minimum of 10 surgeries weekly will undergo standardized eye lens dose and dual dose monitoring through personal dose testing institutions. Throughout the monitoring period, personnel in the operating room and on duty will complete the "Interventional Surgery Registration Form" (Table 5). Physical doses collected annually from participants will be imported into their personal information, and the investigator will compile form data into a dedicated sensitive organ dose reconstruction database.
Table 5
Summary of Interventional Surgery Registration Form and Nuclear Medicine Workload Registration Form
Variable Category | Variable Name |
Interventional Surgery Registration Form | Surgical date Medical staff name Operator: First, Second, Third Surgical types: cerebrovascular, thoracic, cardiovascular, peripheral vascular, abdominal, other Operation program types: fluorescence intervention operation program, CT guided intervention operation program, digital subtraction angiography, other Surgery start time Wearing position of the intraocular lens dosimeter: beside the left eye, beside the right eye, beside both eyes, not worn Wearing situation of personal protective equipment: lead glasses, lead glasses, face screen, others, not worn Tube position: under the bed, on the bed Accumulated time of instrument outflow during surgery Exposure frame rate Fluoroscopy cumulative dose Air specific release energy area product Usage of machine shielding and protective equipment |
Nuclear Medicine Workload Registration Form | Personnel Name Specific job positions Department Starting time of wearing wrist dosimeter (year, month, day) End time of wearing wrist dosimeter (year, month, day) Wrist dose (mSv) Starting time for wearing dual dosimeters End time of wearing dual dosimeters Dose on the torso inside the lead apron (mSv) Dose at the neckline position corresponding to the collarbone on the lead apron (mSv) |
In the case of nuclear medicine workers, standardized monitoring of wrist dose and dual dose will be implemented, with workers independently completing the "Nuclear Medicine Workload Registration Form" (Table 5). The research team will assess the feasibility of wrist dose monitoring through the form. Annual physical doses will be collected by the investigator and imported into the specialized sensitive organ dose reconstruction database.
Biological samples
This study will involve the collection of 600 samples from individuals, comprising 200 samples each from interventional radiology workers, nuclear medicine workers, and diagnostic radiology workers. Each individual's sample set will consist of 1 ml serum, 1 ml plasma, and 2 ml whole blood. Fresh blood will be utilized for conducting chromosome aberration experiments, while the remaining samples will be stored at -80°C. In this study, blood samples will serve as the basis for analyzing gene methylation, glucolipid metabolism, hormones, and micronutrients, facilitating a comprehensive examination of various biological markers.
Interventional measurements
Throughout the follow-up period, participants in the CRWs exhibiting abnormal doses-specifically quarterly doses exceeding 1.25 mSv, annual effective eye lens doses surpassing 20 mSv, and annual effective skin doses exceeding 500 mSv—will undergo investigation by the research team. In cases where abnormal doses result from excessive radiation exposure, interventions will be implemented. These may include physical examinations, workload reduction, work cessation, job changes, etc. The research team will document intervention details, encompassing abnormal dose specifics, investigation results, physical examination results, decisions regarding position changes or workload reduction, and post-intervention dose levels, among other relevant parameters. The primary objective is to assess the impact of occupational radiation exposure on health and NCDs.
Outcomes
Primary outcome
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Diagnosis of specific NCDs, encompassing respiratory system diseases, circulatory system diseases, digestive system diseases, endocrine and nutritional metabolic diseases, as well as musculoskeletal system and connective tissue diseases.
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Diagnosis of cancers.
Secondary outcome
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Diagnosis of mental and behavioral disorders.
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Abnormality in SDS and CPSS scores.
Follow-up and assessment
Blood samples
Differences in gene methylation, glucose and lipid metabolism, hormones, and micronutrients among groups will be analyzed using blood samples. Biomarkers displaying differential expression will be selected and subsequently validated through molecular experiments, such as PCR and Western blotting.
Dose estimation
The Ministry of Health and Family Planning of the People's Republic of China has issued the method of dose estimation employing chromosome translocation with fluorescence in situ hybridization (GBZ/T 249–2014). This method will be utilized by the investigator to estimate the biological dose of CRWs participants over the past decade.
The investigator will accumulate the physical dose of CRWs according to the statistical standard outlined in the Specifications for Individual Monitoring of Occupational External Exposure (GBZ 128–2019). This standard will be employed to ascertain if cohort participants exhibit abnormal doses. In the event of abnormal doses, an investigation and intervention will be conducted to identify the cause, as mentioned above.
The investigator will conduct occupational health supervision for cohort participants based on the standard outlined in the Specifications for Occupational Health Surveillance for Radiation Workers (GBZ 235–2011). NCDs in the outcomes will be classified according to ICD-10.SDS, and the comprehensive psychopathological rating scale (CPSS) will be utilized to assess the mental health of CRWs participants. A summary of the cohort follow-up is available in Table 6.
Table 6
Complete overview of radiation worker follow-up used in the CRWs
Domain | Variable Name | Time points of radiation worker follow-up |
1-2y 3-4y 5-6y 7-8y 9-10y 11-12y 13-14y 15-16y 17-18y 19-20y dose abnormal |
Biological sample | Chromosome Serum Plasma Whole blood | √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ |
Accumulate dose | Organ Dose Personal dose | √ √ √ √ √ √ √ √ √ √ √ √ √ √ |
Occupational health | Health questionnaire Health examination | √ √ √ √ √ √ √ √ √ √ √ |
Mental health | SDS CPSS | √ √ √ √ √ √ √ √ √ √ |
Note: SDS, Self- Rating Depression Scale; CPSS, Chinese Perceived Stress Scale. |
Statistical analysis
Data analysis will be conducted using the statistical product and service solutions (SPSS 26). Categorical variables will be presented as numbers and percentages. For continuous variables, comparisons will be made using the T-test or Mann-Whitney test, while categorical variables will undergo comparison using χ2 or Fisher’s tests. Dose-response curves will be calculated using the linear square model "y = aD2 + bD + c." Linear and non-linear regression models will be employed to investigate causal inferences regarding the initiation and development of NCDs, incorporating factors such as radiation dose, lifestyle, pressure, and behavior. All analyses in this study will be conducted with a 95% confidence interval, and statistical significance will be considered at a level of 5%.
Ethics and dissemination
This study, involving human participants, obtained approval from the Ethics Committee of Chongqing Center for Disease Control and Prevention (NO. KY-2023-004-1). Ethical clearance was granted for all research procedures. The cohort is registered in the medical research registration and filing system by the Science and Technology Education Department of the National Health Commission (https://www.medicalresearch.org.cn/login), with the trial registration number MR-50-23-009837. Access to study data is restricted to investigators associated with the study and the Ethics Committee. The results of this study will be presented at national conferences and considered for publication in a peer-reviewed scientific journal. All results presented will be aggregate data, ensuring the confidentiality and non-identifiability of individual participants.