Nambiema J Bodin

Marie Bellemare

Bertrais, S Aboubakari Nambiema
email: aboubakari.nambiema@univ-angers.fr

Evanoff, B., Descatha, A., Roquelaure Y Proportion

psychosocial risk factors in a working population

Keywords: Upper-extremity MSD, occupational risk factor, combined effect, population attributable fraction, preventable case, prevention Cohort study, France, upper-extremity MSD, occupational risk factor, combined effect, preventable cases, prevention. NAMBIEMA Aboubakari |

le citer en l'attribuant de la manière indiquée par l'auteur (mais pas d'une manière qui suggérerait qu'il approuve votre utilisation de l'oeuvre).

Titre : Impact potentiel des interventions de prévention des troubles musculo-squelettiques (TMS) à l'échelle populationnelle : scénarios de réduction de l'exposition aux facteurs de risque de TMS Mots clés : TMS du membre supérieur ; facteur de risque professionnel ; effet combiné ; fraction attribuable en population ; cas évitable ; prévention.

Résumé : Les troubles musculo-squelettiques du membre supérieur (TMS-MS) constituent aujourd'hui l'une des questions les plus préoccupantes en santé au travail et santé publique du fait d'un coût humain et socioprofessionnel considérable. La prévention efficace et durable des TMS-MS reste un défi pour les praticiens et les décideurs en matière de santé publique. L'impact modéré des plans de prévention mis en oeuvre au cours des dernières décennies nécessite d'approfondir la réflexion sur les stratégies de prévention à l'échelle de la population active. L'objectif de ce travail de thèse était d'estimer et de comparer les effets potentiels de la réduction des expositions professionnelles aux principaux facteurs de risque (FdR) biomécaniques et psychosociaux sur l'incidence des TMS-MS dans la cohorte COSALI. Cette thèse a révélé qu'une proportion importante et un grand nombre de TMS-MS pourraient être évités si l'exposition aux FdR modifiables tels que les efforts physiques élevés, les postures contraignantes de l'épaule et le faible soutien social, était réduite. De plus, elle a montré qu'une intervention multidimensionnelle qui combinerait à la fois une réduction de l'exposition aux efforts physiques élevés et une amélioration du soutien social, permettrait de prévenir un plus grand nombre de cas. En conclusion, cette thèse a permis d'estimer l'impact potentiel des interventions sur le nombre de cas de TMS-MS dans une population active salariée. Elle apporte aussi la preuve que pour être efficace, la prévention des TMS-MS ne peut se limiter à la réduction de l'exposition aux FdR biomécaniques mais nécessite une approche multidimensionnelle qui prend également en compte les FdR psychosociaux.

Title: Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD Keywords: Upper-extremity MSD; occupational risk factor; combined effect; population attributable fraction; preventable case; prevention.

Abstract:

Upper-extremity musculoskeletal disorders (UEMSD) constitute one of the most worrying issues in occupational and public health due to their considerable human, social and occupational costs. Effective and sustainable prevention of UEMSD continues to be a challenge for public health practitioners and policymakers. The moderate impact of the prevention plans implemented over the last few decades requires further reflection on prevention strategies at the working population level. The objective of this thesis work was to estimate and compare the potential effects of reducing work-related exposures to the main biomechanical and psychosocial risk factors on the incidence of UEMSD in the COSALI cohort. This thesis revealed that an important proportion and a large number of UEMSD could be avoided if exposure to the modifiable risk factors, such as high physical exertion, uncomfortable shoulder postures and social support, were reduced in the working population. Moreover, this study showed that a multidimensional combining both a reduction of exposure to high physical exertion and improved social support would reduce a larger number of cases.

In conclusion, this thesis made it possible to estimate the potential impact of interventions on the number of UEMSD cases in a working population. It also provides evidence that to be effective, UEMSD prevention cannot be limited to reducing exposure to biomechanical risk factors but requires a multidimensional approach that also takes into account psychosocial risk factors. List of Tables Table 1: Prevalence and incidence of UEMSD in the general population and the working population ............... 10

List of Figures/Charts

Introduction

The first part of this thesis presents a background literature review of work-related musculoskeletal disorders (MSD) on studies conducted worldwide including their economic and social impact, prevention, project rationale, and demonstrates how this thesis will address the knowledge gaps in the current (epidemiological) literature. In addition, it briefly synthesizes previous studies on risk factors.

Background and significance

1.1.

Musculoskeletal disorders

MSD are a group of soft-tissue injuries and disorders that affect the musculoskeletal system (i.e. muscles, tendons, joints, nerves, cartilages). These disorders are listed in the 10 th revision of the International Classification of Diseases (ICD-10) (WHO, 2008), and refer to medically diagnosed periarticular diseases of the limbs and spine, as well as multiple or localized pain syndromes [START_REF] Roquelaure | Musculoskeletal Disorders and Psychosocial Factors at Work[END_REF]. Regarding the World Health Organization (WHO) definition, work-related diseases such as MSD are multifactorial diseases in which the work environment and the performance of work contribute significantly to the causation of the disease (WHO Expert Committee on Identification and Control of Work-Related Diseases & World Health Organization, 1985). With a large majority of cases occurring in the upper extremity, these disorders result from repeated or sustained exposure to workrelated activities, such as working in the same posture for long periods of time, repetitive tasks, awkward postures, excessive efforts to carry and lift heavy objects, whole-body vibration, and lack of adequate recovery time [START_REF] Aptel | Work-related musculoskeletal disorders of the upper limb[END_REF][START_REF] Aublet-Cuvelier | Troubles musculosquelettiques des membres supérieurs d'origine professionnelle[END_REF][START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF][START_REF] Kittusamy | Whole-body vibration and postural stress among operators of construction equipment: A literature review[END_REF]Kozak et al., 2015;[START_REF] Punnett | Work-related musculoskeletal disorders: the epidemiologic evidence and the debate[END_REF]Roquelaure, 2015;Sluiter et al., 2001). The International Labor Organization (ILO) (ILO, 2015) estimated that about 160 million cases of non-fatal work-related diseases occur annually in the world among which a high number of MSD. According to a recent WHO Global Burden of Disease (GBD) data which enables comparisons among different diseases and different populations, MSD (in general) ranked among the top five diseases in the world (#4) in terms of disease burden, representing about 8% of the total 1.8 billion Disability-Adjusted Life Years (DALYs) [START_REF] Roser | Burden of disease[END_REF]. In the international literature, a diversity of terms, assuming a link between the clinical disorder(s) and the potential risk factor or mechanism of injury, has been used to describe these disorders. These terms include repetitive strain injury (RSI), cumulative trauma disorder (CTD), occupational cervicobrachial disorder (OCD), occupational overuse syndrome (OOS), and work-related MSD (WRMSD) [START_REF] Luttmann | Preventing Musculoskeletal Disorders in the Workplace[END_REF][START_REF] Punnett | Work-related musculoskeletal disorders: the epidemiologic evidence and the debate[END_REF]Sluiter et al., 2001).

Furthermore, case definitions of these disorders sometimes vary in different countries, so the associated risk factors may also vary.

The above-mentioned problems make it difficult to compare the results of different epidemiological studies and to assess and compare the magnitude and nature of WRMSD between different countries and sometimes within the same country. Against this background and in order to facilitate more uniform collection, recording, and reporting of information on work-related upper extremity MSD (UEMSD) in the European Union (EU), an expert group developed in 2001 a protocol providing evidence-or consensus-based case definitions, as well as criteria for identifying and classifying them (Sluiter et al., 2001). The published document deals with 11 specific and non-NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 8 specific UEMSD occurring in the different regions of the upper extremity (shoulder/arm, elbow/forearm, and hand/wrist) and neck. These UEMSD are listed below: In the present doctoral thesis, the main focus is on major MSD affecting the upper extremity known to be very common in the workplace (Sluiter et al., 2001). These disorders refer to the following areas of the body:

shoulder/arm, elbow/forearm, and hand/wrist.

Upper extremity musculoskeletal disorders Prevalence and incidence

Several epidemiological studies conducted around the world have provided estimates of prevalence and/or incidence (rate of proportion) of UEMSD. Some of these estimates, presented in Table 1, vary across countries, study designs (cross-sectional, cohort, systematic review and meta-analysis) and populations (general/working).

A systematic review by Luime et al. [START_REF] Luime | Prevalence and incidence of shoulder pain in the general population; a systematic review[END_REF]) conducted in the general population showed a prevalence of shoulder complaints ranging between 4.7% and 46.7%, and an incidence proportion varying between 0.1% and 2.5%. Regarding the working population, a systematic review conducted by Huisstede et al. (Huisstede et al., 2006) showed a clinically diagnosed prevalence of UEMSD ranging from 9.3 to 26.9% and a 12-month prevalence ranging from 2.3 to 41.0%. A meta-analysis by Spahn et al. [START_REF] Spahn | Metaanalysis for the evaluation of risk factors for carpal tunnel syndrome (CTS) Part II. Occupational risk factors[END_REF] found a prevalence of carpal tunnel syndrome ranging between 8.2% and 10.9%, and an incidence rate between 1.8 and 17.3 cases/1000 person-years.

In many countries, UEMSD account for a major proportion of all occupational diseases (registered or compensable or both) [START_REF] Roquelaure | Musculoskeletal Disorders and Psychosocial Factors at Work[END_REF]. According to the United States (US) Bureau of Labor Statistics (BLS) revealed that in 2015, there were 358 890 new UEMSD cases (incidence rate: 3.2 cases/1000 full-time workers) for nonfatal occupational injuries and illnesses cases involving days away from work (Bureau of Labor Statistics, 2016). In Québec, the incidence rate was estimated at 15.4 cases/1000 full-time workers in 2006, a decrease of 4.5% compared to 2001 [START_REF] Michel | Portrait national des troubles musculosquelettiques (TMS) 1998-2007: TMS sous surveillance[END_REF]. In France, an epidemiologic surveillance study of work-related UEMSD NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 9

in the Pays de la Loire (PdL) region found a prevalence of clinically diagnosed UEMSD of approximately 13% (11% in men and 15% in women) [START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]. According to estimates from the French cohort, CONSTANCES ("CONSulTANts des Centres d'Examens de Santé") [START_REF] Carton | Prévalence des troubles musculo-squelettiques et des facteurs biomécaniques d'origine professionnelle : premières estimations à partir de Constances[END_REF], the prevalence of persistent pain (≥30 days in the past 1 year) varied between 11.6% (at the elbow), 19.8% (at the wrist) and 20.7% (at the shoulder) in women, 9.4%, 12.0% and 15.5% for men (respectively for the same locations). In addition, recent social health insurance data for 2018 revealed that UEMSD accounted for 80% (39 555 cases) of all occupational diseases, an increase of about 3% compared to 2017 (Cnam. Direction des Risques Professionnels : Mission statistiques & Département tarification, 2019).

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 10 NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 12

Economic and social burden

Throughout the world, UEMSD affect workers in all sectors and occupations and constitute the main cause of morbidity, work-related disabilities, and absenteeism from work in many developed countries such as the US, Canada and EU-28 [START_REF] Côté | Quebec Research on Work-related Musculoskeletal Disorders: Deeper Understanding for Better Prevention[END_REF][START_REF] De Kok | Workrelated musculoskeletal disorders: prevalence, costs and demographics in the EU[END_REF]GBD 2017 Disease andInjury Incidence andPrevalence Collaborators, 2018;[START_REF] Roquelaure | Musculoskeletal Disorders and Psychosocial Factors at Work[END_REF][START_REF] Storheim | Musculoskeletal disorders and the Global Burden of Disease study[END_REF][START_REF] Summers | Musculoskeletal Disorders, Workforce Health and Productivity in the United States[END_REF]. These disorders constitute one of the most serious occupational and public health problems in many countries due to their considerable human and social costs, in terms of pain and discomfort in work and daily life, sometimes irreversible functional sequelae, reduced ability to work, the risk of career breaks and low quality of life, and their economic impact on companies particularly in terms of costs related to production loss (Bevan, 2015;[START_REF] Bhattacharya | Costs of occupational musculoskeletal disorders (MSDs) in the United States[END_REF] de [START_REF] De Kok | Workrelated musculoskeletal disorders: prevalence, costs and demographics in the EU[END_REF][START_REF] Lang | intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors[END_REF][START_REF] March | Burden of disability due to musculoskeletal (MSK) disorders[END_REF]Moradi-Lakeh et al., 2017;[START_REF] Oh | The economic burden of musculoskeletal disease in Korea: A cross sectional study[END_REF]Roquelaure, 2015;[START_REF] Smith | The global burden of other musculoskeletal disorders: estimates from the Global Burden of Disease 2010 study[END_REF][START_REF] Storheim | Musculoskeletal disorders and the Global Burden of Disease study[END_REF][START_REF] Summers | Musculoskeletal Disorders, Workforce Health and Productivity in the United States[END_REF]United States Bone and Joint Initiative, 2015;[START_REF] Weinstein | The Burden of Musculoskeletal Conditions[END_REF].

From 1997 to 2005 in Washington state, 127 885 workers' compensation claims were accepted for UEMSD representing 10.3% of all claims, of which 36.9% were compensable resulting in direct costs of $1.49 billion [START_REF] Silverstein | Work-related musculoskeletal disorders of the neck, back, and upper extremity in Washington State, 1997-2005[END_REF]. According to the United States Bureau of Labor Statistics (BLS) in 2015, one-third of lost-time work-related injuries and illnesses were due to UEMSD (Bureau of Labor Statistics, 2016). A report from the United States Bone and Joint Initiative (USBJI) (United States Bone and Joint Initiative, 2015) showed that, the annual estimated direct (compensation of victims, treatment, medication, etc.) and indirect costs (loss of production, replacement costs, absenteeism, lost wages, etc.) attributable to persons with MSD are estimated to be approximately $213 billion per year in lost wages and treatment, or 1.4% of the U.S. Gross Domestic Product (GDP) in 2011. A recent report of the USBJI has estimated the annual direct and indirect costs attributable to persons suffering from MSD to be at $322 billion in 2012-2014(United States Bone and Joint Initiative, 2018).

Between 1998 and 2007 in Québec, UEMSD accounted for an average of 27% of all MSD compensated annually [START_REF] Michel | Portrait national des troubles musculosquelettiques (TMS) 1998-2007: TMS sous surveillance[END_REF]. In addition, UEMSD were compensated for the longest periods of time with an average compensation period of 81.1 days (median of 20 days). These disorders ranked among the top five most expensive conditions (#3) in terms of the value of lost production due to morbidity (CAN$3.1 billion), representing about 23% of the total CAN$13.3 billion allocated morbidity costs in Canada (Public Health Agency of Canada, 2018). Furthermore, the total direct and indirect costs were estimated at $8.7 billion, or 7% of the total costs of the Economic Burden of Illness in Canada (EBIC) (CAN$130.8 billion) in 2010 (Public Health Agency of Canada, 2018). In 2017, according to the GBD data, these disorders ranked among the top five diseases (#3) in terms of burden of disease in Canada, or 14% of the total 7.8 million DALYs [START_REF] Roser | Burden of disease[END_REF]. In the high-income Asia-Pacific region, WHO data on the GBD showed that in 2017, MSD represented about 8% of the total 336.9 million DALYs in this area of Asia [START_REF] Roser | Burden of disease[END_REF].

A review conducted by [START_REF] Buckle | The nature of work-related neck and upper limb musculoskeletal disorders[END_REF] on the basis of scientific data and the consensual opinion of experts, union bodies and government agencies across the EU concluded that UEMSD are a major problem in the EU in terms of poor health and costs. In France, according to social health insurance data NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 13 from 2018, the costs related to all MSD (mainly UEMSD, i.e. 91% of all MSD) were estimated at €2 billion for companies (Cnam. Direction des Risques Professionnels, 2019).

In summary, MSD remain widespread and costly in the working population. The overwhelming majority of cases involve the back and the upper extremities [START_REF] Aptel | Work-related musculoskeletal disorders of the upper limb[END_REF][START_REF] Aublet-Cuvelier | Troubles musculosquelettiques des membres supérieurs d'origine professionnelle[END_REF][START_REF] Michel | Portrait national des troubles musculosquelettiques (TMS) 1998-2007: TMS sous surveillance[END_REF].

Risk factors of UEMSD

UEMSD may result from repeated or sustained exposure to different groups of risk factors related to the work environment together with other risk factors not related to work. Numerous studies conducted worldwide in the working population have revealed that multiple risk factors including person-related factors, biomechanical factors, psychosocial factors and organizational factors commonly interact with each other in creating the overall risk [START_REF] Aptel | Work-related musculoskeletal disorders of the upper limb[END_REF][START_REF] Bodin | Déterminants professionnels des troubles musculo-squelettiques de l'épaule : intérêt de la prise en compte des facteurs organisationnels[END_REF][START_REF] Bodin | Risk Factors for Shoulder Pain in a Cohort of French Workers: A Structural Equation Model[END_REF][START_REF] Bongers | Are psychosocial factors, risk factors for symptoms and signs of the shoulder, elbow, or hand/wrist?: A review of the epidemiological literature[END_REF][START_REF] Bongers | Epidemiology of work related neck and upper limb problems: psychosocial and personal risk factors (part I) and effective interventions from a bio behavioural perspective (part II)[END_REF][START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF]Descatha et al., 2016;Hauke et al., 2011;[START_REF] Jackson | Occupational biomechanical risk factors for radial nerve entrapment in a 13-year prospective study among male construction workers[END_REF]Kozak et al., 2015;[START_REF] Punnett | Work-related musculoskeletal disorders: the epidemiologic evidence and the debate[END_REF]Roquelaure et al., 2009bRoquelaure et al., , 2020;;van der Molen et al., 2017;van Rijn et al., 2009avan Rijn et al., , 2009b[START_REF] Van Rijn | Associations between work-related factors and specific disorders of the shoulder -a systematic review of the literature[END_REF]Widanarko et al., 2014).

A number of theoretical models have been suggested in the ergonomics literature concerning different possible pathways of association and potential influences of different factors contributing to the development of MSD [START_REF] Aptel | Quels modèles pour comprendre et prévenir les TMS ? Pour une approche holistique et dynamique[END_REF][START_REF] Armstrong | A conceptual model for work-related neck and upper-limb musculoskeletal disorders[END_REF][START_REF] Bellemare | La transformation des situations de travail par une approche participative en ergonomie : une recherche intervention pour la prévention des troubles musculo-squelettiques 124[END_REF][START_REF] Carayon | Work Organization, Job Stress, and Work-Related Musculoskeletal Disorders[END_REF][START_REF] Hagberg | Les Lésions attribuables au travail répétitif ouvrage de référence sur les lésions musculo-squelettiques liées au travail[END_REF][START_REF] Karsh | Theories of work-related musculoskeletal disorders: Implications for ergonomic interventions[END_REF][START_REF] Kumar | Theories of musculoskeletal injury causation[END_REF]National Research Council and Institute of Medicine, 2001;[START_REF] Punnett | A conceptual framework for integrating workplace health promotion and occupational ergonomics programs[END_REF][START_REF] Sauter | Beyond biomechanics: psychosocial aspects of musculoskeletal disorders in office work[END_REF][START_REF] Stock | Quelle est la relation entre les troubles musculosquelettiques (TMS) liés au travail et les facteurs psychosociaux ?: Survol de diverses conceptions des facteurs psychosociaux du travail et proposition d'un nouveau modèle de la genèse des TMS[END_REF]. Some of these models considered biomechanical risk factors as a primary cause of MSD, and other factors (e.g. organizational and psychosocial) as intermediate variables [START_REF] Armstrong | A conceptual model for work-related neck and upper-limb musculoskeletal disorders[END_REF][START_REF] Hagberg | Les Lésions attribuables au travail répétitif ouvrage de référence sur les lésions musculo-squelettiques liées au travail[END_REF][START_REF] Sauter | Beyond biomechanics: psychosocial aspects of musculoskeletal disorders in office work[END_REF]. The model proposed by Karsh [START_REF] Karsh | Theories of work-related musculoskeletal disorders: Implications for ergonomic interventions[END_REF] takes into account many mechanisms and factors (e.g. aging, strength, posture, job control, social support, etc.) as contributing to the development of MSD and shows the role of work organization in influencing biomechanical exposure. [START_REF] Stock | Quelle est la relation entre les troubles musculosquelettiques (TMS) liés au travail et les facteurs psychosociaux ?: Survol de diverses conceptions des facteurs psychosociaux du travail et proposition d'un nouveau modèle de la genèse des TMS[END_REF] presented a conceptual model of the development of MSD capitalizing the findings of epidemiological and ergonomic studies which also integrates the authors' view of the psychosocial work environment and the possible mediating role of psychological distress. Recently, Roquelaure [START_REF] Roquelaure | Promoting a Shared Representation of Workers' Activities to Improve Integrated Prevention of Work-Related Musculoskeletal Disorders[END_REF] proposed an organizational model (see Figure 1) to visualize the effects of different risk factors on MSD, which can be applied to most countries and industries.

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 14 Based on the findings of epidemiological, clinical and ergonomic research conducted in the workplace, Roquelaure [START_REF] Roquelaure | Musculoskeletal Disorders and Psychosocial Factors at Work[END_REF] has provided a summary of the main UEMSD risk factors that have been identified in these investigations. The classification of results is summarized with some references in Table 2 and the findings of some of these studies (cohort study or systematic reviews or meta-analyses) are presented in the subsections below.

Risk factors References

Non-occupational factors [START_REF] Becker | An evaluation of gender, obesity, age and diabetes mellitus as risk factors for carpal tunnel syndrome[END_REF][START_REF] Cazares-Manríquez | A Review of Carpal Tunnel Syndrome and Its Association with Age, Body Mass Index, Cardiovascular Risk Factors, Hand Dominance, and Sex[END_REF][START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF][START_REF] Fan | Associations between workplace factors and carpal tunnel syndrome: A multi-site cross sectional study: Workplace Factors and Prevalence of Carpal Tunnel Syndrome[END_REF][START_REF] Franceschi | Obesity as a Risk Factor for Tendinopathy: A Systematic Review[END_REF][START_REF] Harris-Adamson | Personal and workplace psychosocial risk factors for carpal tunnel syndrome: a pooled study cohort[END_REF][START_REF] Larsson | Work related neck-shoulder pain: a review on magnitude, risk factors, biochemical characteristics, clinical picture and preventive interventions[END_REF][START_REF] Leong | Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis[END_REF][START_REF] Malchaire | Review of the factors associated with musculoskeletal problems in epidemiological studies[END_REF][START_REF] Meems | Prevalence, course and determinants of carpal tunnel syndrome symptoms during pregnancy: a prospective study[END_REF][START_REF] Moghtaderi | An evaluation of gender, body mass index, wrist circumference and wrist ratio as independent risk factors for carpal tunnel syndrome[END_REF]National Research Council and Institute of Medicine, 2001;[START_REF] Nilsen | Physical Exercise, Body Mass Index, and Risk of Chronic Pain in the Low Back and Neck/Shoulders: Longitudinal Data From the Nord-Trøndelag Health Study[END_REF][START_REF] Okunribido | Ageing and work-related musculoskeletal disorders[END_REF][START_REF] Padua | Systematic review of pregnancy-related carpal tunnel syndrome[END_REF][START_REF] Riccò | Personal risk factors for carpal tunnel syndrome in female visual display unit workers[END_REF][START_REF] Sayampanathan | Risk factors of lateral epicondylitis: A meta-analysis[END_REF][START_REF] Shiri | The effect of excess body mass on the risk of carpal tunnel syndrome: a meta-analysis of 58 studies: Obesity and carpal tunnel syndrome[END_REF][START_REF] Spahn | Metaanalysis for the evaluation of risk factors for carpal tunnel syndrome (CTS) Part II. Occupational risk factors[END_REF]van der Molen et al., 2017;[START_REF] Viikari-Juntura | Risk factors of atherosclerosis and shoulder pain -Is there an association? A systematic review[END_REF][START_REF] Violante | Carpal tunnel syndrome and manual work: the OCTOPUS cohort, results of a ten-year longitudinal study[END_REF]

Medical and surgical history

o History of tendinopathies/tunnel syndromes o Diabetes o Inflammatory rheumatism o Severe hypothyroidism (CTS) [START_REF] Fan | Associations between workplace factors and carpal tunnel syndrome: A multi-site cross sectional study: Workplace Factors and Prevalence of Carpal Tunnel Syndrome[END_REF][START_REF] Leong | Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis[END_REF][START_REF] Pourmemari | intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk[END_REF][START_REF] Shiri | prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk[END_REF][START_REF] Spahn | Metaanalysis for the evaluation of risk factors for carpal tunnel syndrome (CTS) Part II. Occupational risk factors[END_REF][START_REF] Viikari-Juntura | Risk factors of atherosclerosis and shoulder pain -Is there an association? A systematic review[END_REF] NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 15 [START_REF] Cail | Facteurs de risque pour le membre supérieur dans le travail sur écran : synthèse bibliographique[END_REF][START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF]Descatha et al., 2016;Harris-Adamson et al., 2016, 2015;[START_REF] Kozak | Musculoskeletal health, work-related risk factors and preventive measures in hairdressing: a scoping review[END_REF]Kozak et al., , 2015;;[START_REF] Larsson | Work related neck-shoulder pain: a review on magnitude, risk factors, biochemical characteristics, clinical picture and preventive interventions[END_REF][START_REF] Leong | Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis[END_REF][START_REF] Malchaire | Review of the factors associated with musculoskeletal problems in epidemiological studies[END_REF][START_REF] Mayer | Longitudinal evidence for the association between work-related physical exposures and neck and/or shoulder complaints: a systematic review[END_REF][START_REF] Miranda | Physical work and chronic shoulder disorder. Results of a prospective population-based study[END_REF]National Research Council and Institute of Medicine, 2001;[START_REF] Palmer | Carpal tunnel syndrome and its relation to occupation: a systematic literature review[END_REF]Sluiter et al., 2001;[START_REF] Spahn | Metaanalysis for the evaluation of risk factors for carpal tunnel syndrome (CTS) Part II. Occupational risk factors[END_REF]van der Molen et al., 2017;[START_REF] Van Der Windt | Occupational risk factors for shoulder pain: a systematic review[END_REF][START_REF] Van Rijn | Associations between work-related factors and specific disorders of the shoulder -a systematic review of the literature[END_REF]van Rijn et al., , 2009bvan Rijn et al., , 2009avan Rijn et al., , 2009b [START_REF] Bernal | Work-related psychosocial risk factors and musculoskeletal disorders in hospital nurses and nursing aides: A systematic review and meta-analysis[END_REF][START_REF] Bongers | Epidemiology of work related neck and upper limb problems: psychosocial and personal risk factors (part I) and effective interventions from a bio behavioural perspective (part II)[END_REF][START_REF] Bongers | Are psychosocial factors, risk factors for symptoms and signs of the shoulder, elbow, or hand/wrist?: A review of the epidemiological literature[END_REF][START_REF] Cail | Facteurs de risque pour le membre supérieur dans le travail sur écran : synthèse bibliographique[END_REF][START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF][START_REF] Harris-Adamson | Personal and workplace psychosocial risk factors for carpal tunnel syndrome: a pooled study cohort[END_REF]Hauke et al., 2011;[START_REF] Kraatz | The incremental effect of psychosocial workplace factors on the development of neck and shoulder disorders: a systematic review of longitudinal studies[END_REF][START_REF] Lang | Psychosocial work stressors as antecedents of musculoskeletal problems: A systematic review and meta-analysis of stability-adjusted longitudinal studies[END_REF][START_REF] Larsson | Work related neck-shoulder pain: a review on magnitude, risk factors, biochemical characteristics, clinical picture and preventive interventions[END_REF][START_REF] Luttmann | Preventing Musculoskeletal Disorders in the Workplace[END_REF][START_REF] Macfarlane | Evaluation of work-related psychosocial factors and regional musculoskeletal pain: results from a EULAR Task Force[END_REF][START_REF] Malchaire | Review of the factors associated with musculoskeletal problems in epidemiological studies[END_REF]National Research Council and Institute of Medicine, 2001;[START_REF] Paul | The Role of Organizational Factors in Development and Progression of Wrist Disorders: Psychosocial Aspects[END_REF][START_REF] Roquelaure | Musculoskeletal Disorders and Psychosocial Factors at Work[END_REF]Roquelaure et al., 2020;Sluiter et al., 2001;[START_REF] Sobeih | Psychosocial factors and musculoskeletal disorders in the construction industry: a systematic review[END_REF]van der Molen et al., 2017;[START_REF] Van Der Windt | Occupational risk factors for shoulder pain: a systematic review[END_REF][START_REF] Van Rijn | Associations between work-related factors and specific disorders of the shoulder -a systematic review of the literature[END_REF]van Rijn et al., , 2009a;;[START_REF] Vargas-Prada | Psychological and psychosocial determinants of musculoskeletal pain and associated disability[END_REF] [START_REF] Bodin | Déterminants professionnels des troubles musculo-squelettiques de l'épaule : intérêt de la prise en compte des facteurs organisationnels[END_REF][START_REF] Bodin | Risk Factors for Shoulder Pain in a Cohort of French Workers: A Structural Equation Model[END_REF][START_REF] Bongers | Are psychosocial factors, risk factors for symptoms and signs of the shoulder, elbow, or hand/wrist?: A review of the epidemiological literature[END_REF][START_REF] Cail | Facteurs de risque pour le membre supérieur dans le travail sur écran : synthèse bibliographique[END_REF][START_REF] Larsson | Work related neck-shoulder pain: a review on magnitude, risk factors, biochemical characteristics, clinical picture and preventive interventions[END_REF][START_REF] Leider | Effects of job rotation on musculoskeletal complaints and related work exposures: a systematic literature review[END_REF][START_REF] Malchaire | Review of the factors associated with musculoskeletal problems in epidemiological studies[END_REF]National Research Council and Institute of Medicine, 2001;[START_REF] Paul | The Role of Organizational Factors in Development and Progression of Wrist Disorders: Psychosocial Aspects[END_REF][START_REF] Petit | Risk factors for carpal tunnel syndrome related to the work organization: A prospective surveillance study in a large working population[END_REF][START_REF] Roquelaure | L'organisation du travail et le management en question[END_REF]Roquelaure et al., 2020Roquelaure et al., , 2020;;Sluiter et al., 2001)

Occupational factors

Organizational

Non-occupational factors

Non-occupational factors such as personal risk factors including both personal characteristics (e.g. age, gender) and medical history (e.g. obesity, diabetes, rheumatoid arthritis) have been reported in the literature to be linked to UEMSD [START_REF] Roquelaure | Pathologies professionnelles musculo-squelettiques: priorité à la prévention et à la coordination des prises en charge[END_REF]. These factors act in combination with work-related factors to increase the risk of UEMSD.

Previous studies have shown that women are more at risk of certain UEMSD (e.g. CTS) [START_REF] Heilskov-Hansen | Exposure-response relationships between movements and postures of the wrist and carpal tunnel syndrome among male and female house painters: a retrospective cohort study[END_REF][START_REF] Hooftman | Gender differences in the relations between work-related physical and psychosocial risk factors and musculoskeletal complaints[END_REF][START_REF] Lund | Movements of the wrist and the risk of carpal tunnel syndrome: a nationwide cohort study using objective exposure measurements[END_REF][START_REF] Silverstein | Gender adjustment or stratification in discerning upper extremity musculoskeletal disorder risk?[END_REF]. The review by da [START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF] found that female gender was positively associated with the development of work-related wrist/hand disorders (with reasonable evidence) and work-related elbow/forearm disorders (with insufficient NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 16 evidence). Moreover, a longitudinal population-based study of [START_REF] Andorsen | High prevalence of chronic musculoskeletal complaints among women in a Norwegian general population: the Tromsø study[END_REF] conducted among in a Norwegian general population revealed that women have a higher burden of musculoskeletal complaints than men (63.4% versus 52.9%). In a pooled cohort study of musculoskeletal outcomes to measure CTS frequency, Dale et al. [START_REF] Dale | Prevalence and incidence of carpal tunnel syndrome in US working populations: pooled analysis of six prospective studies[END_REF] found a higher combined prevalence of CTS in women than in men (10.0% versus 5.8%). Furthermore, a recent review [START_REF] Cazares-Manríquez | A Review of Carpal Tunnel Syndrome and Its Association with Age, Body Mass Index, Cardiovascular Risk Factors, Hand Dominance, and Sex[END_REF] based on 72 studies showed that the risk of CTS was positively associated with female sex.

An increasing prevalence of CTS in older age categories [<30 (3.7%), 30-39 (6.4%), 40-49 (10.7%), and ≥50 years (11.9%)] was observed in the study by [START_REF] Dale | Prevalence and incidence of carpal tunnel syndrome in US working populations: pooled analysis of six prospective studies[END_REF]. In their systematic review, Okunribido and Wynn [START_REF] Okunribido | Ageing and work-related musculoskeletal disorders[END_REF] concluded that older workers were more likely to suffer from UEMSD than younger workers due to reduced functional capacity, which increases the probability of developing these disorders. In their study, da Costa and Vieira (da Costa and Vieira, 2010) found an increased risk of workrelated wrist/hand disorders (with reasonable evidence) or work-related elbow/forearm disorders (with insufficient evidence) with older age. A recent systematic review and meta-analysis [START_REF] Leong | Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis[END_REF] showed, with strong evidence, that age above 50 years among the working population was associated with an increased risk of rotator cuff tendinopathy (RCT) (OR=3.31 [2.30-4.76]). Another review showed an increased risk of CTS with age [START_REF] Cazares-Manríquez | A Review of Carpal Tunnel Syndrome and Its Association with Age, Body Mass Index, Cardiovascular Risk Factors, Hand Dominance, and Sex[END_REF].

Using criteria consistent with Hill's work [START_REF] Hill | The environment and disease: association or causation?[END_REF][START_REF] Hill | The Environment and Disease: Association or Causation?[END_REF] and a strict "level of evidence" classification, a systematic review (da Costa and Vieira, 2010) found that a high body mass index (BMI) was associated with an increased risk of UEMSD with a reasonable level of evidence of a causal relationship. More specifically, high BMI was found to be associated with the development of work-related wrist/hand disorders (with reasonable evidence)

and with the development work-related elbow/forearm disorders (with insufficient evidence). These associations of high BMI with UEMSD are supported by a meta-analysis of 58 studies [START_REF] Shiri | The effect of excess body mass on the risk of carpal tunnel syndrome: a meta-analysis of 58 studies: Obesity and carpal tunnel syndrome[END_REF] which showed that excess BMI was associated with the risk of CTS. A review by Franceschi et al. [START_REF] Franceschi | Obesity as a Risk Factor for Tendinopathy: A Systematic Review[END_REF] indicated that obesity is a risk factor for tendinopathy including LE. However, the authors suggested that further studies should be conducted to establish the real strength of the association for each type of tendinopathy. Recent results from a systematic review also suggested that BMI was associated with an increased risk of CTS [START_REF] Cazares-Manríquez | A Review of Carpal Tunnel Syndrome and Its Association with Age, Body Mass Index, Cardiovascular Risk Factors, Hand Dominance, and Sex[END_REF].

Regarding medical conditions, findings of a systematic review and meta-analysis [START_REF] Shiri | prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk[END_REF] found an increased risk of CTS in persons suffering from rheumatoid arthritis (pooled adjusted odds ratio [pOR]: 1.96 (95% confidence interval [95%CI]: 1.57-2.44)) with no evidence of publication bias. In another systematic review and meta-analysis [START_REF] Pourmemari | intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk[END_REF], diabetes has been shown to be associated with an increased risk of CTS (pOR: 1.69 (95%CI: 1.45-1.96)) with no evidence of publication bias. In their systematic review and recent meta-analysis, [START_REF] Leong | Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis[END_REF] showed, with strong evidence, that diabetes was associated with an increased risk of RCT (OR=2.24 [1.37-3.65]) among the general and working population. In their study designed to assess the incidence of LE in workers exposed physically, Descatha et al. [START_REF] Descatha | Self-reported physical exposure association with medial and lateral epicondylitis incidence in a large longitudinal study[END_REF], found a positive association between medical conditions (diabetes, rheumatoid arthritis or osteoarthrosis) and NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 17 the incidence of LE in bivariate analyses but not in multivariate analyses. In addition, in a case-control study [START_REF] Titchener | Risk factors in lateral epicondylitis (tennis elbow): a case-control study[END_REF] the medical conditions mentioned above were not found to be associated with LE.

Occupational factors

Occupational factors, considered to be related to the working situation, are categorized into three groups: .47-2.47]) and shoulder load (OR=2.00 [1.90-2.10]), and low to very low evidence with hand force exertion (OR=1. 50 [1.25-1.87]) and hand-arm vibration (OR=1.30 [1.01-1.77]). A recent systematic review and meta-analysis by [START_REF] Leong | Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis[END_REF] showed, with moderate evidence, that working with the shoulder above 90 degrees was associated with an increased risk of rotator cuff tendinopathy (OR=2.41 [1.31-4.45]) among the working population. In their scoping review, Kozak et al. [START_REF] Kozak | Musculoskeletal health, work-related risk factors and preventive measures in hairdressing: a scoping review[END_REF] found that the common risk factors for WRMSD in hairdressers included repetitive movements, forceful exertion of upper extremities, working with arms above shoulder level, awkward postures and movements, high mechanical workload and standing position.

b) Psychosocial factors

It is increasingly recognized that psychosocial factors also play a role in the development of UEMSD. Factors such as low social support from supervisors or co-workers, low job decision latitude, or high psychological demands can aggravate the consequences of UEMSD [START_REF] Luttmann | Preventing Musculoskeletal Disorders in the Workplace[END_REF]. The findings of a meta-analysis by Hauke et al. (Hauke et al., 2011) analysis by [START_REF] Lang | Psychosocial work stressors as antecedents of musculoskeletal problems: A systematic review and meta-analysis of stability-adjusted longitudinal studies[END_REF] found positive associations between psychosocial work stressors including high job demands, low job control, low social support at work and highly monotonous work (pooled odd ratio between 1.17 and 1.57) and neck/shoulder symptoms, and with upper extremity symptoms separately.

These results are consistent with those of Kraatz et al.'s systematic review [START_REF] Kraatz | The incremental effect of psychosocial workplace factors on the development of neck and shoulder disorders: a systematic review of longitudinal studies[END_REF] which included 18 prospective longitudinal studies of neck/shoulder disorders. Indeed, this review showed that there was strong evidence for adverse effects of low social support, high job demands, low job control, and high job strain, on the onset of neck and/or shoulder disorders. However, findings from a recent meta-analysis including only longitudinal studies (van der Molen et al., 2017) revealed low to very low evidence for the association between the incidence of specific shoulder disorders (clinically diagnosed) and psychosocial job demands (OR=1. 10 [1.01-1.25]).

Recently, a study [START_REF] Bodin | Risk Factors for Shoulder Pain in a Cohort of French Workers: A Structural Equation Model[END_REF] using structural equation models to explore the direct and indirect relationships between shoulder pain and workplace risk factors showed that high psychological demands indirectly increased the risk of shoulder pain by influencing perceived stress and biomechanical risk factors. In addition, an association was found between coworker support and biomechanical risk factors suggesting that workers exposed to high physical demands receive more social support from their coworkers [START_REF] Bodin | Risk Factors for Shoulder Pain in a Cohort of French Workers: A Structural Equation Model[END_REF]. A similar study (Roquelaure et al., 2020) explored the direct and indirect relationships between CTS and occupational risk factors in French workers and found that psychosocial factors such as decision authority and skill discretion indirectly increased the risk of CTS by influencing biomechanical exposure. Recently, a study by [START_REF] Bodin | Shoulder pain among male industrial workers: Validation of a conceptual model in two independent French working populations[END_REF] aimed to assess whether their previous structural equation model [START_REF] Bodin | Risk Factors for Shoulder Pain in a Cohort of French Workers: A Structural Equation Model[END_REF] could be replicated in a large manufacturer of pharmaceutical preparations, and found an indirect impact of psychosocial factors on shoulder pain by acting on biomechanical exposure and perceived stress.

c) Organizational factors

Organizational factors relate to how the work is designed and performed including allocation of tasks, working procedures, work pace, production methods and management practices. Previous studies have shown that, in addition to personal factors, biomechanical and psychosocial work-related factors, organizational work factors also contribute to the onset of UEMSD indirectly by influencing the intensity or duration of biomechanical and psychosocial exposures (figure 1) [START_REF] Bodin | Déterminants professionnels des troubles musculo-squelettiques de l'épaule : intérêt de la prise en compte des facteurs organisationnels[END_REF][START_REF] Roquelaure | Promoting a Shared Representation of Workers' Activities to Improve Integrated Prevention of Work-Related Musculoskeletal Disorders[END_REF]Roquelaure et al., 2020).

A literature review by Malchaire et al. [START_REF] Malchaire | Review of the factors associated with musculoskeletal problems in epidemiological studies[END_REF] suggested that several organizational factors (e.g. monotony, high work rate, high time pressure) were associated with MSD of the neck/shoulder region with a low level of evidence, but not with MSD of the hand-wrist. A review by Sluiter et al. (Sluiter et al., 2001) revealed a strong level of evidence for the lack of recovery time. A prospective cohort study (Bodin et al., 2012a) found an organizational factor (working together with temporary workers) to be positively associated with incident RCS in the female working population. A similar study [START_REF] Petit | Risk factors for carpal tunnel syndrome related to the work organization: A prospective surveillance study in a large working population[END_REF] found positive associations between organizational factors such as payment on a piecework basis and work pace dependent on automatic rate and the risk of CTS. In 2014, a study by [START_REF] Koukoulaki | The impact of lean production on musculoskeletal and psychosocial risks: An examination of sociotechnical trends over 20 years[END_REF] found an impact of lean production on MSD symptoms and workers' mental health, and on the risk factors for these latter, especially in the aut omotive industry. The author concluded that the reported findings might reflect the inflexible lean implementation approaches used in the automotive industry in the 1990s, when just-in-time work environments with an increasing NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 19

pace of work and a decreasing amount of time available for recovery were introduced. In addition, studies from this period report the most adverse effects.

A dissertation by Bodin [START_REF] Bodin | Déterminants professionnels des troubles musculo-squelettiques de l'épaule : intérêt de la prise en compte des facteurs organisationnels[END_REF] showed the importance of organizational factors in understanding the occurrence of shoulder pain and UEMSD in general. Indeed, these factors may influence the conditions of exposure to occupational biomechanical and psychosocial factors among workers. For example, it has been shown that exposure to manufacturing constraints increased exposure to biomechanical factors and influenced exposure to psychosocial factors. Conversely, exposure to market constraints (e.g. work pace dependent on customers' demand) decreased exposure to biomechanical factors and influenced exposure to psychosocial factors [START_REF] Bodin | Déterminants professionnels des troubles musculo-squelettiques de l'épaule : intérêt de la prise en compte des facteurs organisationnels[END_REF]. Recently, a study by Roquelaure et al. (Roquelaure et al., 2020) concluded to an indirect impact of organizational factors on incident CTS. Indeed, authors showed that, exposure to machine-paced work had an indirect impact on increasing the risk of CTS, either by raising biomechanical exposure or by lowering decision authority and skill discretion, which in turn increased biomechanical exposure. Another recent study [START_REF] Bodin | Shoulder pain among male industrial workers: Validation of a conceptual model in two independent French working populations[END_REF] analyzing a sample from an industrial company showed that organizational factors such as automatic speed of a machine/movement of a product had an indirect impact on the risk of chronic shoulder pain by acting on biomechanical and psychosocial exposure.

Prevention of UEMSD

Effective and sustainable prevention of work-related UEMSD continues to be a challenge for public health practitioners and policy makers. The incidence and impact of UEMSD can be prevented or reduced by improving the ergonomic aspects of work and workplaces that can lead to a reduction or even elimination of exposures to occupational risk factors. However, there is little consensus on the most suitable interventions. The various strategies for successful prevention interventions for these disorders are categorized in three levels according to the scientific literature (Kennedy et al., 2010;[START_REF] Michaelis | evidence-based effects and prioritised national strategies in other countries[END_REF][START_REF] Podniece | Work-related musculoskeletal disorders : prevention report[END_REF]: primary prevention, secondary prevention and tertiary prevention. The goal of primary prevention is to limit the inciden ce of UEMSD by reducing or eliminating risk factors. Primary interventions are based on the assumption according to which:

reducing and/or eliminating the risk factor(s) having a significant impact on UEMSD should in some way lead to a reduction in the incidence of that disorder. Secondary prevention focuses on early detection of symptoms and stopping their progression. More related to treatment and rehabilitation, tertiary prevention strategies are designed for individuals with long-term disabling UEMSD and aim to reduce the progression of the disorder to facilitate maintenance of fitness for work and/or early return-to-work.

The available literature on the prevention of UEMSD or upper extremity musculoskeletal symptoms in the workplace describes a range of interventions that have been implemented and evaluated [START_REF] Hoe | prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors[END_REF][START_REF] Hoe | Ergonomic design and training for preventing workrelated musculoskeletal disorders of the upper limb and neck in adults[END_REF][START_REF] Lowe | Workplace Exercise for Control of Occupational Neck/Shoulder Disorders: A Review of Prospective Studies[END_REF][START_REF] Nastasia | Topics and trends in research on non-clinical interventions aimed at preventing prolonged work disability in workers compensated for work-related musculoskeletal disorders (WRMSDs): a systematic, comprehensive literature review[END_REF][START_REF] Stock | Are work organization interventions effective in preventing or reducing work-related musculoskeletal disorders? A systematic review of the literature[END_REF][START_REF] Van Der Molen | Effectiveness of measures and implementation strategies in reducing physical work demands due to manual handling at work[END_REF][START_REF] Van Eerd | Effectiveness of workplace interventions in the prevention of upper extremity musculoskeletal disorders and symptoms: an update of the evidence[END_REF][START_REF] Varatharajan | Are Work Disability Prevention Interventions Effective for the Management of Neck Pain or Upper Extremity Disorders? A NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 116 Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration[END_REF]. Despite this scientific knowledge accumulated over the past few years, the prevention of UEMSD remains an ongoing challenge. Difficulties in preventing these disorders in the workplace can be explained by the complexity of their determinants related to the multi-factorial nature of this condition involving biomechanical and psychosocial factors, as well as organizational factors within companies [START_REF] Roquelaure | Promoting a Shared Representation of Workers' Activities to Improve Integrated Prevention of Work-Related Musculoskeletal Disorders[END_REF].

Furthermore, the implementation of effective and sustainable prevention programs remains a challenge for public NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 20 health practitioners and policy makers in changing industrial environments, which means that very few interventions are actually implemented in companies.

In recent years, studies have been conducted to address these UEMSD. These studies have been mainly limited to workplace interventions aimed at "reducing the biomechanical load" and introducing technical or organizational measures to reduce workers' exposure to uncomfortable work postures and/or intense and/or repetitive physical efforts (Kennedy et al., 2010;[START_REF] Muñoz-Poblete | Effectiveness of Workplace-Based Muscle Resistance Training Exercise Program in Preventing Musculoskeletal Dysfunction of the Upper Limbs in Manufacturing Workers[END_REF][START_REF] Van Eerd | Effectiveness of workplace interventions in the prevention of upper extremity musculoskeletal disorders and symptoms: an update of the evidence[END_REF][START_REF] Van Oostrom | Workplace interventions for preventing work disability[END_REF].

Furthermore, various systematic reviews [START_REF] Cole | Effectiveness of participatory ergonomic interventions: a systematic review[END_REF][START_REF] Etuknwa | A Systematic Review on the Effectiveness of Ergonomic Training Intervention in Reducing the Risk of Musculoskeletal Disorder[END_REF]Kennedy et al., 2010;[START_REF] Lowe | Workplace Exercise for Control of Occupational Neck/Shoulder Disorders: A Review of Prospective Studies[END_REF][START_REF] Rivilis | Effectiveness of participatory ergonomic interventions on health outcomes: A systematic review[END_REF][START_REF] Soares | Preventive factors against work-related musculoskeletal disorders: narrative review[END_REF][START_REF] Stock | Are work organization interventions effective in preventing or reducing work-related musculoskeletal disorders? A systematic review of the literature[END_REF][START_REF] Van Eerd | Effectiveness of workplace interventions in the prevention of upper extremity musculoskeletal disorders and symptoms: an update of the evidence[END_REF] and Cochrane reviews [START_REF] Hoe | prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors[END_REF][START_REF] Hoe | Ergonomic design and training for preventing workrelated musculoskeletal disorders of the upper limb and neck in adults[END_REF] It follows from all of the above that, in order to better target interventions in the workplace, it would be useful to quantify the proportion and number of UEMSD cases that could be prevented if exposure to the modifiable risk factors were reduced to levels that minimize the risk of UEMSD. Such information may provide an estimate of the theoretical maximum potential impact of preventive programs in the workplace [START_REF] Punnett | Work-related musculoskeletal disorders: the epidemiologic evidence and the debate[END_REF][START_REF] Roquelaure | Theoretical impact of simulated workplace-based primary prevention of carpal tunnel syndrome in a French region[END_REF].

The next sub-section will present additional tools that can help public health practitioners and policy-makers better direct UEMSD prevention interventions based on the modifiable risk factors having the greatest impact the burden of UEMSD in order to prioritize interventions that reduce exposure to these risk factors.

Population attributable fraction (PAF)

It is important and common in epidemiology to assess the association between the exposure to some factors and the occurrence of health outcomes (e.g. injury, disease, disorder). In public health, it is even more important to quantify the impact of that exposure on the occurrence of these events within the population. This information will be very relevant for public health decisions and, in this instance, for prevention. Various measures are available for assessing the impact of exposure on the occurrence of disease within the population, including the population attributable fraction (PAF). The concept of the PAF was initially introduced by [START_REF] Levin | The occurrence of lung cancer in man[END_REF] to quantify the impact of smoking on the occurrence of lung cancer. This method was first proposed for a simple binary exposure [START_REF] Levin | The occurrence of lung cancer in man[END_REF] and then extended to the case of a multi-level categorical exposure [START_REF] Walter | The Estimation and Interpretation of Attributable Risk in Health Research[END_REF] and a continuous quantitative exposure [START_REF] Bruzzi | Estimating the population attributable risk for multiple risk factors using case-control data[END_REF][START_REF] Lloyd | Estimating Attributable Response as a Function of a Continuous Risk Factor[END_REF].

The PAF has the advantage of simultaneously considering the prevalence of the exposure to the risk factor within the population and the strength of its association with the disease (B Rockhill et al., 1998). Moreover, the PAF can be computed using a multivariable approach to quantify the relative impact of one or more exposures, or even co-exposure, on the occurrence of disease [START_REF] Bruzzi | Estimating the population attributable risk for multiple risk factors using case-control data[END_REF][START_REF] Dartois | Proportion of premenopausal and postmenopausal breast cancers attributable to known risk factors: Estimates from the E3N-EPIC cohort[END_REF][START_REF] Hamel | Software for Unbiased Estimation of Attributable Risk[END_REF][START_REF] Marant-Micallef | Approche et méthodologie générale pour l'estimation des cancers attribuables au mode de vie et à l'environnement en France métropolitaine en[END_REF][START_REF] Rajaobelina | Population attributable fractions of the main type 2 diabetes mellitus risk factors in women: Findings from the French E3N cohort[END_REF]Roquelaure et al., 2009a;[START_REF] Van Der Molen | How to improve the assessment of the impact of occupational diseases at a national level? The Netherlands as an example[END_REF]. Assuming that other risk factors remain unchanged and that there is a causal relationship between the risk factor and the disease, the PAF provides an estimate of the proportion of disease cases that would not have occurred if the NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 22 exposure to a risk factor was eliminated or reduced to an alternative ideal exposure scenario (e.g. no alcohol consumption) (B Rockhill et al., 1998). Usually expressed as a percentage, the PAF is the epidemiological measure widely used to quantify the public health impact of the exposure on the burden of the disease within the population. This quantity represents the proportion or percentage of disease cases that can be attributed to a specific risk factor (exposure) in the target population [START_REF] Levin | The occurrence of lung cancer in man[END_REF]. Benichou provided an overview of these methods by discussing the appropriate implementation of the estimation techniques of the PAF and interpretation of when considering several risk factors at the same time [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF][START_REF] Benichou | A review of adjusted estimators of attributable risk[END_REF] in different designs of observational studies (cross-sectional, case-control and cohort). This multivariate approach is also used to take into account confounding or interaction factors.

Several denominations have been used in the literature to refer to this statistical approach, which could lead to a confusion in terminology [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF]). However, a review of the literature in recent years shows that the terms most commonly used as synonyms are: population attributable fraction [START_REF] Azimi | Calculating Population Attributable Fraction for Cardiovascular Risk Factors Using Different Methods in a Population Based Cohort Study[END_REF][START_REF] Brooks-Pollock | Defining the population attributable fraction for infectious diseases[END_REF][START_REF] Dartois | Proportion of premenopausal and postmenopausal breast cancers attributable to known risk factors: Estimates from the E3N-EPIC cohort[END_REF][START_REF] Flegal | Estimating population attributable fractions to quantify the health burden of obesity[END_REF][START_REF] Laaksonen | Population Attributable Fraction (PAF) in epidemiologic follow-up studies[END_REF][START_REF] Mansournia | Population attributable fraction[END_REF][START_REF] Marant Micallef | Cancers in France in 2015 attributable to occupational exposures[END_REF][START_REF] Mohammadi | Population-attributable fraction of hypertension associated with obesity, abdominal obesity, and the joint effect of both in the Central Provinces of Iran[END_REF][START_REF] Rajaobelina | Population attributable fractions of the main type 2 diabetes mellitus risk factors in women: Findings from the French E3N cohort[END_REF][START_REF] Soerjomataram | Cancers related to lifestyle and environmental factors in France in 2015[END_REF][START_REF] Van Der Molen | How to improve the assessment of the impact of occupational diseases at a national level? The Netherlands as an example[END_REF][START_REF] Violante | Carpal tunnel syndrome and manual work: the OCTOPUS cohort, results of a ten-year longitudinal study[END_REF], attributable fraction [START_REF] Dahlqwist | Model-based estimation of the attributable fraction for cross-sectional, case-control and cohort studies using the R package AF[END_REF][START_REF] Di Maso | Attributable fraction for multiple risk factors: Methods, interpretations, and examples[END_REF][START_REF] Eide | Attributable fractions for partitioning risk and evaluating disease prevention: a practical guide: A practical guide to attributable fractions[END_REF][START_REF] Soit Ilg | Conceptual problems in the definition and interpretation of att ributable fractions[END_REF][START_REF] Heeringa | Attributable fraction estimation from complex sample survey data[END_REF][START_REF] Rückinger | An illustration of and programs estimating attributable fractions in large scale surveys considering multiple risk factors[END_REF][START_REF] Steenland | An Overview of Methods for Calculating the Burden of Disease Due to Specific Risk Factors[END_REF], attributable risk [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF][START_REF] Benichou | A review of adjusted estimators of attributable risk[END_REF][START_REF] Benichou | Attributable risk[END_REF][START_REF] Cox | Model-based estimation of the attributable risk in case-control and cohort studies[END_REF][START_REF] Cox | Model-Based Estimation of the Attributable Risk: A Loglinear Approach[END_REF][START_REF] Gassama | Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017[END_REF][START_REF] Rämsch | Point and interval estimation of partial attributable risks from case-control data using the R-package 'pARccs[END_REF], and population attributable risk [START_REF] Brenner | The burden of cancer attributable to modifiable risk factors in Canada: Methods overview[END_REF][START_REF] Crowson | Attributable Risk Estimation in Cohort Studies[END_REF]Spiegelman et al., 2007;[START_REF] Tamimi | Population Attributable Risk of Modifiable and Nonmodifiable Breast Cancer Risk Factors in Postmenopausal Breast Cancer[END_REF][START_REF] Tseng | Calculation of population attributable risk for alcohol and breast cancer (United States)[END_REF].

To date, the PAF has been used as an impact measure in health research around the world to quantify the proportion of cases of diseases such as cancer [START_REF] Brenner | The burden of cancer attributable to modifiable risk factors in Canada: Methods overview[END_REF][START_REF] Dartois | Proportion of premenopausal and postmenopausal breast cancers attributable to known risk factors: Estimates from the E3N-EPIC cohort[END_REF][START_REF] Engmann | Population-Attributable Risk Proportion of Clinical Risk Factors for Breast Cancer[END_REF][START_REF] Marant Micallef | Cancers in France in 2015 attributable to occupational exposures[END_REF][START_REF] Shield | The impact of historical breastfeeding practices on the incidence of cancer in France in 2015[END_REF][START_REF] Soerjomataram | Cancers related to lifestyle and environmental factors in France in 2015[END_REF]Spiegelman et al., 2007;[START_REF] Tamimi | Population Attributable Risk of Modifiable and Nonmodifiable Breast Cancer Risk Factors in Postmenopausal Breast Cancer[END_REF], diabetes [START_REF] Rajaobelina | Population attributable fractions of the main type 2 diabetes mellitus risk factors in women: Findings from the French E3N cohort[END_REF], cardiovascular disease [START_REF] Azimi | Calculating Population Attributable Fraction for Cardiovascular Risk Factors Using Different Methods in a Population Based Cohort Study[END_REF][START_REF] Pirani | Population Attributable Fraction for Cardiovascular Diseases Risk Factors in Selected Countries: A comparative study[END_REF][START_REF] Tunaiji | Population attributable fraction of leading noncommunicable cardiovascular diseases due to leisure-time physical inactivity: a systematic review[END_REF], hypertension [START_REF] Mohammadi | Population-attributable fraction of hypertension associated with obesity, abdominal obesity, and the joint effect of both in the Central Provinces of Iran[END_REF], musculoskeletal disorders [START_REF] Hamel | Software for Unbiased Estimation of Attributable Risk[END_REF]Roquelaure et al., 2009a;[START_REF] Van Der Molen | How to improve the assessment of the impact of occupational diseases at a national level? The Netherlands as an example[END_REF][START_REF] Violante | Carpal tunnel syndrome and manual work: the OCTOPUS cohort, results of a ten-year longitudinal study[END_REF] attributable to risk factors.

Contribution of epidemiology to ergonomics in the prevention of UEMSD

In the framework of UEMSD prevention, the objective of the ergonomic approach is to intervene effectively in the workplace by acting on various work determinants (e.g. tasks, working conditions, social environment) that contribute most to the development of these UEMSD. The identification of these determinants is therefore an essential step and will allow the implementation of interventions acting on these determinants, particularly the modifiable ones that have the greatest impact within the population.

The main contribution of epidemiology to the prevention of UEMSD is the gradual increase over several years in the literature on risk models, particularly through epidemiological and ergonomic studies but also through exchanges between epidemiologists, physiologists and ergonomists. Epidemiological studies have contributed important and necessary scientific knowledge to ergonomics that is needed for the prevention of UEMSD, in particular by providing growing evidence of causality in the relationship between occupational exposures and the occurrence of UEMSD (identification of risk factors) [START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF]Descatha et al., 2016;Kozak et NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 23 al., 2015;[START_REF] Mansfield | Psychosocial Risk Factors and the Association With Carpal Tunnel Syndrome: A Systematic Review[END_REF][START_REF] Punnett | Work-related musculoskeletal disorders: the epidemiologic evidence and the debate[END_REF]Roquelaure et al., 2020;van der Molen et al., 2017) and statistical justification for recognizing the contribution of these occupational exposures to the development of UEMSD [START_REF] Dalbøge | Cumulative occupational shoulder exposures and surgery for subacromial impingement syndrome: a nationwide Danish cohort study[END_REF][START_REF] Melchior | Why are manual workers at high risk of upper limb disorders? The role of physical work factors in a random sample of workers in France (the Pays de la Loire study)[END_REF]National Research Council and Institute of Medicine, 2001;[START_REF] Rossignol | Carpal tunnel syndrome: what is attributable to work? The Montreal study[END_REF][START_REF] Van Der Molen | How to improve the assessment of the impact of occupational diseases at a national level? The Netherlands as an example[END_REF][START_REF] Violante | Carpal tunnel syndrome and manual work: the OCTOPUS cohort, results of a ten-year longitudinal study[END_REF]. These contributions from epidemiology can be made by (a) modelling the determinants of UEMSD, (b) identifying the modifiable and non-modifiable risk factors associated with these UEMSD, and finally (c) modelling the effectiveness of prevention by estimating the PAF associated with modifiable UEMSD risk factors (Yves Roquelaure et al., 2012). This information will make it possible to design better prevention strategies based on the modifiable work-related risk factors with the greatest effect within the working population. In addition, contributions from epidemiology have also made it possible to support the implementation of reparation-compensation procedures for affected workers.

With regard to points (a) and (b), there is international scientific consensus in the literature on a bio-psychosocial model of UEMSD that integrates certain psychological, social and organizational characteristics of work situations [START_REF] Bongers | Epidemiology of work related neck and upper limb problems: psychosocial and personal risk factors (part I) and effective interventions from a bio behavioural perspective (part II)[END_REF]Descatha et al., 2016[START_REF] Descatha | Lateral epicondylitis: New evidence for work relatedness[END_REF]Hauke et al., 2011;[START_REF] Kraatz | The incremental effect of psychosocial workplace factors on the development of neck and shoulder disorders: a systematic review of longitudinal studies[END_REF][START_REF] Leider | Effects of job rotation on musculoskeletal complaints and related work exposures: a systematic literature review[END_REF]National Research Council and Institute of Medicine, 2001;van der Molen et al., 2017;[START_REF] Van Rijn | Associations between work-related factors and specific disorders of the shoulder -a systematic review of the literature[END_REF]. In recent years, the results of epidemiological studies have contributed significantly to the evidence of a causal relationship between exposure several risk factors and the occurrence of UEMSD [START_REF] Bernal | Work-related psychosocial risk factors and musculoskeletal disorders in hospital nurses and nursing aides: A systematic review and meta-analysis[END_REF][START_REF] Bongers | Are psychosocial factors, risk factors for symptoms and signs of the shoulder, elbow, or hand/wrist?: A review of the epidemiological literature[END_REF][START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF]Descatha et al., 2016;Harris-Adamson et al., 2016, 2015;Kozak et al., 2015;[START_REF] Kraatz | The incremental effect of psychosocial workplace factors on the development of neck and shoulder disorders: a systematic review of longitudinal studies[END_REF][START_REF] Lang | Psychosocial work stressors as antecedents of musculoskeletal problems: A systematic review and meta-analysis of stability-adjusted longitudinal studies[END_REF][START_REF] Leider | Effects of job rotation on musculoskeletal complaints and related work exposures: a systematic literature review[END_REF][START_REF] Mayer | Longitudinal evidence for the association between work-related physical exposures and neck and/or shoulder complaints: a systematic review[END_REF][START_REF] Punnett | Work-related musculoskeletal disorders: the epidemiologic evidence and the debate[END_REF]Sluiter et al., 2001;van der Molen et al., 2017;[START_REF] Van Rijn | Associations between work-related factors and specific disorders of the shoulder -a systematic review of the literature[END_REF]. These risk factors include personal factors (e.g. age, female gender, obesity), biomechanical factors (e.g. high repetitive movements, intense efforts, uncomfortable postures), psychosocial factors (e.g. lack of decision-making autonomy, lack of support from co-workers or managers) and organizational factors (e.g. working under time pressure, lack of time to recover, inflexibility of procedures and checks). To date, the impact of these risk factors remains substantial for workers and companies even though most of them are potentially avoidable (e.g. those related to work conditions) [START_REF] Aublet-Cuvelier | Pratique d'exercices physiques au travail et prévention des TMS : que dit la littérature ?[END_REF][START_REF] Hoe | prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors[END_REF][START_REF] Hoe | Ergonomic design and training for preventing workrelated musculoskeletal disorders of the upper limb and neck in adults[END_REF]Roquelaure, 2015;[START_REF] Van Eerd | Effectiveness of workplace interventions in the prevention of upper extremity musculoskeletal disorders and symptoms: an update of the evidence[END_REF] or modifiable through biomedical interventions or prevention programs combining health promotion and reduction of the constraints of work situations (e.g. obesity, diabetes) (Kennedy et al., 2010). This evidence from various epidemiological studies constitutes a strong rationale for the prevention of UEMSD through workplace interventions, in particular by eliminating or reducing worker exposure to the main modifiable risk factors.

Based on the identification of risk factors, the effectiveness of the prevention intervention to be implemented in the workplace can be assessed theoretically by estimating the fraction of UEMSD potentially preventable by this prevention action i.e. the proportion of UEMSD cases (CTS, RCS, etc...) that could be prevented if workers were not or less exposed to the risk factor. A Swedish study based on the review of epidemiologic studies [START_REF] Hagberg | Impact of occupations and job tasks on the prevalence of carpal tunnel syndrome[END_REF]) concluded that at least 50%, and as much as 90%, of all of the CTS cases in working populations exposed to physical work load factors (e.g. repetition) appeared to be attributable to physical work load.

A Montreal study [START_REF] Rossignol | Carpal tunnel syndrome: what is attributable to work? The Montreal study[END_REF] estimating the attributable fraction in exposed people by comparing the incidence of CTS surgery among different working groups concluded that 55% of surgical CTS in women and 76% in men were attributable to work among manual workers. In the US, findings from the 2001 National Research NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 24

Council extensive review (National Research Council and Institute of Medicine, 2001) concluded that improving low social support of coworkers and supervisors in exposed workers could potentially reduce the risk for UEMSD by 28-52%. In a French study, Roquelaure et al. [START_REF] Roquelaure | Attributable risk of carpal tunnel syndrome according to industry and occupation in a general population[END_REF] showed that the proportion of CTS that could be attributed to industry sectors and occupational categories ranged between 36 and 93%.

A study conducted in the French region of PdL [START_REF] Melchior | Why are manual workers at high risk of upper limb disorders? The role of physical work factors in a random sample of workers in France (the Pays de la Loire study)[END_REF] to investigate the reasons for the excess risk of UEMSD among manual workers estimated that over 50% of the excess risk in manual workers was explained by biomechanical exposures, particularly repetitive movements and forceful exertion at work. In addition, results revealed that, up to 23-31% of cases of UEMSD could have been prevented by reducing biomechanical exposures in the working population, particularly among manual workers [START_REF] Melchior | Why are manual workers at high risk of upper limb disorders? The role of physical work factors in a random sample of workers in France (the Pays de la Loire study)[END_REF].

A prospective cohort study [START_REF] Dalbøge | Cumulative occupational shoulder exposures and surgery for subacromial impingement syndrome: a nationwide Danish cohort study[END_REF] conducted in the Danish general working population showed that 24% of all first-time events of surgery for RCS could be attributed to occupational exposures.

The OCTOPUS cohort study conducted in Italy [START_REF] Violante | Carpal tunnel syndrome and manual work: the OCTOPUS cohort, results of a ten-year longitudinal study[END_REF] showed that about one third of CTS cases could be attributed to forceful manual work (exposure above levels of Action Limit) i.e. approximatively 30% of CTS could be avoided if workers exposure to forceful manual were low (under the Action Limit). Recently, a study by [START_REF] Van Der Molen | How to improve the assessment of the impact of occupational diseases at a national level? The Netherlands as an example[END_REF] among the Dutch working population revealed that 25% of LE cases and 10% of shoulder soft tissue disorders could theoretically be avoided if workers did not exert force during work or did so only occasionally. The study also showed that, a proportion of 15% of LE cases and 9% of shoulder soft tissue disorders were attributable to awkward posture defined as a combined physical exposure of the wrist and elbow. Due to the multi-factorial nature of UEMSD, one can reasonably assume that the proportion of preventable cases would be even higher if comprehensive workplace interventions involved a more diverse range of risk factors. These results, although theoretical, suggest that prevention interventions should focus as a priority on the risk factors having the greatest impact on UEMSD; i.e. those that are both associated with UEMSD and have a high prevalence. It should be noted, however, that even ideally effective interventions could not completely reduce the incidence of UEMSD. In contrast, epidemiological models can guide ergonomic intervention by considering different scenarios based on the impact of the modifiable risk factor(s).

Objectives of the thesis

Today, UEMSD are a major concern for occupational and public health due to the considerable human, social and occupational costs. There is therefore a great need for prevention, which remains an occupational health priority.

The moderate impact of the prevention plans implemented over the last few decades requires further studies on prevention strategies at the working population level. In order to better design prevention programs, it is essential to know the modifiable risk factors that have the greatest impact in the working population to enhance the effectiveness of interventions. The proportion of UEMSD attributable to work (therefore theoretically preventable through workplace interventions) varies by occupation/industry and exposure to risk factors for UEMSD. However, few available studies have estimated the potential impact of various prevention scenarios on the incidence of UEMSD in the working population.

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 25

The principal objective of this doctoral thesis work was to estimate and compare the potential effects of reducing work-related exposures to the main biomechanical and psychosocial risk factors on the incidence of UEMSD using data from the French COSALI (COhorte des SAlariés LIgériens) cohort. Three studies in the form of research papers presented in the "results" section were conducted to attain this objective.

(a) the first study examined the associations between potential risk factors and the incidence of UEMSD, and estimated the proportion of UEMSD cases that could be attributed to each of these risk factors through the calculation of PAF;

(b) the second study estimated the proportion and number of incident UEMSD cases that could be potentially prevented in the working population in the PdL region;

(c) the last study assessed the combined effect of biomechanical and psychosocial risk factors on the incidence of UEMSD and estimated the proportion and number of UEMSD cases attributable to these risk factors in the working population in the PdL region.

In the framework of the present thesis, organizational risk factors were not investigated due to the complex interrelationships between these risk factors and the development of UEMSD (see figure 1 for the conceptual causation model linking organizational risk factors to UEMSD) [START_REF] Bao | Impact of Work Organizational Factors on Carpal Tunnel Syndrome and Epicondylitis[END_REF][START_REF] Roquelaure | Promoting a Shared Representation of Workers' Activities to Improve Integrated Prevention of Work-Related Musculoskeletal Disorders[END_REF]. As shown in the conceptual causation model, organizational factors are not at the same level on the chain of determinants as biomechanical and psychosocial risk factors, as they act as indirect determinants in the development of UEMSD [START_REF] Bodin | Risk Factors for Shoulder Pain in a Cohort of French Workers: A Structural Equation Model[END_REF]Roquelaure et al., 2020). These factors, at the level of the work structure (meso-level), influence the exposure to biomechanical and psychosocial risk factors at the individual level (micro-level)

(figure 1). Conventional modelling methods (e.g. logistic regression, Cox regression) would not take into account the complex interrelationships between organizational, biomechanical and psychosocial risk factors involved in the development of UEMSD, which may lead to problems of collinearity [START_REF] Bao | Impact of Work Organizational Factors on Carpal Tunnel Syndrome and Epicondylitis[END_REF][START_REF] Roquelaure | Promoting a Shared Representation of Workers' Activities to Improve Integrated Prevention of Work-Related Musculoskeletal Disorders[END_REF]. To better account for the weight of these risk factors together in the risk models, structural equation models are increasingly used to obtain an integrated assessment of the complex associations between UEMSD and risk factors [START_REF] Bodin | Shoulder pain among male industrial workers: Validation of a conceptual model in two independent French working populations[END_REF][START_REF] Bodin | Risk Factors for Shoulder Pain in a Cohort of French Workers: A Structural Equation Model[END_REF][START_REF] Bodin | Forms of work organization and associations with shoulder disorders: Results from a French working population[END_REF]Roquelaure et al., 2020). To the best of our knowledge, structural equation models, which better account for the weight of organizational factors in the risk models, do not enable the calculation of PAFs and hence the number of attributable cases.

As a result of all the above, organizational variables were therefore not studied in this thesis, which focused mainly on the calculation of PAFs and numbers of potentially preventable cases of UEMSD.

Organization of the thesis

The first part of this doctoral thesis dealt with a background literature review of work-related MSD studies worldwide, including their economic and social impact and prevention, and also provided a brief synthesis of previous risk factor studies and the rationale for this thesis project. The next part (part two) presents details regarding the database used in this thesis including the study design and population, how UEMSD were diagnosed based on a standardized clinical examination, data collection techniques, and description of the analysis variables.

This part also explains in detail the statistical techniques and analyses used to compute the estimates. The results of analyses in the current thesis are presented in part three. These results are presented in the form of three NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 26 research articles (published or in progress). The presentation of each manuscript is preceded by a short summary of the main results of the manuscript. Part four provides a summary of the key findings and a general discussion of the thesis. Part five relates to the conclusions of the current thesis including its contributions, recommendations for future research, and finally a summary in French.

All appendices are presented at the end of the references section. They include self-questionnaire, the clinical notebook describing the French translation of the clinical protocol with diagnostic criteria charts, the clinical guide using photographs of clinical tests and results of descriptive statistics.

Material and methods

Setting and study design

The present thesis used the data from the COSALI cohort, a prospective study of MSD and their risk factors in the working population. This cohort was based on two successive surveys of workers in the French region of PdL (Bodin et al., 2012b). The study received approval from France's Advisory Committee on the Processing of French working population, and its diversified socioeconomic structure was similar to that of France as a whole [START_REF] Ha | The French Musculoskeletal Disorders Surveillance Program: Pays de la Loire network[END_REF].

Study population

The study population of the present thesis was based only on data from the component (b) of the pilot network presented above. To provide data comparable with other European countries, the surveillance protocol of the sentinel network globally followed the recommendations of the European consensus criteria document (the SALTSA consensus) (Sluiter et al., 2001).

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 27

Inclusion period Sentinel network of occupational physicians

In France, all salaried workers, including those in temporary and part-time employment, undergo a mandatory annual health examination by a qualified occupational physician (OP). The OPs were salaried by occupational health services in charge of the medical surveillance of the companies. Each OP worked across several companies at a time and supervised the health of approximately 1400 to 1700 part-time workers and 2800 to 3200 full-time workers. As part of the sentinel network, all OPs who practiced in the PdL region (n=460) were invited to participate in the study, and 83 of them (18%) volunteered to take part in the study. These OPs were characteristic of the region's OPs in terms of medical practice, working time, geography, and economic sectors covered [START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF].

Inclusion of workers

Between Out of 184 600 workers under surveillance, 3710 participants (2.0% of workers under surveillance; 2161 men, 1549 women) undergoing a regularly scheduled annual health examination were included. More than 90% of the selected workers participated in this study (<10%: no shows, refusals, duplications). Women were slightly underrepresented in the sample (42% vs. 47% in the region, P<0.001) [START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]. Overall, the distribution of occupations in the sample was close to that of the regional workforce, except for the occupations not surveyed by OPs (e.g. farmers, shopkeepers, and self-employed workers) [START_REF] Ha | The French Musculoskeletal Disorders Surveillance Program: Pays de la Loire network[END_REF]Roquelaure et al., 2009b[START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF].

Follow-up period

A self-questionnaire follow-up between February 2007-May 2009 and a medical follow-up between January 2007-September 2010 of the workers initially included was undertaken (figure 2). This period coincided with a major economic crisis in the PdL region during 2008-2009, in which the regional salaried workforce declined by 3.4%

(33.7% in temporary employment agencies) [START_REF] Hautbois | Crise en Pays de la Loire : industrie et interim dans la tourmente (Etude No. 88[END_REF]. Workers usually supervised by a non-participant OP, people on parental or long-term sick leave, retired people, and those who had lost their job were excluded from the follow-up. Several reminders were sent out to all occupational medicine services, and then to each OP now responsible for the medical surveillance of at least one worker of the cohort. For workers who had changed NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 28

OP, the research team systematically contacted the last OP responsible for their medical surveillance [START_REF] Sérazin | Difficulties of a longitudinal epidemiological follow-up study in French occupational medicine[END_REF].

Of the 3710 workers initially included, a total of 1611 clinical examinations were carried out during the follow-up, for an overall response rate of 43% and 65%, considering all workers initially included and only those whose OP was known at the time of follow up, respectively [START_REF] Sérazin | Difficulties of a longitudinal epidemiological follow-up study in French occupational medicine[END_REF]. The information collected on the general characteristics of the professional activity (contract, schedules, etc.) was modeled after by major French epidemiological investigations [START_REF] Anact | Affections périarticulaires des membres supérieurs et organisation du travail[END_REF][START_REF] Leclerc | Carpal tunnel syndrome and work organisation in repetitive work: a cross sectional study in France. Study Group on Repetitive Work[END_REF] NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 29 2004MSD 29 , 1998)), SUMER [START_REF] Dares | Surveillance médicale des expositions aux risques professionnels (Sumer) : édition 2003[END_REF] and Estev [START_REF] Cassou | Chronic neck and shoulder pain, age, and working conditions: longitudinal results from a large random sample in France[END_REF]). The organization of work was assessed using items from the main French epidemiological investigations [START_REF] Anact | Affections périarticulaires des membres supérieurs et organisation du travail[END_REF][START_REF] Cassou | Chronic neck and shoulder pain, age, and working conditions: longitudinal results from a large random sample in France[END_REF][START_REF] Dares | Surveillance médicale des expositions aux risques professionnels (Sumer) : édition 2003[END_REF][START_REF] Roquelaure | Réseau expérimental de surveillance épidémiologique des troubles musculo-squelettiques (TMS) d'origine professionnelle[END_REF] and supplemented by questions from the SALTSA consensus (Sluiter et al., 2001).

Items were designed using a 4-level Likert-type scale [START_REF] Likert | A technique for the measurement of attitudes[END_REF][START_REF] Robinson | Likert Scale[END_REF] as follows: "totally disagree" (scored 1), "disagree" (scored 2), "agree" (scored 3), and "totally agree" (scored 4) for the JCQ, and "never or almost never", "rarely (<2 hours/day)", "often (2-4 hours/day)", and "always (≥4 hours/day)" for items concerning the other occupational exposures. The questions on biomechanical factors presented awkward postures in picture form to facilitate workers' understanding and thus increase the validity of posture selfassessment [START_REF] Halpern | The test-retest reliability of a new occupational risk factor questionnaire for outcome studies of low back pain[END_REF]. The perceived physical exertion (force) was evaluated using the Borg Rating

Perceived Exertion (RPE) scale [START_REF] Borg | Psychophysical bases of perceived exertion[END_REF] ranging from 6 (no exertion at all) to 20 (maximal exertion).

Concerning psychosocial factors, the Karasek's Job Content Questionnaire (JCQ) [START_REF] Karasek | The Job Content Questionnaire (JCQ): An instrument for internationally comparative assessments of psychosocial job characteristics[END_REF] in its validated French version with 26 questions [START_REF] Niedhammer | Psychometric properties of the French version of the Karasek Job Content Questionnaire: a study of the scales of decision latitude, psychological demands, social support, and physical demands in the GAZEL cohort[END_REF][START_REF] Niedhammer | Psychometric properties of the French version of Karasek's "Job Content Questionnaire" and its scales measuring psychological pressures, decisional latitude and social support: the results of the SUMER[END_REF] evaluating three dimensions of the psychosocial environment at work: decision latitude (9 items), psychological demands (9 items) and social support (8 items).

Clinical data

Data on diagnosed UEMSD were collected in observation notebooks by performing a standardized clinical examination. Additional, personal factors (e.g. gender and birthday year) and medical and surgical history including information on diabetes mellitus, inflammatory arthritis, history of MSD were ascertained during the clinical examination and by a self-administered questionnaire. The case definition for each specific UEMSD was based on both symptoms and signs.

The clinical examination was based on the presence of MS over the past 12 months according to the standardized clinical approach of the SALTSA consensus to diagnose UEMSD (Sluiter et al., 2001). Each included worker (participant) underwent the clinical examination performed by the OP immediately. If symptoms occurred during the past 12 months, the OP performed a clinical examination lasting from 2 to 15 minutes strictly applying the methodology and clinical tests of the SALTSA consensus to diagnose UEMSD.

All data were collected in observation notebooks that included diagnostic criteria in diagrams, which provided physicians with a standardized diagnostic tool. The diagrams provide a visual aid to the decision process that occurs when the criteria are applied to the case definitions. The clinical examination protocol for the diagnosis of UEMSD and the clinical manipulations performed during the examination are presented in Appendix 2.

In order to reduce the inter-operator variability, all participating OPs were trained to perform a standardized clinical examination that strictly applied the methodology and clinical tests of the SALTSA consensus to diagnose UEMSD (Sluiter et al., 2001). Each participating OP in charge of the medical surveillance of salaried workers

Follow-up period

A total of 1611 workers included at baseline were re-examined by their OPs using the same procedure as in the initial assessment (Sluiter et al., 2001). In order to reduce the inter-operator variability, all new participating OPs included were given the same training as at inclusion to perform a standardized clinical examination that strictly applied the methodology and clinical tests of the SALTSA consensus to diagnose UEMSD (Sluiter et al., 2001).

The same clinical data as for inclusion were collected. For the purposes of this thesis, only workers who underwent a follow-up clinical examination were analyzed.

Analysis variables

4.1.

Outcomes of interest

The outcome of interest for the present study was defined as incident cases of UEMSD including only workers free of the following six main clinically diagnosed UEMSD at baseline but who met the criteria for at least one of the disorders at follow-up: 1-Rotator cuff syndrome (RCS), 2-Lateral epicondylar tendinopathy (LET), 3-Carpal tunnel syndrome (CTS), 4-Ulnar tunnel syndrome, 5-Flexor-extensor peritendinitis or tenosynovitis of the forearm-wrist region, and 6-De Quervain's tenosynovitis. Cases were assessed by subject, and therefore bilateral cases of UEMSD counted as one disorder, not two.

Potential risk factors

The known or suspected to be potential risk factors for at least one of the disorders under study on the basis of epidemiological and ergonomic studies.

(a) Personal factors and medical history

Female gender

Female gender was defined as an indicator variable (yes/no).

Age

Age at the date of filling out the inclusion questionnaire was divided into three categories (

Rheumatoid arthritis and diabetes mellitus status

These two variables were defined as binary (yes/no) variables based on the information collected by the occupational physicians during the clinical examination.

(b) Work-related biomechanical factors

The considered biomechanical variables were as follows:

-high repetitiveness of tasks (≥4 hours/day);

-use of vibrating hand tools (≥2 hours/day);

-repeated/sustained elbow movements (flexion/extension) (≥2 hours/day);

-repeated/sustained posture with arms above shoulder level (≥2 hours/day);

-repeated/sustained posture with shoulder abduction (approximately 60°);

-pronation and supination movements (≥2 hours/day);

-wrist twisting movements (≥2 hours/day);

-use of the pinch grip (≥4 hours/day);

-high perceived physical exertion (RPE Borg Scale≥12 and ≥13).

All these variables listed above were defined using the cut-offs of the SALTSA consensus (SALTSA cut-offs) (Sluiter et al., 2001) except for the variable "repeated/sustained posture with shoulder abduction" defined as workers who reported being exposed "rarely (<2 hours/day)", "often (2-4 hours/day)" or "always (≥4 hours/day)" due to low number of exposed workers according to the SALTSA threshold: ≥2 hours/day). In addition, the "high perceived physical exertion" was assessed using the Rating Perceived Exertion Borg scale (RPE Borg Scale) [START_REF] Borg | Psychophysical bases of perceived exertion[END_REF] ranging from 6 (no exertion at all) to 20 (maximal exertion). The variable was defined as a binary variable

(c) Work-related psychosocial factors

Psychosocial factors were assessed using the twenty-six items of the French version of the Karasek JCQ [START_REF] Karasek | The Job Content Questionnaire (JCQ): An instrument for internationally comparative assessments of psychosocial job characteristics[END_REF]. Median values of the national French SUMER study [START_REF] Niedhammer | Psychometric properties of the French version of Karasek's "Job Content Questionnaire" and its scales measuring psychological pressures, decisional latitude and social support: the results of the SUMER[END_REF] to classify exposed and unexposed workers were used to define the following variables: low decision latitude (≤70), low social support (≤23) and high psychological demands (≥22).

Other analysis variables

The other analysis variables included variables related to work history such as:

Seniority in current job

This variable represents the duration of the worker's current employment at the date of inclusion. It was divided into four classes: <1 year, 1-2 years, 3-10 years, and >10 years.

Temporary employment

Temporary employment was defined as an indicator variable (yes/no) according to whether the worker had a temporary employment contract (e.g. fixed-term contract, interim, seasonal contract, trainee) or not (permanent contract or official).

Occupational class

This variable was defined into five categories using the French classification of occupations (1994 version, 1-digit numerical code): 2=craftsmen, salespersons and managers, 3=professionals, 4=technicians and associate professionals, 5=low-grade white-collar workers, and 6=blue-collar workers.

Economic sector

The variable of economic sector was categorized using the French classification of economic sectors (2000 version): agriculture, industry, construction, and trade and services.

Statistical methods

This section focuses on the statistical methodologies related to the main objective of this thesis and which were implemented throughout this work.

The population attributable fraction method

At the population level, the effect of a risk factor on a disease can be quantified by the computation of the population attributable fraction (PAF). This measure can be estimated from the main types of epidemiologic studies, namely cross-sectional, case-control, cohort, and case-cohort studies [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF][START_REF] Benichou | A review of adjusted estimators of attributable risk[END_REF].

(a) Estimation of the PAF in the case of a binary exposure (exposed 𝑬 vs unexposed 𝑬)

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 33

The 𝑃𝐴𝐹 is defined according to Levin's equation [START_REF] Levin | The occurrence of lung cancer in man[END_REF]:

PAF = P 𝑟 (D) -P 𝑟 (D\𝐸) P 𝑟 (D) (1)
where P 𝑟 (𝐷), refers to the probability of the disease (incidence) in the population consisting of both exposed subjects 𝐸 and unexposed subjects 𝐸, and P 𝑟 (D\𝐸, ) refers to the hypothetical probability of the disease in the same population after elimination of all exposure. This formula by Levin quantifies the additional probability of the disease in the population that is associated with the presence of the exposure. Thus, 𝑃𝐴𝐹 measures the additional probability of disease in the population that is associated with the presence of exposure in the population [START_REF] Walter | The Estimation and Interpretation of Attributable Risk in Health Research[END_REF].

Walter [START_REF] Walter | Prevention for multifactorial diseases[END_REF] showed that Levin's estimate would be biased and overestimated in view of the often multifactorial nature of the conditions under study, since the sum of cases attributable to all the exposure factors investigated is systematically greater than the total number of events observed. In public health, 𝑃𝐴𝐹 is interpreted as a measure of the proportion of the disease attributable to one or several exposures. However, for this interpretation to be correct, three conditions must be met [START_REF] Walter | The Estimation and Interpretation of Attributable Risk in Health Research[END_REF]:

o The estimate of attributable risk must be unbiased;

o Exposure must be causal and not simply associated with the disease;

o Elimination of exposure should not affect the distribution of other risk (or protective) factors in the population.

In epidemiology, it is often difficult to state the causal nature of a relationship between an exposure and a disease.

Demonstrating an association between exposure and disease is not sufficient to conclude that there is a causal relationship. This problem of causality has been discussed by several authors (Greenland and [START_REF] Soit Ilg | Conceptual problems in the definition and interpretation of att ributable fractions[END_REF][START_REF] Robins | Estimability and estimation of excess and etiologic fractions[END_REF][START_REF] Rothman | Modern Epidemiology[END_REF].

Since 𝑃𝐴𝐹 depends on both the strength of the association between disease and exposure, and the prevalence of exposure in the population, equation ( 1) can be rewritten as follows using Bayes' theorem [START_REF] Cole | Attributable risk percent in case-control studies[END_REF][START_REF] Levin | The occurrence of lung cancer in man[END_REF]:

PAF = 𝑃 𝑟 (𝐸)(𝑅𝑅 -1) 1 + 𝑃 𝑟 (𝐸)(𝑅𝑅 -1) = 1 - 1 1 + 𝑃 𝑟 (𝐸)(𝑅𝑅 -1) = 1 - 1 ∑ 𝑃 𝑟 (𝐸) 𝑠 𝑅𝑅 𝑠 2 𝑠=1
(2)

where P 𝑟 (𝐸), refers to the prevalence of the risk factor (exposure) in the population under consideration, 𝑠, the indicator variable of the two strata determined by the value of the risk factor, and 𝑅𝑅, the relative risk associating the exposure to the disease. The formula (2) can be rewritten as [START_REF] Miettinen | Proportion of disease caused or prevented by a given exposure, trait or intervention[END_REF]:

PAF = 𝑃 𝑟 (𝐸\𝐷)(𝑅𝑅 -1) 𝑅𝑅 (3)
where P 𝑟 (𝐸\𝐷), refers to the prevalence of the risk factor in the affected population.

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 34

A high 𝑅𝑅 may correspond to a low or high 𝑃𝐴𝐹 depending on the prevalence of exposure. This leads to very different public health consequences, as the prevalence of exposure can vary considerably in populations that are spatially and temporally separated [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF].

When restricted to exposed subjects, the attributable fraction (𝐴𝐹) is a measure of the proportion of disease attributable to exposure in exposed subjects [START_REF] Levin | The occurrence of lung cancer in man[END_REF][START_REF] Miettinen | Proportion of disease caused or prevented by a given exposure, trait or intervention[END_REF]. 𝐴𝐹 depends on 𝑅𝑅 only [START_REF] Benichou | Methods of adjustment for estimating the attributable risk in case-control studies: A review[END_REF] and is defined as follows:

AF 𝐸 = P 𝑟 (D\E) -P 𝑟 (D\𝐸) P 𝑟 (D\E) (4)
(b) Estimation of the PAF in the case of multi-level exposure or an adjustment factor

Miettinen [START_REF] Miettinen | Proportion of disease caused or prevented by a given exposure, trait or intervention[END_REF] was the first to propose a generalization of the definition of 𝑅𝐴 in the case of multilevel exposure with the following formula:

𝑃𝐴𝐹 = ∑ 𝑃 𝑟 (𝐸|𝐷) 𝑠 (𝑅𝑅 𝑠 -1) 𝑅𝑅 𝑠 𝑆 𝑠=1 = 1 -∑ 𝑃 𝑟 (𝐸|𝐷) 𝑠 𝑅𝑅 𝑠 𝑆 𝑠=1 (5)
where 𝑠 = 1, … , 𝑆, denotes the level of exposure, 𝑃 𝑟 (𝐸|𝐷) 𝑠 , the prevalence of s-level exposure in the population of cases, and 𝑅𝑅 𝑠 is the associated 𝑅𝑅 relative to the chosen reference exposure.

Later, Walter [START_REF] Walter | The Estimation and Interpretation of Attributable Risk in Health Research[END_REF] proposed an extension of Levin's formula to multi-level categorical exposure (formula 6). This new definition is often the most widely used.

𝑃𝐴𝐹 = ∑ 𝑃 𝑟 (𝐸) 𝑠 (𝑅𝑅 𝑠 -1)

𝑆 𝑠=1

1 + ∑ 𝑃 𝑟 (𝐸) 𝑠 (𝑅𝑅 𝑠 -1) 𝑆 𝑠=1

= 1 -1 ∑ 𝑃 𝑟 (𝐸) 𝑠 𝑅𝑅 𝑠 𝑆 𝑠=1 (6) where 𝑃 𝑟 (𝐸) 𝑠 denotes the prevalence of s-level exposure.

Property of the PAF

There are two important properties of 𝑃𝐴𝐹 that should be noted:

o Reference level dependence: 𝑃𝐴𝐹 values are highly dependent on the definition of the reference level for exposure. This level corresponds to a total absence or the lowest level of exposure. The narrower the reference level by not including the most exposed subjects (and therefore in principle the most at risk), the higher the 𝑃𝐴𝐹 values. This property has a major impact on estimates of the 𝑃𝐴𝐹 and has been illustrated by Benichou [START_REF] Benichou | Methods of adjustment for estimating the attributable risk in case-control studies: A review[END_REF] and Wacholder et al. [START_REF] Wacholder | Attributable Risk: Advantages of a Broad Definition of Exposure[END_REF].

o Distributivity: This property of the 𝑃𝐴𝐹 applies strictly to crude 𝑃𝐴𝐹 estimates and adjusted estimates calculated on the basis of a full model including all major effects and possible interactions [START_REF] Benichou | Methods of adjustment for estimating the attributable risk in case-control studies: A review[END_REF]. It applies approximately to adjusted estimates that are not based on a full model [START_REF] Wacholder | Attributable Risk: Advantages of a Broad Definition of Exposure[END_REF]. Thus, if several exposure categories are considered instead of one, then the sum of the 𝑃𝐴𝐹 of each exposure category is equal to the overall 𝑃𝐴𝐹 calculated by combining these exposure categories NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 35 into one, regardless of the division of the exposure categories, on condition that the reference category remains the same [START_REF] Benichou | Methods of adjustment for estimating the attributable risk in case-control studies: A review[END_REF][START_REF] Wacholder | Attributable Risk: Advantages of a Broad Definition of Exposure[END_REF][START_REF] Walter | The Estimation and Interpretation of Attributable Risk in Health Research[END_REF].

Since the 𝑃𝐴𝐹 is often estimated in multifactorial situations when assessing the individual and joint impact of multiple exposures, a problem of non-additivity of the 𝑃𝐴𝐹 for separate exposures arises since the individual contributions of exposures to the 𝑃𝐴𝐹 are usually non-additive. Walter [START_REF] Walter | Effects of interaction, confounding and observational error on attributable risk estimation[END_REF]) demonstrated that the sum of the separate 𝑃𝐴𝐹𝑠 for each exposure, i.e. 𝑃𝐴𝐹 1 + 𝑃𝐴𝐹 2 , does not equal the joint 𝑃𝐴𝐹 (𝑃𝐴𝐹 12 ) unless at least one of the following two specific conditions is met:

o There is no joint exposure to the different exposures in the population;

o The effects of exposures on the risk of disease are additive.

The 𝑃𝐴𝐹 can be estimated from the main types of epidemiological studies, namely cohort studies, case-cohort studies, case-control studies and cross-sectional studies [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF][START_REF] Benichou | A review of adjusted estimators of attributable risk[END_REF][START_REF] Benichou | Attributable risk[END_REF].

The computation of the PAF can be implemented using several statistical software packages such as SAS [START_REF] Hertzmark | The SAS PAR Macro[END_REF][START_REF] Laaksonen | Population Attributable Fraction (PAF) in epidemiologic follow-up studies[END_REF][START_REF] Mezzetti | Software for Attributable Risk and Confidence Interval Estimation in Case-Control Studies[END_REF], R [START_REF] Chen | paf': Attributable Fraction Function for Censored Survival Data, R package version 1.0. Cnam. Direction des Risques Professionnels[END_REF][START_REF] Dahlqwist | AF': Model-Based Estimation of Confounder-Adjusted Attributable Fractions[END_REF][START_REF] Rämsch | Point and interval estimation of partial attributable risks from case-control data using the R-package 'pARccs[END_REF][START_REF] Schenck | Attribrisk': Population attributable risk, R package version 0[END_REF] or STATA [START_REF] Newson | PUNAF: Stata module to compute population attributable fractions for cohort studies[END_REF][START_REF] Newson | Attributable and unattributable risks and fractions and other scenario comparisons[END_REF].

Within the framework of this PhD thesis, the following 𝑃𝐴𝐹 formula (Spiegelman et al., 2007), implemented in the SAS software, was applied: [START_REF] Da Costa | Incidence and prevalence of upper-limb work related musculoskeletal disorders: A systematic review[END_REF] where 𝑡 denotes a stratum of unique combinations of levels of all background risk factors which are not under study, 𝑡 = 1; . . . ; 𝑇 and 𝑅𝑅 2𝑡 is the relative risk in combination 𝑡 relative to the lowest risk level, where 𝑅𝑅 2,𝑡 = 1.

𝑃𝐴𝐹 = ∑ ∑ 𝑝 𝑠𝑡 𝑅𝑅 1𝑠 𝑅𝑅 2𝑡 𝑇 𝑡=1 𝑆 𝑠=1 -∑ ∑ 𝑝 𝑠𝑡 𝑅𝑅 2𝑡 𝑇 𝑡=1 𝑆 𝑠=1 ∑ ∑ 𝑝 𝑠𝑡 𝑅𝑅 1𝑠 𝑅𝑅 2𝑡 𝑇 𝑡=1 𝑆 𝑠=1 = 1 - ∑ 𝑝 .𝑡 𝑅𝑅 2𝑡 𝑆 𝑠=1 ∑ ∑ 𝑝 𝑠𝑡 𝑅𝑅 1𝑠 𝑅𝑅 2𝑡 𝑇 𝑡=1 𝑆 𝑠=1
𝑠 indicates an index exposure group defined by each of the unique combinations of the levels of the index risk factors, that is, those risk factors to which the 𝑃𝐴𝐹 applies, 𝑠 = 1; . . . ; 𝑆, and 𝑅𝑅 1𝑠 is the relative risk corresponding to combinations relative to the lowest risk combination, 𝑅𝑅 1,1 = 1. The joint prevalence of exposure group 𝑠 and stratum 𝑡 is denoted by 𝑝 𝑠𝑡 , and 𝑝 .𝑡 = ∑ 𝑝 𝑠𝑡 𝑆 𝑠=1 .

Weighting adjustment: the calibration method

All survey research is likely to have various types of errors (e.g. nonresponse issues, unequal selection probabilities) that affect different parts of the survey process. When present in the sample, non-response may in some cases lead to the data collected not being representative of the population, and therefore have different implications for data quality, particularly for prevention. In order to produce correct statistics, it is essential to remove any error. To correct for unequal selection probabilities and nonresponse, a weighting adjustment procedure is often carried out.

Weighting adjustment is a frequently applied statistical correction technique that is used and applied in surveys to overcome these problems, and also to make sample-weighted estimates as consistent as possible with known external population totals by improving the efficiency of estimates [START_REF] Bethlehem | Weighting Adjustment, in: Applied Survey Methods: A Statistical Perspective[END_REF][START_REF] Kalton | Weighting methods[END_REF][START_REF] Szymkowiak | Weighting and Estimation -Calibration[END_REF][START_REF] Zhang | A method of weighting adjustment for survey data subject to nonignorable nonresponse[END_REF]. This technique is based on the use of auxiliary information, NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 36

i.e. information available on a certain number of variables (called auxiliary variables) and assigns an adjustment weight to each survey respondent with a large weight for subjects in under-represented groups, and a small weight for those in over-represented groups.

A number of adjustment weighting techniques are available, among which simple poststratification, linear weighting, multiplicative weighting, and calibration estimation of which linear weighting and multiplicative weighting are special cases [START_REF] Bethlehem | Weighting Adjustment, in: Applied Survey Methods: A Statistical Perspective[END_REF]. Linear and multiplicative weighting methods can be applied in situations where the poststratification is not possible. The most frequently used method is the calibration approach when only the marginal distributions of the auxiliary variables (also called calibration variables) are known [START_REF] Kalton | Weighting methods[END_REF][START_REF] Szymkowiak | Weighting and Estimation -Calibration[END_REF]. This is the case in practice, since often the cross-classification cell counts of auxiliary variables is usually insufficient, or the size of the cells is very small (Smith et al., 2015).

Deville and Särndal [START_REF] Deville | Generalized Raking Procedures in Survey Sampling[END_REF][START_REF] Deville | Calibration Estimators in Survey Sampling[END_REF] were the first to develop and formalize the general idea of the calibration estimation method; although, many previous work [START_REF] Deming | On a Least Squares Adjustment of a Sampled Frequency Table When the Expected Marginal Totals are Known[END_REF][START_REF] Stephan | An iterative method of adjusting sample frequency tables when expected marginal totals are known[END_REF] have already used similar methods. With the calibration method, weights are assigned to all survey respondents in order to make the sample as representative as possible of the inference population. Overrepresented groups will then have a small weight and under-represented groups a large weight. The weighted sample will thus become more representative of the population, resulting in estimates with a lower bias than those that are unweighted. The calibration approach is based on the use of auxiliary information defined as a set of variables that have been measured in the survey and for which information on the population distribution is available. This can be done through census data or other large surveys. The efficiency of the estimates is one of the major reasons why calibration method should be used in survey sampling. This efficiency can be obtained by using external data and can result in a low variance of estimators that are based on calibration weights. The calibration method is used around the world in many surveys by many statistical offices: in Canada [START_REF] Estevao | Methodological principles for a generalized estimation system at Statistics Canada[END_REF], the United Kingdom (Office For National Statistics. Social Survey Division, 2017), Belgium [START_REF] Vanderhoeft | Generalised calibration at Statistics Belgium : SPSS module g-CALIB-S and current practices[END_REF], the Netherlands [START_REF] Nieuwenbroek | Bascula 4.0 reference manual[END_REF] and France [START_REF] Sautory | La macro Calmar. Redressement d'un échantillon par calage sur marges (Document de travail n°F9310 de la DSDS)[END_REF]. See [START_REF] Aude | Calage sur marges de la base des cliniques privées pour améliorer l'estimation de la situation économique[END_REF][START_REF] Davies | Examination of approaches to calibration in survey sampling[END_REF][START_REF] Kalton | Weighting methods[END_REF][START_REF] Sautory | Les méthodes de calage (Document No. Version n°1[END_REF]Smith et al., 2015) for more details of the weighting adjustment method with examples.

In the present doctoral thesis, the calibration method, the most commonly used weighting adjustment method, was used to adjust the distribution of the weighted sample for auxiliary variables available in both the COSALI cohort and the 2007 French population census for the PdL region to make it consistent with the distribution of the PdL working population. The objective was to compute an estimate of the projected number of incident UEMSD cases in the working population at the PdL region level using the new weights. Furthermore, through the calibration method, potential improvements in the accuracy of the estimates can be expected [START_REF] Szymkowiak | Weighting and Estimation -Calibration[END_REF].

Principle of the calibration method

The principle behind this approach, developed and formalized by Deville et al. [START_REF] Deville | Generalized Raking Procedures in Survey Sampling[END_REF][START_REF] Deville | Calibration Estimators in Survey Sampling[END_REF], consists in modifying the unit weights by adjusting the margins of the sample to population margins using available auxiliary available on a set of variables referred to as calibration variables or margins NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 37 (Roux andArmoogum, 2010, 2008), and meeting the equality requirements specified in (a) and (b) further below.

This helps minimize the sampling variance and, in certain cases, reduce the bias due to unit non-response.

The method involves minimizing a distance function between the base weights and final weights to obtain an optimal set of survey weights i.e. that the final weights produce totals that match external population totals. It consists in replacing, by reweighting individuals, the base weights, which are generally the "sampling weights" of individuals, with "final weights" (also called "calibration weights" or "new weights") as similar as possible using calibration variables. For these calibration variables, the population totals as well as the sample values are known.

This can be done through census data or other large surveys.

Practically, after applying the method (Smith et al., 2015), the weights obtained will be such that:

(a) the weighted frequencies of the categories of the variable in the sample will be equal to the corresponding counts known in the population after adjustment, if the calibration variable is qualitative (categorical);

(b) the weighted total of the variable in the sample will be equal to the known total in the population after adjustment, if the calibration variable is quantitative (numeric).

Theoretical aspects of calibration

The calibration problem

Consider a population U = {1. . . k. . . N} of N individuals from which a sample 𝑠 of size n was drawn. For any individual k of U, π k denotes its inclusion probability in 𝑠 (π k = n/N for any k in the case of a simple random sampling).

Suppose 𝑌 a variable of interest, which needs to be estimated for the total in the population. It can be obtained from the following formula:

Y = ∑ y k k∈U (8)
The estimator of 𝑌 conventionally used is the Horvitz-Thompson estimator (𝐇𝐓) formulated as follows:

Y ̂HT = ∑ 1 π k y k k∈s = ∑ d k y k k∈s (9)
Using this unbiased estimator of 𝑌 (Y ̂HT ) means assigning to each individual in the sample a weight 𝑑 𝑘 equal to the inverse of his inclusion probability (i.e. "extrapolation coefficient" N/n = 1/π k in the case of a simple random sampling).

Let X 1 , . . . , X j , . . . , X J be 𝐽 auxiliary variables (e.g. gender, degree, income, occupation, economic activity, etc...) available for all observations in the sample 𝑠, with known population totals (for quantitative variables) or marginal counts (for qualitative variables). These variables are referred to as "calibration variables". The total of the calibration variable X j in the population 𝑈 can be obtained by the following formula: To account for this information, and the total 𝑌 will be estimated using the adjustment weighting that replaces the Horvitz-Thompson estimator Y ̂HT with a new estimator Y ̂CAL (calibration estimator). This estimator can be formulated as follows:

X j = ∑ x jk k∈U (
Y ̂CAL = ∑ w k y k k∈s (11)
where 𝑤 𝑘 , equals 𝑑 𝑘 × 𝑒 𝑘 , denotes the calibration weight of unit 𝑘, accounting for both the sample weights and the values of selected auxiliary population variables 𝑋 to which the sample estimate is adjusted, 𝑒 𝑖 denotes the correction weight generated by the weighting adjustment method.

Furthermore, 𝑤 𝑘 , as close as possible to the original sample weights in the meaning of certain "distance function" 𝐺, ensure the calibration on the totals of the variables X j i.e. verify the calibration constraints as follows:

∀ j = 1 … J ∑ w k x jk k∈s = X j (12)

Theoretical resolution

The idea is to find an adapted Horvitz-Thompson estimator (to replace the Horvitz-Thompson estimator) that

This calibration problem depends on the chosen distance function, and in some cases also on boundary constraints. It can be resolved by using by the following formula ( 7) by introducing a vector 𝜆 of 𝐽 Lagrange multipliers associated with the constraints (5) and the application of the Newton iterative method.

𝑤 𝑘 = 𝑑 𝑘 𝐹(x 𝑘 ′ 𝜆) (14)
where x 𝑘 ′ = (x 1𝑘 … x 𝐽𝑘 ) and 𝐹, called the calibration function, is the inverse of the derivative of the function 𝐺.

Selection of the calibration method (distance functions)

Several calibration methods are possible among which four calibration methods corresponding to four types of distance functions are the most commonly used [START_REF] Sautory | La macro Calmar. Redressement d'un échantillon par calage sur marges (Document de travail n°F9310 de la DSDS)[END_REF]. Each of these four types of distance functions, presented below, has specific properties of 𝐺 and 𝐹. Figure 3 provides a graphical representation of the method.

Notice that, all calibrated estimators have the same asymptotic accuracy [START_REF] Deville | Calibration Estimators in Survey Sampling[END_REF], regardless of the method used when the sample size is sufficiently large.

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 39

After the use of calibration, the following quality indicators should be checked and verified in order to evaluate the final results and which method to use: lowest dispersion, smallest extent and general appearance of the distribution of initial and final weights. The calibration function chosen will determine the adjustments to be performed by the calibration function. The following functions are the most commonly used in practice:

1) "linear" method: based on the Chi-squared quadratic distance function, this method which systematically converges, is the fastest because Newton's algorithm always converges after two iterations, and the weights are not upper bounded. One of the disadvantages of this method is that calibrated weights 𝑤 𝑘 can be negative, which is undesirable. However, this can be avoided by limiting the weight ratios 𝑟 (gweights) as with the "truncated linear" method, which imposes limits.

2) "exponential" or "raking ratio" method: proposed by Deming and Stephan [START_REF] Deming | On a Least Squares Adjustment of a Sampled Frequency Table When the Expected Marginal Totals are Known[END_REF], is frequently used in quota surveys. This method converges quasi-systematically, always produces positive weights as opposed to the linear method. However, it can lead to weights below 1 or with quite large values.

3) "logit" method provides positive weights and ensures that the ratios "new_weights/initial_weights" are in the range ]L, U[. With successive approximations to determine L and U, there is usually a maximum value Lmax (<1) for L, and a minimum value Umin (>1) for U, depending on the data and margins of the calibration. The more the sample structure differs from the population structure regarding the calibration variables, the further away these values are from 1.

4) "truncated linear" method also provides positive weights with "new_weights/initial_weights" ratios that are within the [L, U] range.

NOTE: Methods 3) and 4) allow the maximum weight deformations induced by calibration to be controlled via parameters L and U, but do not always converge.

Practical aspects of the calibration

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 40

The calibration approach is used to adjust the distribution of the weighted sample for auxiliary variables (also called "calibration variables") and can only be applied in situations, as is often the case in practice, where the auxiliary variables are available. The auxiliary variables refer to variables for which individual values are assumed to be known for the whole finite population or for which totals are known. Such variables have to be measured in the survey, their population distribution must be known, and they must be (strongly) correlated with the target variable of the survey, i.e. the dependent variable (variable of interest). With the calibration method, weights are assigned to all survey respondents in order to make the sample as representative as possible of the (inference) population. Over-represented groups then have a small weight and under-represented groups a large weight. The resulting weights are called calibration weights, new weights or final weights.

An auxiliary variable, known as a calibration variable, can only be used in the calibration approach if, and only if, it is available for each of the observations from the calibration sample and its total is known in the target population. For instance, it may be a variable in the sampling frame, or a variable measured in a survey and for which the total is known from other sources. In the case where the total is known from other sources, it is important that the variable available in the sample corresponds exactly to the variable for which the total is known, i.e. variables must be measured at the same time, according to the same concepts and the total on which the calibration is applied must correspond to the population which the sample seeks to describe. Ideally, this total should be known exactly.

The calibration method being quite sophisticated and the calculations quite complex, it is important to note that programs are available for various statistical software packages including SAS [START_REF] Sautory | La macro Calmar. Redressement d'un échantillon par calage sur marges (Document de travail n°F9310 de la DSDS)[END_REF], STATA [START_REF] Álvarez | postweight or calibrate? Survey post-adjustments in Stata 16[END_REF][START_REF] Souza | CALIBRATE: Stata module to calibrate survey datasets to population totals[END_REF][START_REF] Souza | A Stata program for calibration weighting (No. 02), United Kingdom Stata Users' Group Meetings 2010[END_REF][START_REF] Luca | Stata program to compute calibrated weights from scientific usefile and additional database 32[END_REF][START_REF] Pitblado | Calibrating Survey Weights in Stata[END_REF] and R [START_REF] Lumley | Package 'survey' Version 4[END_REF][START_REF] Rebecq | icarus: Calibrates and Reweights Units in Samples[END_REF][START_REF] Rebecq | Icarus: un package r pour le calage sur marges et ses variantes[END_REF] for the calculation of calibration weights so that researchers can apply these techniques.

Within the framework of this thesis, the calibration method was implemented by using the program available for the SAS software [START_REF] Sautory | La macro Calmar. Redressement d'un échantillon par calage sur marges (Document de travail n°F9310 de la DSDS)[END_REF].

Statistical analysis

For analyses within the framework of this doctoral thesis, only workers who took part in the follow-up clinical examination were considered (1611 of the 3710 workers included at baseline).

All statistical analyses were performed using the Statistical Analysis System (SAS) software, version 9.4

TS Level 1M6 (SAS Institute Inc., Cary, NC, USA).

Description of study population

Study population characteristics were described according to the follow-up status (who underwent the second clinical examination: yes/no), the presence of missing data (yes/no) and the gender with the significance of differences between percentages for qualitative variables determined using Chi-square or Fisher's exact tests.

These descriptions are presented in Appendices 3A, 3B and 3C, respectively.

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 41

Analysis of risk factors

A complete case analysis was conducted by excluding individuals with missing values for at least one risk factor To investigate the risk of incident UEMSD and its association with potential risk factors, Cox multivariable regression models with constant follow-up time for each subject and robust variance [START_REF] Dwivedi | Methods for estimating relative risk in studies of common binary outcomes[END_REF] were used according to a 2-stage process (age-adjusted and multivariate analyses). Age-adjusted analyses were performed only in the first part of the thesis (article 1). Concerning parts 2 and 3 of the thesis (articles 2 and 3), the investigations were conducted based on the multivariate model obtained previously i.e. in the first article.

The Cox regression model with robust variance or modified Poisson regression approach is recommended when examining the association of exposure with a binary outcome in cohort studies where the high incidence of the outcome is higher than 10% [START_REF] Dwivedi | Methods for estimating relative risk in studies of common binary outcomes[END_REF], instead of the logistic regression which is frequently used.

Indeed, the logistic regression model may overestimate the effect of the exposure (risk factor) when the incidence of the outcome is high (more than 10%) [START_REF] Dwivedi | Methods for estimating relative risk in studies of common binary outcomes[END_REF][START_REF] Zhao | Proper estimation of relative risk using PROC GENMOD in population studies[END_REF]. The use of the Cox regression with robust variance approach will result in exactly the same estimates and standard errors as when using the modified

Poisson regression [START_REF] Barros | Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio[END_REF][START_REF] Dwivedi | Methods for estimating relative risk in studies of common binary outcomes[END_REF][START_REF] Zhao | Proper estimation of relative risk using PROC GENMOD in population studies[END_REF][START_REF] Zou | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors[END_REF]. However, the Cox model provides the covariance matrix needed to compute the PAF estimate with the SAS macro proposed by Spiegelman et al. (Spiegelman et al., 2007).

Analyses were systematically conducted for the entire cohort. In addition, sex-stratified analyses were performed to account for possible differences [START_REF] Silverstein | Gender adjustment or stratification in discerning upper extremity musculoskeletal disorder risk?[END_REF][START_REF] Treaster | Gender differences in prevalence of upper extremity musculoskeletal disorders[END_REF] in exposure to work between men and women.

Age-adjusted analyses

Age-adjusted analyses were performed to assess the relationship between each of the potential explanatory variables and the incident UEMSD. Age-adjusted Cox regression models with equal follow-up time and robust variance were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) of UEMSD risk associated with each potential risk factor. Only factors with a Wald test p-value of less than 0.20 (Bouyer et al., 2009a) in the age-adjusted models were included in the multivariate models.

Multivariate analyses

Multivariate Cox regression models with equal follow-up time and robust variance were used to estimate RRs and 95% CIs of UEMSD risk associated with the risk factors. Age being recognized as a major risk factor for UEMSD in the literature (da Costa and Vieira, 2010; Okunribido and Wynn, 2010), we decided to force it into all multivariate models even if it was not statistically significant in age-adjusted models.

Estimation of the PAF in the COSALI cohort

To quantify the attributable proportion of UEMSD incident cases, the PAF associated with a risk factor with the assumption of a causal relationship was estimated, all other factors remaining unchanged. Point estimates and 95% CIs were computed using a method for the estimation of PAFs in cohort studies, described by Spiegelman et al. (Spiegelman et al., 2007). The estimation of PAF took into account exposure (risk factor) prevalence and RR of UEMSD risk associated with that exposure in multivariate models. PAFs were estimated separately for each factor included in the model and expressed as the percentage of UEMSD cases that could be attributed to a NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 43 scenario in which all workers were in the lower risk group (usually the reference category); the artificial removal of exposure could potentially prevent associated cases.

Estimation of the number of UEMSD cases attributable to risk factors in the working population at the regional level

The computation of the estimated number of incident UEMSD cases attributable to risk factors in the working population of the PdL region was implemented in two steps.

In the first step of the procedure, the study sample was weighted to provide estimates of incident UEMSD cases, which were representative of the PdL working population, using data from the 2007 population census of the PdL region (conducted by the French National Institute of Statistics and Economic Studies (INSEE)). The calibration on margins method proposed by Deville et al. [START_REF] Deville | Generalized Raking Procedures in Survey Sampling[END_REF][START_REF] Deville | Calibration Estimators in Survey Sampling[END_REF] was used to take the characteristics of the PdL working population into account. Weights are assigned to all survey respondents in order to make the sample as representative as possible of the working population in the PdL region.

The new weights were calculated using the following auxiliary variables (also called calibration variables): sex, age (seven categories: 20-24, 25-29, 30-34, 35-39, 40-44, 45-49, and ≥50 years), occupational class (four categories: "professionals", "technicians, associate professionals", "low-grade white-collar workers" and "bluecollar workers") and economic sectors (three categories: "industry", "construction", and "trade and services").

These auxiliary variables were measured in both the COSALI cohort and the 2007 French population census for the PdL region, i.e. their population distribution was known. The "linear" calibration method was used to compute the new weights from the CALMAR (CALibration on MARgins) macro developed by Sautory [START_REF] Sautory | La macro Calmar. Redressement d'un échantillon par calage sur marges (Document de travail n°F9310 de la DSDS)[END_REF]. The program calculates new weights, based on the method described in point 5.2 of the statistical methods section.

At the second step, the estimated number of incident cases of UEMSD in the working population at the regional level (and the variation range) attributable to risk factor was obtained by multiplying the PAF (and the 95% CI)

by the projected number of incident UEMSD in the PdL region in 2007.

Results

Study sample characteristics and incident UEMSD diagnosed at follow-up Study sample characteristics

A comparison of baseline characteristics of workers with follow-up (who underwent the second clinical examination) and workers without follow-up demonstrated that workers lost to follow-up were significantly more likely to be younger, temporary workers or individuals with a short length of service at baseline (Appendix 3A).

Overall, no difference was observed in working conditions under study except for working posture with arms above shoulder level (followed: 11.8% vs 14.2 %: not followed; p=0.035), elbow movements (flexion/extension) (30.9% vs 34.5%; p=0.020) and low social support (36.8% vs 40.9%; p=0.011).

A description according to gender of characteristics and working conditions at baseline is provided in Appendix 3C

and showed that the prevalence of being overweight/obese was higher in men than in women (p < 0.001). Most NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 44 men worked as blue-collar workers in the industry sector, while most women were low-grade white-collar workers and worked in the trade and services sectors (p < 0.001). No difference was observed considering the history of diabetes mellitus, rheumatoid arthritis and seniority in the current job.

Incident UEMSD diagnosed at follow-up

At least one of the six UEMSD was diagnosed at follow up in 143 workers free from UEMSD at baseline (76 men vs 67 women; p=0.122) out of the 1275 followed (study 1: article 1). Regarding studies 2 and 3, there were 139 UEMSD cases (incidence proportion in the study sample: 11.2%) corresponding to a projected number of 129 320 new UEMSD cases in the PdL region in 2007 (table 3). The incidence proportion of UEMSD observed in the PdL region did not significantly differ between sexes (10.3% for men versus 12.4% for women; P=0.287).

The most common diagnoses at follow-up were RCS (incidence proportion 6.5%), LET (incidence proportion 2.2%)

and CTS (incidence proportion 2.0%). The estimate of the projected number of workers in the PdL with two or more UEMSD at follow-up was 19 404 (1.7%) workers. o This study showed that 7% of incidents UEMSD were attributable to working with arms above shoulder level in the overall working population. Furthermore, a noticeable proportion of UEMSD (15%) could be attributed to working with shoulder abduction in female workers.

o The results of this study suggest that an estimated 12% of incident cases of UEMSD could potentially be prevented by improving social support from coworkers and supervisors in the workplace.

Concerning personal risk factors:

o The present study suggests that female gender is associated with 12% of UEMSD cases occurring in the working population.

o Advanced age may contribute importantly to the incidence of UEMSD; about 13% and 20% of cases of UEMSD were attributable to the age groups 35-44 years and ≥ 45 years, respectively.

o A BMI ≥25.0 kg/m 2 (overweight/obesity) may explain 16.5% of incident cases of UEMSD in female workers.

To date, to the best of our knowledge, this is the first prospective study to estimate the PAF related to personal and occupational factors for the incidence of six main UEMSD in a working population. This study adds evidence to the literature that a high proportion of UEMSD can be avoided.

NAMBIEMA

Introduction

Throughout the world, upper-extremity musculoskeletal disorders (UEMSD) (e.g. carpal tunnel syndrome, shoulder tendinopathy) are an important health problem in the working population, with a major impact on workrelated disabilities, quality of life and years lost due to disability 1-3 . Besides their consequences on the health of workers, UEMSD also have a serious impact on workers' careers, absenteeism from work, and on the economic health of the companies they work for, particularly in terms of costs related to production loss, work performance and the sustainability of workers' activities 1,4 . In France, according to 2018 social health insurance data, the costs related to all work-related MSD (mainly UEMSD, which comprise 91% of all MSD) were estimated at €2 billion for companies 5 .

Previous studies have provided estimates of prevalence and/or incidence of UEMSD. A systematic review 6 of worldwide incidence and prevalence studies in the working population showed a 12-month prevalence of UEMSD ranging from 2.3 to 41.0%. A recent review 7 found that the annual incidence and the prevalence worldwide ranged from 0.08 to 6.3% and from 0.14 to 21.9% in the working population, respectively. Furthermore, a large amount of literature documented that UEMSD are associated with multiple risk factors including personal factors (e.g. age), biomechanical factors (e.g. repetitiveness of tasks), psychosocial factors (e.g. low social support) and organizational factors (e.g. machine-paced work) which commonly interact with each other in creating the overall risk 8-12 .

With regard to UEMSD prevention, occupational and public health practitioners and policy makers should prioritize interventions based on modifiable risk factors or on a combination of risk factors with the greatest effect in the working population and which prevent the greatest number of incident cases. In a previous study 13 , population attributable fractions (PAFs) and the number of incident UEMSD attributable separately to each identified risk factor were estimated for French workers in the Pays de la Loire (PdL) region. Based on the results of this previous study, this paper aims to (i) assess the combined effect of occupational biomechanical (e.g. high physical exertion)

and psychosocial (e.g. low social support) risk factors on the incidence of UEMSD among the French workers in the PdL region and (ii) estimate the proportion and number of incident cases attributable to these risk factors in two prevention scenarios in the PdL region.

Methods

Data from the COSALI cohort 13 , which was based on data from a prospective study of MSD and their risk factors in the working population from the French PdL region 14 , were re-analyzed. Briefly, a total of 3710 workers were included by the 83 occupational physicians (OP) (18% of OP in the region) volunteered to take part in the study The study received approval from France's Advisory Committee on the Processing of Information in Health Research ("CCTIRS") and the National Committee for Data Protection ("CNIL"), initially in 2001 and again in 2006.

Each worker provided written informed consent prior to inclusion.

Outcome definition

The outcome was defined as incident cases of six main clinically diagnosed UEMSD among workers free of any of the six main clinically diagnosed UEMSD at baseline and who met the criteria for at least one of the disorders at follow-up (based on the European consensus criteria to diagnose work-related UEMSD for health surveillance of epidemiologic studies) 13 . These UEMSD were carpal tunnel syndrome (CTS), ulnar tunnel syndrome, De Quervain's disease, flexor-extensor peritendinitis or tenosynovitis of the forearm-wrist region, rotator cuff syndrome (RCS), and lateral epicondylar tendinopathy (LET).

Covariates

Previously identified risk factors for UEMSD 13

Statistical analysis

To identify a hypothetical prevention scenario that would prevent more UEMSD from occurring by addressing the modifiable occupational risk factor(s) with the greatest impact on the working population, two multivariate models, each including one of the two combinations of factors mentioned above, were tested, as described below.

a) Model 1: HPPELSS + posture with arms above shoulder level + female sex + age.

b) Model 2: PAASLSS + high perceived physical exertion + female sex + age.

As in the previous study 13 , relative risks, PAFs and population estimated numbers of UEMSD cases attributable to risk factors were computed for each model. To facilitate the comprehension and interpretation of the PAF estimate, the lower limit of its 95% CI was set to zero when this lower limit was negative. All statistical analyses were performed using SAS software, version 9.4 TS Level 1M6.

Results

Of

Discussion

This cohort study analyzed two prevention models of work-related UEMSD and supports the need for prevention programs to adopt a multidimensional approach aims to reduce both biomechanical (particularly for high physical exertion) and psychosocial factors, as this would potentially prevent the occurrence of a larger number of UEMSD cases 16 .

The reduction of exposure to occupational high physical exertion in combination with the improvement of social The main strength of this study was the use of a prospective cohort which included a representative sample of the working population at baseline. Furthermore, information on exposures were collected based on literature definitions or public health recommendations 15,23 . In addition, outcomes were clinically assessed by trained OP using standardized procedures 15 . This study examined the potential impact on UEMSD cases prevented of two multidimensional preventive intervention strategies, one acting on occupational exposure to both high physical exertion and low social support, and the other acting on working posture with arms above the shoulders and low social support.

General discussion

This section presents a summary of the key findings and conclusions that can be drawn from the research.

In this PhD thesis, we investigated the impact of various biomechanical (e.g. physical exertion, repetitiveness of tasks) and psychosocial exposures (e.g. low social support) on the incidence of UEMSD at the level of the working population. Several epidemiological studies have shown an increased risk of UEMSD associated with multiple exposure factors in the workplace. However, few have quantified the impact of these exposures on the incidence of UEMSD in the working population. Furthermore, most of them were based on cross-sectional designs and assessed only one type of MSD as an outcome (e.g. CTS).

In this research work, we specifically estimated 1) the proportion of incident UEMSD that could be attributed t o risk factors (article 1); 2) the proportion and the number of UEMSD that could be potentially avoidable through prevention actions at the working population level (article 2); and 3) the relationship between incident UEMSD and co-exposure to risk factors and the impact of these risk factors at the working population level (article 3). All research for this thesis used data from the COSALI cohort, a prospective study of MSD and their risk factors in the working population conducted in the French PdL region. Moreover, sophisticated weighting adjustment methods for enhancing estimate accuracy were used to extrapolate the number of cases observed in the study sample to the whole working population.

Key findings

The first part of the current thesis (article 1) was the first prospective study in France to estimate the PAF of work-related exposures for the incidence of six main UEMSD in the working population. Based on a standardized clinical diagnosis of cases, the overall incidence proportion was of 11.2% and did not significantly differ between genders (10.1% for men vs 12.9% for women; p=0.122), although female workers were more affected than male workers. We found that the main occupational risk factor with a high impact on the incident of UEMSD was exposure to high perceived physical exertion (PAF: 30%), followed by exposure to low social support from supervisor and co-workers (PAF: 12%), and working with arms above shoulder level (PAF: 7%). The findings concerning biomechanical factors were consistent with previous studies carried out in Italy (OCTOPUS study) [START_REF] Violante | Carpal tunnel syndrome and manual work: the OCTOPUS cohort, results of a ten-year longitudinal study[END_REF] and the Netherlands (van der [START_REF] Van Der Molen | How to improve the assessment of the impact of occupational diseases at a national level? The Netherlands as an example[END_REF] which reported that 28% of CTS cases and 25% of LE cases respectively, could be attributable to high physical exertion. Furthermore, the study in the Netherlands reported that 15% of LE were attributable to posture, 10% and 9% of shoulder soft tissue disorders were attributable to force and posture, respectively (van der [START_REF] Van Der Molen | How to improve the assessment of the impact of occupational diseases at a national level? The Netherlands as an example[END_REF]. Several systematic reviews and meta-analyses also support our results [START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF]Descatha et al., 2016;Kozak et al., 2015;[START_REF] Kraatz | The incremental effect of psychosocial workplace factors on the development of neck and shoulder disorders: a systematic review of longitudinal studies[END_REF]National Research Council and Institute of Medicine, 2001). Moreover, recent meta-analyses revealed with moderate evidence that arm-hand elevation (OR=1.9 [1.47-2.47]) and shoulder load (OR=2.0 [1.90-2.10]) were associated with the risk of shoulder disorders (van der Molen et al., 2017), and that working with the shoulder above 90 degrees was associated with an increased risk of rotator cuff tendinopathy [START_REF] Leong | Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis[END_REF]. Regarding psychosocial risk factors, the meta-analysis by Hauke et al. (Hauke et al., 2011) found an effect of low social support at work on the onset of UEMSD (OR=1.18 [1.06-1.32]). The results of NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 86

another meta-analysis showed that specific psychosocial risk factors such as low social support were relevant risk factors for the development of shoulder symptoms [START_REF] Lang | Psychosocial work stressors as antecedents of musculoskeletal problems: A systematic review and meta-analysis of stability-adjusted longitudinal studies[END_REF].

Besides these work-related risk factors, we also found that with respect to personal risk factors, female gender (PAF: 12%), age [age group 35-44 (PAF: 13%) and age group ≥45 (PAF: 20%)], and a high BMI (only for women) (PAF: 17%) had a significant impact on the incidence of UEMSD in the French working population in the PdL region. The OCTOPUS study [START_REF] Violante | Carpal tunnel syndrome and manual work: the OCTOPUS cohort, results of a ten-year longitudinal study[END_REF] found that a BMI ≥25km/m 2 , female gender and age >35 years contributed to 30%, 34%, and 54% of CTS, respectively. A recent meta-analysis provided strong evidence that age above 50 years (pooled OR=3.3) was associated with an increased risk of rotator cuff tendinopathy [START_REF] Leong | Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis[END_REF]. Another recent meta-analysis revealed that female gender and older age were associated with LE [START_REF] Sayampanathan | Risk factors of lateral epicondylitis: A meta-analysis[END_REF].

Using the same data as for the first study, the main objective of the second part of the thesis was to estimate the proportion and number of UEMSD cases attributable to occupational risk factors (potentially preventable) in the working population at the level of the PdL region. Like the first study, this second part was the first cohort study to estimate the number of potential cases of UEMSD attributable to occupational risk factors in an entire working population. The results from this study highlight the magnitude of the impact of potentially modifiable and preventable occupational exposures on the incidence of UEMSD in the workplace. Specifically, of the projected estimate of 129 320 incident UEMSD cases in PdL in 2007, it is estimated that 26 381 (representing 20.4% of all new projected UEMSD cases), 16 682 (12.9%), and 8535 (6.6%) incident cases were due to high physical exertion, low social support from coworkers and supervisors, and working posture with shoulder abduction, respectively. Therefore, these estimated numbers of attributable cases could potentially be prevented by reducing occupational exposures to physical risk factors, working posture with shoulder abduction, and by improving social support from coworkers and supervisors if fully efficient interventions were implemented.

Concerning the potentially personal modifiable risk factors, our results suggest that an important number of projected incident UEMSD (10 586 cases) could be attributed to high BMI (15.3% of all projected new cases) in female workers.

The third study, based on the same data as the previous ones, (a) investigated the association between incident UEMSD and occupational co-exposure factors, and (b) estimated the proportion and number of UEMSD cases that were attributable to these risk factors under two models of prevention and therefore potentially avoidable by modifying workplace risk factors. Two (potential) multidimensional UEMSD prevention scenarios were analyzed using two statistical models, each including a combination of a biomechanical and psychosocial factor ("high physical exertion + low social support" in model 1, and "working posture with arms above shoulder level + low social support" in model 2).

Results of model 1 showed that 8664 new cases could potentially be prevented by improving social support only, representing 6.7% of all the projected estimate of 129 320 incident UEMSD cases in the PdL region in 2007, of 38 100 jobs. However, due to the economic growth in the region the number of jobs is increasing by an average of 5500 a year over the same period. In addition, a positive trend in the number of jobs has been observed since 2010 according to the PdL ORES (ORES Pays de la Loire, 2016) with a 2.6% increase in the working population over five years (between 2012-and 2017) and a 5.5% increase in the number of jobs (78 000 jobs) over the same period (ORES Pays de la Loire, 2020).

The physicians who volunteered to participate in the study were representative of the region's OPs in terms of medical practice, work time and geographic and economic sectors covered. More than 90% of the selected workers at inclusion participated in this study (<10%: no shows, refusals, duplications). Women were slightly underrepresented in the sample (42% vs. 47% in the region, P<0.001) [START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]. Overall, the distribution of occupations in the final sample was close to that of the regional workforce and of France, except for the occupations not surveyed by OPs (e.g. farmers, shopkeepers, and self-employed workers) [START_REF] Ha | The French Musculoskeletal Disorders Surveillance Program: Pays de la Loire network[END_REF][START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]. During the follow-up period (between 2007 and 2010), a total of 1611 clinical examinations were carried out, for an overall response rate of 43% and 65%, considering all workers initially included and only those whose OP was known at the time of follow up, respectively [START_REF] Sérazin | Difficulties of a longitudinal epidemiological follow-up study in French occupational medicine[END_REF]. This period coincided with a major economic crisis in the PdL region in 2008-2009, during which the regional salaried workforce declined by 3.4% (33.7% in temporary employment agencies) [START_REF] Hautbois | Crise en Pays de la Loire : industrie et interim dans la tourmente (Etude No. 88[END_REF]. Workers usually surveilled by a non-participant OP, people on parental or long-term sick leave, retired people, and those who had lost their jobs were excluded from the follow-up.

The population considered in the COSALI cohort was a population selected only from the working population.

Indeed, OPs performed the clinical examination only for employees. This could be a source of "healthy worker effect" leading to a probable under-representation of subjects suffering from MSD [START_REF] Pearce | Bias in occupational epidemiology studies[END_REF] and therefore a dilution of the effects of the expected associations, or even a loss of these associations. However, this effect may have been limited according to a study published by [START_REF] Roquelaure | Working in temporary employment and exposure to musculoskeletal constraints[END_REF] workers lost to follow-up suffered from UEMSD of the wrist/hand region more often than permanent workers but not in other anatomical regions of the upper extremities.

Concerning the clinical examination at follow-up, approximately 57% of workers included at baseline did not have a follow-up. However, within these non-followed participants, 58% were no longer being monitored by any OP of the network because they had left their baseline job without informing their OP. In some cases, their OP refused to participate in the follow-up period. Furthermore, the follow-up period coincided with the major economic crisis in the PdL region in 2008-2009, during which the regional salaried workforce declined by 3.4% (33.7% in temporary employment agencies) [START_REF] Hautbois | Crise en Pays de la Loire : industrie et interim dans la tourmente (Etude No. 88[END_REF]. The lowest participation rate in this study was among young workers, temporary workers or workers with a short length of service at baseline. According to a study on the effects of drop out in a longitudinal study of MSD [START_REF] Bildt | Effects of Drop out in a Longitudinal Study of Musculoskeletal Disorders[END_REF], the differences between participants and drop out individuals had a very modest influence on the RR for the effects of occupational exposures. We therefore believe that there was no major selection bias associated with the quality of follow-up. Furthermore, the comparison of baseline characteristics and working conditions of workers with follow-up and those without followup (see appendix 3A) showed that follow-up participants did not differ in terms of BMI and rheumatoid arthritis NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 89 but were significantly older than those who did not participate in the follow-up. They were more likely to work in trade and services sectors, to be in temporary employment or have a higher seniority level in their current j ob.

They were less likely to be exposed to working with arms above shoulder level, elbow movements (flexion/extension), and low social support at work, but no difference was observed in other working conditions under study. Moreover, in order to minimize the number of subjects lost to follow-up after major changes in the cohort (OP in charge of workers from other companies, change of work and of OP for a few workers), the investigators made a concerted effort to find each participant's new OP. This contributed to a high mobilization of the regional OPs (only 9 refused to participate among 157 new OPs contacted because they were now responsible for the medical surveillance of at least one individual); so the proportion of workers followed by an OP known by the investigators was relatively correct.

Another potential limitation was the lack of medical information between baseline and follow-up, so cases that may have occurred between the two clinical examinations and were negative at follow-up could not be considered as "incident cases" in our analyses. The single and short window of follow-up in this study after a long follow-up period is another potential limitation. Workers may have had a UEMSD in the period between the first and second clinical examination but recovered and not had a UEMSD at follow-up. This may have resulted in an underestimation of the number of cases diagnosed. In this study, there were many participants, but few events.

This led to a lack of statistical power and thus to potential and/or known associations (e.g. association of UEMSD risk and high repetitiveness of tasks) that could not be detected (Bouyer et al., 2009b).

Another limitation is the exposure assessment, which was based only on workers self-reporting. In spite of that, the use of standardized and validated questions may have ensured better quality of the self-reported exposure measures. Non-differential misclassification of exposures may have occurred due to workers' inability to precisely recall or describe their current work exposures among workers without symptoms. Nevertheless, due to the prospective design of the study, exposure information gathered prior to UEMSD diagnosis resulted in low risk of differential recall bias. To the extent that the risk of UEMSD is increased by cumulative physical exposures, our analyses may have underestimated the true contribution of work exposures to the incidence of UEMSD in our study population.

Lack of measurement precision may also have occurred when quantifying exposures due to the 1 to 4 point ordinal scale used in exposure questions, except for physical exertion which was assessed using the RPE Borg Scale [START_REF] Borg | Psychophysical bases of perceived exertion[END_REF]. To the extent that the risk of UEMSD is increased by cumulative or chronic physical exposures, our analyses may have underestimated the true contribution of work exposures to the incidence of UEMSD in our study population. This may be especially true for RCS, as studies of occupational risk factors for shoulder pain have consistently identified duration of employment as a risk factor (van der [START_REF] Van Der Windt | Occupational risk factors for shoulder pain: a systematic review[END_REF].

A complete case analysis was conducted in this thesis, which could potentially induce a bias in our estimates.

However, a previous doctoral thesis [START_REF] Herquelot | Facteurs de risque professionnels des troubles musculo-squelettiques aux coudes et aux genoux[END_REF] using the same data as in the present thesis showed that analyses on the complete data gave similar results to analyses on the imputed data. We therefore believe that there was a very modest influence on our estimates. The computation of the combined PAF assumes independence NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 90

and the absence of interaction between individual risk factors. However, there may be an interaction between certain occupational risk factors. In such cases, the calculation of the combined PAF may lead to its over-or underestimation. Nevertheless, none of the interactions between occupational exposures explored was statistically significant (Nambiema et al., 2020). In this situation, the joint impact of multiple exposures on the incidence of UEMSD estimated in this study would potentially not be multiplicative. According to Walter's demonstration [START_REF] Walter | Effects of interaction, confounding and observational error on attributable risk estimation[END_REF], this situation would not be additive either. Therefore, the joint impact of multiple exposures estimated would be more than additive. In addition, the lack of statistical power in this study may have led to the non-detection of potential interactions between occupational risk factors (Bouyer et al., 2009b).

It should also be noted that the choice of thresholds used to define exposure levels can have an effect on PAF estimates (B. Rockhill et al., 1998). However, to avoid bias, we chose exposure definitions as close as possible to public health recommendations and those recommended in the scientific literature. The concept of PAF assumes a causal relationship between exposure and UEMSD (Sluiter et al., 2001). Thus, we assume that a reduction in occupational exposure at the working population level would lead to a reduction in the incidence of UEMSD and PAF estimates should therefore be interpreted with caution. The accuracy of the PAF and the number of UEMSD cases attributable to investigated risk factors depends on the precision of the exposure data collected, the relative risk estimates, and the UEMSD incidence data studied. Furthermore, the PAF estimates did not take into account potential protective effects of uninvestigated factors such as regular breaks, physical activity in relation to the risk of UEMSD in the exposed population.

The proportion as well as the number of UEMSD cases attributable to the various occupational risk factors presented in this doctoral thesis, i.e. that would not have occurred if exposure to these modifiable risk factors would have been at an optimal or low level, depends on the variables included in the analyses, their definitions and the reference groups that were chosen. It would therefore be important, for a more objective interpretation of our results, to remember that a number of risk factors for UEMSD [START_REF] Roquelaure | Musculoskeletal Disorders and Psychosocial Factors at Work[END_REF] could not be included in the analyses due to the very low number of UEMSD cases or prevalence of exposure that could lead to a statistical non-association with UEMSD. This was particularly the case for occupational factors (e.g. vibration exposure, working in very cold temperatures) for which the prevalence of exposure or number of UEMSD cases was very low. The estimated number of potentially preventable UEMSD cases therefore does not take into account all the modifiable risk factors to which the working population in the French region of PdL is actually exposed. The estimates did also not take into account certain personal risk factors such as diabetes or rheumatoid arthritis.

All these limitations may in some cases lead to an over-or underestimation of the PAF. Therefore, the findings of this thesis work should be interpreted in light of the available data and the limitations of the methods used to estimate PAFs and the number of potentially preventable UEMSD cases. Finally, it is possible that the 95% CI of the PAF includes the null value, despite the significance of the RR due to the use of nonlinear transformations to compute the 95% CI of the PAF [START_REF] Hertzmark | The SAS PAR Macro[END_REF]. Even so, zero should be close to the 95% CI.

Furthermore, it's important to note that the PAF associated with single risk factors cannot be added to obtain a combined PAF associated with a combination of risk factors and that a combined PAF cannot be subtracted from 100% to determine the "unexplained" proportion of cases (B Rockhill et al., 1998). It is also important to note NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 91 that there is currently a lack of research intervention studies in the literature that have clearly demonstrated a reduction in exposure to biomechanical [START_REF] Hoe | prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors[END_REF][START_REF] Kennedy | The Effect of Psychosocial Factors on Outcomes in Patients With Rotator Cuff Tears: A Systematic Review[END_REF][START_REF] Ferreira Faisting | Effectiveness of ergonomic training to reduce physical demands and musculoskeletal symptoms -An overview of systematic reviews[END_REF][START_REF] Van Eerd | Effectiveness of workplace interventions in the prevention of upper extremity musculoskeletal disorders and symptoms: an update of the evidence[END_REF][START_REF] Van Niekerk | The effectiveness of a chair intervention in the workplace to reduce musculoskeletal symptoms. A systematic review[END_REF], psychosocial [START_REF] Stock | Are work organization interventions effective in preventing or reducing work-related musculoskeletal disorders? A systematic review of the literature[END_REF][START_REF] Van Eerd | Effectiveness of workplace interventions in the prevention of upper extremity musculoskeletal disorders and symptoms: an update of the evidence[END_REF], or organizational [START_REF] Hoe | prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors[END_REF][START_REF] Luger | Work-break schedules for preventing musculoskeletal symptoms and disorders in healthy workers[END_REF][START_REF] Stock | Are work organization interventions effective in preventing or reducing work-related musculoskeletal disorders? A systematic review of the literature[END_REF] risk factors with a strong level of evidence. This could be partly explained by the existence of gaps in the adequate conversion of scientific knowledge into intervention programs that can minimize exposure to ergonomic risk factors associated with a work situation, or to limitations that may exist in the scientific understanding of the effectiveness of some interventions.

This work has also several strengths. To the best of our knowledge today, no prospective study has estimated the proportion and number of incident cases of the six major UEMSD attributable occupational and personal risk factors at the population level.

The use of a prospective cohort including a representative sample of the working population at baseline is a major strength of the present study [START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]. Furthermore, over 90% of workers randomly selected by the OPs accepted to participate. Secondly, outcomes were clinically assessed by trained OPs using standardized procedures [START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]Sluiter et al., 2001). In addition, this study strictly applied the definitions of exposures proposed by the European consensus criteria document (Sluiter et al., 2001), except for the measurement of exposure to forceful exertion which was assessed according to the rating of perceived exertion [START_REF] Borg | Psychophysical bases of perceived exertion[END_REF] and the INRS cut-offs (INRS, 2019). Due to the prospective design of the study, exposure information gathered prior to UEMSD diagnosis resulted in low risk of recall bias.

Another strength is the formula used to estimate the PAF from multivariable regression models, allowing a nonbiased computation of PAF estimates adjusted for covariates (B Rockhill et al., 1998). This regression-based PAF estimation method enables to control for confounding and interaction, and can be used for the main epidemiologic designs [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF]. Lastly, sophisticated weighting adjustment methods [START_REF] Deville | Generalized Raking Procedures in Survey Sampling[END_REF][START_REF] Deville | Calibration Estimators in Survey Sampling[END_REF][START_REF] Sautory | La macro Calmar. Redressement d'un échantillon par calage sur marges (Document de travail n°F9310 de la DSDS)[END_REF] for enhancing estimate accuracy were used to extrapolate the number of cases observed in the study sample to the whole working population. Furthermore, the "linear" calibration method used to calculate the new weights was the one that gave the lowest variance and range of weight ratios (new weights / initial weights). Indeed, it was chosen by considering the following criteria: lowest dispersion, smallest extent and general appearance of the distribution of the new weight distribution; the other calibration methods give calibrated estimators with the same asymptotic accuracy [START_REF] Deville | Calibration Estimators in Survey Sampling[END_REF].

Finally, estimating the number of incident cases of UEMSD in the working population of the PdL region is useful for comparing the population-level impacts of various risk factors on the incidence of UEMSD. Furthermore, these estimates provide additional input for the implementation of prevention programs that target and prioritize the modifiable risk factors with the greatest impact for more effective interventions to reduce the medical, economic and social impact of UEMSD in the working population.

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 92

Conclusions and recommendations

This section outlines the contributions of the current thesis to the fields of occupational and public health in general and UEMSD prevention in particular, provides recommendations for future research and conclusions that can be drawn from the research.

Contributions of the current thesis

This dissertation focused on analyzing data from a prospective cohort of the working population with the aim of providing new and relevant information for occupational hazard prevention and UEMSD burden reduction by improving knowledge of the topic and identifying the modifiable risk factors that have the greatest impact on these MSD. Sophisticated multivariate methods were used to estimate the fraction and number of incident UEMSD cases attributable to various occupational and personal risk factors, and hence the number of cases that would not have occurred if the exposure to a risk factor was reduced or eliminated in the workplace.

Findings from the present doctoral thesis, based on a prospective cohort study of MSD in the French working population of the PdL region, contribute to the literature on the burden of UEMSD risk factors and are of occupational and public health significance in assisting practitioners and policy makers to implement UEMSD prevention programs in the working population. These findings should help to better target and prioritize the modifiable risk factors that have the greatest impact on the onset of UEMSD for more effective interventions to reduce the medical, economic and social impact of these disorders.

More specifically, this thesis points to the importance of modifiable occupational exposures such as high physical exertion, awkward arm posture and low social support in the incidence of UEMSD in the workplace. Indeed, two incident cases of UEMSD out of five projected in 2007 in the working population of the PdL region, i.e.

approximately 50 000 incident UEMSD, were attributable to these occupational exposures. Therefore, preventing UEMSD by reducing exposure to high physical exertion, awkward arm posture, and by improving the quality of working relationships where workers receive little support from supervisors or their coworkers, can be an effective intervention strategy for UEMSD prevention in the working population. Furthermore, the findings of this thesis work regarding the combined effect of biomechanical and psychosocial risk factors i.e. combined exposure to "high physical exertion + low social support" or "working with arms above shoulder level + low social support" increased the risk of developing UEMSD, provide valuable information on different prevention intervention strategies within a working population exposed jointly to biomechanical and psychosocial factors. Indeed, the effect of low social support as an additional exposure to high physical exertion increased the risk of UEMSD and led to many cases. Likewise, exposure to working with arms above shoulder level combined with low social support from co-workers and supervisors increased the risk of UEMSD. These findings show that for prevention interventions aimed at reducing the incidence of UEMSD in companies where workers are exposed to high physical exertion (or working with arms above shoulder level) combined with low social support, other exposures remaining constant, public health practitioners should give priority to the reduction of exposure to physical exertion (or working with arms above shoulder level) over improving low social support when they need to act NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 93 on only one of these two factors. This is the model that would reduce the greatest number of incident cases.

However, by acting jointly on both factors, an even higher number of cases could be prevented.

Besides occupational risk factors, the work presented here indicates that there are also potentially modifiable personal risk factors, especially overweight and obesity. These findings regarding personal factors are also clinically relevant, as obesity is a known strong risk factor for UEMSD, particularly CTS, and efforts should be made to promote healthy weights in the working population. Finally, since the diverse socio-economic structure of the PdL region is similar to that of France as a whole [START_REF] Ha | The French Musculoskeletal Disorders Surveillance Program: Pays de la Loire network[END_REF], the results of this work may also lead to similar UEMSD prevention strategies for the rest of the country.

Using a prospective cohort data and sophisticated statistical methods, this research work provides valuable new information to the limited epidemiological knowledge available on the proportion and number of incident UEMSD cases that could potentially be avoided by preventive actions that target and prioritize exposure to modifiable risk factors and, thus reduce the medical, economic and social impact of UEMSD. This work also highlights both public health and clinical significance for the prevention of UEMSD in the working population. Therefore, this work also contributes to the literature on the burden of UEMSD risk factors. More specifically, it increases knowledge on two relatively under-studied topics regarding UEMSD, namely the PAF and the number of potentially preventable cases. The main contributions are as follows:

• an increase in the body of epidemiological knowledge available on the proportion of UEMSD cases attributable to different risk factors;

• a quantification of the proportions and numbers of incident UEMSD cases that could potentially be prevented by modifying risk factors in the workplace;

• appropriate recommendations based on the findings and limitations of this work with suggestions for future research.

The findings could be useful to public health practitioners and policy makers in designing prevention programs to improve the reduction of exposures to occupational risk factors with a significant impact on the incidence of UEMSD among the working population of the PdL region and possibly throughout France. These stakeholders must continue to prioritize efforts in the primary prevention of UEMSD in order to reduce the incidence of UEMSD among the working population. However, primary prevention policies for UEMSD should not only concentrate on reducing occupational exposures that have a major impact on the occurrence of these MSD, but also on collective health promotion efforts.

In conclusion, this thesis made it possible to estimate the potential impact of UEMSD prevention interventions on the number of potentially preventable cases in a working population, and thus to quantify the expected benefits of the prevention measures that could be implemented. It provides evidence that to be effective, UEMSD prevention cannot be limited to reducing exposure to biomechanical risk factors but requires a comprehensive approach that also takes into account psychosocial risks. For example, for preventive actions targeting the upper extremities, it should be necessary to combine the prevention of static workload (e.g. shoulders) and repetitive work (e.g. elbow), while for the lower extremities actions could focus mainly on preventing the effects of static workload due to prolonged standing. More specifically, this thesis showed that an intervention that would combine NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 94 both a reduction of exposure to high physical exertion (or working with arms above shoulder level) and improving social support at work would reduce the incidence of UEMSD, thereby preventing a large number of cases.

However, some known occupational exposures or personal risk factors could not be included in our analyses either because the data were not available or because the prevalence of these exposures or the incidence of UEMSD was low for these exposures. In the latter case, the results of the risk models concluded that there was no association with these MSD. Therefore, further studies are needed to corroborate our findings.

Recommendations for future research

The main objective of this dissertation was to estimate and compare the potential effects of reducing work-related exposures to the main biomechanical and psychosocial risk factors on the incidence of UEMSD.

Several epidemiological studies conducted in working populations have shown that UEMSD are multifactorial and can be caused by organizational, psychosocial, biomechanical and personal factors, with these factors interacting with each other most of the time. Due to these multiple risk factors, it is becoming increasingly clear that prevention efforts to reduce the incidence of UEMSD must be based on a combined approach to be effective. but they need to be complemented by more widespread efforts to improve working conditions and management practices at the level of regions, industries or economic sectors. This broad approach to UEMSD prevention is essential to guarantee long-term socio-economic success. Furthermore, clinical trials are needed to determine the effectiveness of interventions that may be implemented based on the results of this thesis.

Certain risk factors (e.g. vibration exposure, working in very cold temperatures) were not included in our analyses due to their low prevalence. Estimating fractions and numbers of preventable UEMSD in future studies with larger samples would be necessary to support our conclusions and provide additional evidence for more effective prevention strategies. Furthermore, it would also be interesting and very useful to conduct similar analyses, i.e.

to estimate the proportion and number of cases related to exposure to occupational risk factors in high-risk occupations and economic sectors. This will provide additional information to better guide UEMSD prevention interventions in the workplace. Therefore, future research on the issue of UEMSD through longitudinal studies with larger samples is needed in order to obtain a solid scientific basis to confirm our results and to conduct similar analyses in different occupations and economic sectors as well as to investigate the "dose-response" relationships and interactions between the different factors. For example, data from the French "CONSTANCES" cohort [START_REF] Zins | The French CONSTANCES population-based cohort: design, inclusion and follow-up[END_REF][START_REF] Zins | The CONSTANCES cohort: an open epidemiological laboratory[END_REF], a large population-based longitudinal study, could be analyzed together with health data from the French National Health Data System (SNDS) matched for each participant. The CONSTANCES cohort used the same inclusion questions as the COSALI cohort for data collection on musculoskeletal symptoms NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 95 and biomechanical factors. Research should also be warranted on methods to better identify workers with a high risk of occupational marginalization and to intervene at an earlier stage.

Conclusion

Findings from this dissertation are informative, relevant and useful, particularly for prioritizing and targeting future prevention efforts. This information could assist public health practitioners and policy makers in implementing UEMSD prevention programs, as well as help researchers planning to conduct prevention intervention research on these MSD in the working population. Nevertheless, they must be interpreted by taking into consideration the available data used, in particular the variables included in the analyses and the limitations of the statistical methods used. Finally, it should be noted that, despite the consideration of adjustment factors, the analyses may in some cases have led to an under-or over-estimation of the number of attributable cases.

Despite the limitations, estimates from this work highlight that a large number of UEMSD could be avoided if the working population were optimally exposed to the modifiable risk factors studied that have a high impact on the incidence of UEMSD, such as physical exertion, awkward shoulder postures, and social support from coworkers and supervisors. Moreover, this thesis has shown that, to be effective, the prevention of UEMSD in the workplace should not be limited to reducing exposure to biomechanical risk factors but requires a comprehensive approach that also takes into account other occupational factors, in particular psychosocial factors. [START_REF] Aublet-Cuvelier | Troubles musculosquelettiques des membres supérieurs d'origine professionnelle[END_REF][START_REF] Da Costa | Risk factors for work-related musculoskeletal disorders: a systematic review of recent longitudinal studies[END_REF]Kozak et al., 2015;Roquelaure, 2015;Sluiter et al., 2001). L'Organisation internationale du travail (ILO, 2015) a estimé qu'environ 160 millions de cas de maladies non mortelles liées au travail se produisent chaque année dans le monde, parmi lesquels un nombre élevé de TMS. Selon des données récentes de l'Organisation mondiale de la santé sur la charge mondiale de morbidité, les TMS se classent parmi les cinq premières maladies au monde (4 ème ) en termes de charge de morbidité [START_REF] Roser | Burden of disease[END_REF].

TAKE HOME MESSAGE

Dans la présente thèse de doctorat, l'accent est mis sur les TMS les plus fréquemment retrouvés sur le lieu du travail, c'est-à-dire les TMS affectant le membre supérieur (TMS-MS) (Sluiter et al., 2001). Ces troubles concernent les zones du corps suivantes : épaule/bras, coude/avant-bras et main/poignet.

Plusieurs études épidémiologiques menées à travers le monde ont fourni des estimations de prévalence et d'incidence des TMS-MS (da Costa et al., 2015;[START_REF] Dale | Incident CTS in a large pooled cohort study: associations obtained by a Job Exposure Matrix versus associations obtained from observed exposures[END_REF]Descatha et al., 2016;Huisstede et al., 2006;[START_REF] Leclerc | Incidence of Shoulder Pain in Repetitive Work[END_REF]Roquelaure et al., 2009b;[START_REF] Spahn | Metaanalysis for the evaluation of risk factors for carpal tunnel syndrome (CTS) Part II. Occupational risk factors[END_REF][START_REF] Thygesen | Subacromial shoulder disorders among baggage handlers: an observational cohort study[END_REF][START_REF] Van Der Molen | Incidence rates of occupational diseases in the Dutch construction sector, 2010-2014[END_REF]. Ces estimations varient selon les pays, la conception de l'étude (transversale, de cohorte, revue systématique et méta-analyse) et la population concernée (générale/active). La revue systématique de Luime et al. [START_REF] Luime | Prevalence and incidence of shoulder pain in the general population; a systematic review[END_REF] [START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]. Selon les estimations de la cohorte française CONSTANCES [START_REF] Carton | Prévalence des troubles musculo-squelettiques et des facteurs biomécaniques d'origine professionnelle : premières estimations à partir de Constances[END_REF] (Bevan, 2015;Roquelaure, 2015;[START_REF] Summers | Musculoskeletal Disorders, Workforce Health and Productivity in the United States[END_REF]. Ces TMS représentent également l'un des problèmes professionnels les plus graves en raison de leur impact sur le fonctionnement et l'économique des entreprises (absentéisme, remplacement de salariés, coûts liés à la perte de production) (Bevan, 2015;[START_REF] De Kok | Workrelated musculoskeletal disorders: prevalence, costs and demographics in the EU[END_REF][START_REF] Lang | intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors[END_REF]Roquelaure, 2015;[START_REF] Storheim | Musculoskeletal disorders and the Global Burden of Disease study[END_REF][START_REF] Summers | Musculoskeletal Disorders, Workforce Health and Productivity in the United States[END_REF][START_REF] Weinstein | The Burden of Musculoskeletal Conditions[END_REF]. Les TMS-MS touchent les travailleurs de tous les secteurs et de toutes les professions et constituent la principale cause de morbidité, d'incapacités liées au travail et d'absentéisme au travail dans de nombreux pays développés tels que les États-Unis, le Canada et les pays de l'Union européenne (UE) [START_REF] Côté | Quebec Research on Work-related Musculoskeletal Disorders: Deeper Understanding for Better Prevention[END_REF][START_REF] De Kok | Workrelated musculoskeletal disorders: prevalence, costs and demographics in the EU[END_REF]GBD 2017 Disease andInjury Incidence andPrevalence Collaborators, 2018;[START_REF] Roquelaure | Musculoskeletal Disorders and Psychosocial Factors at Work[END_REF][START_REF] Storheim | Musculoskeletal disorders and the Global Burden of Disease study[END_REF][START_REF] Summers | Musculoskeletal Disorders, Workforce Health and Productivity in the United States[END_REF]. Entre 1997Entre et 2005, 127 , 127 (absentéisme, baisse de production). L'écrasante majorité des cas de ces TMS concerne par ailleurs le membre supérieur [START_REF] Aptel | Work-related musculoskeletal disorders of the upper limb[END_REF][START_REF] Aublet-Cuvelier | Troubles musculosquelettiques des membres supérieurs d'origine professionnelle[END_REF][START_REF] Michel | Portrait national des troubles musculosquelettiques (TMS) 1998-2007: TMS sous surveillance[END_REF].

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 98

Objectifs

L'impact modéré des plans de prévention mis en oeuvre au cours des dernières décennies nécessite des études supplémentaires sur les stratégies de prévention au niveau de la population active. Afin de mieux concevoir les programmes de prévention, il est essentiel de connaître les facteurs de risque (FdR) modifiables qui ont le plus grand impact sur la population active salariée pour améliorer l'efficacité des interventions.

L'objectif principal de ce travail de thèse de doctorat était d'estimer et de comparer les effets potentiels de la réduction des expositions professionnelles aux principaux FdR biomécaniques et psychosociaux sur l'incidence des TMS-MS en utilisant les données de la cohorte française COSALI (COhorte des SAlariés LIgériens). Trois études correspondant à trois articles de recherche, ont été menées.

Matériel et méthodes

Population d'étude

La cohorte COSALI est une étude prospective des TMS et de leurs FdR dans la population active basée sur deux enquêtes successives auprès des salariés de la région française des PdL (centre-ouest de la France, 3 305 000 habitants et 1 247 839 salariés en 2002) (Bodin et al., 2012a;[START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]. Cette région représentait 5,5 % de la population française et 5,6 % de la population active française en 2002, et sa structure socio-économique diversifiée était similaire à celle de la France dans son ensemble [START_REF] Ha | The French Musculoskeletal Disorders Surveillance Program: Pays de la Loire network[END_REF]. (Bodin et al., 2012a;[START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF]

Analyse statistique

Pour les analyses dans le cadre de cette thèse, seuls les salariés ayant participé à l'examen clinique standardisé de suivi ont été pris en compte (1611 salariés sur les 3 710 présents à l'inclusion).

Les risques relatifs (RR) et leurs intervalles de confiance (CI) à 95 % ont été estimés à partir des modèles de régression multivariée de Cox avec une variance robuste et un temps de suivi constant pour chaque sujet [START_REF] Dwivedi | Methods for estimating relative risk in studies of common binary outcomes[END_REF]. Pour quantifier la proportion de cas de TMS-MS attribuables à chaque FdR, une FRAP a été estimée pour chaque FdR ou combinaison de FdR dans le modèle multivarié. Les estimations des FRAP et leur IC à 95 % de la FRAP ont été calculées en utilisant la méthode décrite par Spiegelman et al. (Spiegelman et al., 2007a).

L'estimation de la FRAP prend en compte la prévalence de l'exposition et le RR du TMS-MS associé à cette exposition (Spiegelman et al., 2007a).

Pour estimer le nombre de cas de TMS-MS incidents attribuables aux FdR professionnels dans la région des PdL, le nombre total de TMS-MS (NT) dans la population active salariée dans la région a d'abord été estimé après redressement de l'échantillon (calcul de pondération) en utilisant les données du recensement de 2007 de la région des PdL. Ensuite, le nombre de TMS-MS attribuables aux FdR a été obtenu en multipliant la FRAP par le NT.

Toutes les analyses statistiques ont été réalisées à l'aide du logiciel SAS version 9.4. [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF]Spiegelman et al., 2007), sont plus faibles chez les salariés exposés aux facteurs combinés comparées aux salariés exposés à un seul de ces FdR.

Résultats principaux

Conclusions et perspectives

SI OUI, VEUILLEZ ENTOURER LA (ES) CASE(S) GRISEE(S) CORRESPONDANT

IV. ARBRES DIAGNOSTIQUES

Pour chaque TMS, il est nécessaire de préciser si l'arbre diagnostique s'y rapportant est à compléter ou non.

• En l'absence de symptômes au cours des 12 DERNIERS MOIS

Figure

  Figure 1. A conceptual model integrating the multidimensional nature of MSD (adapted from Roquelaure

Figure 2 .Figure 3 .Figure 4 . 41 Figure 5 .

 234415 Figure 1. A conceptual model integrating the multidimensional nature of MSD (adapted from Roquelaure (Roquelaure, 2016)). ............................................................................................................................. 14 Figure 2. Schematic organization of the COSALI cohort .............................................................................. 28 Figure 3. Graphical representation of the Calibration method (Smith et al., 2015) ........................................ 39 Figure 4. Study and analysis populations .................................................................................................. 41 Figure 5. Study population flow diagram .................................................................................................. 41

4 ) 7 )

 47 Ulnar nerve compression at the elbow: cubital tunnel syndrome 5) Radial nerve compression: radial tunnel syndrome 6) Flexor-extensor peritendinitis or tenosynovitis of the forearm-wrist region De Quervain's disease 8) Carpal tunnel syndrome 9) Ulnar nerve compression at the wrist: Guyon canal syndrome 10) Raynaud's phenomenon (vibration white finger) and peripheral neuropathy associated with hand-arm vibration 11) Osteoarthrosis of the distal upper-extremity joints 12) Nonspecific upper-extremity musculoskeletal disorders

Figure 1 .

 1 Figure 1. A conceptual model integrating the multidimensional nature of MSD (adapted from Roquelaure (Roquelaure, 2016)).

o

  Working under time pressure o Very short cycle times o Lack of time to recover o Inflexibility of procedures and checks o Lack of individual/collective leeway o Lack of resources to carry out high-quality work o Monotonous tasks o Gender-based division of work

  biomechanical, psychosocial and organizational factors. Critical reviews of the epidemiological literature show good evidence of associations of work-related risk factors with UEMSD, and in particular, when workers are exposed to multiple risk factors in combination. to workplace physical demands (e.g. repetitive motions, handling of heavy loads, awkward postures). Several systematic reviews and meta-analyses have demonstrated the risk of UEMSD associated with prolonged exposure to physical demands in working situations. Da Costa et al.'s review (da Costa and Vieira, 2010) based on 63 longitudinal studies demonstrated that high biomechanical demands (e.g. heavy physical work) were associated with UEMSD with a causal relationship with at least reasonable evidence; the most commonly biomechanical risk factors for UEMSD included excessive repetition, awkward postures, and heavy lifting. The repetitive motion involves the repetitive use (e.g. every few seconds) of the same muscle groups through frequent movements for long periods of time during a typical working day, which prevents recovery and can lead to muscle tensions and fatigue. The results of a review of prospective studies and meta-analysis by Descatha et al. (Descatha et al., 2016) strongly supported the assumption that there is an association between biomechanical exposure involving the wrist and/or elbow at work and the incidence of LE. Nevertheless, a recent meta-analysis (van der Molen et al., 2017) revealed moderate evidence for associations of shoulder disorders with arm-hand elevation (OR=1.90 [95% CI 1

  Information in Health Research ("CCTIRS") and the National Committee for Data Protection ("CNIL"), initially in 2001 and again in 2006. In 2002, the French National Institute for Health Surveillance (merged in 2016 with other health agencies to form the current French National Public Health Agency: SpFrance) and the former Laboratory of ergonomics and epidemiology in occupational health (LEEST) implemented a pilot epidemiological surveillance system for workrelated MSD in the PdL region. This pilot network involved the University of Angers, the Regional Directorate of Labour, Employment and Vocational Training (DIRECCTE), SpFrance and the occupational health services of the PdL region, and consisted of three components: (a) epidemiological surveillance of sentinel health events in the general population: CTS, the most commonly reported nerve entrapment syndrome, was chosen as the sentinel event for UEMSD and lumbar disc surgery as the sentinel event for low back pain. (b) epidemiological surveillance of the main UEMSD and exposure to risk factors in the workplace. (c) registration of notification data on compensation claims for work-related diseases related to MSD. The program was set up in the PdL region (Loire valley area, west central France, 3 305 000 inhabitants and 1 247 839 salaried workers in 2002). This region represented 5.5% of the French population and 5.6% of the

  April 2002 and April 2005, the 83 volunteer OPs in the sentinel network selected participants among the many workers attending their regularly scheduled mandatory health examination. OPs selected workers by following a 2-stage sampling standardized random selection procedure: first, 15-30 half days of scheduled examinations for each OP were chosen for sampling by the investigators; second, each OP was asked to randomly select from the schedule 1 of 10 workers on the selected half days of worker examinations. Workers aged between 20 and 59 years of age (according to the classifications of INSEE, the French National Institute of Statistics and Economic Studies), working in the PdL region regardless of their type of employment contract, and under surveillance by the 83 OPs were eligible for inclusion. Each worker provided informed written consent to participate in this study.

Figure 2 .

 2 Figure 2. Schematic organization of the COSALI cohort

  received guidelines describing the French translation of the clinical protocol (including diagnostic criteria charts and photographs of clinical tests) and underwent a 3-hour training program to standardize clinical examinations.See[START_REF] Roquelaure | Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the working population[END_REF] for specific details. NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 30 In this study, the standardized clinical examination focused on six specific UEMSD presented below with the corresponding codes of the ICD-10 (WHO, 2008). (a) Rotator cuff syndrome (M75.1); (b) Lateral epicondylitis (M77.1); (c) Ulnar tunnel syndrome (G56.2); (d) Carpal tunnel syndrome (G56.0); (e) Flexor-extensor peritendinitis or tenosynovitis of the forearm-wrist region (M70.0); (f) De Quervain's disease (M65.4). The following three classifications of UEMSD were possible from the clinical examination according to the frequency of symptoms: (a) Latent case if symptoms exist, but the temporal criteria may not be met. (b) Symptom case if symptoms are present at the time of examination or in the immediate past (present on the date of the examination or for at least 4 days in the preceding week prior to the examination or at least 4 days in any one week during the past 12 months), but there are no positive signs on clinical examination. (c) Confirmed case if symptoms are at the time of examination or present at least 4 days in the week prior to the examination and there are positive signs on clinical examination.

  examined risk factors assessed at baseline included: (a) personal factors, medical history and history of the work, (b) exposure to work-related biomechanical and work-related psychosocial factors. These variables are NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 31

  10) NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 38

"

  calibrates" the sample on the totals of the auxiliary variables. To this end, Deville and Särndal[START_REF] Deville | Calibration Estimators in Survey Sampling[END_REF]) introduced a "distance function" 𝐺 with argument 𝑟 = 𝑤 𝑘 /𝑑 𝑘 for measuring the distances between 𝑤 𝑘 and 𝑑 𝑘 in some way. This function 𝐺 is positive and convex and verifies 𝐺(1) = 0. The inverse of the derivative of 𝐺 is called the calibration function 𝐹(. ) = 𝐺' -1 (. ) which allows one to calculate the calibration weights 𝑤 𝑘 .Once the function 𝐺 has been chosen, the problem consists in determining the weights 𝑤 𝑘 minimizing the following quantity 𝐷 under calibration constraints according to formula(5) i.e. minimizing a weighted sum (by the 𝑑 𝑘 ) of the distances between the sample weights 𝑑 𝑘 and the new weights 𝑤 𝑘 under calibration constraints. 𝐷 = ∑ 𝑑 𝑘 𝐺(𝑤 𝑘 /𝑑 𝑘 ) 𝑘∈𝑠

Figure 3 .

 3 Figure 3. Graphical representation of the Calibration method(Smith et al., 2015)

(

  covariate) or with an unknown diagnosis of UEMSD at follow-up. Figures4 and 5present the study population and the one included in the analyses. In the first study of the thesis (article 1), a total of 1275 complete case data were analyzed. For the analyses in studies 2 and 3 (articles 2 and 3), 29 observations were excluded in order to standardize auxiliary variable data between the study sample and the 2007 French population census data of the PdL region prior to the computation of the sample weights by the calibration on margins method. After this exclusion, the final sample for studies 2 and 3 analyses consisted of 1246 participants.

Figure 4 .Figure 5 .

 45 Figure 4. Study and analysis populations

  of the six UEMSD was diagnosed at follow-up in 143 workers (incidence rate 11.2). The most common diagnoses UEMSD was RCS (incidence rate 6.4%).Concerning work-related risk factors:o High physical exertion plays an important role in the development of UEMSD, 30% of cases of incident UEMSD could potentially be avoided by lowering the physical exertion on the RPE Borg scale below 12 (RPE Borg scale range = 6 to 20) in the working population.

  between 2002-2005. They completed a self-administered questionnaire and underwent a standardized clinical examination performed by the OP. Between 2007-2010, 1611 workers were re-examined by their OP. From the 1611 workers re-examined at follow-up, a complete case analysis including 1246 workers was conducted by excluding workers with baseline UEMSD and those with missing values for at least one covariate. NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 78

  support at work may theoretically prevent 20 443 new cases; i.e. 16% of all the 129 320 UEMSD cases projected in the PdL region in 2007 among workers. To the best of our knowledge, this is the first study estimating the number of cases that could be potentially prevented by multidimensional interventions acting on both biomechanical (i.e. high physical exertion) and psychosocial (i.e. low social support) exposure. Several studies have estimated the combined effect of biomechanical factors on the occurrence of UEMSD14,17-20 , but only one study 21 evaluated the combined effect of biomechanical and psychosocial factors. The study showed an increased risk of neck/shoulders symptoms with the combination of awkward or tiring position + awkward grip or hand movements + work stress. However, PAFs and numbers of cases of UEMSD attributable to the risk factors were not evaluated 21 .In the model of reducing exposure to working postures with arms above the shoulders combined with improved social support, around 5000 new cases of UEMSD (3.9% of all new UEMSD) could theoretically be avoided. The lower number of potentially preventable cases when acting upon these two risk factors can be explained by the low proportion of workers exposed to the combination of both risk factors (joint prevalence), and the low number of UEMSD cases corresponding to the combination of both risk factors among these exposed workers. Indeed, these two key indicators (prevalence and number of UEMSD cases) that are taken into account in the calculation of the PAF 22 are lower among workers exposed to the combined factors than among those exposed to only one of these risk factors.

  Furthermore, research indicated that workplace interventions based on single actions appear unlikely to prevent UEMSD. Interventions addressing a single risk factor are likely to be less effective than a combination of interventions targeting multiple factors. Efforts to prevent UEMSD need to target different levels (micro: in the clinical setting, meso: in the workplace, and macro: at the national level) of the determinants chain. Changes in work situations based on interventions at the level of individual services and companies in primary prevention are still needed to reduce the biomechanical and psychosocial risk factors that exist prior to the onset of UEMSD,

  885 demandes d'indemnisation des travailleurs ont été acceptées pour les TMS-MS dans l'État de Washington, ce qui représentait 10,3 % de l'ensemble des demandes, avec 36,9 % des demandes indemnisables entraînant des coûts directs de 1,49 milliard de dollars[START_REF] Silverstein | Work-related musculoskeletal disorders of the neck, back, and upper extremity in Washington State, 1997-2005[END_REF]. Selon le Bureau of Labor Statistics des Etats-Unis (Bureau of Labor Statistics, 2016), en 2015, un tiers des accidents et maladies professionnels avec arrêt de travail étaient dû aux TMS-MS. Entre 1998 et 2007 au Québec, les TMS-MS ont représenté en moyenne 27 % de l'ensemble des TMS indemnisés annuellement[START_REF] Michel | Portrait national des troubles musculosquelettiques (TMS) 1998-2007: TMS sous surveillance[END_REF]. En outre, ces TMS-MS étaient ceux qui étaient compensés pour des périodes plus longues avec une période de compensation moyenne de 81,1 jours (médiane de 20 jours). Une étude menée par Buckle et Devereux[START_REF] Buckle | The nature of work-related neck and upper limb musculoskeletal disorders[END_REF] a conclu que les TMS constituent un problème majeur dans l'UE en termes de santé et de coûts. En France, selon les données de l'Assurance Maladie, le montant des coûts facturés liés à l'ensemble des TMS (principalement des TMS-MS, soit 91 % de l'ensemble des TMS) a été estimé à 2 milliards d'euros liés aux TMS-MS pour les entreprises en 2018 (Cnam. Direction des Risques Professionnels, 2019). En résumé, les TMS restent très répandus dans la population active avec un coût humain et socioprofessionnel considérable (douleurs et gênes dans le travail et la vie quotidienne) et coûtent cher aux entreprises

  (a) la première étude a examiné les associations entre les FdR potentiels et l'incidence des TMS -MS, et a estimé la proportion de cas de TMS-MS pouvant être attribués à chacun de ces FdR par le calcul de fraction attribuable dans la population (FRAP) ;(b) la deuxième étude a estimé la proportion et le nombre de cas de TMS-MS incidents qui pourraient être potentiellement évités dans la population active salariée de la région française des Pays de la Loire (PdL) ;(c) la troisième étude a évalué l'effet combiné des FdR biomécaniques et psychosociaux sur l'incidence de TMS-MS, et a estimé la proportion et le nombre de cas de TMS-MS attribuables à ces FdR dans la population active salariée de la région des PdL.

  pour plus de détails sur la cohorte COSALI]. L'étude COSALI a reçu l'approbation du Comité consultatif sur le traitement de l'information dans le domaine de la recherche en santé (CCTIRS) et de la Commission nationale de l'informatique et des libertés (CNIL), d'abord en 2001, puis en 2006. Chaque salarié a donné son consentement éclairé par écrit avant de participer à l'étude. Les cas incidents de TMS-MS ont été définis comme des salariés exempts des six principaux TMS-MS cliniquement diagnostiqués à l'inclusion et qui ont eu un diagnostic d'au moins un des six au suivi. Les six principaux TMS-MS étaient : 1-syndrome de la coiffe des rotateurs (SCR), 2-épicondylite latérale (EPI), 3-syndrome du tunnel cubital, 4-tendinite des extenseurs/fléchisseurs de la main et des doigts, 5-ténosynovite de De Quervain et 6-syndrome du canal carpien (SCC).

  anatomique précise figure entre parenthèses. REMARQUES : ………………………………………………………………………………………………………………… ....................................................................................................................................................... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 137

SYNDROME 1 )SYNDROME 2 ) 2 )Cas 2 )Cas 2 )SYNDROMECasSYNDROMECasCas 2 ) 2 )CasCas

 1222222 Au moins une douleur intermittente de l'épaule, sans paresthésie Accentuée par l'élévation active de l'épaule G (comme pour se gratter le haut du dos) Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 139 …………………………………………………………….………………... ............................................................................................................... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 140 SYNDROME DE LA COIFFE DES ROTATEURS DROITE (p 1/2) Recherche d'une forme latente ou symptomatique Symptômes dans la région de l'épaule D Au moins une douleur intermittente de l'épaule, sans paresthésie Accentuée par l'élévation active de l'épaule D (comme pour se gratter le haut du dos) avérée de tendinite de la coiffe des rotateurs D OU NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 141 ............................................................................................................ NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for Recherche d'une forme avérée OU REMARQUES : ……………......................................................................... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for Recherche d'une forme avérée OU REMARQUES : …………………………………………………………….………………... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 144 Recherche d'une forme avérée REMARQUES : …………………………………………………………….………………... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 145 Recherche d'une forme avérée REMARQUES : …………………………………………………………….………………...NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 146 intermittentes dans au moins deux des trois premiers doigts qui peuvent être présentes la nuit. La douleur peut siéger dans la paume de la main, le poignet ou avoir une irradiation proximale. Symptômes présents actuellement ou au moins pendant 4 jours au cours des 7 derniers jours Symptômes présents au moins 4 jours pendant au moins une semaine au cours des 12 derniers mois avérée de syndrome du canal carpien OU NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 147 .………………... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 148 intermittentes dans au moins deux des trois premiers doigts qui peuvent être présentes la nuit. La douleur peut siéger dans la paume de la main, le poignet ou avoir une irradiation proximale. Symptômes présents actuellement ou au moins pendant 4 jours au cours des 7 derniers jours Symptômes présents au moins 4 jours pendant au moins une semaine au cours des 12 derniers mois avérée de syndrome du canal carpienOU NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 149 .………………... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 150 Reproduction de la douleur par la palpation des tendons correspondants ou crépitation palpable dans la zone concernée ou tuméfaction visible du dos du poignet ou de l'avant-bras NON OUI Recherche d'une forme avérée OU REMARQUES : …………………………………………………….................…... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 151 Cas avéré de tendinite des fléchisseurs / extenseurs des doigts D (CIM M70.0, M70.8) Reproduction de la douleur par la palpation des tendons correspondants ou crépitation palpable dans la zone concernée ou tuméfaction visible du dos du poignet ou de l'avant-bras NON OUI Recherche d'une forme avérée OU REMARQUES : ………….....…... ..........................................Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 152 .................…... NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 153 …………………………………………………….................…...

Table 2 :

 2 Risk factors for UEMSD (Adapted from Roquelaure (Roquelaure, 2018)) ......................................... 14

Table 3 :

 3 Distribution of the six upper-extremity musculoskeletal disorders (UEMSD) among the study population and its projection at the regional level. .................................................................................................... 44

Table 1 :

 1 Prevalence and incidence of UEMSD in the general population and the working population : clinical examination, CS: cross-sectional, CTS: carpal tunnel syndrome, EV: ergonomic evaluation, IP: incidence proportion, IR: incidence rate, LE: lateral epicondylitis, MA: Meta-analysis, PY: person-years, PC: prospective cohort, Prev: prevalence, Q: Questionnaire, RC: retrospective cohort, RCS: rotator cuff syndrome, SOII: Surve y of Occupational Injuries and Illnesses, SP: shoulder pain, SR: systematic review, UK: United Kingdom, US: United States.

	Reference	Country	Study design	Study population; N	Outcome measures	assessment	Prevalence/incidence
	(Rossignol et al., 1997)	Canada	RC	Island of Montreal general population, N=1.1 million	CTS	Surgical cases	IP=0.1%
	(Walker-Bone et al., 2004)	UK	CS	General population in Southampton, N=1960	LE, RCS, CTS, de Quervain's disease, Tenosynovitis of the wrist	Q and CE	Prev=0.5 to 4.5% for men and 1.1 to 6.1% for women
	(Luime et al., 2004)	-	SR of 18 studies	General population	Incidence and 1-year prevalence of shoulder complaints	Q and/or CE	Prev=4.7 to 46.7% IP=0.1 to 2.5%
	(Miranda et al., 2008)	Finland	PC	General population, N=883	Chronic shoulder disorders CE	IP=7.1%
	(Spahn et al., 2012)	-	MA of 87 studies	General and working population	CTS	Q and CE or Surgery cases	Prev: 8.2% and 10.9% IR=1.8 and 17.3 cases/1000 PY
	(Miranda et al., 2001)	Finland	PC	Forestry company; N=2094	Incidence and persistence of SP	Q	IP=13.6%
	(Roquelaure et al., 2002)	France	PC	Shoe factory workers, N=191	LE, RCS, CTS	Q and CE	Prev=2.1 to 12.0%
	(Leclerc et al., 2004)	France	PC	Working population exposed to repetitive work, N=326	Incidence SP: experienced months at least 1 day within the 6	Q	IP=23.0%
	(Huisstede et al., 2006)	-	SR of 6 studies	Working population	UEMSD in the past 1 year	Q and/or CE	Prev=9.3 to 26.9% (CE) Prev=2.3 to 41.0% (Q)
	(Mattioli et al., 2009)	Italy	RC	Workers in Tuscany, N=8801	CTS	Surgery cases	IR= 2.6 and 0.5 cases/1000 PY for women and for men
	(Fan et al., 2014)	US	PC	Working population, N=611	LE	Q and CE	IR=49.1 cases/1000 PY
	(Dalbøge et al., 2014)	Denmark	PC	Working population, N=2.4 million	Subacromial impingement syndrome	Surgical cases	IR=1.1/1000 PY

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to CE

Table 2 :

 2

Risk factors for UEMSD (Adapted from Roquelaure

[START_REF] Roquelaure | Musculoskeletal Disorders and Psychosocial Factors at Work[END_REF]

  Lack of decision-making autonomy o Lack of support from line managers o Lack of support from co-workers o Lack of recognition for work done

	Psychosocial
	o Job-related stress
	o Heavy mental load
	o

  have been published on this subject.

	Regarding Cochrane reviews, a study of Hoe et al. (Hoe et al., 2012) based on thirteen randomized controlled
	trials (RCTs) studies and evaluating the effectiveness of ergonomic equipment, supplementary breaks or reduced
	work hours, ergonomic training, a combination of ergonomic training and equipment, and patient lifting
	interventions for preventing UEMSD and neck in adults has found a reduction in the incidence of neck/shoulder
	disorders related to the use of arm support with an alternative mouse with moderate-quality evidence (risk ratio
	[RR]=0.52; 95% confidence interval [95%CI]: 0.27─0.99). In addition, very-low-to low-quality evidence was
	found suggesting that other ergonomic interventions do not prevent UEMSD, although this finding should be put
	into perspective due to the rarity and heterogeneity of the available studies. The authors finally concluded that
	there is a need for high-quality RCTs on the prevention of UEMSD. A recent Cochrane review by Hoe et al. (Hoe
	et al., 2018) confirms the previous conclusions. In addition, this new review found that there is very low-quality
	Most controlled prevention studies have focused on the reduction of UEMSD and have mostly been conducted evidence of an effect on upper extremity discomfort in the form of supplementary breaks but no evidence
	among professional computer users (e.g. alternative keyboards, work environment). Often based largely on low-concerning the effect of training and multifaceted interventions on upper extremity pain or discomfort.
	quality prevention interventions, most of these trials have provided limited or often inconsistent evidence of
	positive effects. In a systematic review based on 31 interventional studies for the prevention and management
	of neck/upper extremity musculoskeletal conditions, Boocock et al. (Boocock et al., 2007) provided evidence to
	support the use of certain mechanical and modification interventions as approaches for the prevention and
	management of UEMSD, and moderate evidence of the effectiveness of alternative keyboards. Another systematic
	review by Kennedy et al. (Kennedy et al., 2010) based on 36 interventions studies to reduce UEMSD found that
	the combination of different type of interventions produced mixed levels of evidence and the disappearance of
	messages that emerges from more specific categories of intervention: the levels of evidence for interventions
	were moderately positive for arm supports and limited for ergonomic training in combination with workstation
	adjustments, new chairs, and breaks. An updated review of workplace-based interventions for preventing and
	managing UEMSD by Van Eerd et al. (Van Eerd et al., 2016) based on 30 different types of interventions revealed
	that implementing a resistance training exercise program in the workplace can help prevent and manage UEMSD
	and symptoms with strong evidence. The study also found moderate evidence for the effectiveness of stretching
	programs, vibration feedback on the use of the mouse and workstation forearm supports with moderate evidence.
	Stock et al.'s systematic review (Stock et al., 2018) showed, with moderate evidence, that additional breaks were
	effective in reducing the intensity of musculoskeletal symptoms compared to conventional break times. For the
	other types of organizational or psychosocial interventions investigated by researchers, the levels of evidence
	were low to very low. They concluded that better quality research is needed to provide definitive conclusions
	about the effectiveness of organizational or psychosocial interventions in the workplace to prevent or redu ce
	work-related MSD. Recently, a systematic review by Proper and van Oostrom (Proper and van Oostrom, 2019)
	found strong evidence for positive effects of workplace interventions, especially resistance exercise training on
	MSD prevention. The narrative review by Soares et al. (Soares et al., 2020) concluded to a benefit of workplace
	exercise programs for both employers and workers. Benefits for companies included reduced absenteeism, time-
	off requests, costs and sick leave, and improved subjective employability and work ability, while benefits for
	workers included reduced muscle activity during tasks and increased speed of movements. In addition, the
	authors found a decrease in the rate of MSD among workers who exercise.
	NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the
	population level: scenarios for reduced exposure to risk factors for MSD	21

Table 3 :

 3 Distribution of the six upper-extremity musculoskeletal disorders (UEMSD) among the study population and its projection at the regional level.

				Study sample			Projection of the study sample at the level of the PdL region
		Overall (N=1246)	Men (N=734)	Women (N=512)	p ¶	Overall (N=1 141 324) ¥	Men (N=582 950) ¥	Women (N=558 373) ¥	p #
		n	%	n	%	n	%		n	%	n	%	n	%
	Rotator cuff syndrome (RCS)	78	6.3	41 5.6 37 7.2	0.242	73 858	6.5	32 827	5.6 41 032 7.3 0.259
	Lateral epicondylar tendinopathy (LET)	28	2.3	22 3.0	6	1.2	0.032	24 767	2.2	18 117	3.1	6650	1.2 0.033
	Carpal tunnel syndrome (CTS)	24	1.9	7	1.0 17 3.3	0.003	22 456	2.0	7228	1.2 15 228 2.7 0.084
	Ulnar tunnel syndrome	12	1.0	7	1.0	5	1.0 1.000* 12 022	1.1	7796	1.3	4227	0.8 0.332
	De Quervain tenosynovitis	10	0.8	4	0.6	6	1.2 0.334*	7878	0.7	2159	0.4	5719	1.0 0.138
	Flexor-extensor
	peritendinitis or
	tenosynovitis of	9	0.7	5	0.7	4	0.8 1.000*	9399	0.8	3988	0.7	5410	1.0 0.625
	the forearm-wrist
	region
	At least one of the six UEMSD	139 11.2 74 10.1 65 12.7 0.149 129 320 11.3 60 133 10.3 69 187 12.4 0.287
	At least two of the six UEMSD	20	1.6	11 1.5	9	1.8	0.720	19 404	1.7	10 921	1.9	8483	1.5 0.652
	¶ p-value of Chi-square test;

* Fisher's exact test; ¥ Weighted; # p-value of the Rao-Scott Chi-square test for weighted samples.

Paper2: Upper extremity musculoskeletal disorders: how many cases can be prevented? Estimates from the COSALI cohort ORIGINAL RESEARCH Published on July 8, 2020 in the "Scandinavian Journal of Work, Environment & Health" Key Findings and Messages o

  Of the total projected estimate of 129 320 new cases of UEMSD in the working population of the French region of PdL in 2007, an estimated 53

Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 59

3.

021 would be attributable to all the occupational risk factors in

  the multivariate model, i.e. 41.0% of all new projected incident UEMSD cases.

	o High physical exertion was responsible for the largest number of cases (an estimated 26 381
	cases of UEMSD, representing 20.4% of all new projected UEMSD cases). It was followed by low social
	support from coworkers and supervisors (16 682 incident cases, i.e. 12.9%), and working posture with
	arms above shoulder level (8535 incident cases, i.e. 6.6%). Furthermore, a significant number of new
	UEMSD cases (10 863 cases, i.e. 8.4%) could be attributed to working posture with shoulder abduction
	despite the associated relative risk not reaching the 5% statistical significance level.

o The observed relationship between incident UEMSD and high physical exertion or low social support was primarily observed among men, and the relationship observed between incident UEMSD and shoulder abduction or working with arms above shoulder level was primarily observed among women.

o The total projected estimate of UEMSD incident cases was higher in female workers than in male workers (69 187 cases in women vs 60 133 cases in men). However, estimated

fractions and numbers of UEMSD cases were higher in males than in females;

	35 899 new cases in males and 29 411 in
	females were attributable to all occupational risk factors in the model, representing 59.7% and 42.5% of
	all new cases, respectively.
	o Out of the projected total estimate of 60 133 UEMSD incident cases among male workers, 25 015 were
	attributable to high physical exertion (41.6% of all new cases) while 8599 (14.3%) could be attributed
	to low social support. Similarly, of the projected estimate of 69 187 new UEMSD cases in women, 12 315
	(17.8% of all new cases) were attributable to working with shoulder abduction while 5258 (7.6%) could
	be attributed to working with arms above shoulder level.
	o Among the potentially personal modifiable risk factors, the present study suggests that an important
	number of projected incident UEMSD could be attributed to high BMI (overweight/obesity: 10
	586 incident UEMSD, i.e. 15.3% of all new cases) in the PdL female working population.
	To our knowledge, this is a first

prospective cohort study estimating the number of potential cases of UEMSD attributable to occupational risk factors

in an entire working population. According to our findings, an important proportion and a large number of incident UEMSD in the workplace in the PdL region could potentially be prevented by reducing occupational exposures such as physical exertion, working with shoulder abduction, and improving social support from coworkers and supervisors. NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 73 4.

Paper3: Proportion and number of upper extremity musculoskeletal disorders attributable to the combined effect of biomechanical and psychosocial risk factors in a working population Submitted for publication Key Findings and Messages

	As part of a prevention strategy to reduce the incidence of UEMSD among workers in the French PdL region
	exposed to both high physical exertion and low social support from coworkers and supervisors, it was estimated
	that:
	o 8664 new cases could potentially be prevented by improving social support only, representing 6.7%
	of all the projected estimate of 129 320 incident UEMSD cases in the PdL region in 2007
	o 19 010 new cases (14.7%) could potentially be prevented by reducing exposure to high physical
	exertion only,

o and 20 443 new cases (15.8%) could potentially be prevented by acting on both factors.

In conclusion, this study showed that a multidimensional prevention intervention that would combine both a reduction of exposure to high physical exertion and an improvement of social support at work could reduce the incidence of UEMSD, thereby preventing a large number of cases.

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 74 Proportion

and number of upper-extremity musculoskeletal disorders attributable to the combined effect of biomechanical and psychosocial risk factors in a working population

  Aboubakari Nambiema, MSc, MPH 1* , Julie Bodin, PhD 1 , Susan Stock, MD, MSc, FRCPC2,3 , Agnès Aublet-Cuvelier, MD 4 , Alexis Descatha, MD, PhD1,5 , Bradley Evanoff, MD, MPH6 , Yves Roquelaure, MD, PhD 1

  in the PdL region in 2007, low social support at work only led to an estimate of 8664 new cases representing 6.7% of all new cases, high perceived physical exertion at work only led to 19 010 (14.7%), and the combination of both factors led to 20 433 (15.8%) new UEMSD cases. In model 2, 16 294 new cases (12.6% of all new cases in the PdL region) were attributable to low social support at work only, 6983 (5.4%) to working posture with arms above shoulder level at work only and only 5043 (3.9%) were attributable to the combination of both factors.

	the 1246 workers (59% men, mean age: 38 years ± 8.6 at baseline), 139 (11.2%) developed UEMSD during

follow-up, amounting to a projected number of 129 320 new UEMSD cases in the PdL region working population in 2007 13. Table

1

gives the results of RR for incident UEMSD, PAFs and population estimated numbers of UEMSD cases attributable to risk factors, with the lowest risk group as a reference. In model 1: of the 129 320 new NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 79

UEMSD cases estimated

Table 1 . Proportion and population estimated number (PEN) of incident UEMSD attributable to exposure to occupational risk factors in t he working population in the PdL region Estimates in the COSALI cohort Estimates at the level of the

 1 : Upper-extremity musculoskeletal disorders. Prev*: Prevalence of risk factor. RR: relative risk; 95% CI: 95% confidence interval. Th e PAF, adjusted for all factors in the model, was calculated using the lowest risk group for each factor as the reference group, with all other factors remaining unchanged. PAF: Population attributable fraction. PEN: Population estimated number of UEMSD. The PEN factor was calculated by multiplying the PAF by the projected number of incident UEMSD cases in the Pays de la Loire region in 2007. their combination or the small number of UEMSD cases related to the risk factors led to low PAFs and therefore of numbers of attributable cases in this work. This was particularly the case with the combination of reducing working with arms above the shoulders and improving social support, which would prevent fewer UEMSD than if only one of the two factors was acted upon in this study. Given to the above mentioned limitations, future research on estimating preventable UEMSD attributable to work should be carried out in longitudinal studies with larger sample sizes in order to obtain a solid scientific basis to confirm our conclusions and also to conduct similar analyses in different occupations and industrial sectors with a high risk of UEMSD. Future studies should evaluate the effectiveness and cost-effectiveness of such interventions.In conclusion, this study demonstrated the potential relevance of multidimensional preventive interventions acting on several occupational factors at the same time. The findings suggest that an intervention that would both reduce exposure to high physical exertion and improve social support at work could potentially reduce the incidence of work-related UEMSD, thereby preventing a large number of cases. These conclusions support the implementation of interventions that target a combination of occupational risk factors in order to maximize the number of potentially preventable cases whose effectiveness should be evaluated in future studies.

	PdL region

The prevalence of certain risk factors (e.g. working with arms above the shoulders, low social NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 80 UEMSDNAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 81 support) or

  Les troubles musculo-squelettiques (TMS) sont regroupe un ensemble de lésions et de troubles des tissus mous qui affectent l'appareil locomoteur (c'est-à-dire les muscles, les tendons, les articulations, les nerfs, les cartilages). Ces affections se traduisent principalement par des douleurs et des gênes dans le travail et la vie quotidienne. Elles sont provoquées ou aggravées par une exposition répétée ou soutenue à des activités liées au travail, telles que les postures inconfortables pendant de longues périodes, les tâches répétitives, les efforts excessifs pour porter et soulever des objets lourds, les vibrations du corps et un manque de temps de récupération (Aublet

	Résumé en français
	1. Introduction
	1. This dissertation is the first study to estimate the proportion and number of incident UEMSD cases that
	could be potentially prevented by potential multidimensional preventive interventions;
	2. Combined exposure to occupational a high physical exertion or an awkward shoulder posture with a low
	social support at work increased the risk of developing UEMSD;
	3. A large number and important proportion of UEMSD cases (more than 50 000 cases; 41%) could be
	prevented in the working population;
	4. Prevention programs must adopt a multi-dimensional approach including biomechanical ans psychosocial
	risk factors;
	5. Not all cases of UEMSD can be prevented by multidimensional preventive interventions ➔ need for an
	integrated occupational health policy.
	NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the
	population level: scenarios for reduced exposure to risk factors for MSD	96

  Bureau of Labor Statistics, 2016). Dans l'ensemble du Québec, le taux d'incidence a été estimé à 15,4 cas/1000 travailleurs à temps plein en 2006, soit une diminution de 4,5 % par rapport à 2001[START_REF] Michel | Portrait national des troubles musculosquelettiques (TMS) 1998-2007: TMS sous surveillance[END_REF]. En France, une étude de surveillance épidémiologique du TMS-MS d'origine professionnelle NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 97 dans la région des Pays de la Loire (PdL) a révélé une prévalence d'environ 13 % (11 % chez les hommes et 15 % chez les femmes) des TMS-MS cliniquement diagnostiqués

	réalisée dans la population générale a retrouvé une prévalence comprise entre 4,7 % et
	46,7 % et une incidence cumulée comprise entre 0,1 % et 2,5 %. En ce qui concerne la population active, une
	étude systématique menée par Huisstede et al. (Huisstede et al., 2006) a retrouvé une prévalence variant entre
	9,3 et 26,9 % pour les TMS-MS diagnostiqué cliniquement et une prévalence variant entre 2,3 et 41,0 % pour
	les douleurs au cours des 12 derniers mois. La méta-analyse de Spahn et al. (Spahn et al., 2012) a révélé une
	prévalence comprise entre 8,2 % et 10,9 %, et un taux d'incidence compris entre 1,8 et 17,3 cas/1000 personnes-
	années.
	Dans de nombreux pays, les TMS-MS représentent une proportion importante de l'ensemble des maladies
	professionnelles (enregistrées ou indemnisables, ou les deux) (Roquelaure, 2018). Selon le Bureau of Labor
	Statistics des États-Unis, en 2015, il y a eu 358 890 nouveaux cas de TMS-MS (taux d'incidence : 3,2 cas/1000
	travailleurs à temps plein) pour des accidents du travail et des maladies professionnelles non mortels impliquant
	des jours d'arrêt de travail (

  , la prévalence des douleurs persistantes (≥30 jours au cours des 12 derniers mois) variait entre 11,6 % (au niveau du coude), 19,8 % (au niveau du poignet) et 20,7 % (au niveau de l'épaule) chez les femmes, 9,4 %, 12,0 % et 15,5 % chez les hommes (respectivement pour les mêmes localisations). En outre, selon le dernier Rapport annuel de l'Assurance Maladie en France, les MS constituent l'une des questions les plus préoccupantes en santé au travail et santé publique du fait d'un coût humain et socioprofessionnel considérable en termes de douleurs et gênes dans le travail et la vie quotidienne, de réduction d'aptitude au travail et de risque de rupture de carrière

	TMS-MS représentaient 80 % (39 555 cas) de toutes les maladies professionnelles en 2018, soit une hausse
	d'environ 3 % par rapport à 2017 (Cnam. Direction des Risques Professionnels : Mission statistiques &
	Département tarification, 2019).
	Aujourd'hui les TMS-

  Sluiter et al., 2001). Chaque MT participant, chargé de la surveillance médicale des travailleurs NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 99 salariés, a reçu des documents décrivant le protocole clinique (comprenant les tableaux des critères de diagnostic et les photographies des tests cliniques) et a suivi un programme de formation de 3 heures visant à standardiser les examens cliniques. Entre 2007 et 2010, les MT ont réexaminé 1 611 travailleurs en utilisant la même procédure qu'à l'inclusion [voir

	Entre 2002 et 2005, 83 médecins du travail (MT) (18 % des MT de la région) se sont portés volontaires pour
	participer à l'étude. A l'occasion de la visite médicale périodique des salariés, ces MT ont inclus aléatoirement
	3 710 salariés (2 161 hommes, 1 549 femmes) correspondant à 2 % des 184 600 salariés sous la surveillance
	des 83 MT. Plus de 90 % des salariés sélectionnés ont participé à cette étude (<10 % : absences, refus, doubles
	emplois). Les femmes étaient légèrement sous-représentées dans l'échantillon (42 % contre 47 % dans la région,
	p<0,001). Dans l'ensemble, la répartition des professions dans l'échantillon était proche de celle de la main-
	d'oeuvre régionale, sauf pour les professions non examinées par les MT (agriculteurs, commerçants et travailleurs
	indépendants). Les données sur les caractéristiques personnelles et les conditions de travail ont été recueillies au
	moyen d'un auto-questionnaire. Le MT procédait à un examen clinique standardisé des participants en appliquant
	strictement la démarche diagnostique des TMS-MS (méthodologie et tests cliniques) du groupe de consensus
	européen SALTSA (

  Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 100La première partie de la présente thèse a estimé la proportion de cas de TMS-MS incidents attribuables aux FdR personnels et professionnels. L'incidence cumulée globale était de 11,2 % et ne différait pas significativement entre les sexes (10,1 % pour les hommes contre 12,9 % pour les femmes ; p=0,122). Le principal FdR professionnel ayant un impact élevé sur l'incidence des TMS-MS était l'exposition aux efforts physiques perçus élevés (FRAP : 30 %), suivi d'un faible soutien social de la part des collègues et de la hiérarchie (FRAP : 12 %), et du travail avec les bras au-dessus des épaules (FRAP : 7 %). Concernant la deuxième étude, les résultats ont mis en évidence l'ampleur des expositions professionnelles potentiellement modifiables et évitables dans l'apparition des TMS-MS. Plus précisément, sur l'estimation projetée de 129 320 cas de TMS-MS dans les PdL en 2007, on a estimé que 26 381 (représentant 20,4 % de tous les nouveaux cas de TMS-MS prévus), 16 682 (12,9 %) et 8 535 (6,6 %) cas incidents de TMS-MS étaient attribuables respectivement aux efforts physiques élevés, au faible soutien social de la part des collègues et de la hiérarchie, et aux postures de travail avec les bras au-dessus des épaules. Par conséquent, ces nombres estimés de cas attribuables pourraient potentiellement être évités en réduisant les expositions professionnelles aux efforts physiques élevés, au travail avec les bras au-dessus des épaules, et en améliorant le soutien social des collègues et de la hiérarchie si des interventions efficaces étaient mises en oeuvre. MS, qui serait potentiellement évités (5 043 cas) en agissant sur les deux FdR plutôt que sur un seul, était inattendu. Néanmoins, cela pourrait s'expliquer, d'une part, par la faible proportion de salariés exposée aux deux FdR en même temps (prévalence conjointe) et, d'autre part, par le faible nombre de cas de TMS-MS correspondant NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 101 à la combinaison des deux FdR chez ces salariés exposés. En effet, ces deux mesures clés (prévalence et nombre de cas de TMS-MS), qui sont prises en compte dans le calcul de la FRAP

	Au cours du suivi, au moins un des six TMS-MS a été diagnostiqué chez 143 salariés (soit 11,2 % de l'échantillon d'étude ; 10,1 % des hommes vs 12,9 % des femmes ; p=0,122) sur les 1 275 suivis exempts de TMS-MS à l'inclusion (étude 1 : article 1). En ce qui concerne les études 2 et 3, il y a eu 139 cas de TMS-MS (11,2 % de l'échantillon d'étude), ce qui correspond à un nombre prévu de 129 320 nouveaux cas de TMS-MS projetés dans la population active salariée de la région des PdL en 2007. Les diagnostics de TMS-MS les plus fréquents au suivi étaient le SCR (6,5 %), l'EPI (2,2 %) et le SCC (2,0 %). (FRAP : 12 %), l'âge [groupe d'âge 35-44 ans (FRAP : 13 %) et groupe d'âge ≥45 (FRAP : 20 %)], et le surpoids/obésité (uniquement pour les femmes) (FRAP : 17 %) avaient un impact significatif sur l'incidence des TMS-MS dans la population active salariée. En ce qui concerne les FdR personnels potentiellement modifiables, les résultats suggèrent qu'un nombre important de TMS-MS incidents (10 586 cas) pourrait être attribué au surpoids/obésité (15,3 % de tous les nouveaux cas projetés) chez les femmes actives. Dans la troisième étude, deux scénarios potentiels de prévention multidimensionnelle des TMS-MS ont été analysés à l'aide de deux modèles statistiques, comprenant chacun une combinaison d'un FdR biomécanique et d'un FdR psychosocial (« efforts physiques élevés + faible soutien social » dans le modèle 1, et « posture de travail avec les bras au-dessus des épaules + faible soutien social » dans le modèle 2). Les résultats du scénario 1 ont montré que 8 664 nouveaux cas pourraient potentiellement être évités en améliorant le soutien social uniquement, ce qui représente 6,7 % des 129 320 cas de TMS-MS projetées dans la population active salariée de la région des PdL en 2007, 19 010 nouveaux cas (14,7 %) en réduisant l'exposition aux efforts physiques élevés uniquement, et 20 443 nouveaux cas (15,8 %) en agissant sur les deux facteurs. Avec le scénario 2, 19 010 nouveaux cas (12,6 %) pourraient potentiellement être évités en améliorant le soutien social uniquement, 6983 nouveaux cas (5,4 %) en réduisant l'exposition à la posture de travail avec les bras au-dessus des épaules NAMBIEMA Aboubakari | Outre ces FdR liés au travail, les résultats ont montré aussi que les FdR personnels tels que le genre féminin uniquement et 5 043 nouveaux cas (3,9 %) en agissant sur les deux facteurs. Le faible nombre de cas de TMS-

si vous jugez votre effort plutôt fort, vous cocherez :

  En résumé, cette thèse a montré que certaines expositions professionnelles à des FdR biomécaniques (par exemple, les efforts physiques élevés, les postures contraignantes de l'épaule) et psychosociaux (par exemple, le faible soutien social) étaient indépendamment associées à l'incidence des TMS-MS et entraîneraient un grand nombre de ces TMS dans la population active salariée. Lorsque ces facteurs indépendants étaient combinés, le risque d'apparition des TMS-MS augmentait ainsi le nombre de cas attribuables. Ainsi, l'exposition combinée aux « efforts physiques perçus élevés + faible soutien social au travail » ou aux « travail avec les bras au-dessus de l'épaule + faible soutien social au travail » augmentait le risque d'apparition des TMS-MS et donc ses conséquences. Ces résultats indiquent que la réduction des niveaux d'exposition aux différentes catégories de FdR professionnels biomécaniques (par exemple, les efforts physiques élevés) combinée à une amélioration des pratiques managériales (amélioration du soutien social au travail) permettrait de beaucoup plus réduire l'incidence Cependant, ces conclusions doivent être interprétées en tenant compte des données disponibles utilisées, notamment des variables incluses dans les analyses ainsi que des limites liées aux calculs de la FRAP. Malgré cela, les estimations issues de ces travaux soulignent qu'un grand nombre de TMS-MS pourrait être évité si la population active salariée était faiblement exposée aux FdR modifiables étudiés qui ont un impact élevé sur l'incidence des TMS-MS (efforts physiques élevés, travail avec les bras au-dessus des épaules et le faible soutien social). En outre, cette thèse a montré que, pour être efficace, la prévention des TMS-MS sur le lieu de travail ne doit pas se limiter à la réduction de l'exposition aux FdR biomécaniques, mais nécessite une approche multidimensionnelle qui prend également en compte d'autres FdR professionnels, en particulier les FdR psychosociaux. conclusions et fournir des preuves supplémentaires en vue de stratégies de prévention plus efficaces. En outre, il serait également intéressant et très utile de mener des analyses similaires, c'est-à-dire d'estimer la proportion et le nombre de cas liés à l'exposition aux FdR professionnels dans les professions et les secteurs économiques à haut risque tels que l'industrie et la construction. Ces analyses permettront d'obtenir des informations supplémentaires pour mieux orienter les interventions de prévention des TMS-MS (sur le lieu de travail) dans ces secteurs d'activité. Par conséquent, les futures recherches sur la question des TMS-MS par le biais d'études longitudinales avec des échantillons plus importants sont nécessaires afin d'obtenir une base scientifique solide pour confirmer nos résultats. De plus, l'analyse de données d'enquêtes de grande taille permettront aussi le calcul des estimations de fractions et de nombres cas attribuables dans différentes professions et différents secteurs économiques, ainsi que l'étude des relations « dose-réponse » et interactions entre les différents facteurs. Par exemple, les données de la cohorte française CONSTANCES[START_REF] Zins | The French CONSTANCES population-based cohort: design, inclusion and follow-up[END_REF][START_REF] Zins | The CONSTANCES cohort: an open epidemiological laboratory[END_REF] pourraient être analysées avec les données de santé du Système National de Données de Santé (SNDS) appariées pour chaque participant.

	Effort nul |_____|_____|_____|_____|_____|_____|_____|_____|_____|_____| Effort maximal
	Nous vous remercions de bien vouloir répondre avec précision au questionnaire suivant et de le remettre à votre
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des TMS-MS comparé à l'action sur un seul facteur (exemple : les efforts physiques perçus uniquement). Cette thèse a permis d'estimer l'impact potentiel des interventions de prévention des TMS-MS sur le nombre de cas potentiellement évitables dans une population active salariée, et donc de quantifier les bénéfices attendus des mesures de prévention qui pourraient être mises en oeuvre. Les résultats de cette thèse sont informatifs, pertinents et utiles, notamment pour prioriser et améliorer le ciblage des interventions sur les expositions professionnelles conduisant à un nombre de cas évitables de TMS-MS potentiellement élevé. Ils permettront entre autres d'enrichir la réflexion sur les politiques nationales et régionales de prévention des TMS-MS qui sont actuellement principalement basées sur des données de sinistralité. Ces résultats pourront aussi aider les chercheurs qui prévoient de mener des recherches sur les interventions de prévention de ces TMS-MS dans la population active salariée. Certains FdR de TMS-MS (par exemple, l'exposition aux vibrations, le travail à des températures très froides) n'ont pas pu être inclus dans les analyses en raison de leur faible prévalence. L'estimation des FRAP et du nombre de TMS-MS évitables dans de futures études portant sur des échantillons plus importants serait nécessaire pour NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 102 appuyer nos NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 103 Par exemple,

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	4 -Etes-vous ?	Droitier(ère) … 	Gaucher(ère) …	Ambidextre … 
	5

-Quel est votre poids ? |__|__|__| kg 6 -Quelle est votre taille ? |__|__|__| cm CONCERNANT VOTRE SANTE

7 -Avez-vous eu, au cours des 12 derniers mois, des problèmes (courbatures, douleurs, gêne, engourdissement) au niveau des zones du corps suivantes

		Oui….	Non… Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	3. Coude/ avant-bras	Oui….	Non… Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	4. Main / poignet	Oui….	Non… Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	5. Doigts	Oui….	Non… Si oui,	du côté droit…	du côté gauche…	des deux côtés…

? Pour chacune des zones du corps, cochez la case correspondante

1. Nuque / cou

Oui…. Non…

2. Epaule / bras

6. Haut du dos Oui…. Non… 7. Bas du dos

		Oui….	Non…
	8. Hanche / cuisse	Oui….	Non… Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	9. Genou / jambe	Oui….	Non… Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	10. Cheville / pied	Oui….	Non… Si oui,	du côté droit…	du côté gauche…	des deux côtés…

Si vous avez répondu Non à toutes ces questions, passez directement à la question 12.

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 123

8-

Durant ces 12 derniers mois, combien de temps, au total, avez-vous souffert ?

  Pour chacune des zones du corps, cochez la case qui correspond le mieux à votre réponse

		Moins de 24 heures	De 1 à 7 jours	De 8 à 30 jours	Plus de 30 jours	En permanence
	1. Nuque / cou					
	2. Epaule / bras					
	3. Coude/ avant-bras					
	4. Main / poignet					
	5. Doigts					
	6. Haut du dos					
	7. Bas du dos					
	8. Hanche / cuisse					
	9. Genou / jambe					
	10. Cheville / pied					
	9 -

Si vous avez souffert de douleurs du bas du dos (lombalgies) au moins un jour au cours des 12 derniers mois, s'agissait-il de ? Sciatique, avec des douleurs s'étendant plus bas que le genou Oui……

	.	Non…….

Sciatique, avec des douleurs ne dépassant pas le genou

		Oui…….	Non…….
	Lumbago (douleur lombaire aiguë localisée)	Oui…….	Non…….
	Autre type de lombalgie	Oui…….	Non…….

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 124 10 -

Avez-vous eu, au cours des 7 derniers jours, des problèmes (courbatures, douleurs, gêne, engourdissement) au niveau des zones du

	corps suivantes ?
	Pour chacune des zones du corps, cochez la case correspondante
	1. Nuque / cou	Oui….	Non…
	2. Epaule / bras	Oui….	Non…	Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	3. Coude/ avant-bras	Oui….	Non…	Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	4. Main / poignet	Oui….	Non…	Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	5. Doigts	Oui….	Non…	Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	6. Haut du dos	Oui….	Non…
	7. Bas du dos	Oui….	Non…
	8. Hanche / cuisse	Oui….	Non…	Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	9. Genou / jambe	Oui….	Non…	Si oui,	du côté droit…	du côté gauche…	des deux côtés…
	10. Cheville / pied	Oui….	Non…	Si oui,	du côté droit…	du côté gauche…	des deux côtés…

Si vous avez répondu Non à toutes ces questions, passez directement à la question 12. 11 -Comment évaluez-vous l'intensité de ce problème au moment où vous remplissez le questionnaire, sur l'échelle ci-dessous ?

	Pour chacune des zones du corps, entourez la case correspondante
	1. Nuque / cou	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	2. Epaule / bras	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	3. Coude/ avant-bras Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	4. Main / poignet	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	5. Doigts	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	6. Haut du dos	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	7. Bas du dos	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	8. Hanche / cuisse	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	9. Genou / jambe	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable
	10. Cheville / pied	Ni gêne ni douleur	→ |_0_|_1_|_ 2_|_3_|_4_|_5_|_6_|_7_|_8_|_9_|_10_|  gêne ou douleur intolérable

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 125 CONCERNANT

VOTRE TRAVAIL 12 -En quelle année avez-vous commencé votre vie professionnelle

  ? …………………………………………………………………………….

		|__|__|__|__|
	13 -Dans quel département travaillez-vous actuellement ? (notez le numéro du département 44, 49, 53, 72 ou 85)………………………
		|__|__|
	-Dans quel secteur d'activité travaillez-vous actuellement ?	Cochez une seule case
	1. Agriculture ………………………………………………………………………………………………………….……………………………	 1
	2. Secteur privé non agricole …………………………………………………………………………………………………………………………	 2
	3. Secteur public ………………………………………………………………………………………………………………………………………	 3
	-Etes-vous ?	Cochez une seule case
	1. Manoeuvre ou ouvrier(ère) spécialisé(e) (OS1, OS2, OS3, etc.) ………………………………………………….………………………………. 2. Ouvrier(ère) qualifié(e) ou hautement qualifié(e) (P1, P2, P3, TA, OQ) ………………………………………………………….…………….	 1  2
		 3
		 4
		 5
		 6
		 7
		 8
		 9
		 10
		 11
	-

3. Agent de maîtrise dirigeant les ouvriers, maîtrise administrative ou commerciale ……………………………………………………………….. 4. Agent de maîtrise dirigeant des techniciens ou d'autres agents de maîtrise …………………………………………………….…………………. 5. Technicien(en), dessinateur(rice), VRP (non cadre) ………………………………………………………………………………………………. 6. Instituteur(rice), assistant(e) social(e), infirmier(ère) et autre personnel de catégories B de la fonction publique ……….……………. 7. Ingénieur ou cadre …………………………………………………………………………………………………………………..…………….. 8. Professeur et personnel de catégories A de la fonction publique …………………………………………………………………………………. 9. Employé(e) de bureau ou employé(e) de commerce ……………………………………………………………………………………………… 10. Agent de service, aide soignant(e) ou gardien(ne) d'enfant……………………………………………………………………….……………… 11. Autre cas (précisez en clair) : __________________________________________________________________________

Quel est votre contrat de travail actuel ?

  Emploi sans limite de durée (CDI) ………………………………………………………………………………………….…..………………… 2. Sous contrat à durée déterminée (CDD) ou autre emploi à durée limitée (contrat saisonnier, etc.) ………………………….…………………… 3. Intérimaire (placé par une agence d'intérim)…………………………………………………………………………………….………………… 4. Fonctionnaire …………………………………………………………………………………………………………………….…..……………. 5. Apprenti(e) ou contrat de formation à l'emploi en alternance………………………………………………………..…………….……………… 6. Stagiaire ou contrat de mesure pour l'emploi ……………………………………………………………………………………………………..

	Cochez une seule case
	1.  1
	 2
	 3
	 4
	 5
	 6
	17 -Quel emploi occupez-vous actuellement ? (Précisez en clair l'intitulé) : ________________________________________________________

ne pas remplir PCS|__|__|__|__| NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 126 18 -

Quelle est votre ancienneté dans l'emploi actuel ?

	Moins de 1 an … 1	1 -2 ans… 2	3 -10 ans… 3	Plus de 10 ans… 4

19 -Pouvez-vous décrire les principales tâches ou activités que vous devez accomplir dans votre emploi actuel ? _______________________ _________________________________________________________________________________________________________________ _________________________________________________________________________________________________________________ 20 -Quel nombre d'heures de travail avez-vous effectué lors de la dernière semaine travaillée

		? ………..	|__|__| heures
	21 -Votre durée de travail hebdomadaire est-elle variable ?	Oui … Non …
	22 -Vous arrive-t-

il de travailler, certains jours ou certaines semaines, plus longtemps que l'horaire officiellement prévu ?

	Oui … Non …
	23 -

Quel type d'horaires de travail avez-vous ? (une seule réponse)

	Horaire normal ou régulier………………………………….	 1
	Horaires variables ou décalés…………………………….…….	 2
	24

-Travaillez vous en équipe postée? (une seule réponse)

	Non ………………………………………………….……………	 1
	Oui, en équipe fixe …………………………………………  2
	Oui, en équipe alternante (en 2 x 8, en 3 x 8 ou plus) ………	 3
	25 -

Quand vous embauchez le matin ou en début de poste, savez-vous quelles sont les tâches que vous aurez à effectuer au cours de votre journée de travail ?

	Jamais … 1	Rarement … 2	Souvent … 3	Toujours… 4

26-Travaillez-vous souvent avec des collègues qui se trouvent en situation précaire (CDD, intérimaires) ?

	Jamais … 1	Rarement … 2	Souvent … 3	Toujours… 4
	27 -Occupez-

vous différents postes ou fonctions (polyvalence) au cours de votre travail ?

	Presque jamais / jamais ……..……	 1
	1 à 3 jours par mois …………….... 1 jour par semaine ……………….. 2 à 4 jours par semaine …………...	 2  3  4  5
	Tous les jours …………………….

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 127 -Y a-t-

il dans votre travail des changements de fabrication ou de produits ?

	Au cours de la journée	Oui … 	Non … 	Sans objet … 
	Au cours d'une heure de travail	Oui … 	Non … 	Sans objet … 
	-

Certains éléments de votre salaire dépendent-ils de la quantité ou de la qualité de votre travail ?

	Oui … 	Non … 

Les questions suivantes se rapportent à une journée typique de travail AU COURS DES 12 DERNIERS MOIS -Comment évaluez-vous l'intensité des efforts physiques de votre travail au cours d'une journée typique de travail ? Entourez le chiffre correspondant

  à votre choix sur l'échelle graduée de 6 à 20 ci-dessous, qui va de "pas d'effort du tout" à "épuisant" :

	6 ….. pas d'effort du tout
	7 ….. extrêmement léger
	8
	9 ….. très léger
	10
	11 ….. léger
	12
	13 ….. un peu dur
	14
	15 ….. dur
	16
	17 ….. très dur
	18
	19 ….. extrêmement dur
	20 ….. épuisant

31 -Au cours d'une journée de travail typique, votre rythme de travail vous est-il imposé par ? 1.

  Le déplacement automatique d'un produit ou d'une pièce …………………………………………………………..

	1. Le salarié a-t-il eu, au cours des 12 derniers mois, des problèmes (courbatures, douleurs, gêne,
	engourdissement) au niveau des zones du corps suivantes ? Pour chacune des zones du corps, cochez la case
	correspondante
		Oui	Non		Du côté gauche	Du côté droit	Des deux côtés
	Nuque / cou	❑	❑
	Epaule / bras	❑	❑	Si oui :	❑	❑	❑
	Coude/ avant-bras	❑	❑	Si oui :	❑	❑	❑
	Main / poignet	❑	❑	Si oui :	❑	❑	❑
	Doigts	❑	❑	Si oui :	❑	❑	❑
	Bas du dos	❑	❑
	Si
								Oui….	Non…
	2. La cadence automatique d'une machine ………………………………………………………………………….…	Oui….	Non…
	3. D'autres contraintes techniques ………………………………………………………………………………….….	Oui….	Non…
	4. La dépendance immédiate vis-à-vis du travail d'un ou plusieurs collègues ………………………………………...	Oui….	Non…
	5. Des normes de production, ou des délais, à respecter ………………………………………………………………	Oui….	Non…
	6. Une demande extérieure (public, client) ……………………………………………………………………………	Oui….	Non…
	7. Les contrôles ou une surveillance permanents………………………………………………………………………	Oui….	Non…

vous avez répondu NON à toutes ces questions, L'EXAMEN CLINIQUE STANDARDISE EST TERMINE.

1 dans une région considérée, aucun diagnostic

  n'est à évoquer et aucun arbre de la région considérée n'est à compléter.• Dans le cas contraire, vous devez adopter la démarche suivante pour chaque région pour laquelle des symptômes ont été déclarés (cases grises entourées du tableau de la page précédente) : ✓ 1 er arbre : Est-ce une forme latente ou symptomatique du TMS ? ✓ 2 ème arbre : Est-ce une forme avérée du TMS (résultats positifs aux tests et manoeuvres cliniques) ?

La démarche diagnostique doit être effectuée séparément pour le côté gauche et le côté droit .

  Si le salarié présente une symptomatologie bilatérale, remplir les deux arbres, droit et gauche.Ces arbres diagnostiques reprennent les critères qui figurent dans les tableaux du guide des manoeuvres cliniques.Ce dernier précise les modalités de réalisation de chaque manoeuvre dans des tableaux et sur des photos numérotées.

Lorsque plusieurs tests sont proposés et qu'un seul test positif est nécessaire au diagnostic du TMS considéré, il est possible d'arrêter la démarche diagnostique dès que l'un des tests est positif. Pour cela, il faut effectuer les manoeuvres en respectant l'ordre proposé de haut en bas et/ou de gauche à droite.

• A chaque étape de l'arbre diagnostique, il faut entourer :

• L'une des bulles « cas symptomatique », « cas latent » ou « recherche autre TMS »

• Ensuite, si une forme avérée doit être recherchée, entourer le(s) test(s) positifs et barrer le(s) test(s) non réalisé(s).

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 138

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD

-Comment estimez-vous la force habituellement requise par votre travail ? (mettez une croix dans la case correspondant au niveau d'effort auquel vous vous situez)

Ainsi, si les derniers symptômes remontent à 18 mois, il n'est pas nécessaire de procéder à l'examen dans la région considérée.

ACKNOWLEDGEMENTS

Many people deserve to be thanked and helped me during this doctoral thesis and, in general, throughout my education. It is impossible to mention all of them. However, there are some that I must specifically mention.

First, I would like to express my sincere gratitude to my advisor and head of the team (ESTER), Pr. Yves Roquelaure. I am only lucky to have him as my advisor. Thank you for your support, encouragement, scientific expertise and the trust you have placed in me by accepting me as a PhD student. I appreciated the freedom you gave me throughout this work and our very useful and enriching

Acknowledgments

We acknowledge the following occupational physicians involved in the sentinel network : Doctors Abonnat, Adam,

Funding

This project was supported by Santé publique France, the French national public health agency, Saint-Maurice, France (Grant 9/25/2002-5 "reseau experimental de surveillance des troubles musculo-squelettiques") and the French National Research Program for Environmental and Occupational Health of Anses (Grant EST-2016/1/42).

None of the mentioned sources of funding had any role in the design, analysis or writing of this article.

Authors' contributions

YR participated to the design of the study. AN analyzed the data, performed the statistical analysis and wrote the manuscript. YR had full access to all of the data in the study and takes responsibility for the integrity of the data. JB, SS, AAC, AD, BE, and YR reviewed and commented on the final manuscript. All authors read and approved the final manuscript to be published.

Conflicts of interest

The authors have none to declare.

Ethics approval and consent to participate

Each worker provided informed written consent to participate in this study, and the study received the approval of the French Advisory Committee on the Processing of Information in Health Research ("CCTIRS") and the National Committee for Data Protection ("CNIL").

NAMBIEMA Aboubakari | Potential impact of prevention intervention of musculoskeletal disorders (MSD) at the population level: scenarios for reduced exposure to risk factors for MSD 87

and 20 443 new cases (15.8%) could potentially be prevented by acting on both. With the model 2, 19 010 new cases (12.6%) could potentially be prevented by improving social support only, 6983 new cases (5.4%) could potentially be prevented by reducing exposure to working posture with arms above shoulder level only, and only 5043 new cases (3.9%) could potentially be prevented by acting on both factors. The lower number of potentially preventable cases when acting upon the two risk factors rather than just one was unexpected.

Nevertheless, this could be explained by, on the one hand, the low proportion of workers exposed to the combination of the two risk factors (joint prevalence) and, on the other hand, the low number of UEMSD cases corresponding to the combination the two risk factors among these exposed workers. Indeed, these two key measures (prevalence and number of UEMSD cases) that are taken into account in the calculation of the PAF [START_REF] Benichou | Biostatistics and epidemiology: measuring the risk attributable to an environmental or genetic factor[END_REF]Spiegelman et al., 2007) are lower among workers exposed to the combined factors than among those exposed to only one of these risk factors.

In summary, this dissertation found that some occupational exposures to biomechanical (e.g. high phy sical exertion, awkward shoulder postures) and psychosocial (e.g. low social support) factors were independently associated with the incidence of UEMSD and lead to a large number of these disorders in the working population.

When these single independent factors were combined, the risk of incident UEMSD and the number of attributable cases changed. Combined exposure to "high physical exertion + low social support" or "working with arms above shoulder level + low social support" increased the risk of developing of UEMSD and therefore its consequences.

These findings indicate that in order to reduce the incidence of UEMSD, prevention programs must adopt a multidimensional approach: focus on reducing exposure to biomechanical factors (e.g. physical exertion or working with arms above shoulder level) as well as psychosocial factors (e.g. improving social support at work).

Strengths and limitations

The interpretation of the results of this PhD thesis must take into account the limitations of the analyses, particularly with respect to data availability, the estimation method used for PAFs as well as the calibration method used to compute the study sample weights in order to provide estimates of UEMSD incident cases at the PdL region level.

Some potential limitations

Pousser ou tirer des charges (cartons, tiroirs, etc.) Jamais ou presque jamais ……………………… Rarement (moins de 2 heures / jour)…… Souvent (2 à 4 heures / jour)……………….. La plupart du temps (plus de 4 heures/jour)

-Au cours d'une journée typique de travail, conduisez-vous un engin de chantier, un tracteur ou un chariot automoteur ?

Non ou presque jamais …

CLASSIFICATION PHARMACOLOGIQUE DES ANTALGIQUES

A. Les antalgiques périphériques (non dérivés de l'opium) : Ils exercent essentiellement leur action en périphérie au niveau des tissus lésés. Ils sont très souvent utilisés pour traiter des douleurs légères de palier I. Ils se répartissent de la façon suivante 1) Antalgiques anti-inflammatoires anti-pyrétiques ce sont les anti-inflammatoires non stéroïdiens ou A.l.N.S. Leur chef de file est l'aspirine. Parmi les autres membres de cette classe, on peut citer le nalgésic*, le nurofen*.

2) Antalgiques antipyrétiques : chef de file, le paracétamol (efferalgan*, doliprane*). Son pouvoir antalgique est comparable à celui de l'aspirine. On y trouve également la noramidopyrine mais celle-ci est réservée au traitement des douleurs de palier Il. Elle est surtout commercialisée sous forme d'associations de principes actifs dont les plus connues sont : baralgine*, viscéralgine forte*, optalidon* ou salgydal*.

3) Antalgiques "purs" : une spécialité est encore commercialisée à ce jour. Il s'agit de l'idarac dont le pouvoir antalgique est légèrement supérieur à celui de l'aspirine ou du paracétamol.

B. Les antalgiques centraux :

Ce sont des opiacés puissants ayant pour chef de file la morphine. Ils servent à traiter les douleurs de palier III. On divise les morphiniques en :

. Produits naturels : morphine, codéine . Produits semi-synthétiques : héroïne, buprénorphine (temgésic), nalbuphine (topalgic)

. Produits synthétiques : méthadone, dextromoramide (palfium), dextropropoxyphène (antalvic), pentazocine

RÉSUMÉ

Les troubles musculo-squelettiques du membre supérieur (TMS-MS) constituent aujourd'hui l'une des questions les plus préoccupantes en santé au travail et santé publique du fait d'un coût humain et socioprofessionnel considérable. La prévention efficace et durable des TMS-MS reste un défi pour les praticiens et les décideurs en matière de santé publique. L'impact modéré des plans de prévention mis en oeuvre au cours des dernières décennies nécessite d'approfondir la réflexion sur les stratégies de prévention à l'échelle de la population active. L'objectif de ce travail de thèse était d'estimer et de comparer les effets potentiels de la réduction des expositions professionnelles aux principaux facteurs de risque (FdR) biomécaniques et psychosociaux sur l'incidence des TMS-MS dans la cohorte COSALI. Cette thèse a révélé qu'une proportion importante et un grand nombre de TMS-MS pourraient être évités si l'exposition aux FdR modifiables tels que les efforts physiques élevés, les postures contraignantes de l'épaule et le faible soutien social, était réduite. De plus, elle a montré qu'une intervention multidimensionnelle qui combinerait à la fois une réduction de l'exposition aux efforts physiques élevés et une amélioration du soutien social, permettrait de prévenir un plus grand nombre de cas.

En conclusion, cette thèse a permis d'estimer l'impact potentiel des interventions sur le nombre de cas de TMS-MS dans une population active salariée. Elle apporte aussi la preuve que pour être efficace, la prévention des TMS-MS ne peut se limiter à la réduction de l'exposition aux FdR biomécaniques mais nécessite une approche multidimensionnelle qui prend également en compte les FdR psychosociaux.

ABSTRACT

Upper-extremity musculoskeletal disorders (UEMSD) constitute one of the most worrying issues in occupational and public health due to their considerable human, social and occupational costs. Effective and sustainable prevention of UEMSD continues to be a challenge for public health practitioners and policy-makers. The moderate impact of the prevention plans implemented over the last few decades requires further reflection on prevention strategies at the working population level. The objective of this thesis work was to estimate and compare the potential effects of reducing work-related exposures to the main biomechanical and psychosocial risk factors on the incidence of UEMSD in the COSALI cohort. This thesis revealed that an important proportion and a large number of UEMSD could be avoided if exposure to the modifiable risk factors, such as high physical exertion, uncomfortable shoulder postures and social support, were reduced in the working population. Moreover, this study showed that a multidimensional combining both a reduction of exposure to high physical exertion and improved social support would reduce a larger number of cases.

In conclusion, this thesis made it possible to estimate the potential impact of interventions on the number of UEMSD cases in a working population. It also provides evidence that to be effective, UEMSD prevention cannot be limited to reducing exposure to biomechanical risk factors but requires a multidimensional approach that also takes into account psychosocial risk factors.