Frédéric Dutheil

Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality associated with cardiometabolic disorders including dyslipidaemia, insulin resistance, and cachectic obesity. Tumour necrosis factor inhibitors and interleukin 6 receptor blocker licensed for the treatment of RA decrease inflammation and could thus improve cardiovascular risk, but their effects on body composition and metabolic profile need to be clarified. We investigated the effects of tocilizumab (TCZ), a humanized anti‐interleukin 6 receptor antibody, on body composition and metabolic profile in patients treated for RA.

Long-term cost reduction of routine medications following a residential programme combining physical activity and nutrition in the treatment of type 2 diabetes: a prospective cohort study

Objectives To demonstrate that lifestyle modifications will reduce the cost of routine medications in individuals with type 2 diabetes (T2D), through a mechanism involving glycaemic control. Design A within-trial cost-medication analysis with a 1-year time horizon. Setting Controlled environment within the spa resort of Chatel-Guyon, France. Participants Twenty-nine participants (aged 50–70 years) with T2D. Interventions A 1-year follow-up intervention, beginning with a 3-week residential programme combining high exercise volume (15–20 hours/week), restrictive diet (−500 kcal/day) and education. Participants continued their routine medication, independently managed by their general practitioner. Main outcome measures Number of medications, number of pills, cost of medications and health-related outcomes. Results Twenty-six participants completed the 1-year intervention. At 1 year, 14 patients out of 26 (54%) stopped/decreased their medications whereas only 5 (19%) increased or introduced new drugs (χ2=6.3, p=0.02). The number of pills per day decreased by 1.3±0.3 at 12 months (p<0.001). The annual cost of medications for T2D were lower at 1 year (€135.1±43.9) versus baseline (€212.6±35.8) (p=0.03). The regression coefficients on costs of routine medication were 0.507 (95% CI 0.056 to 0.959, p=0.027) for HbA1c and 0.156 (95% CI −0.010 to 0.322, p=0.06) for blood glucose levels. Diabetics patients with HbA1c >6.5% in the highest (last) quartile doubled their routine medication costs (66% vs 33%, p=0.037). Conclusions Individuals with T2D reduced routine medication costs following a long-term lifestyle intervention that started with a 3-week residential programme. Combining high exercise volume, restrictive diet and education effectively supported the health of T2D. The main factor explaining reduced medication costs was better glycaemic control, independent of weight changes. Despite limitations precluding generalisability, cost-effective results of reduced medication should contribute to the evidence base required to promote lifestyle interventions for individuals with T2D. Trial registration number NCT00917917; Post-results.

At-risk and intervention thresholds of occupational stress using a visual analogue scale

Background The visual analogue scale (VAS) is widely used in clinical practice by occupational physicians to assess perceived stress in workers. However, a single cut-off (black-or-white decision) inadequately discriminates between workers with and without stress. We explored an innovative statistical approach to distinguish an at-risk population among stressed workers, and to establish a threshold over which an action is urgently required, via the use of two cut-offs. Methods Participants were recruited during annual work medical examinations by a random sample of workers from five occupational health centres. We previously proposed a single cut-off of VAS stress in comparison with the Perceived Stress Scale (PSS14). Similar methodology was used in the current study, along with a gray zone approach. The lower limit of the gray zone supports sensitivity (“at-risk” threshold; interpreted as requiring closer surveillance) and the upper limit supports specificity (i.e. “intervention” threshold–emergency action required). Results We included 500 workers (49.6% males), aged 40±11 years, with a PSS14 score of 3.8±1.4 and a VAS score of 4.0±2.4. Using a receiver operating characteristic curve and the PSS cut-off score of 7.2, the optimal VAS threshold was 6.8 (sensitivity = 0.89, specificity = 0.87). The lower and upper thresholds of the gray zone were 5 and 8.2, respectively. Conclusions We identified two clinically relevant cut-offs on the VAS of stress: a first cut-off of 5.0 for an at-risk population, and a second cut-off of 8.2 over which an action is urgently required. Future investigations into the relationships between this upper threshold and deleterious events are required.

The Need for Objective Measures of Stress in Autism

Despite the numerous definition of stress, the meaning of stress could refer to the adaptive behavioral or mental responses willing to address the common life consequences of stressors, such as increased attention to perform a mentally demanding task. The stressor can be real or perceived, pleasant, or unpleasant (Woda et al., 2016). Permanent adaptation to normal daily stressors is needed, via the physiological stress system. The physiological stress response triggers metabolic adaptations to the acute stressors (via activation of the autonomic nervous systemmostly resulting in release of epinephrine by the adrenal medulla) and anticipates what may happen (via activation of the hypothalamo-pituitary adrenal axis resulting in release of corticosteroids by the cortical medulla) (McEwen, 2000; Woda et al., 2016). Morbid consequences can be expected when an individual is affected by a failure of the stress response system to stressors. Therefore, in its commonplace, the term “stress” is often viewed as a negative concept, with morbid consequences (Woda et al., 2016). One of these negative effects is anxiety. With anxiety, fear overcomes all emotions and is accompanied by worry and apprehension (Sylvers et al., 2011; Adhikari, 2014). While there is a definite overlap between stress and anxiety, we will use the term stress as a negative physiological and psychological impact of stressors.

Evaluation of 'I-Preventive': a digital preventive tool for musculoskeletal disorders in computer workers-a pilot cluster randomised trial.

Objectives I-Preventive is a digital preventive tool for musculoskeletal disorders (MSDs) in computer workers. We sought to determine its impact on pain in computer workers with upper limb MSDs and visual discomfort. Methods We conducted a pilot cluster randomised trial in 2 different sites of a tyre factory in France. We randomised 200 employees to either an intervention group (I-Preventive) or control group, each comprising symptomatic and asymptomatic employees. The workers were followed up for 5 months. The main outcome was overall recovery from symptoms following 1 months intervention based on Nordic-style and eyestrain questionnaires. Results We included 185/200 workers: 96 in the intervention group (mean age 41.8±1.4 years; 88.5% males) and 79 in the control group (mean age 42.9±12.0 years; 94.5% males). The most painful areas (numerical scale ≥2) were the neck (40.0%), upper back (18.8%) and shoulders (15.7%). For the most painful anatomical area, the Nordic score significantly decreased after 1 month in the intervention group (p=0.038); no change was observed in the control group (p=0.59). After 1 months use, the intervention group reported less pain in the painful area and less visual discomfort symptoms (p=0.02). Adherence to the I-Preventive program was 60%. Conclusions I-Preventive is effective in the short term on musculoskeletal symptoms and visual discomfort by promoting active breaks and eyestrain treatment. This easy-to-use digital tool allows each worker to focus on areas of their choice via personalised, easy exercises that can be performed in the workplace. Trial registration number NCT02350244; Pre-results.

Incidence of ill-health related job loss and related social and occupational factors. The “unfit for the job” study: a one-year follow-up study of 51,132 workers

Objective The analysis of ill-health related job loss may be a relevant indicator for the prioritization of actions in the workplace or in the field of public health, as well as a target for health promotion. The aim of this study was to analyze the medical causes, the incidence, and the characteristics of employees medically unfit to do their job. Methods This one-year prospective study included all workers followed by occupational physicians in an occupational health service in the south of France. The incidence of unfitness for work have been grouped according to the main medical causes and analyzed. We performed a multivariate analysis in order to adjust the observed risk of job loss based on the age groups, sex, occupation and the activity sectors. Results A total of 17 occupational physicians followed up 51,132 workers. The all-cause incidence of being unfit to return to one’s job was 7.8‰ (n = 398). The two main causes of being unfit for one’s job were musculoskeletal disorders (47.2%, n = 188) and mental ill-health (38.4%, n = 153). Being over 50 years old (Odds ratio (OR) 2.63, confidence interval 95% CI [2.13–3.25]) and being a woman (OR 1.52, 95% CI [1.21–1.91]) were associated with the all-cause unfitness, independent of occupation and activity sector. Conclusions Identification of occupational and demographic determinants independently associated with ill-health related job loss may provide significant and cost-effective arguments for health promotion and job loss prevention.

Glucose dysregulation in Parkinson's disease: Too much glucose or not enough insulin?

OBJECTIVE To detect changes in glucose regulation in moderate to advanced Parkinsons disease (PD) patients in response to oral glucose intake. METHODS Blood glucose and insulin kinetics during a 75-g Oral Glucose Tolerance Test (OGTT) were compared between 50 PD patients and 50 healthy controls (CT) matched for body mass index (BMI), age and sex. Potential relationships between changes in glucose kinetics and clinical parameters were analyzed including Parkinsons disease severity and autonomic function using SCOPA-AUT (Scales for Outcomes in Parkinsons disease, Autonomic dysfunction). RESULTS Blood glucose was significantly higher at T90 (p = 0.04) and T150 (p = 0.01) in PD patients compared to healthy matched controls. Moreover, the total area under time curve (AUC) for the blood glucose levels was significantly higher in PD patients compared to healthy controls (1187 ± 229 vs 1101 ± 201 mmol min.l-1; p = 0.05). Simultaneously, no significant increase of insulin levels was observed in PD patients compared to controls. Higher blood glucose levels were associated with higher BMI (p < 0.001), female gender (p < 0.033), longer duration of PD (p = 0.001), lower dose of dopaminergic treatment (p = 0.023), and higher score of dysautonomia (p = 0.017). CONCLUSION Glucose control is impaired in moderate to advanced non-diabetic PD patients, due to impaired adaptive insulin response which may be a novel non-motor consequence of PD associated dysautonomia.

Influence of uncertainty on framed decision-making with moral dilemma

In cases of impending natural disasters, most events are uncertain and emotionally relevant, both critical factors for decision-making. Moreover, for exposed individuals, the sensitivity to the framing of the consequences (gain or loss) and the moral judgments they have to perform (e.g., evacuate or help an injured person) constitute two central effects that have never been examined in the same context of decision-making. In a framed decision-making task with moral dilemma, we investigated whether uncertainty (i.e., unpredictably of events) and a threatening context would influence the framing effect (actions framed in loss are avoided in comparison to the ones framed in gain) and the personal intention effect (unintentional actions are more morally acceptable in comparison to intentional actions) on the perceived moral acceptability of taking action. Considering the impact of uncertainty and fear on the processes underlying these effects, we assumed that these emotions would lead to the negation of the two effects. Our results indicate that the exposure to uncertain events leads to the negation of the framing effect, but does not influence the moral acceptability and the effect of personal intention. We discuss our results in the light of dual-process models (i.e. systematic vs. heuristic), appraisal theories, and neurocognitive aspects. These elements highlight the importance of providing solutions to cope with uncertainty, both for scientists and local populations exposed to natural hazards.

Different modalities of exercise improve macrovascular function but not microvascular function in metabolic syndrome: The RESOLVE randomized trial

OBJECTIVE To determine which modality of exercise program (endurance and/or resistance dominance) is the most effective for improving vascular function in the micro- and macrocirculation in metabolic syndrome (MetS). METHODS Sixty-two MetS patients were enrolled in a 6-month lifestyle intervention program based on diet and exercise training. Each participant was randomly assigned to one of 3 groups categorized by exercise modality (e.g. high-intensity resistance or endurance training, or combined moderate-intensity). Measurements of anthropometrics, biological blood markers, physical fitness and vascular function were performed at baseline, at the end of the 3-week residential program, and at 3 and 6 months after baseline. Brachial artery flow-mediated dilation (FMD) and the response to sublingual nitrate were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated using laser Doppler flowmetry in conjunction with iontophoresis of acetylcholine and sodium nitroprusside. RESULTS Regardless of the training program, FMD significantly increased from baseline to 3 weeks in all groups with no further changes at 3 and 6 months. Changes in central fat, diastolic blood pressure, triglycerides, interleukin-6 and physical fitness were independent predictors of increased FMD. Nitrate-mediated dilation increased from baseline to 3 months and then remained unchanged up to 6 months. Endothelium-dependent and endothelium-independent function of the skin microcirculation did not change significantly in all groups. CONCLUSIONS In MetS patients, exercise training, regardless of its endurance or resistance dominance, is able to improve vascular function in large vessels only. Lifestyle intervention programs including exercise training must be encouraged in those with MetS. NCT00917917.

Evidence of Rapid Modulation by Social Information of Subjective, Physiological, and Neural Responses to Emotional Expressions.

Recent research suggests that conceptual or emotional factors could influence the perceptual processing of stimuli. In this article, we aimed to evaluate the effect of social information (positive, negative, or no information related to the character of the target) on subjective (perceived and felt valence and arousal), physiological (facial mimicry) as well as on neural (P100 and N170) responses to dynamic emotional facial expressions (EFE) that varied from neutral to one of the six basic emotions. Across three studies, the results showed reduced ratings of valence and arousal of EFE associated with incongruent social information (Study 1), increased electromyographical responses (Study 2), and significant modulation of P100 and N170 components (Study 3) when EFE were associated with social (positive and negative) information (vs. no information). These studies revealed that positive or negative social information reduces subjective responses to incongruent EFE and produces a similar neural and physiological boost of the early perceptual processing of EFE irrespective of their congruency. In conclusion, the article suggests that the presence of positive or negative social context modulates early physiological and neural activity preceding subsequent behavior.