On the subjective side of stress measurement, there are the stress-assessing tests with their most commonly used representatives: the Trier Social Stress Test (TSST) and the State Trait Anxiety Inventory (STAI). TSST is used to assess the stress response in human subjects that are placed in investigative setting. It is known to reliably increases hypothalamic-pituitary-adrenal axis activation.^[7] It consists of an interview and solving mathematical problems for a limited amount of time.^[8] The meta-analysis of Dickerson and Kemeny examining the tests and conditions that result in cortisol activation concludes that TSST is an appropriate tool for inducing and further studying of stress hormones. ^[9] STAI is a subjective tool for evaluating the quantity and quality of the stress that certain circumstances or case in the clinical practice induces. The questionnaire is completed at baseline and immediately after the challenge, and it is established that the higher the score, the greater the stress experienced. STAI is often combined and compared to other stress indices.^[10]

The most common cardiac stress marker is heart rate variability (HRV). It is traditionally calculated by digital processing of electrocardiograms (ECG). The amount of time between consecutive heartbeats usually fluctuates so slightly that these fluctuations can only be measured with specific devices. HRV portrays those variations in consecutive R-R intervals. In recent times, with the technological development of modern devices for measuring cardiac indices, HRV has become a very sensitive indicator for dysregulation of the autonomic tone.^[11] The accumulation of chronic stress has been associated with a predominance of sympathetic activity, resulting in reduced HRV and reduced parasympathetic modulation.^[12] In a systematic review regarding HRV as an index of work stress, emergency physicians’ data analysis showed that subjects had a higher intraoperative HR and a low expression of HRV.^[13]

Eccrine glands on the hairy skin are activated by heat, as opposed to the ones found on the glabrous skin of the hands and feet, which are triggered by deep respiration, mental stress, and tactile stimulation. As these processes are dictated by autonomic stimuli, the result in shifts of electrodermal conductivity and electrodermal activity (EDA) is measured. The so called “emotional sweating” has been studied in order to be used in the assessment of sympathetic function and limbic activity.^[14]

In the Villanueva et al. study, the electrodermal activity of students was measured before and after an exam session. The session consisted of writing a self-report on one’s academic achievements, accompanied by an interview. Before, during the sessions, and shortly after them, the students wore devices that estimated EDA, and salivary biomarkers (cortisol, estradiol, progesterone, testosterone, and DHEA-S) were collected. Both methods showed that stress elevation was unrelated to the exam type, but EDA increased during both emotional activation and recollection of data.^[15]

Moreover, acute stress induces thermogenesis on the base of sympathetic nervous system (SNS) activation. Studies show that the hyperthermia is proportional to the intensity of the stressor.^[16] Initially, the measurement of skin temperature was performed via contact devices. Nowadays, infrared thermography (IRT) offers a non-contact way of assessing skin temperature that presents an alternative to conductive devices, ensuring maximum comfort for test subjects.^[17] In a test study with fifteen male participants, Engert et al. used IRT and established stress markers (HR, HRV, finger temperature, sAA, and sC) to assess stress during the cold pressor test and the TSST. In the study, thermal imaging of the face was performed and was found to correlate with mood changes rather than with stress. A weak correlation between IRT results and the other stress markers was established.^[18]

Saliva is a promising diagnostic fluid in stress measurement for many reasons, the main one being that its collection is noninvasive and causes no additional distress to the subjects. It can be collected at short intervals of time. Moreover, obtaining saliva does not require trained health care professionals or specific medical equipment and is estimated to be almost 50% cheaper than blood collection.^[5,19] Salivary levels of cortisol, alpha-amylase, secretory immunoglobulin A and chromogranin A have been associated with stress state.

Salivary cortisol (sC) is the most studied stress marker of the above-mentioned and is widely considered as a valid indicator of free cortisol and the hypothalamus-pituitary-adrenocortical-axis.^[20] Research indicates that the increase in sC levels occurs 5 minutes after the increase in plasma cortisol, peaking 31 to 40 minutes after stressor onset. Furthermore, there is a strong correlation between sC levels and plasma cortisol concentrations.^[21] In a study of 38 army nurses exposed to a combat, casualty simulation data showed that an increase in cortisol levels was observed for the majority of the army nurses, who showed an average increase of 136% for cortisol over baseline levels. In this study, salivary cortisol remained elevated over baseline levels 30 minutes after the conclusion of the task.^[22] Moreover, medical students’ salivary cortisol levels showed elevation during an ambulatory and in hospital patient consultation.^[23]

Salivary chromogranin A (sCgA) has been known to greatly react to psychosomatic as well as academic assessment stress.^[24] Kanamaru et al. found a rapid increase in sCgA levels in 14 airplane pilots from before a cognitive test, within the test, and 20 minutes after its start. They found that sCgA secretion increased in the anticipation of the task, remained high during, and was still elevated after it.^[25] On the other hand, Nomura et al. found that sCgA concentration increased during arithmetic tasks and decreased shortly after them, thus illustrating the value of sCgA as a biomarker for a short-term cognitive stress.^[26]

Salivary immunoglobulin A (sIgA) levels are known to show inconsistent results when it comes to stress reactions. A study analyzed the sC and sIgA levels in saliva and cardiac indices heart rate and systolic blood pressure in three groups of oral surgeons (senior, experts and junior) while they performed operations of different levels of difficulty. sIgA variations were not significant in any of the groups examined and did not show collinearity with the sC or the cardiac indices.^[2]

Salivary alpha-amylase (sAA) is the least studied of the aforementioned biomarkers. In a study of 30 male subjects being submitted to TSST and speaking in front of an audience, sAA was found to correlate with plasma catecholamine levels. Results showed sAA to be sensitive to psychological stress and to have positive relationship with the sympathetic activity.^[27]

Simulation training is a well-established method that provides standardized environment with set variable for educational purposes as well as for research.^[28] It is assumed that a high-fidelity simulator can replicate real-life cases and duplicate the stress experienced by the operators. This way, trainees can experience multiple critical situations and perform diagnostic and therapeutic techniques as many times as needed without the risk of harming the patient, resulting in lower stress levels after their training.^[29,30] There are four types of endoscopic simulators: mechanical, ex vivo animal tissue models, live animal-based models, and virtual reality (VR) computer simulators.^[31] In our literature review, we focus solely on the virtual reality computer simulators. Although, the majority of clinical trials revolving around the validity of virtual simulation as an education method, are performed in the field of surgery, there are a number of studies that incorporate endoscopy training.

VR simulators provide objective measures of performance, such as procedural completion and other endpoints such as the extent to which the lumen was visualized. Additionally, a summary describing several other performance parameters including the total time of the examination, recognition of pathologic findings, the amount of air insufflation, the degree of patient discomfort, the use of a virtual attending physician, and ability to perform retroflexion or other therapeutic maneuvers is presented at the end of the procedure. This allows for customization of benchmarks to define competency assessment.^[32]