Depression is common in people with coronary heart disease (CHD) and is associated with worse physical outcomes. The nature of the causal association between CHD and depression, and the mechanism underpinning the association of depression with worse physical outcomes, remains unclear. Perseverative negative thinking may contribute to the development of depression in people with CHD. The aim of this thesis was to investigate the prospective association of perseverative negative thinking with depression, anxiety and worse physical outcomes in people with CHD, and to explore factors that may mediate this association. First, a systematic review identified 30 studies, of which the majority found an association between measures of perseverative negative thinking and subsequent depression, anxiety or emotional distress in people with long term conditions. Studies that controlled for covariates showed more mixed results, though the majority (15 / 25) still supported a significant association, with effects being small in magnitude. Findings were limited mainly to the association of rumination and/or catastrophizing with subsequent depression, and study quality was limited. Next, in an observational prospective cohort study 169 inpatients and outpatients with recent acute coronary syndrome (ACS) completed self-report assessments of rumination (Ruminative Responses Scale brooding subscale), worry (Penn State Worry Questionnaire), depression (Patient Health Questionnaire-8), anxiety (Beck Anxiety Inventory), and health-related quality of life (EuroQol-5D health-related quality of life, Seattle Angina Questionnaire) after hospitalisation, and at 2 month and 6 month follow-up. Additionally, assessments of potential mechanistic factors (social support, problem solving, instrumental behaviours and negative cognitive biases) were made. Baseline brooding was a significant independent predictor of depression at 6 months after controlling for the effects of important confounding variables, accounting for 2% of the variance. Findings suggested that the association of brooding with depression may be explained by deficits in problem solving ability. Rumination and problem solving may provide useful targets for the development of evidence-based interventions to improve depression among people with CHD, although the findings presented here fall short of proving a causal relationship. Future trials could be used to investigate the causal nature of the association of rumination and problem solving with depression in people with ACS.

Temporomandibular disorders (TMD) embrace pain and dysfunction in the temporomandibular joint (TMJ) and jaw muscles. TMD is a prevalent condition in the population and constitutes a significant health problem. Knowledge of factors influencing the onset and course of TMD is important in preventive care and development of treatment strategies as well as in clinical decision making. The aim of this thesis was to gain knowledge of whether variations in dental occlusion, bruxism, spinal pain and gender predicted the development and course of TMD. The study population comprised 371 undergraduate dental students. A questionnaire was used to obtain case histories. Clinical examination included the function of the TMJ, jaw muscles, maximal jaw mobility, the morphological occlusion, and contact patterns in centric and eccentric positions. The examinations were performed at start, and after 12 and 24 months. In total, 280 subjects were examined at all three occasions. The incidence of TMJ pain and dysfunction was high among both males and females. The course composed onset, recovery and maintenance resulting in a fluctuating pattern. Females were more likely to have persistent TMJ pain and dysfunction than males. The incidence and persistence of jaw muscle signs and symptoms was high and significantly more common in females. A similar fluctuating pattern as for TMJ pain and dysfunction was found. Crossbite predicted onset and persistence of TMJ pain and dysfunction; mandibular instability in centric positions predicted persistent TMJ pain and dysfunction, as well as persistent jaw muscle signs or symptoms. Reported bruxism increased the risk for TMJ pain and dysfunction but did not significantly affect the course of jaw muscle signs and symptoms. Spinal pain at baseline predicted the onset of jaw pain, headaches, and TMD pain. Signs of TMD at baseline predicted the onset of non-pain symptoms of TMD, jaw pain, headaches, and spinal pain. In conclusion, the results in this thesis show high incidence rates for TMD, headaches, and spinal pain among dental students. Crossbite, mandibular instability, reported bruxism, as well as female gender were identified as contributing risk factors. Spinal pain and TMD mutually predicted each other, indicating common pathophysiological mechanisms and individual vulnerability. The findings support a multidisciplinary approach, and it is recommended that the status and function of the jaw system be considered in patients with spinal pain.

Disertacijoje analizuojami pusantrų metų amžiaus kūdikių emocijų ir elgesio sunkumai bei juos prognozuojantys biomedicininiai, psichologiniai bei socialiniai veiksniai. Atliktas perspektyvusis kohortinis kūdikių, gimusių 2009 m. gegužės – rugsėjo mėnesiais LSMU ligoninėje Kauno klinikose, tyrimas. Duomenys surinkti vykdant tris tyrimo etapus: (1) ligoninėje surinkti biomedicininiai duomenys bei atlikta anketinė motinų apklausa, (2) atlikta anketinė motinų apklausa kūdikiams sulaukus trijų mėnesių amžiaus ir (3) anketinė motinų apklausa kūdikiams sulaukus pusantrų metų amžiaus. Pusantrų metų amžiaus kūdikių emocijų ir elgesio sunkumai buvo įvertinti naudojant Vaiko elgesio aprašo (CBCL/1½–5) (Achenbach, Rescorla, 2000) Lietuvoje adaptuotą ir standartizuotą versiją (Jusienė, Raižienė, 2006). Emocijų ir elgesio sunkumai buvo labiau išreikšti kūdikiams, kurie gimė atliekant cezario pjūvį bei kurių fiziologinė būklė po gimimo nebuvo optimali. Tyrimas atskleidė tokių psichologinių ir socialinių veiksnių svarbą prognozuojant emocijų ir elgesio sunkumus, kaip sudėtingas motinos emocinis nėštumo priėmimas, negatyviai motinos vertinami santykiai su vyru / partneriu nėštumo metu, dažnas motinos negatyvių emocijų patyrimas, dideliu nerimu dėl vaiko pasižymintis motinos pogimdyminis prieraišumas ir nelanksčios, į tėvus orientuotos motinos nuostatos kūdikio auginimo atžvilgiu. Disertacijoje taip pat analizuojamos ir aptariamos tirtų biomedicininių, psichologinių ir socialinių veiksnių... [toliau žr. visą tekstą] / The Dissertation analyses infants’ emotional and behavioral problems at the age of 1.5 years and their predictive biomedical and psychosocial factors. The Dissertation is based on data from prospective birth-cohort study. Study participants were infants born in the Hospital of Lithuanian University of Health Sciences (LUHS) Kauno Klinikos from May to September in 2009. The analysis included the data from three stages of the study: (1) biomedical data during and after childbirth and a questionnaire survey given to mothers 2 to 3 days after childbirth in hospital, (2) questionnaire survey of mothers three months postpartum, and (3) questionnaire survey of mothers 1.5 years postpartum. Emotional and behavioral problems were more expressed in infants born via caesarean section and whose physiological functioning after birth was not optimal. Study also revealed the importance of such psychosocial predictors of emotional and behavioral problems as complicated emotional acceptance of pregnancy, poor couple’s relationship during pregnancy, frequent negative maternal emotions, maternal postpartum attachment characterized by high anxiety regar¬ding child, and inflexible and parent-oriented attitudes toward infant-rearing. The associations between biomedical and psychosocial factors are also analyzed and discussed.

The prevalence of dementia is increasing globally and is linked to obesity and unfavorable dietary habits. The present study analyses the association of alcohol intake from wine and non wine alcoholic beverages (non-wine) in g/d, as well as coffee and tea in cups/d, with incident dementia. Over 4.2 million person-years, 4270 dementia cases occurred in 351,436 UK Biobank participants. Hazard ratios (HRs) for incident dementia were defined with Cox proportional hazard regression models in which beverage intake was fitted as penalized cubic splines. Wine intake showed a significant U-shaped association with the lowest risk for incident dementia (nadir) ranging from 21 to 23 g alcohol/d in all participants and in males. In contrast, non-wine consumption was significantly and dose-dependently associated with incident dementia, and the nadir was found at 0 g alcohol/d. Coffee consumption was not related to dementia risk, while moderate-to-high tea intake was negatively associated with incident dementia. Taken together, the current study shows on a population level that moderate consumption of wine and moderate-to-high tea intake is associated with a decreased risk of incident dementia. In contrast, non-wine is positively related to dementia risk in a linear fashion, and no clear association is found for coffee.

Background: Diabetes mellitus and vascular diseases have a significant impact on the eye. / Aim: To determine the prevalence, risk factors, and racial/ethnic differences of major eye conditions, particularly retinal conditions, associated with diabetes and vascular diseases. / Scope: To date, the majority of studies have examined the association of retinal vascular calibre and diabetes in predominantly white Caucasian populations. Further elucidation of ethnic differences in effects of hyperglycaemia on early microvascular disease is relevant, particularly amongst Asians where diabetes is likely to see the largest increase in prevalence over the next decade. We therefore examined these findings from three Asian population-based studies, the Singapore Malay Eye Study (n=3280), Singapore Prospective Cohort Study and Singapore Cardiovascular Cohort Study 2 (n=3748). / Results: The prevalence of diabetic retinopathy in the Singapore Malay Eye Study was 35%, and associated with longer duration of diabetes, poorer glycemic and blood pressure control. More importantly, 9.0% had vision-threatening retinopathy, and retinopathy was found in 6.0% of people without diabetes. Retinal vascular calibre changes were incriminated in diseases such as diabetes and hypertension, independent of traditional cardiovascular risk factors. Wider venular calibre was independently associated with early age-related macular degeneration. We also found a novel association between peripheral artery disease and glaucoma, stronger in persons with diabetes, independent of vascular risk factors, supporting the vascular theory of glaucoma. / Implications: Subtle changes in retina, including retinal vascular calibre may be early markers of widespread microvascular changes in diabetes, resulting from chronic hyperglycaemia and other pathogenic processes. These results will have broad implications for understanding the impact of both microvascular and macrovascular complications of diabetes in the Asia Pacific region and targeting relevant therapeutic interventions.

Both spinal pain and temporomandibular disorders (TMD) commonly occur in the general population. Previous studies demonstrate neurophysiologic and biomechanical couplings between the trigeminal and cervical regions. This investigation tested the null hypothesis of no relationship between spinal pain (neck, shoulder and/or low back) and TMD, by using questionnaires and clinical examinations of the jaw function. In an age- and sex-matched case-control study, the specific aim was to compare the prevalence of signs and symptoms of TMD among cases with long-term spinal pain and controls without spinal pain. The results showed that subjects with spinal pain had signs and symptoms of TMD significantly more often than did controls. The associations remained after excluding all participants with jaw pain. Furthermore, the comorbidity pattern was similar, regardless of location of spinal pain. In a cross-sectional study, the specific aim was to test whether there is a reciprocal cross-sectional dose-response-like relationship between spinal pain and TMD. Two different designs were used, one with frequency/severity of spinal pain as independent variable, and the other, with frequency/severity of TMD symptoms as independent variable. The analysis showed increasing odds for presence of TMD symptoms with increasing frequency/severity of spinal pain, and increasing odds for presence of spinal pain with increasing frequency/severity of TMD symptoms. In a case-control study within a 2-year prospective cohort, the specific aim was to test whether there is a reciprocal temporal relationship between signs and symptoms in trigeminally, and symptoms in spinally, innervated areas. Incidence of symptoms in these areas was analyzed in relation to presence of spinal pain, headaches, and signs and symptoms of TMD at baseline. The main findings were that presence of signs of TMD at baseline increased the onset of spinal pain and symptoms in the trigeminal area, and that spinal pain increased the onset of symptoms in the trigeminal area. An augmentation effect between the significant baseline variables was observed for the incidence of headaches and jaw pain. In conclusion, the investigation demonstrated a cross-sectional and temporal relationship between spinal pain and TMD; thus, the null hypothesis was rejected. The results indicate common pathophysiological mechanisms in the development of spinal pain and TMD. The comorbidity and reciprocal influence that were found call for an integrated and multidimensional approach in the management of individuals with long-term spinal pain and TMD.

Background: To assess the long-term course of the feasibility and safety of orally administered heroin [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted opioid users. Design: Open-label, prospective cohort study with 2 non-randomly assigned treatment arms: DAM tablets only (n = 128) or DAM tablets combined with injected DAM and/or other opioids (n = 237). The average duration of the observation period was 62 months. Study endpoints were the time to discharge from treatment and the number of serious adverse events. Results: Both patient groups had a higher than 70% retention rate after the first 48 months of treatment, with similar long-term retention rates (after 8 years both groups had retention over 50%). The physician-verified rate of serious adverse events was 0.01 events per application year among the exclusively oral substitution group (intention-to-treat analysis) during the last year of observation, and 0.005 events per application year in the other group. Conclusions: Because of their feasibility and safety over years, DAM tablets may be a valuable long-term therapeutic alternative. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Les antidépresseurs figurent parmi les médicaments les plus prescrits dans les pays industrialisés, incluant la France. L’utilisation croissante de ces médicaments dans la population générale suscite de multiples préoccupations quant à leurs effets indésirables sur la santé des populations. Plusieurs travaux de recherche se sont récemment intéressés à l’impact de l’utilisation prolongée de ces médicaments sur le risque cardiométabolique. Toutefois, les résultats produits sont contradictoires, limitées et ne concernaient pas la population Française. L’objectif général de ce travail de thèse consiste donc à étudier, à partir des données de deux grandes cohortes françaises (E3N et D.E.S.I.R.), l’association entre l’utilisation de médicaments antidépresseurs et le risque cardiométabolique, en essayant d’en comprendre les mécanismes sous-jacents. La première étude a montré que l’utilisation d’antidépresseurs était associée à un risque accru de diabète de type II. Cependant, l’association était évidente uniquement chez les femmes qui avaient plus de consultations médicales au cours des douze derniers mois. Les résultats de la seconde étude n’ont montré aucune association entre l’utilisation d’antidépresseurs et les marqueurs physio-biologiques qui caractérisent le diabète tels que : la glycémie à jeun, l’hémoglobine glyquée, la fonction des cellules β et la sensibilité à l’insuline. Enfin la troisième étude de ce travail de thèse a mis en évidence un risque accru de syndrome métabolique chez les utilisateurs d’antidépresseurs même si l’effet semblait se potentialiser chez les hommes uniquement. Les résultats de ces études apportent des éléments en faveur de l’hypothèse d’un biais de détection pour expliquer l’association observée entre utilisation d’antidépresseurs et diabète. Ce travail de thèse a permis de clarifier l’association entre l’utilisation d’antidépresseurs chez l’adulte et le risque cardiométabolique. Les implications scientifiques, cliniques et de santé publique sont discutées. / Antidepressants are among the most frequently prescribed medications in industrialized countries, including France. The increasing use of antidepressants in the general population has led to concerns about their adverse effects on health. Recently, important research work has focused on the impact of the prolonged use of antidepressants on cardiometabolic risk. However, the results produced were conflicting, limited and were not based on French population. The general objective of this thesis is therefore to study, based on data from two large French cohorts (E3N and D.E.S.I.R.), the association between the use of antidepressant drugs and cardiometabolic risk, with the ambition to understand the underlying mechanisms. The first study showed antidepressant medication use to be associated with an increased risk of type II diabetes. However, this association was evident only in women with more medical visits in the last twelve months. The results of the second study shows no association between antidepressant medication use and physio-biological markers that characterize diabetes such as fasting plasma glucose, glycated haemoglobin, β-cell function and insulin sensitivity. Finally, the third study showed an increased risk of metabolic syndrome among users of antidepressants, although the effect was apparent in men only. The results of these studies provide evidence supporting the hypothesis of a detection bias to explain the observed association between antidepressants use and diabetes. This work has helped to clarify the association between the use of antidepressants in adults and cardiometabolic risk. The scientific, clinical and public health implications are discussed.

Background: Although lifestyle modification is the cornerstone of GDM management, the evidence base on which dietary recommendations to prevent GDM is diverse and has not been synthesized in a consistent fashion. Objectives: The overall objective of this thesis is to assess the relationship of diet patterns, foods, and nutrients with GDM risk. Specifically, we seek to: 1) Quantify the relationship between dietary factors and GDM and metabolic disorders of pregnancy; 2) Compare the effects of dietary factors on markers of glycemic control, such as fasting glucose, fasting insulin, HbA1c, and the homeostatic model assessment for insulin resistance (HOMA-IR); 3) Assess the association and interaction between carbohydrate quality, and genetic load on the risk of developing GDM using data from 2 prospective birth cohort studies. Methods: We follow the approach set by the Cochrane Group’s Handbook for Systematic Review of Interventions to conduct meta-analyses and assess the quality of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. We analyze prospective cohort data of 2,504 women from the CHILD and START studies, which enrolled women of White-Caucasian and South Asian ethnicity. We quantify carbohydrate quality by deriving the glycemic index and load (GL), and total and added sugar intake. We construct a gene score using 102 loci that were previously associated with type 2 diabetes in genome-wide association studies. Results: 1) The meta-analysis identified high-quality evidence that red meat increases GDM risk; however, most associations of foods and nutrients with GDM and other metabolic disorders of pregnancy are of low-quality; 2) The network meta-analysis identified that most dietary interventions given with gestational weight gain advice will lower fasting glucose; 3) In South Asians, a high GL coupled with a high genetic load increased GDM risk six fold, but a high total sugar intake in the presence of a high genetic load reduced GDM risk. This paradoxical finding may be explained by a high correlation between total sugars and other healthy foods. Conclusions: Few valid associations between dietary factors and GDM risk exist. GL and total sugars may modify the genetic risk of GDM in South Asians but not in White-Caucasians. Further research is needed to determine effective interventions that can assist women in adopting healthier eating habits during pregnancy. / Thesis / Doctor of Philosophy (PhD) / Gestational diabetes mellitus (GDM) is glucose intolerance that first appears during pregnancy. Although lifestyle modification is the cornerstone of GDM management, dietary recommendations for GDM prevention are sparse. The overarching objective of this thesis is to describe the relationships between diets, foods, and nutrients and GDM and metabolic disorders of pregnancy and to understand whether carbohydrate quality can modify a genetic predisposition to diabetes. In the systematic literature reviews, high-quality evidence showed that red meat increases GDM risk. Moderate-quality evidence showed that several dietary factors also influence the risk of GDM and metabolic disorders of pregnancy, but most of the existing evidence is of low-quality. More high-quality studies are needed before dietary interventions can be implemented In our genetic study, we observed that carbohydrate quality may modify the genetic risk of diabetes in South Asians but not in White-Caucasians and conclude that carbohydrate quality may provide only a limited assessment of overall diet quality.

En chirurgie, les critères d’évaluation des soins sont surtout relatifs à la technique et à la biologie, et les facteurs psychologiques et sociaux sont peu présents. En particulier, la subjectivité du chirurgien et son rôle dans les soins prodigués sont des aspects peu étudiés, malgré (i) un taux de burnout des chirurgiens proche de 40%, (ii) la singularité du chirurgien (son expérience, sa personnalité, ses choix de prise en charge, etc.), variable clé dans les soins prodigués (comme le psychothérapeute en psychothérapie), (iii) l’environnement social et culturel particulier dans lequel travaillent les chirurgiens. L’objectif de cette thèse est d’explorer les facteurs psychosociaux qui peuvent influencer la pratique de la chirurgie et le bien-être des chirurgiens. Trois études ont été menées. La première est une revue systématique de la littérature qualitative (méta-synthèse) portant sur comment les chirurgiens vivent leur pratique. A l’issue de la première étude, nous avons approfondi les résultats au travers d’une étude qualitative sur l’expérience émotionnelle des chirurgiens hépatobiliaires (chirurgie à haut risque ; surtout oncologique). Une troisième étude prospective de cohorte s’est intéressée à la détermination de l’influence des facteurs psychologiques du patient (dépression et anxiété) sur l’outcome de la chirurgie hépatique, et a permis d'explorer comment les chirurgiens prennent en compte ces facteurs dans leur pratique. Nous avons discuté les implications de nos résultats par rapport à la santé mentale et aux burnouts des chirurgiens, ainsi que par rapport à la mise en œuvre du modèle bio-psycho- social dans les soins des patients chirurgicaux. / In surgery, psychological and social factors are not widely studied, and the only variables considered important in surgical care are those related to operating technique and biology. Additionally, surgeons’ experience of their practice is neglected, despite the fact that (i) epidemiological studies showed a 40% burnout rate among surgeons, (ii) the difference between individual surgeons is a key variable in the performed care (like psychotherapists in psychotherapy), and (iii) surgeons work in a high salient social and cultural environment. The aim of this PhD thesis is to explore the psychosocial factors influencing surgical practice and surgeons’ wellbeing. Our findings are based on three studies. First, we performed a systematic review of international qualitative studies (metasynthesis) in order to describe how surgeons experience their practice from their perspective. Then, a second qualitative study extended the findings of the previous one exploring in-depth the everyday emotional experience of liver surgeons (high risk surgery, mainly cancer-related). Finally, a prospective cohort study investigated the influence of preoperative patient-related psychological factors (depression and anxiety) on the outcome of liver surgery, and how surgeons take these data into account in their practice. Several implications of our findings have been discussed, concerning surgeons’ mental wellbeing and burnout, as well as the implementation of the bio-psycho-social model in the care of surgical patients.