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Abstract

Objective

Work-related stress is a public health issue. Stress has multiple physical and psychological consequences, the most serious of which are increased mortality and cardiovascular morbidity. The ThermStress protocol was designed to offer a short residential thermal spa program for work-related stress prevention that is compatible with a professional context.

Methods

Participants will be 56 male and female workers aged 18 years or above. All participants will undergo a 6-day residential spa program comprising psychological intervention, physical activity, thermal spa treatment, health education, eating disorder therapy and a follow-up. On six occasions, participants’ heart rate variability, cardiac remodelling and function, electrodermal activity, blood markers, anthropometry and body composition, psychology and quality of life will be measured using questionnaires and bone parameters.

Results

This study protocol reports the planned and ongoing research for this intervention.

Discussion

The ThermStress protocol has been approved by an institutional ethics committee (ANSM: 2016 A02082 49). It is expected that this proof of concept study will highlight the effect of a short-term specific residential thermal spa program on the prevention of occupational burnout and work-related stress. The findings will be disseminated at several research conferences and in published articles in peer-reviewed journals.

Trial Registration: ClinicalTrials.gov (NCT 03536624, 24/05/2018)

Keywords

Stress burnout prevention heart rate variability spa bath work biomarkers

Introduction

Stress at work is both a public health issue and an economic issue.^1,2 The main consequences of stress on health are increased cardiovascular morbidity and mortality.³ Stress particularly affects autonomic nervous system functioning.⁴ One of the main cardiovascular health effects of stress is deregulation of the sympathovagal balance.⁵ The most common measures of autonomic nervous system activity are heart rate variability (HRV) and electrodermal activity.⁶ Conveniently, there are non-intrusive and pain-free measures of HRV and electrodermal activity.⁷ Some genetic polymorphisms linked with stress, such as polymorphism of angiotensin converting enzymes^8–11 or of serotonin,^12–14 are also associated with cardiovascular risk. Stress also causes arterial ischemic pathology¹⁵ via complex mechanisms involving changes in arterial endothelial and microvascular atherosclerosis.¹⁵ These microvascular changes are linked to systemic inflammation caused by stress,¹⁶ and changes within the hypothalamic–pituitary axis (e.g. dehydroepiandrosterone sulphate (DHEAS),^17,18 cortisol,^17,18) and at a central level (e.g. neuropeptide Y,¹⁹ brain-derived natriuretic factor (BDNF),²⁰). Stress can also lead to obesity through inappropriate eating behaviours.²¹ Stressed individuals also find it difficult to lose weight.²² Possible biological mechanisms that link obesity and stress involve the action of stress on leptin,²³ an anorectic hormone secreted by adipose tissue and proposed as a biomarker of stress.²⁴ Stress, particularly stress at work, is responsible for multiple somatic diseases.^25,26 For example, long-term mental stress can have negative effects on bone tissue, leading to osteoporosis and increased bone fracture risk.²⁷ Therefore, an assessment of the association between bone parameters and stress is needed. Moreover, our program may modify bone parameters and decrease bone fracture risk.^6,28 More interestingly, peripheral quantitative computed tomography (pQCT) can be used to measure muscles and intra- and inter-muscular fat content,^29–31 which can also be modified by our program³² and may be biomarkers of stress. Many stress biomarkers are secreted by adipose tissue.³³ Moreover, it has been demonstrated that limb composition reflects total body composition, particularly fat.^29–31

The psychological consequences of stress are numerous and include dissatisfaction, anxiety, depression and burnout.²⁶ Non-pharmacological methods of stress management include psychological interventions, physical activity^34,35 and therapy for stress-induced eating disorders.³⁶ Several psychological interventions have demonstrated positive effects on work-related stress, such as cognitive-behavioural therapy,³⁷ acceptance and commitment therapy^38,39 and mindfulness.^40,41 The benefits of any type of physical activity on the physical and mental health of individuals at any age are indisputable.⁴²

A recent systematic review highlighted the effects of balneotherapy (bathing in mineral springs) and spa therapy on stress biomarkers. This review of 15 studies (684 subjects) emphasised the potential benefits of such treatment on cortisol levels.⁴³ In France, there are five spa resorts that specialise in the treatment of psychosomatic disorders. The usual duration for a residential thermal program in these resorts is 3 weeks. Previous research has demonstrated the positive effects of a 3-week spa therapy intervention on burnout.⁴⁴ However, a shorter residential thermal spa program may be more compatible with a professional context because of the availability of individuals. In addition, it would be useful to focus on work-related stress prevention (i.e. before the state of burnout).

Objective

This ThermStress proof of concept study was developed to provide a new approach to the management of stress disorders. The main aim of the study is to assess the ability of a short residential spa program to increase HRV and manage work-related stress.

Methods

Protocol design: This 1-year study with repeated measures on six occasions (inclusion (one to five months prior to the beginning of the spa program – M-1 to M-5), 6 days before the start (D-6), at the start (D0), at the end of the spa program (D6), at 6 months (M6) and at 12 months (M12)), will allow us to explore the effect of a specific short-term residential thermal spa program on the prevention of occupational burnout and work-related stress in workers, focusing on measures of well-being and cardiovascular morbidity. Each participant will undergo a 6-day residential spa program comprising psychological intervention, physical activity, thermal spa treatment, health education and eating disorder therapy and a follow-up. Each participant will be his/her own control and we will compare variations in parameters between intervention/control periods (short-term variations: D6/D0 and D0/D6; long-term variations: inclusion/D0 compared with D0/M6–M12) (Figure 1).

Figure 1.

The ThermStress protocol. M-5: 5 months before the study; M-1: 1 month before the study.

Selection criteria

Inclusion criteria: Volunteers will be workers aged 18 years to retirement, with a stress visual analogue scale score greater than 50 mm, who wish to follow a residential spa thermal program to manage work-related stress. Participants must have had a stable weight during the last 3 months and have no uncontrolled cardiac, hepatic, renal or endocrine diseases.³² In compliance with human ethics guidelines, participants must be covered by social health insurance and must sign consent forms.

Exclusion criteria: Potential participants will be excluded if major treatment and/or protocol deviations are observed. Other exclusion criteria are drugs and medical conditions that significantly affect the primary outcome of HRV (e.g. alpha or beta-blockers; arrhythmias or conduction disorders such as bundle branch block, atrioventricular heart block).⁴⁵

Power analysis: The rationale for the sample size estimation is based on HRV, which is a biomarker of both stress and morbidity/mortality.^46,47 In particular, within multiple parameters of HRV, we considered log low frequency (LF)/high frequency (HF) HRV for sample size calculation because it is the parameter that traditionally represents sympathovagal balance, together with global HRV (see description of LF/HF below in the description of the primary outcome section).^4,46 A log LF/HF with low values is associated with good autonomic nervous system adaptation. Based on previous work,⁴⁸ we assumed a statistical power greater than 80%, a two-sided type I error of 5% and an individual correlation coefficient set at 0.5 (each subject as his/her own control). Based on the results of a pilot study, we assumed that our response will promote an absolute decrease of the log LF/HF by 20% (with a standard deviation of 45%).⁴⁹ Therefore, we need to include n = 43 subjects. Finally, to take into account lost to follow-up, it is proposed to include 56 subjects.

Participants: Participants will be male and female volunteers aged 18 years to retirement. Following ethics committee approval, and based on our calculation, 56 volunteers will be enrolled to account for potential dropouts. All participants will be given written information regarding the project and will have to sign consent forms before enrolment. Workers will be recruited by the spa centres using flyers and website announcements. Participants will also be recruited using advertisements provided by the CHU of Clermont-Ferrand or by the Clermont Auvergne University.

Intervention programs: Participants will attend a short-term residential spa program lasting 6 days, which combines psychological intervention, physical activity, thermal spa treatment, health education and eating disorder therapy. Physical activity will be diverse (endurance, strength, circuit training) to offer a personalised program compatible with the desires of each participant. The benefits of all types of physical activity on the physical and mental health of individuals of any age are indisputable. Psychological interventions will include various validated therapies for work-related stress, such as cognitive-behavioural therapy, acceptance and commitment therapy and mindfulness. Details on intervention components are shown in Table 1 and the agenda of the intervention program is shown in Table 2.

Table 1.

Description of intervention components.

Intervention	Dose	Description
Spa treatment	6 × 120 min	Spa treatment is a combination of spa bath (i.e. thermal mud, jets), spa shower (i.e. hydromassage) and body massage
Psychological workshop	6 × 120 min	Cognitive-behavioural therapy, acceptance and commitment therapy, and mindfulness
Nutrition workshop	4 × 90 min	Participants must understand: concept of energetic balance, calculation of energy intake, calculation of energy expenditure (of physical activity, thermic effect of food), effects of stress on energy intake (quantity and type of intake), effects of physical activity on food intake regulation, cooking sessions (to cook healthy meals)
	+1 breakfast	During the breakfast session, participants will be provided with information and advice related to the preparation of a healthy breakfast
Supervised physical activity	5 × 120 min	Supervised physical activity will be delivered every day by a qualified exercise physiologist. Physical activity will be delivered as circuit training and will include resistance and aerobic training
Biomarkers of Stress workshop	1 × 90 min	Understanding the purpose of biological changes owing to stress and burnout

Table 2.

Agenda of the intervention program.

	Sunday	Monday	Tuesday	Wednesday	Thursday	Friday	Saturday
7h30–8h00		Breakfast	Breakfast	Breakfast with dietician	Breakfast	Breakfast	Breakfast
8h15–10h15		Spa treatment	Spa treatment	Spa treatment	Spa treatment	Spa treatment	Spa treatment
10h30–12h30		Psychological workshop	Psychological workshop	Psychological workshop	Psychological workshop	Psychological workshop	Psychological workshop
12h45–13h45		Lunch	Lunch	Lunch	Lunch	Lunch	Lunch
13h55–15h25	*	Nutrition workshop	Nutrition workshop	Biomarkers of Stress workshop	Nutrition workshop	Nutrition workshop
15h25–15h30	*	Collation^†	Collation^†	Collation^†	Collation^†	Collation^†
15h30–17h30	*	Supervised physical activity	Supervised physical activity	Supervised physical activity	Supervised physical activity	Supervised physical activity
17h30–19h30	Free time	Free time	Free time	Free time	Free time	Free time
19h30–20h30	Dinner	Dinner	Dinner	Dinner	Dinner	Dinner

Arrival of participants at their desired time on Sunday afternoon.

†

Collation is any kind of healthy combination, such as fruits/yogurt or any other low glycaemic index carbohydrates and protein sources.

Follow-up: After the intervention phase of the study, participants will undergo a 1-year at-home follow-up.

Measurements: Each participant will undergo a battery of tests (described below). Data collection will be performed six times, as previously described, except for dual-energy X-ray absorptiometry (DXA) and pQCT, which will be performed at inclusion and after 12 months, and cardiac remodelling and function, which will be performed at inclusion and after 6 months. Table 3 outlines all the study outcomes.

Table 3.

Outcomes.

Variables	Type of measure	Measurement modality	References
Biomarkers of stress and cardiovascular risk	Skin conductance	Wrist band electrodes – Movisens	⁷
	Blood flow velocity	Laser speckle contrast imaging	^78,79
	Myocardial longitudinal strain	Speckle-tracking echocardiography	^85,86
Genetic polymorphisms	Polymorphism of angiotensin converting enzymes	Blood cells	^8–11
Genetic polymorphisms	Polymorphism of serotonin	Blood cells	^12–14
Demographics	Age, gender, qualification, personal work status, ethnicity, life and occupational events	Questionnaire	⁴
Clinical measurements		Height, weight, blood pressure, heart rate, waist circumference
Body composition	Muscle mass, fat mass, bone structure	Impedance meter	⁸⁰
		Densitometry X-ray absorption	⁶
		Peripheral quantitative computed tomography	^73–75
		Quantitative ultrasound	⁸¹
Psychology and quality of life	Depression	Hamilton Anxiety Rating Scale	⁶²
	Anxiety	Hamilton Anxiety Rating Scale	⁶²
		State–Trait Anxiety Inventory	^60,61
	General health	General Health Questionnaire (SF-12)	⁷¹
	Stress, fatigue, sleep	Visual analogue scale	⁴
	Burnout	Maslach Burnout Inventory	⁵⁹
	Mindfulness	Freiburg Mindfulness Inventory	^22,23
	Coping	Brief COPE Questionnaire	⁶³
	Emotions	Emotion Regulation Questionnaire	⁶⁴
	Perception of work	Karasek’s Job Content Questionnaire	⁶⁵
	Self-efficacy	Perceived Self-efficacy Scale	⁶⁶
	Addiction to work	Work Addiction Risk test	⁶⁷
	Alexithymia	Toronto Alexithymia Scale	^68,82,83
	Illness perception	Brief Illness Perception Questionnaire, adapted for stress at work	^69,84
	Metacognition	Metacognitions Questionnaire-30	⁷⁰
Lifestyle	E.g., smoking, alcohol consumption, coffee consumption, food intake	Questionnaires	⁴
Lifestyle	Physical activity	Recent Physical Activity Questionnaire	⁷²
Alloplastic load	HbA1c, HDLc and LDLc, TG	Ethylenediaminetetraacetic acid tube	⁶
	Cortisol	Dry tube, serum isolation and deep-freezing	^17,85
	DHEAS	Dry tube, serum isolation and deep-freezing	^17,85
	Leptin	Dry tube, serum isolation and deep-freezing	⁶
	BDNF	Dry tube, serum isolation and deep-freezing	^20,86,87
	Pro-inflammatory cytokines: IL-1β, IL-6, IL-1, TNFα	Dry tube, serum isolation and deep-freezing	⁶
	NPY	Dry tube, serum isolation and deep-freezing	¹⁹
	Telomere length	Blood; Southern blot or polymerase chain reaction analyses	⁸⁸
	Heart rate variability	Holter	⁸⁹
	Skin conductance – electrodermal activity	Wristband electrodes	⁸⁹

A total of 25 mL of blood will be sampled (i.e. 100 mL in 1 year). HbA1c: haemoglobin A1c; HDLc: high-density lipoprotein cholesterol; LDLc: low-density lipoprotein cholesterol; TG: triglycerides; DHEAS: dehydroepiandrosterone sulphate; BDNF: brain-derived neurotrophic factor; IL: interleukin; TNFα: tumour necrosis factor α; NPY: neuropeptide Y.

Primary outcome: To assess the ability of a short residential spa program to manage work-related stress and increase HRV, a biomarker of both stress and morbidity/mortality.^46,47

Heart rate variability: HRV parameters will be assessed over 26 hours using a heart rate transmitter belt simply positioned on the chest, with a 26-hour recording time, a beat per minute within a 25 to 240 range and respiratory rate within a 3 to 70 range (Zephyr™ BioHarness™ BT, Zephyr Technology, Annapolis, USA). The HRV data will be examined according to the recommendations of the European Society of Cardiology and the North American Society (Task Force).⁵⁰ HRV will be explored in time and frequency domains.⁵¹ A methodology developed by our team will also be used.⁵² Premature atrial and ventricular beats will be automatically discarded and visually checked. In the time domain, R-R intervals, standard deviation of R-R intervals, square root of the mean squared difference of successive R-R intervals (rMSSD), and number of adjacent N-N differing by more than 50 ms divided by the total number of N-N intervals (pNN50) will be analysed. The rMSSD and pNN50 are associated with HF power and hence parasympathetic activity. In the spectral domain, we will analyse LF power (0.04–0.15 Hz), an index of both sympathetic and parasympathetic activity, and HF power (0.15–0.4 Hz), representing the most efferent vagal (parasympathetic) activity to the sinus node. Very low frequency (VLF; 0.003–0.04 Hz) partially reflects thermoregulatory mechanisms, fluctuation in activity of the renin–angiotensin system and the function of peripheral chemoreceptors. LF and HF will also be assessed in normalised units (nu), which represent the relative value of each power component in proportion to the total power minus the VLF component. Thus, LFnu and HFnu are considered to represent best sympathetic and parasympathetic activity, respectively.⁵³ The LF/HF ratio (i.e. the sympathovagal balance) will also be calculated.⁴⁶

Secondary outcomes: Secondary outcomes will be (1) to demonstrate an improvement in perceived stress and other stress biomarkers following the short residential spa program, (2) to study the influence of genetic polymorphisms on stress and on the response to our stress management program, (3) to examine the relationship between subjective (questionnaire responses) and objective (biomarker) variables, (4) to propose a salient biomarker or a salient composite index of biomarkers of stress and (5) to study the effect on stress of observance to the program at follow-up.

Anthropometry: The following anthropometric measures will be obtained according to the recommendations of the International Society for the Advancement of Kinanthropometry⁵⁴: standing height (m) and body mass (kg), waist circumference (cm), and lower limb bone length/breadth (cm).⁵⁴

Body composition: Body composition (muscle mass and fat mass) will be measured using DXA (DXA, QDR-4500A, Hologic, Inc., Waltham, MA, USA).⁶ and impedancemeter.⁸⁰

Biomarkers of stress and cardiovascular risk: Skin conductance will be measured using wristband electrodes with sampling rates at 2, 4, 8, 16 and 32 Hz during phases 1 to 3. The SC sensor (Q-Sensor®-Affectiva®, Massachusetts Institute of Technology, USA) is set on a wristband and has a 24-hour battery life when logging. In addition, it measures wrist movements with a built-in 3-axis accelerometer.

Blood flow velocity and myocardial longitudinal strain will be measured using speckle echocardiography (Vivid Q, GE Healthcare Biosciences, Piscataway, NJ, USA). All 2-dimensional (2D), time-motion, Doppler and 2D-strain acquisitions and measurements will be performed according to recent guidelines.^55,56 Left ventricular (LV) volumes and ejection fractions will be measured using Simpson’s biplane method.⁵⁷ LV mass will be calculated using the Devereux formula and indexed for height (Cornell adjustment). Pulsed Doppler LV transmitral velocities, including early and atrial waves, will be obtained using the apical 4-chamber view. Tissue Doppler imaging measures of myocardial systolic, early diastolic and atrial velocities will be assessed at the mitral annulus level in the apical 4- and 2-chamber views. The early transmitral flow velocity to the early diastolic tissue velocity ratio was used as an index of LV filling pressure. ⁵⁸ Left atrium volume will be assessed using apical 4- and 2-chamber views. A graduation of LV diastolic dysfunction will be obtained according to recent guidelines. ⁵⁸ 2D cine-loops (frame rate >70 ips) of at least five cycles will be recorded in the short-axis views (base, mid, apex), as well as in the apical 4-, 3- and 2-chamber views. 2D-strain analysis will be performed post-processing using EchoPAC 201TM software (GE Healthcare Biosciences, Piscataway, NJ, USA). Longitudinal and circumferential strains and strain rates, as well as apex and base rotations, will be directly obtained from the six-segment model. Twist mechanics will be computed from apical and basal rotational data using dedicated software (Scilab, Paris, France). For each view, the three cardiac cycles displaying the best image quality will be selected. Blood pressure and heart rate will be continuously monitored, and the systolic meridional wall stress, an index of afterload, will be calculated. LV end-diastolic volumes will also be obtained as a preload index.

Endocrine assays: Blood samples will be collected by a qualified paediatric nurse after participants have fasted overnight. Blood will be collected using a venepuncture at the brachial vein. After collection, blood will be centrifuged and aliquots will be stored (−80°) for subsequent analysis.

(triglycerides,6 cholesterol,6 low-density lipoprotein cholesterol,6 high-density lipoprotein cholesterol,6 glycaemia,6 insulin,6 ultra-sensitive C-reactive protein,6 cortisol,17,18 DHEAS17,18) as well as all other biochemical measures (leptin,6 brain-derived neurotrophic factor,20,87 interleukin-1b,6 interleukin-6,6 interleukin-1,6 tumour necrosis factor a,6 and neuropeptide Y19) will be assessed in the biochemistry laboratory of Clermont-Ferrand University Hospital. All analyses will be conducted by the same technician. Polymorphism of the angiotensin converting enzyme8-11 and polymorphism of serotonin12-14 will be measured from blood cells, as welll as telomere length.⁸⁸

Complementary measures: Questionnaire measures of the following variables will be obtained: stress and fatigue (visual analogue scale of 100 mm),⁴ burnout (Maslach Burnout Inventory),⁵⁹ depression and anxiety (Hospital Anxiety and Depression Scale,⁶⁰ State–Trait Anxiety Inventory (STAI-Y),⁶¹ 7-item Hamilton Anxiety Rating Scale),⁶² mindfulness (Freiburg Mindfulness Inventory),²² coping strategies (Brief COPE Questionnaire),⁶³ emotions (Emotion Regulation Questionnaire),⁶⁴ perception of work (Karasek’s Job Content Questionnaire),⁶⁵ self-efficacy (Perceived Self-efficacy Scale),⁶⁶ addiction to work (Work Addiction Risk test),⁶⁷ alexithymia (20-item Toronto Alexithymia Scale),⁶⁸ illness perception (Brief Illness Perception Questionnaire, adapted for stress at work),⁶⁹ metacognition (Metacognitions Questionnaire-30),⁷⁰ general health (12-item General Health Questionnaire (SF-12)),⁷¹ lifestyle (e.g. smoking, alcohol consumption)⁴ and physical activity (Recent Physical Activity Questionnaire).⁷²

Bone parameters: Bone microarchitecture will be measured using pQCT (XCT 3000 Stratec Medizintechnik Pforzheim, Germany).^73–75 Bone mineral content (BMC) (g/cm), volumetric cortical and trabecular BMC (mg/cm³), total area (mm²), cortical and trabecular area (mm²) and density (g/cm²), and bone strength (mm³) will be assessed at the distal (4%) and proximal (66%) sites of the non-dominant tibia and radius. A planar scout scan was first conducted to determine the anatomical reference line for both the radius and tibia. Tomographic slices of 2 mm thickness were obtained at the 4% and 66% sites measured distally. Scan speed and voxel size were 20 mm/s and 0.4 mm, respectively. To ensure measurement quality, calibration checks will be performed by scanning a standard phantom with known densities prior to each scan. To calculate BMC, volumetric cortical BMC, volumetric trabecular BMC, cortical bone area, cortical density, trabecular area, trabecular density and stress strain index will be analysed using the Stratec pQCT manufacturer’s software. Contour mode 1 with a threshold of 180 mg/cm³ will be used to separate soft tissue and bone to analyse trabecular bone. Cortical bone will be identified and removed using a constant default threshold of 710 mg/cm³. A contour mode 3 with peel mode 1 at a threshold of 40 mg/cm³ will be used to assess muscle and fat cross-sectional areas.

Bone densitometry will be conducted using DXA (QDR-4500A, Hologic, Inc., Waltham, MA, USA). Bone mineral density (g/cm²), BMC (g) and bone area (cm²) will be determined for each participant. The DXA measurements will be taken for the whole body, the lumbar spine (L2–L4) and the non-dominant hip (including the femoral neck, and the trochanteric and intertrochanteric regions). All DXA scans will be conducted by the same technician and quality assurance checks will be performed routinely. The in-vivo coefficient of variation is 0.5%.

Statistical analysis: Statistical analysis will be performed using Stata software (version 13; StataCorp LP, College Station, TX, USA). All statistical tests will be two-sided and p < 0.05 will be considered significant. After testing for normal distribution (Shapiro–Wilk test), data will be treated either by parametric or non-parametric analyses according to statistical assumptions.

Mixed models will be used to analyse longitudinal data for fixed effects (before and after the residential thermal program), time-point evaluation and group × time interaction taking into account between- and within-participant variability (as random effects). A Sidak’s type I error correction will be applied to take into account multiple comparisons. The normality of residuals will be examined using the Shapiro–Wilk test. If necessary, a logarithmic transformation will be used to achieve normality for the dependent outcome. Multivariable analyses will be carried out with adjustment for covariates fixed according to epidemiological relevance and physical activity. Particular attention will be paid to the covariates ‘time between inclusion and beginning of the intervention’ (variable for each subject) and ‘time between beginning of the intervention and the follow-up’ (fixed for each subject).

Analysis of non-repeated data will be performed using analysis of variance (ANOVA) or Kruskal–Wallis tests. When appropriate (omnibus p-value less than 0.05), a post-hoc test for multiple comparisons will be used: the Tukey–Kramer test following ANOVA and the Dunn test following the Kruskal–Wallis test. Categorical variables will be compared using chi-squared or Fisher’s test. The Marascuilo procedure will be performed for multiple comparisons. Relations between quantitative outcomes will be analysed using correlation coefficients (Pearson or Spearman, according to statistical distribution). Fisher’s z transformation and William’s T2 statistic will be used to compare correlations between variables and within a single group of subjects.

A sensitivity analysis will be used to study the statistical nature of missing data (random or non-random); that is, baseline characteristics of participants with complete follow-up and those lost to follow-up will be compared using the aforementioned statistical tests. Even if random-effects models permit the analysis of data when a participant is lost to follow-up, the most appropriate imputation data method according to the statistical nature of missing data (multiple imputation data, last observation carried out (LOCF)) will be applied. More precisely, if a participant drops out of the study before it ends, then his or her last observed score on the dependent variable is used for all subsequent (i.e. missing) observation points if the LOCF imputation approach is used.

Confidentiality: Data will be stored in the principal investigator’s office on a password-protected computer only accessible to members of our research team. In the electronic database, participants’ names will be replaced with numeric identity codes. Blood samples will also be labelled with the numeric identity codes and samples will be stored in our laboratories. Only aggregate results will be reported, ensuring participants’ anonymity.

Radiation: Both DXA and pQCT provide measures of body composition and bone properties by exposing participants to low-level radiation: 0.0056 mSv from DXA scans (whole body, lumbar and hip) and 0.0014 mSv from pQCT scans (tibia and radius measures).⁷⁶ Over the duration of the study, the effective dose of 0.014 mSv will be administered.

Ethics approval and consent to participate: The ThermStress protocol complies with the ethics guidelines for clinical research (Declaration of Helsinki) and has been approved by an ethics committee (CPP Tours Région centre Ouest 1, France - ANSM: 2016 A02082 49). The protocol has also been registered with the database ClinicalTrials.gov (NCT03536624). In accordance with ethical considerations, the chief investigator will be responsible for ensuring that participants understand the potential risks and benefits of study participation. Moreover, the chief investigator will be responsible for obtaining written consent from participants. The results will be disseminated at several research conferences and published in peer-reviewed journals.

Concluding remarks

The ThermStress protocol was designed to provide a better understanding of the effect of a short residential spa program to improve HRV and prevent work-related stress. The idea is to adapt a 3-week thermal cure for occupational burnout to a 6-day program, which is more accessible to workers and hopefully will produce similar results for work-related stress and burnout prevention. The long-term success of lifestyle interventions such as those proposed in work-related stress prevention depends on treatment observance (psychology, physical activity, nutrition).⁷⁷ We previously demonstrated that spa programs can play a major role in prompting sustainable lifestyle changes.²⁸ This shorter program may lead to better treatment observance during the 1-year follow-up, as psychological interventions, physical activity and diet will be supervised in the spa resort and participants will be accompanied by health care professionals. Findings from this protocol are expected to offer a more appropriate thermal program for burnout and work-related stress prevention that is accessible to the public.

Footnotes

Declaration of conflicting interest

The authors declare that there is no conflict of interest.

Funding

The study is integrally funded by the Région Auvergne Rhône-Alpes by the University Hospital of Clermont-Ferrand, by the European Regional Development Fund (FEDER, Fonds Europeen de Développement Economique et Régional) and by the spa resort of Néris-les-Bains. The funding source had no role in the design, conduct, or reporting of the study. The authors wish to thank Ms Frédérique BRIAT for her commitment to setting up and monitoring the program. The authors wish also to thank Mr Bertrand BLOYER for promoting a short residential thermal spa program to prevent work-related stress/burnout.

References

Quine

Workplace bullying in NHS community trust: staff questionnaire survey.

BMJ 1999; 318: 228–232.

Plus de 3 millions de Français au bord du burn-out. Le Monde. 2014 (24 janvier).

Backe

Seidler

Latza

, et al. The role of psychosocial stress at work for the development of cardiovascular diseases: a systematic review. Int Arch Occup Environ Health 2012; 85: 67–79.

Dutheil

Boudet

Perrier

, et al. JOBSTRESS study: comparison of heart rate variability in emergency physicians working a 24-hour shift or a 14-hour night shift - a randomized trial. Int J Cardiol 2012; 158: 322–325.

Tsuji

Larson

Venditti

Jr , et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation 1996; 94: 2850–2855.

Courteix

Valente-Dos-Santos

Ferry

, et al. Multilevel approach of a 1-year program of dietary and exercise interventions on bone mineral content and density in metabolic syndrome - the RESOLVE randomized controlled trial. PLoS One 2015; 10: e0136491.

Dutheil

Chambres

Hufnagel

, et al. ‘Do Well B.': design Of WELL Being monitoring systems. A study protocol for the application in autism. BMJ Open 2015; 5: e007716.

Montgomery

Clarkson

Barnard

, et al. Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training. Lancet 1999; 353: 541–545.

Henrion

Benessiano

Philip

, et al. The deletion genotype of the angiotensin I-converting enzyme is associated with an increased vascular reactivity in vivo and in vitro. J Am Coll Cardiol 1999; 34: 830–836.

10.

Gard

PR.

The role of angiotensin II in cognition and behaviour.

Eur J Pharmacol 2002; 438: 1–14.

11.

Thayer

Merritt

Sollers

3rd , et al. Effect of angiotensin-converting enzyme insertion/deletion polymorphism DD genotype on high-frequency heart rate variability in African Americans. Am J Cardiol 2003; 92: 1487–1490.

12.

Hariri

Drabant

Weinberger

DR.

Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing.

Biol Psychiatry 2006; 59: 888–897.

13.

Hariri

Weinberger

DR.

Functional neuroimaging of genetic variation in serotonergic neurotransmission.

Genes Brain Behav 2003; 2: 341–349.

14.

McCaffery

Bleil

Pogue-Geile

, et al. Allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cardiovascular reactivity in young adult male and female twins of European-American descent. Psychosom Med 2003; 65: 721–728.

15.

Proietti

Mapelli

Volpe

, et al. Mental stress and ischemic heart disease: evolving awareness of a complex association. Future Cardiol 2011; 7: 425–437.

16.

Elenkov

Iezzoni

Daly

, et al. Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 2005; 12: 255–269.

17.

Lac

Dutheil

Brousse

, et al. Saliva DHEAS changes in patients suffering from psychopathological disorders arising from bullying at work. Brain Cogn 2012; 80: 277–281.

18.

Danhof-Pont

van Veen

Zitman

FG.

Biomarkers in burnout: a systematic review.

J Psychosom Res 2011; 70: 505–524.

19.

Krystal

Neumeister

Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience.

Brain Res 2009; 1293: 13–23.

20.

Karege

Perret

Bondolfi

, et al. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 2002; 109: 143–148.

21.

Sinha

Jastreboff

AM.

Stress as a common risk factor for obesity and addiction. Biol Psychiatry 2013; 73: 827–835.

22.

Robinson

Hunger

Daly

Perceived weight status and risk of weight gain across life in US and UK adults. Int J Obes (Lond) 2015; 39: 1721–1726.

23.

Haleem

DJ.

Investigations into the involvement of leptin in responses to stress.

Behav Pharmacol 2014; 25: 384–397.

24.

Konishi

Otaka

Odashima

, et al. Systemic stress increases serum leptin level. J Gastroenterol Hepatol 2006; 21: 1099–1102.

25.

Kawakami

Haratani

Epidemiology of job stress and health in Japan: review of current evidence and future direction.

Ind Health 1999; 37: 174–186.

26.

Cohen

Janicki-Deverts

Miller

GE.

Psychological stress and disease.

JAMA 2007; 298: 1685–1687.

27.

Wippert

Rector

Kuhn

, et al. Stress and alterations in bones: an interdisciplinary perspective. Front Endocrinol (Lausanne) 2017; 8: 96.

28.

Courteix

Valente-Dos-Santos

Ferry

, et al. Correction: multilevel approach of a 1-year program of dietary and exercise interventions on bone mineral content and density in metabolic syndrome - the RESOLVE randomized controlled trial. PLoS One 2015; 10: e0140307.

29.

Butner

Creamer

Nickols-Richardson

, et al. Fat and muscle indices assessed by pQCT: relationships with physical activity and type 2 diabetes risk. J Clin Densitom 2012; 15: 355–361.

30.

Frank-Wilson

Johnston

Olszynski

, et al. Measurement of muscle and fat in postmenopausal women: precision of previously reported pQCT imaging methods. Bone 2015; 75: 49–54.

31.

Sherk

Thiebaud

Chen

, et al. Associations between pQCT-based fat and muscle area and density and DXA-based total and leg soft tissue mass in healthy women and men. J Musculoskelet Neuronal Interact 2014; 14: 411–417.

32.

Dutheil

Lac

Lesourd

, et al. Different modalities of exercise to reduce visceral fat mass and cardiovascular risk in metabolic syndrome: the RESOLVE randomized trial. Int J Cardiol 2013; 168: 3634–3642.

33.

Dutheil

Gordon

Naughton

, et al. Cardiovascular risk of adipokines: a review. J Int Med Res 2018; 46: 2082–2095.

34.

Stults-Kolehmainen

Sinha

The effects of stress on physical activity and exercise.

Sports Med 2014; 44: 81–121.

35.

Hansen

Blangsted

Hansen

, et al. Physical activity, job demand-control, perceived stress-energy, and salivary cortisol in white-collar workers. Int Arch Occup Environ Health 2010; 83: 143–153.

36.

Kiecolt-Glaser

JK.

Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.

Psychosom Med 2010; 72: 365.

37.

van der Klink

Blonk

Schene

, et al. The benefits of interventions for work-related stress. Am J Public Health 2001; 91: 270–276.

38.

Bond

Bunce

The role of acceptance and job control in mental health, job satisfaction, and work performance.

J Appl Psychol 2003; 88: 1057–1067.

39.

Brinkborg

Michanek

Hesser

, et al. Acceptance and commitment therapy for the treatment of stress among social workers: a randomized controlled trial. Behav Res Ther 2011; 49: 389–398.

40.

Davies

WR.

Mindful meditation: healing burnout in critical care nursing. Holist Nurs Pract 2008; 22: 32–36.

41.

Cohen-Katz

Wiley

Capuano

, et al. The effects of mindfulness-based stress reduction on nurse stress and burnout: a quantitative and qualitative study. Holist Nurs Pract 2004; 18: 302–308.

42.

Bhui

Dinos

Stansfeld

, et al. A synthesis of the evidence for managing stress at work: a review of the reviews reporting on anxiety, depression, and absenteeism. J Environ Public Health 2012; 2012: 515874.

43.

Antonelli

Donelli

Effects of balneotherapy and spa therapy on levels of cortisol as a stress biomarker: a systematic review. Int J Biometeorol 2018; 62: 913–924.

44.

Blasche

Leibetseder

Marktl

Association of spa therapy with improvement of psychological symptoms of occupational burnout: a pilot study.

Forsch Komplementmed 2010; 17: 132–136.

45.

Elghozi

Girard

Laude

Effects of drugs on the autonomic control of short-term heart rate variability.

Auton Neurosci 2001; 90: 116–121.

46.

Boudet

Walther

Courteix

, et al. Paradoxical dissociation between heart rate and heart rate variability following different modalities of exercise in individuals with metabolic syndrome: the RESOLVE study. Eur J Prev Cardiol 2017; 24: 281–296.

47.

Hufnagel

Chambres

Bertrand

, et al. The need for objective measures of stress in autism. Front Psychol 2017; 8: 64.

48.

Takada

Ebara

Kamijima

Heart rate variability assessment in Japanese workers recovered from depressive disorders resulting from job stress: measurements in the workplace.

Int Arch Occup Environ Health 2010; 83: 521–529.

49.

Ronser

Fundamentals of Biostatistics. Belmont, CA: Duxbury Press, 1995.

50.

Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Circulation 1996; 93: 1043–1065.

51.

Tochikubo

Ikeda

Miyajima

, et al. Effects of insufficient sleep on blood pressure monitored by a new multibiomedical recorder. Hypertension 1996; 27: 1318–1324.

52.

Khalfa

Bertrand

Boudet

, et al. Heart rate regulation processed through wavelet analysis and change detection: some case studies. Acta Biotheoretica 2012; 60: 109–129.

53.

Sandercock

Normative values, reliability and sample size estimates in heart rate variability.

Clin Sci (Lond) 2007; 113: 129–130.

54.

Marfell-Jones

Stewart

de Ridder

International standards for anthropometric assessment. International Society for the Advancement of Kinanthropometry, 2012.

55.

Lang

Badano

Mor-Avi

, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28: 1–39.e14.

56.

Mor-Avi

Lang

Badano

, et al. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications: endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr 2011; 24: 277–313.

57.

Otterstad

JE.

Measuring left ventricular volume and ejection fraction with the biplane Simpson’s method. Heart 2002; 88: 559–560.

58.

Nagueh

Smiseth

Appleton

, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2016; 29: 277–314.

59.

Choron

Dutheil

Lesage

FX.

Are nurses burned out?

Int J Nurs Stud 2016; 58: 80–81.

60.

Spiess

Sachs

Moser

, et al. Psychological moderator variables and metabolic control in recent onset type 1 diabetic patients–a two year longitudinal study. J Psychosom Res 1994; 38: 249–258.

61.

Julian

LJ.

Measures of anxiety: State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A).

Arthritis Care Res (Hoboken) 2011; 63: S467–S472.

62.

Hung

Liu

Wang

, et al. The cut-off points of the Depression and Somatic Symptoms Scale and the Hospital Anxiety and Depression Scale in detecting non-full remission and a current major depressive episode. Int J Psychiatry Clin Pract 2012; 16: 33–40.

63.

Endler

Parker

JD.

Multidimensional assessment of coping: a critical evaluation.

J Pers Soc Psychol 1990; 58: 844–854.

64.

Ioannidis

Siegling

AB.

Criterion and incremental validity of the emotion regulation questionnaire. Front Psychol 2015; 6: 247.

65.

Trousselard

Dutheil

Naughton

, et al. Stress among nurses working in emergency, anesthesiology and intensive care units depends on qualification: a Job Demand-Control survey. Int Arch Occup Environ Health 2016; 89: 221–229.

66.

Luszczynska

Scholz

Schwarzer

The general self-efficacy scale: multicultural validation studies.

J Psychol 2005; 139: 439–457.

67.

Robinson

Post

Validity of the Work Addiction Risk Test.

Percept Mot Skills 1994; 78: 337–338.

68.

Zhang

Guo

, et al. The association between alexithymia as assessed by the 20-item Toronto Alexithymia Scale and depression: a meta-analysis. Psychiatry Res 2015; 227: 1–9.

69.

Broadbent

Petrie

Main

, et al. The brief illness perception questionnaire. J Psychosom Res 2006; 60: 631–637.

70.

Wells

Cartwright-Hatton

A short form of the metacognitions questionnaire: properties of the MCQ-30.

Behav Res Ther 2004; 42: 385–396.

71.

Amiel

Lebigre

[A new rapid test for the evaluation of mental health. Its use for early detections. Its importance in health surveys].

Ann Med Psychol (Paris) 1970; 1: 565–580.

72.

Golubic

May

Benjaminsen Borch

, et al. Validity of electronically administered Recent Physical Activity Questionnaire (RPAQ) in ten European countries. PLoS One 2014; 9: e92829.

73.

Sornay-Rendu

Boutroy

Munoz

, et al. Cortical and trabecular architecture are altered in postmenopausal women with fractures. Osteoporos Int 2009; 20: 1291–1297.

74.

Boutroy

Bouxsein

Munoz

, et al. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab 2005; 90: 6508–6515.

75.

Stein

Liu

Nickolas

, et al. Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures. J Bone Miner Res 2010; 25: 2572–2581.

76.

Damilakis

Adams

Guglielmi

, et al. Radiation exposure in X-ray-based imaging techniques used in osteoporosis. Eur Radiol 2010; 20: 2707–2714.

77.

Fappa

Yannakoulia

Pitsavos

, et al. Lifestyle intervention in the management of metabolic syndrome: could we improve adherence issues? Nutrition 2008; 24: 286–291.

78.

Puissant

Abraham

Durand

, et al. Reproducibility of non-invasive assessment of skin endothelial function using laser Doppler flowmetry and laser speckle contrast imaging. PLoS One 2013; 8: e61320.

79.

Souza

De Lorenzo

Huguenin

, et al. Impairment of systemic microvascular endothelial and smooth muscle function in individuals with early-onset coronary artery disease: studies with laser speckle contrast imaging. Coron Artery Dis 2014; 25: 23–28.

80.

Pateyjohns

Brinkworth

Buckley

, et al. Comparison of three bioelectrical impedance methods with DXA in overweight and obese men. Obesity (Silver Spring) 2006; 14: 2064–2070.

81.

Gluer

, et al. Ultrasound characterization of bone demineralization. Calcif Tissue Int 1998; 62: 133–139.

82.

Bagby

Parker

Taylor

GJ.

The twenty-item Toronto Alexithymia Scale–I. Item selection and cross-validation of the factor structure.

J Psychosom Res 1994; 38: 23–32.

83.

Bagby

Taylor

Parker

JD.

The Twenty-item Toronto Alexithymia Scale–II. Convergent, discriminant, and concurrent validity.

J Psychosom Res 1994; 38: 33–40.

84.

Broadbent

Wilkes

Koschwanez

, et al. A systematic review and meta-analysis of the Brief Illness Perception Questionnaire. Psychol Health 2015; 30: 1361–1385.

85.

Lesage FX, Choron G, and Dutheil F. Multifaceted Program to Reduce Job Strain in ICU Nurses. JAMA 2019; 321: 1410–1411.

86.

Karege

Bondolfi

Gervasoni

, et al. Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 2005; 57: 1068–1072.

87.

Shimizu

Hashimoto

Okamura

, et al. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 2003; 54: 70–75.

88.

Epel

Blackburn

Lin

, et al. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A 2004; 101: 17312–17315.

89.

Elefteriou

Ahn

Takeda

, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 2005; 434: 514–520.

Effects of a short residential thermal spa program to prevent work-related stress/burnout on stress biomarkers: the ThermStress proof of concept study

Abstract

Objective

Methods

Results

Discussion

Keywords

Introduction

Objective

Methods

Selection criteria

Concluding remarks

Footnotes

Declaration of conflicting interest

Funding

References