Validation of a natural language processing algorithm using national reporting data to improve identification of anesthesia-related ADVerse evENTs: The "ADVENTURE" study.

BACKGROUND: Reporting and analysis of adverse events (AE) is associated with improved health system learning, quality outcomes, and patient safety. Manual text analysis is time-consuming, costly, and prone to human errors. We aimed to demonstrate the feasibility of novel machine learning and natural language processing (NLP) approaches for early predictions of adverse events and provide input to direct quality improvement and patient safety initiatives. METHODS: We used machine learning to analyze 9559 continuously reported AE by clinicians and healthcare systems to the French National Health accreditor (HAS) between January 1, 2009, and December 31, 2020 . We validated the labeling of 135,000 unique de-identified AE reports and determined the associations between different system's root causes and patient consequences. The model was validated by independent expert anesthesiologists. RESULTS: The machine learning (ML) and Artificial Intelligence (AI) model trained on 9559 AE datasets accurately categorized 8800 (88%) of reported AE. The three most frequent AE types were "difficult orotracheal intubation" (16.9% of AE reports), "medication error" (10.5%), and "post-induction hypotension" (6.9%). The accuracy of the AI model reached 70.9% sensitivity, 96.6% specificity for "difficult intubation", 43.2% sensitivity, and 98.9% specificity for "medication error." CONCLUSIONS: This unsupervised ML method provides an accurate, automated, AI-supported search algorithm that ranks and helps to understand complex risk patterns and has greater speed, precision, and clarity when compared to manual human data extraction. Machine learning and Natural language processing (NLP) models can effectively be used to process natural language AE reports and augment expert clinician input. This model can support clinical applications and methodological standards and used to better inform and enhance decision-making for improved risk management and patient safety. TRIAL REGISTRATION: The study was approved by the ethics committee of the French Society of Anesthesiology (IRB 00010254-2020-20) and the CNIL (CNIL: 118 58 95) and the study was registered with ClinicalTrials.gov (NCT: NCT05185479).

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

OBJECTIVES: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. DESIGN: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. RESULTS: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. CONCLUSION: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER: NCT02059538.

Public health potential of guidelines-based dietary scores for non-communicable diseases mortality prevention: simulation study using the Preventable Risk Integrated ModEl (PRIME) model.

OBJECTIVE: Dietary indexes measure the adherence of individuals to a set of nutritional recommendations. However, the health gains associated with adherence to various dietary indexes may vary. Our objective was to compare the magnitude of estimated avoided deaths by chronic diseases obtained by improving diet quality in the French population, measured by a variety of dietary indexes. DESIGN: Simulation study based on observational data. SETTING: Weighted data from a French population-based cohort study. PARTICIPANTS: In participants from the NutriNet-Santé cohort, we computed dietary scores reflecting the adherence to various recommendations (Medi-Lite, Healthy Diet Indicator (HDI), Programme National Nutrition Santé/National Nutrition and Health Program - Guidelines Score, Diet Quality Index (DQI), Alternative Healthy Eating Index (AHEI) and the modified Food Standards Agency nutrient profiling system dietary index (FSAm-NPS DI)). Quintiles of the food groups' consumption and dietary intakes were used as input in a simulation model (Preventable Risk Integrated ModEl (PRIME)), yielding the number of delayed or avoided deaths in nutrition-related non-communicable diseases, comparing between very high or very low nutritional quality of the diet and medium nutritional quality. RESULTS: A modification of dietary intakes from medium quality to very low quality (i.e. from the middle quintile to the quintile with the lowest nutritional quality) was associated with an increased number of deaths ranging from 3485 (95 % uncertainty interval (CI) 4002, 2987) for HDI and 3379 (95 % CI 3881, 2894) for FSAm-NPS DI to 838 (95 % CI 1163, 523) for Medi-Lite. Conversely, a modification of dietary intakes from medium quality to very high quality was associated with a decrease in the number of deaths ranging from 1995 (95 % CI 1676, 2299) for Probability of Adequate Nutrient intake diet, 1986 (95 % CI 1565, 2361) for DQI-International, 1931 (95 % CI 1499, 2316) for FSAm-NPS DI and 858 (95 % CI 499, 1205) for HDI. CONCLUSIONS: Our results provide some insights as the potential impact of following various dietary guidelines to reduce mortality from nutrition-related diseases.

Associations between untargeted plasma metabolomic signatures and gut microbiota composition in the Milieu Intérieur population of healthy adults.

Host-microbial co-metabolism products are being increasingly recognised to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host-microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton NMR analysis of plasma. The associations between metabolomic variables and α- and ß-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, permutational ANOVA and multivariate associations with linear models, respectively. A multiple testing correction was applied (Benjamini-Hochberg, 10 % false discovery rate). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose and citrate (-0·133 ≤ Spearman's ρ ≤ 0·126). Specific associations between metabolomic signals and abundances of taxa were detected (twenty-five at the genus level and nineteen at the species level): notably, numerous associations were observed for creatinine (positively associated with eleven species and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host-gut microbiota metabolic relationships. In particular, our results support the implication of a 'gut-kidney axis'. More studies providing a detailed exploration of these complex interactions and their implications for host health are needed.

Association of diet quality and physical activity with healthy ageing in the French NutriNet-Santé cohort.

A growing number of studies have explored overall health during ageing in a holistic manner by investigating multidimensional models of healthy ageing (HA). However, little attention has been given to the role of adherence to national nutrition guidelines in that context. This study aimed to investigate the prospective association between adherence to the French nutrition guidelines and HA. The authors analysed data from 21 407 participants of the NutriNet-Santé study with a median baseline age of 55·6 years (2009-2014) and initially free of major chronic diseases. HA was defined as not developing major chronic disease, no depressive symptoms, no function-limiting pain, independence in instrumental activities of daily living, good physical, cognitive and social functioning, as well as good self-perceived health. Adherence to guidelines of the French Nutrition and Health Programme (Programme National Nutrition Santé or PNNS) was measured via the PNNS Guideline Score (PNNS-GS), using baseline data from repeated 24-h dietary records and physical activity questionnaires. After a median follow-up of 5·7 years, 46·3 % of participants met our HA criteria. Robust-error-variance Poisson regression revealed that higher PNNS-GS scores, reflecting higher adherence to nutrition recommendations (including both diet and physical activity guidelines), were associated with a higher probability to age healthily (relative riskquartile 4 v. quartile 1 = 1·17 (95 % CI 1·12, 1·22)). Supplementary analyses revealed that this association may, to a small part, be mediated by weight status. The results suggest that high adherence to the French national nutrition recommendations may be linked to better overall health throughout ageing.

The Inflammatory Potential of the Diet is Directly Associated with Incident Depressive Symptoms Among French Adults.

BACKGROUND: Low-grade chronic inflammation has been suggested to play a substantial role in the etiology of depression; however, studies on the prospective association between the inflammatory potential of the diet and depression are limited. OBJECTIVE: The aim of this study was to investigate the association between the inflammatory potential of the diet (measured using the Alternate Dietary Inflammatory Index, ADII) and incident depressive symptoms. We also tested the potential modulating effect of sex, age, BMI, and lifestyle indicators. METHODS: The study sample consisted of 26,730 participants (aged 18-86 y) from the NutriNet-Santé study. Baseline ADII was computed using repeated 24-h dietary records collected during the first 2 y of the follow-up. Incident cases of depressive symptoms were defined by a Center for Epidemiologic Studies Depression scale ≥17 for men and ≥23 for women at least once during follow-up. HR and 95% CI were estimated using multivariable Cox proportional hazards models. RESULTS: A total of 2221 incident cases of depressive symptoms were identified over a mean follow-up of 5.4 y. After accounting for a wide range of potential confounders, the highest quartile of the ADII was associated with a 15% (95% CI: 2, 31) increase in the risk of depressive symptoms compared with the lowest quartile. In the stratified analyses, associations were statistically significant only among women (HRquartile4 vs. quartile1: 1.19; 95% CI: 1.02, 1.37), middle-age adults (HRquartile4 vs. quartile1: 1.16; 95% CI: 1.00, 1.35), and participants with a BMI ≥25 (HRquartile4 vs. quartile1: 1.29; 95% CI: 1.04, 1.60). CONCLUSIONS: Overall, a proinflammatory diet was associated with a higher risk of depressive symptoms, especially among women, middle-age adults, and participants with overweight or obesity. These findings contribute to the increasing scientific evidence showing a detrimental role of the proinflammatory diet. The NutriNet-Santé study is registered at clinicaltrials.gov as NCT03335644.

Prospective association between ultra-processed food consumption and incident depressive symptoms in the French NutriNet-Santé cohort.

BACKGROUND: Ultra-processed food (UPF) consumption has increased over the last decades in Westernized countries. Our objective was to investigate for the first time the association between the proportion of UPF (%UPF) in the diet and incident depressive symptoms in the NutriNet-Santé cohort. METHODS: The sample included 20,380 women and 6350 men (aged 18-86 years) without depressive symptoms at the first Center for Epidemiologic Studies Depression Scale (CES-D) measurement, using validated cut-offs (CES-D score ≥ 17 for men and ≥ 23 for women). The proportion of UPF in the diet was computed for each subject using the NOVA classification applied to dietary intakes collected by repeated 24-h records (mean = 8; SD = 2.3). The association between UPF and depressive symptoms was evaluated using multivariable Cox proportional hazards models. RESULTS: Over a mean follow-up of 5.4 years, 2221 incident cases of depressive symptoms were identified. After accounting for a wide range of potential confounders, an increased risk of depressive symptoms was observed with an increased %UPF in the diet. In the main model adjusted for sociodemographic characteristics, body mass index, and lifestyle factors, the estimated hazard ratio for a 10% increase in UPF was 1.21 (95% confidence interval = 1.15-1.27). Considering %UPF in food groups, the association was significant only for beverages and sauces or added fats. CONCLUSION: Overall, UPF consumption was positively associated with the risk of incident depressive symptoms, suggesting that accounting for this non-nutritional aspect of the diet could be important for mental health promotion.

Prospective association between adherence to the MIND diet and subjective memory complaints in the French NutriNet-Santé cohort.

OBJECTIVES: Our objective was to examine whether adherence to the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) was associated with SMC (as measured by the cognitive difficulties scale; CDS) in the NutriNet-Santé cohort. METHODS: The study sample consisted of 6011 participants aged ≥ 60 years at baseline, without SMC at the beginning. SMC were defined by a CDS score ≥ 43 (corresponding to the 4th CDS quartile) and SMC cases were participants with SMC at least once during follow-up. The MIND diet score (0-15 points) is a hybrid of the Mediterranean Diet and the Dietary Approaches to Stop Hypertension (DASH) scores, which includes ten brain healthy food groups and five unhealthy food groups. We used Cox proportional hazards models to estimate Hazard Ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Over a mean follow-up of 6 years, approximately 15% and 30% cases of SMC were identified among participants aged 60-69 and ≥ 70 years, respectively. The MIND diet score was not significantly associated with SMC in the full sample and among participants aged 60-69 years. Among participants aged ≥ 70 years, a significant inverse association was observed between adherence to the MIND diet and SMC (HRtertile 3 vs tertile 1 = 0.69, 95% CI = 0.47-0.99). This relationship was strengthened after exclusion of participants with depressive symptoms (HRtertile 2 vs tertile 1 = 0.69, 95% CI = 0.49-0.97; HRtertile 3 vs tertile 1 = 0.62, 95% CI = 0.41-0.93). CONCLUSIONS: These findings suggest that the MIND diet could help to prevent or delay SMC among older adults without depressive symptoms.

Unsaturated Fatty Acid Intakes During Midlife Are Positively Associated with Later Cognitive Function in Older Adults with Modulating Effects of Antioxidant Supplementation.

Background: Given the drastic demographic changes characterized as "population aging," the disease burden related to dementia is a major public health problem. The scientific literature documenting the link between mono- and polyunsaturated fatty acids (MUFAs, PUFAs) and cognitive function during aging is plentiful, but findings are inconsistent. Objectives: We aimed to evaluate the association between intakes of unsaturated fatty acids at midlife and cognitive performance 13 y later in French adults, and to test for a modulating effect of antioxidant supplementation. Methods: Fatty acid intakes were estimated with the use of repeated 24-h records (1994-1996) among 3362 subjects (mean ± SD age: 65.5 ± 4.6 y) of the SU.VI.MAX (Supplementation with Antioxidant Vitamins and Minerals) study, including an intervention phase (1994-2002) during which participants were randomly assigned to an "antioxidant supplementation" or placebo group. Cognitive performance was assessed at follow-up only (in 2007-2009) via a battery of 6 standardized neuropsychological tests. A global cognitive score was calculated as the sum of T-scores of the 6 tests. Multivariable-adjusted regression analyses were performed to provide regression coefficients and 95% CIs. Results: In multivariable models, total MUFAs, total PUFAs, and n-6 PUFAs (ω-6 PUFAs) were positively associated with overall cognitive functioning. n-3 PUFA (ω-3 PUFA) intakes showed positive associations among supplemented participants only (mean difference Tertile3 versus Tertile1: 1.40; 95% CI: 0.30, 2.51; P-trend = 0.01, P-interaction = 0.01). A detrimental role of arachidonic acid for cognitive functioning was only detected in the placebo group (mean difference Tertile3 versus Tertile1: -1.38; 95% CI: -2.57, -0.18; P-trend = 0.02, P-interaction = 0.07). Conclusion: Whereas higher total MUFA and n-6 PUFA intakes may be generally beneficial for maintaining cognitive health during aging, a higher consumption of n-3 fatty acids may only be beneficial among individuals with an adequate antioxidant status. These findings underline the importance of not only focusing on specific nutrients for dementia prevention, but also considering the complex interaction between consumed nutrients. This trial was registered at clinicaltrials.gov as NCT00272428.

Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Santé Prospective Cohort Study.

Importance: Although organic foods are less likely to contain pesticide residues than conventional foods, few studies have examined the association of organic food consumption with cancer risk. Objective: To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults. Design, Setting, and Participants: In this population-based prospective cohort study among French adult volunteers, data were included from participants with available information on organic food consumption frequency and dietary intake. For 16 products, participants reported their consumption frequency of labeled organic foods (never, occasionally, or most of the time). An organic food score was then computed (range, 0-32 points). The follow-up dates were May 10, 2009, to November 30, 2016. Main Outcomes and Measures: This study estimated the risk of cancer in association with the organic food score (modeled as quartiles) using Cox proportional hazards regression models adjusted for potential cancer risk factors. Results: Among 68 946 participants (78.0% female; mean [SD] age at baseline, 44.2 [14.5] years), 1340 first incident cancer cases were identified during follow-up, with the most prevalent being 459 breast cancers, 180 prostate cancers, 135 skin cancers, 99 colorectal cancers, 47 non-Hodgkin lymphomas, and 15 other lymphomas. High organic food scores were inversely associated with the overall risk of cancer (hazard ratio for quartile 4 vs quartile 1, 0.75; 95% CI, 0.63-0.88; P for trend = .001; absolute risk reduction, 0.6%; hazard ratio for a 5-point increase, 0.92; 95% CI, 0.88-0.96). Conclusions and Relevance: A higher frequency of organic food consumption was associated with a reduced risk of cancer. If these findings are confirmed, further research is necessary to determine the underlying factors involved in this association.

How Healthy Lifestyle Factors at Midlife Relate to Healthy Aging.

With increasing life expectancies worldwide, it is an important public health issue to identify factors that influence the quality of aging. We aimed to investigate the individual and combined roles of lifestyle factors at midlife for healthy aging (HA). We analyzed data from 2203 participants of the French ”Supplémentation en Vitamines et Minéraux Antioxydants” (SU.VI.MAX) cohort aged 45⁻60 years at baseline (1994⁻1995), and assessed the combined impact of lifestyle factors (weight, smoking status, physical activity, alcohol consumption, and diet) on HA (absence of chronic diseases and function-limiting pain, good physical and cognitive functioning, functional independence, no depressive symptoms, and good social and self-perceived health) with a five-component healthy lifestyle index (HLI). Relative risks (RR) and 95% confidence intervals (CIs) were estimated using a robust-error-variance Poisson regression. Approximately 39% of our sample aged healthily. After adjustment for potential confounders, a one-point increase in HLI was related to an 11% higher probability of HA (95% CI = 6%, 16%; p < 0.001). The proportions of HA attributable to specific factors based on the “population attributable risk” concept were 7.6%, 6.0%, 7.8%, and 16.5% for body mass index (BMI), physical activity, diet quality, and smoking status, respectively. This study highlights the importance of healthy lifestyle habits at midlife for the promotion of good overall health during aging.

Prospective association between combined healthy lifestyles and risk of depressive symptoms in the French NutriNet-Santé cohort.

BACKGROUND: Several modifiable lifestyle indicators, including diet, smoking, alcohol consumption, weight and physical activity have been associated with depression; however, their combined effect has been less studied. The aim of this study was to calculate a Healthy Lifestyle Index (HLI) composed of the 5 above-mentioned indicators and investigate its association with incident depressive symptoms. METHODS: The study sample consisted of 25,837 participants from the NutriNet-Santé study, initially free of depressive symptoms. The HLI was computed by assigning 1 point to each lifestyle indicator namely healthy diet, healthy weight, moderate or high physical activity, never smoking and low alcohol consumption. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Hazard Ratios were estimated using Cox proportional hazards models and population attributable risks (PAR) were calculated. RESULTS: A total of 2112 incident cases of depressive symptoms were identified over a mean follow-up of 5 years. After accounting for a wide range of potential confounders, a 1-point increase in the HLI was associated with a 10% (95% CI 6%; 13%) reduction in the risk of depressive symptoms. The estimated PAR representing the proportion of cases that are attributable to non-adherence to specific healthy lifestyle indicators were 8% for healthy diet, 5% for healthy weight, 5% for non-smoking and 14% for the non-adherence to a combination of healthy diet, healthy weight and non-smoking. LIMITATIONS: Some unmeasured factors related to both depression and lifestyle indicators, such as family history of depressive disorder, stressful life events, and sleep disorders might have led to potential residual confounding. CONCLUSIONS: Modifying unhealthy lifestyles, especially diet, weight and smoking, is a potential target of major interest in the prevention of depressive symptoms in adults.

Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders.

The disruption of systemic immune homeostasis is a key mediator in the progression of cardiometabolic diseases (CMDs). We aimed to extend knowledge regarding the clinical relevance of CMD-associated variation of circulating mucosal-associated invariant T (MAIT) cell abundance and to explore underlying cellular mechanisms. We analyzed cross-sectional data from 439 participants of the Metagenomics in Cardiometabolic Diseases (MetaCardis) study, stratified into 6 groups: healthy control subjects and patients with metabolic syndrome (MS), obesity, type 2 diabetes mellitus (T2DM), and coronary artery disease (CAD) without, or with congestive heart failure (CAD-CHF). Blood MAIT cell frequency was significantly decreased in all CMD groups, including early (MS) and later (CAD and CAD-CHF) stages of disease progression. Reduced MAIT cell abundance was associated with increased glycosylated hemoglobin, inflammation markers, and deterioration of cardiac function. Glucose dose dependently promoted MAIT cell apoptosis in vitro, independently of anti-CD3 and cytokine-mediated activation. This outcome suggests the prominence of metabolic over an antigenic or cytokine-rich environment to promote MAIT cell reduction in patients with CMD. In summary, all stages of CMDs are characterized by reduced circulating MAIT cells. Chronically elevated blood glucose levels could contribute to this decline. These data extend the pathologic relevance of MAIT cell loss and suggest that MAIT cell abundance may serve as an indicator of cardiometabolic health.-Touch, S., Assmann, K. E., Aron-Wisnewsky, J., Marquet, F., Rouault, C., Fradet, M., Mosbah, H., MetaCardis Consortium, Isnard, R., Helft, G., Lehuen, A., Poitou, C., Clément, K., André, S. Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders.

Prospective association between adherence to dietary recommendations and incident depressive symptoms in the French NutriNet-Santé cohort.

A posteriori healthier dietary patterns and several nutrients have been associated with lower risks of depression in various studies; however, evidence is lacking with regard to the prospective association between adherence to nutritional recommendations (food-based and nutrient-based recommendations) and incident depression or depressive symptoms. In this study, we investigate such associations in the NutriNet Santé cohort. The study sample included 26 225 participants (aged 18-86 years) who were initially free of depressive symptoms. Adherence to nutritional recommendations was measured by four scores namely modified French Programme National Nutrition Santé-Guideline Score (mPNNS-GS), Alternative Healthy Eating Index-2010 (AHEI-2010), Probability of Adequate Nutrient Intake Dietary Score (PANDiet) and Diet Quality Index-International (DQI-I), using non-consecutive dietary record data during the first 2 years of follow-up (mean number of recording days=8, sd 2). Depressive symptoms were defined by a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥17 for men and ≥23 for women. We used Cox proportional hazards models to estimate hazard ratios and 95 % CI, modelling the dietary scores as standardised continuous variables and as tertiles. Over a mean follow-up of 6 years, we identified 2166 incident cases of depressive symptoms. All dietary scores with the exception of the AHEI-2010 were significantly inversely associated with incident depressive symptoms. In the fully adjusted model, an increase of 1 sd in the mPNNS-GS, PANDiet and DQI-I was, respectively, associated with an 8 % (95 % CI 4, 13), 5 % (95 % CI 1, 9) and 9 % (95 % CI 5, 13) reduction in the risk of depressive symptoms. Overall, these findings suggest that diet in accordance with national or international guidelines could have beneficial effects with regard to mental health.

The Mediating Role of Overweight and Obesity in the Prospective Association between Overall Dietary Quality and Healthy Aging.

BACKGROUND: Our objective was to quantify to what extent the association between adherence to the French nutritional recommendations at midlife, measured by the Programme National Nutrition Santé-Guideline Score (PNNS-GS), and healthy aging (HA) is mediated by body mass index (BMI) status. METHODS: We analyzed data from 2249 participants of the French 'Supplementation with Vitamins and Mineral Antioxidants' (SU.VI.MAX-'SUpplémentation en VItamines et Minéraux AntioXydants') cohort. At baseline (1994⁻1995), data on BMI status (<25 vs. ≥25 and <30 vs. ≥30) and diet were collected. At follow-up (2007⁻2009), HA status (yes/no) was evaluated via a multidimensional concept focusing on chronic disease incidence, physical and cognitive functioning, mental and social health, pain, and perceived health. Relative risks (RR) were estimated by extensively adjusted robust-error-variance Poisson regression, and counterfactual-based mediation analysis was performed. RESULTS: Our HA criteria were met by 39% of participants. We identified a positive direct relation of a greater adherence to the French nutritional recommendations, with the probability of HA (RRQuartile 4 vsquartile 1 = 1.31 (95% confidence interval (CI) = 1.13, 1.53)), and an indirect relation mediated by BMI status (1.01 (95% CI: 1.01, 1.02)), accounting for 5% of the total relation. CONCLUSION: These results indicate that high dietary quality may contribute to the preservation of overall health during aging, partly via obesity prevention and partly via other mechanisms.

The Inflammatory Potential of the Diet at Midlife Is Associated with Later Healthy Aging in French Adults.

Background: While low-grade chronic inflammation has been suggested as a major modulator of healthy aging (HA), no study has yet investigated the link between the inflammatory potential of the diet and multidimensional concepts of HA. Objective: We aimed to evaluate the association between the inflammatory potential of the diet at midlife, as measured by the Dietary Inflammatory Index (DII), and HA assessed 13 y later. Methods: We analyzed data from 2796 participants in the French Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study aged 45-60 y at baseline (1994-1995) and initially free of diabetes, cardiovascular disease, and cancer. During the trial phase of the study (1994-2002), participants received either a placebo or a daily nutritional dose of antioxidant supplement (120 mg vitamin C, 6 mg ß-carotene, 30 mg vitamin E, 100 µg Se, 20 mg Zn). HA was assessed in 2007-2009, and defined as having no major chronic disease, good physical and cognitive functioning, independence in daily activities, no depressive symptoms, good social health, good overall self-perceived health, and no function-limiting pain. The DII was calculated based on repeated baseline 24-h dietary records. Its association with HA was assessed by robust-error-variance Poisson regression, providing RR estimates. Results: After adjustment for potential confounders, higher DII scores (reflecting a more proinflammatory diet), were associated with a decreased likelihood of HA: RRtertile 3/tertile 1 = 0.85 (95% CI: 0.74, 0.99); P-trend = 0.03. Secondary analyses revealed that this association was only significant among participants who had been in the placebo group during the trial phase: RRtertile 3/tertile 1 = 0.80 (95% CI: 0.64, 1.00); P-trend = 0.04. Conclusions: This study suggests that a proinflammatory diet may lower the probability of overall HA. The SU.VI.MAX trial was registered at www.clinicaltrials.gov as NCT00272428.

Association Between Adherence to the Mediterranean Diet at Midlife and Healthy Aging in a Cohort of French Adults.

Background: The Mediterranean diet has been suggested as a key element for the prevention of age-related chronic diseases. However, very few studies have examined its relation with multidimensional concepts of healthy aging (HA). Our objective was thus to investigate the association between adherence to the Mediterranean diet at midlife and HA. Methods: We analyzed data from 3,012 participants of the French SUpplémentation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) study aged 45-60 years at baseline (1994-1995) and initially free of major chronic diseases, with available data on HA status in 2007-2009. We defined HA as not developing major chronic disease (cancer, cardiovascular disease, or diabetes), good physical and cognitive functioning (evaluated by validated, standardized tests), independence in instrumental activities of daily living, no depressive symptoms, good social functioning, good self-perceived health, and no function-limiting pain. An index assessing adherence to the Mediterranean diet, the Literature-based Adherence Score to the Mediterranean Diet (LAMD) was calculated using baseline data from repeated 24-hour dietary records. Results: In 2007-2009, 38% of participants met the HA criteria. Multivariable logistic regression revealed that higher scores on the LAMD (ORTertile 3 vs Tertile 1: 1.36 [1.12; 1.65]) were associated with higher odds of HA. Supplementary analyses using structural equation modeling revealed a potential mediation of the observed associations by metabolic health-related factors. Conclusions: Our results suggest a favorable role of a high adherence to the Mediterranean diet at midlife for maintaining good overall health during aging.

Prospective association between adherence to the Mediterranean diet and risk of depressive symptoms in the French SU.VI.MAX cohort.

PURPOSE: This study examines whether adherence to the Mediterranean Diet (MD) measured by several dietary indexes was associated with incident depressive symptoms in a large French cohort. METHODS: The study sample consisted of 3523 participants from the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort who had at least three dietary records at baseline during the first 2 years of follow-up (1994-1996), free of depression at the beginning of the study (1996-1997) and available Center for Epidemiologic Studies Depression Scale (CES-D) data at the end of follow-up (2007-2009). The rMED was computed. Incident depressive symptoms were defined by a CES-D score ≥17 for men and ≥23 for women in 2007-2009. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using multivariable logistic regression models. Several sensitivity analyses were performed. RESULTS: In the present study, 172 incident cases of depressive symptoms were identified during the follow-up (mean = 12.6 years). After adjustment for a wide range of potential confounders, adherence to the rMED score (continuous variable) was significantly associated with incident depressive symptoms in men (OR 0.91; 95% CI 0.83-0.99; p = 0.03), but not in women. Use of the Literature-Based Adherence Score to the Mediterranean Diet (LAMD) and the classic MD score (MDS) provide similar findings. CONCLUSIONS: In the current study, higher adherence to the Mediterranean Diet at midlife was associated with a lower risk of incident depressive symptoms, particularly in men, increasing scientific evidence for a beneficial role of Mediterranean Diet on health. Further investigations in particular among women are needed.

Alimentos orgánicos disminuyen la incidencia de cáncer / Organic foods reduce the incidence of cancer

En todo el mundo, el número de casos nuevos de cáncer se estimó en 2012 en más de 14 millones,1,2 y el cáncer sigue siendo una de las principales causas de mortalidad en Francia. Entre los factores de riesgo ambientales para el cáncer, existen preocupaciones sobre la exposición a diferentes clases de pesticidas, en particular a través de la exposición ocupacional.3 Una revisión reciente4 concluyó que el papel de los pesticidas para el riesgo de cáncer no podía ponerse en duda dado el creciente cuerpo de evidencia que vincula el desarrollo del cáncer a la exposición a plaguicidas. Si bien las respuestas a dosis de tales moléculas o los posibles efectos de coctel no se conocen bien, se ha sugerido un aumento de los efectos tóxicos, incluso a bajas concentraciones de mezclas de pesticidas.5

Worldwide, the number of new cases of cancer was estimated in 2012 at more than 14 million, 1,2 and cancer remains one of the leading causes of death in France. Among the environmental risk factors for cancer, there are concerns about exposure to different kinds of pesticides, particularly through occupational exposure.3 A recent review4 concluded that the role of pesticides in cancer risk could not be put in place. doubt given the growing body of evidence linking the development of cancer to exposure to pesticides. While responses to doses of such molecules or possible cocktail effects are not well known, an increase in toxic effects has been suggested, even at low concentrations of pesticide mixtures.5

Prospective association between body mass index at midlife and healthy aging among French adults.

OBJECTIVE: To assess the association between midlife body mass index (BMI) and healthy aging (HA) in the French SU.VI.MAX cohort. METHODS: HA was assessed in 2007 to 2009 among 2,733 individuals, aged 45 to 60 years and free of diabetes, cardiovascular disease and cancer at baseline (1994-1995). HA was defined as not developing any major chronic disease, good physical and cognitive functioning, no limitations in instrumental activities of daily living, no depressive symptoms, no health-related limitations in social life, good overall self-perceived health, and no function-limiting pain. Associations between anthropometric indicators (measured in 1995-1996) and HA were assessed using robust-error-variance Poisson regression. RESULTS: After adjustment for potential confounders, BMI (continuous) was negatively associated with HA: relative risk (RR) = 0.97 (95% confidence interval = 0.96-0.99). Moreover, the detrimental role of obesity (RRobesity vs. normal weight = 0.67 [0.51-0.88]) was substantially stronger than that of overweight (RRoverweight vs. normal weight = 0.91 [0.81-1.01]). Furthermore, while metabolically healthy individuals with overweight had a similar HA probability as metabolically healthy individuals with normal weight, metabolically unhealthy overweight individuals had a substantially lowered HA probability. CONCLUSIONS: This study provides novel evidence that an elevated BMI at midlife may jeopardize the preservation of health during aging. Our results also highlight the importance of maintaining a healthy metabolic profile during midlife.