Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis.

BACKGROUND & AIMS: We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. METHODS: A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. RESULTS: A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). CONCLUSIONS: Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

Somatic, Anxiety, and Depressive (SAD) Symptoms in Young Adult Latinx Immigrants: Prevalence and Predictors.

Certain immigration factors may increase somatic, anxiety, and depressive (SAD) symptoms in Latinx immigrants. Our study examined prevalence of SAD symptoms in Latinx immigrants 18-29 presenting to primary care with correlates of acculturation, immigration, and legal status. SAD symptoms were measured using the PHQ-14, GAD-7 and PHQ-8. Moderate somatization (37%), anxiety (20%), and depression (25%) were common. Multivariable analysis found five immigration factors predicted a higher composite SAD score and the presence of each additional factor increased likelihood of a SAD score ≥ 20 (OR 1.7; 95% CI, 1.1 to 2.5). SAD scores increased in a dose-response fashion (8.3, 10.5, 14.8, 17.1, 21.7, 29.3) with the added presence of each factor. Elevated SAD scores were not associated with gender, marital status, education, income, country of origin, or acculturation. Screening with our five factor immigration distress index may help identify patients at risk for higher SAD scores during a primary care visit.

Effect of Accelerated Infliximab Induction on Short- and Long-term Outcomes of Acute Severe Ulcerative Colitis: A Retrospective Multicenter Study and Meta-analysis.

BACKGROUND & AIMS: In patients with acute severe ulcerative colitis (ASUC), standard infliximab induction therapy has modest efficacy. There are limited data on the short-term or long-term efficacy of accelerated infliximab induction therapy for these patients. METHODS: In a retrospective study, we collected data from 213 patients with steroid refractory ASUC who received infliximab rescue therapy at 3 centers, from 2005 through 2017. Patients were classified that received standard therapy (5mg/kg infliximab at weeks 0, 2, and 6) or accelerated therapy (>5mg/kg infliximab at shorter intervals). The primary outcome was colectomy in-hospital and at 3, 6, 12, and 24 months. Multivariable regression models were adjusted for relevant confounders. We also performed a meta-analysis of published effects of standard vs accelerated infliximab treatment of ASUC. RESULTS: In the retrospective analysis, 81 patients received accelerated infliximab therapy and 132 received standard infliximab therapy. There were no differences in characteristics between the groups, including levels of C-reactive protein or albumin. Similar proportions of patients in each group underwent in-hospital colectomy (9% receiving accelerated therapy vs 8% receiving standard therapy; adjusted odds ratio, 1.35; 95% CI, 0.38-4.82). There was no significant difference between groups in proportions that underwent colectomy at 3, 6, 12, or 24 months (P > .20 for all comparisons). Among those in the accelerated group, an initial dose of 10 mg/kg was associated with a lower rate of colectomy compared to patients who initially received 5 mg/kg followed by subsequent doses of 5mg/kg or higher. Our systematic review identified 7 studies (181 patients receiving accelerated infliximab and 436 receiving standard infliximab) and found no significant differences in short- or long-term outcomes. CONCLUSION: In a retrospective study and meta-analysis, we found no association between accelerated infliximab induction therapy and lower rates of colectomy in patients with ASUC, compared to standard induction therapy. However, confounding by disease severity cannot be excluded. Randomized trials are warranted to compare these treatment strategies.

The relationship between school lunch attendance and the food intakes of French schoolchildren aged 3-17 years.

OBJECTIVE: Recently, school meal composition regulations have been implemented in France in order to improve the nutritional status of children. The present study investigated the link between school lunch attendance and the food intakes of schoolchildren aged 3-17 years. DESIGN: Second French cross-sectional dietary survey (2006-2007). Eating frequencies were assessed for twenty-four food groups with a 7 d food record. Eating locations were recorded for main meals. Food group intakes at weekday lunches were compared for the school canteen and for other locations. The children's overall dietary intake was compared based on school lunch attendance. SETTING: Mainland France. SUBJECTS: Schoolchildren aged 3-17 years (n 1068). RESULTS: Lunchtime food intake differed between the school canteen and other locations. Some intakes at school canteens were more in accordance with the regulations (more fruit and vegetables, fish and dairy products, and less sandwiches, soft drinks, chocolate and confectionery), whereas others highlighted needs for improvement (more sweet biscuits and pastries, ice cream and dairy desserts, pizzas and salty pastries). Many of these differences were also observed in the children's overall diet: children regularly attending school lunches ate more mashed fruit, fish and sweet biscuits or pastries, and less sandwiches and soft drinks. The link between school lunch attendance and overall diet was less pronounced in secondary-school children. CONCLUSIONS: School canteen attendance is associated with both potentially beneficial and deleterious differences in the lunchtime and overall diets of French children. These findings are important to consider when setting national regulations for school meal composition.

School meals in French secondary state schools: Do national recommendations lead to healthier nutrition on offer?

To improve the dietary offering in schools, the French authorities published recommendations on nutrition in 1999, which were then revised in 2007. The aim of the present study was to assess the nutritional offering in secondary school meals and the extent to which the recommendations promote balanced nutritional offerings. In 2005, a national survey was conducted on a representative sample of secondary schools, either administrated by the Ministry of Education (ES) or the Ministry of Agriculture (AS). Information on school-catering organisation and twenty consecutive meals was collected from each of the 707 secondary schools surveyed. Nutritional composition was estimated according to the French food composition database. Univariate and multivariate analyses were used to investigate the impact of food-group frequency guidelines (FFG) on nutritional offering. It was found that 15 and 26 % of ES and AS schools, respectively, had high compliance with the FFG, at lunch. Macronutrient content was unbalanced in ES school lunches in which 42·8 % lipids, 21·5 % proteins and 35·7 % carbohydrates contributed to the energy. Nevertheless, proper offerings in Fe, Ca and vitamin C content were observed. In addition, a lower offering in lipids and a higher offering in proteins, Ca, vitamin C and Fe were found when the FFG were applied (P < 0·001). Similar results were found for AS schools. This paper confirms the effectiveness of FFG in providing nutritionally balanced school meals. However, others measures such as nutrition promotion and actions to improve children's food habits have to be introduced to make the recommendations more effective and easier to understand.

The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota.

Mucosal surfaces constantly encounter microbes. Toll-like receptors (TLRs) mediate recognition of microbial patterns to eliminate pathogens. By contrast, we demonstrate that the prominent gut commensal Bacteroides fragilis activates the TLR pathway to establish host-microbial symbiosis. TLR2 on CD4(+) T cells is required for B. fragilis colonization of a unique mucosal niche in mice during homeostasis. A symbiosis factor (PSA, polysaccharide A) of B. fragilis signals through TLR2 directly on Foxp3(+) regulatory T cells to promote immunologic tolerance. B. fragilis lacking PSA is unable to restrain T helper 17 cell responses and is defective in niche-specific mucosal colonization. Therefore, commensal bacteria exploit the TLR pathway to actively suppress immunity. We propose that the immune system can discriminate between pathogens and the microbiota through recognition of symbiotic bacterial molecules in a process that engenders commensal colonization.

Socio-economic and demographic variations in school lunch participation of French children aged 3-17 years.

OBJECTIVE: To assess school canteen attendance in a French nationally representative sample of children and to analyse its association with the socio-economic and demographic characteristics of the children and their families. DESIGN: Data from the second French national cross-sectional food consumption survey (INCA2), performed in 2006-2007, were used. Information on usual weekly school canteen attendance was collected through a self-reported questionnaire, and demographic and socio-economic variables through a face-to-face questionnaire. The associations between school canteen attendance and the socio-economic and demographic variables were investigated by multivariate logistic regression analyses. SETTING: The INCA2 sample was representative of the children aged 3-17 years in France. SUBJECT: Analysis was performed on 1413 schoolchildren who completed the school canteen attendance questions. RESULTS: Some 65·6 % of schoolchildren aged 3-17 years had school lunch at least once weekly. This rate of attendance was positively correlated with age. Whatever the school level, school canteen attendance was positively associated with the educational level of the caregiver/parent. In pre- and elementary-school children, enrolment at the school canteen was also higher when the caregiver/parent worked, or in single-parent families. In secondary-school children, school lunch participation decreased with children living in more densely populated areas and increased with the level of the household's living standards. CONCLUSIONS: School canteen attendance was positively associated with children's socio-economic background. This could reduce the effectiveness of the forthcoming school meal composition regulations designed to improve the diet of children from deprived backgrounds, who are more likely to have unhealthy food habits.

Comparison of different maximum safe levels in fortified foods and supplements using a probabilistic risk assessment approach.

Different European institutions have developed mathematical models to propose maximum safe levels either for fortified foods or for dietary supplements. The objective of the present study was to compare and check the safety of these different maximum safe levels (MSL) by using a probabilistic risk assessment approach. The potential maximum nutritional intakes were estimated by taking into account all sources of intakes (base diet, fortified foods and dietary supplements) and compared with the tolerable upper intake levels for vitamins and minerals. This approach simulated the consequences of both food fortification and supplementation in terms of food safety. Different scenarios were tested. They are the result of the combination of several MSL obtained using the previous models. The study was based on the second French Individual and National Study on Food Consumption performed in 2006-7, matched with the French food nutritional composition database. The analyses were based on a sample of 1918 adults aged 18-79 years. Some MSL in fortified foods and dietary supplements obtained independently were protective enough, although some others could lead to nutritional intakes above the tolerable upper intake levels. The simulation showed that it is crucial to consider the inter-individual variability of fortified food intakes when setting MSL for foods and supplements. The risk assessment approach developed here by integrating the MSL for fortified foods and dietary supplements is useful for ensuring consumer protection. It may be subsequently used to test any other MSL for vitamins and minerals proposed in the future.

Trends in food intake in French children from 1999 to 2007: results from the INCA (étude Individuelle Nationale des Consommations Alimentaires) dietary surveys.

The objectives of the present study were to assess the intake of different food groups in French children aged 3-17 years (n 1455), and to analyse trends since a dietary survey undertaken 8 years ago. Dietary intake was evaluated using data from the 2006-7 cross-sectional INCA2 national dietary survey (étude Individuelle Nationale sur les Consommations Alimentaires), based on a 7 d food record. Dietary intake (percentage of subjects consuming the food group and amount eaten) was assessed for thirty-nine food categories. We observed variations in food consumption by age, sex, North-South regional gradient, seasonal period and educational level of the responding parent. Trends in dietary intake between 1999 and 2007 were determined by comparing the INCA1 (n 1126) and the INCA2 surveys. Both surveys had been carried out using the same methodology. The findings showed a decrease in energy intake in children aged 3-14 years, due to a reduction in the consumption of foods of animal origin and sweetened products. In adolescents aged 15-17 years, energy intake remained rather stable; during this 8-year period, the consumption of meat decreased, whereas the consumption of savoury snacks such as sandwiches and hamburgers significantly increased. These trends occurred during a time of growing concern about overweight and the associated co-morbidities in France. A number of public health measures were implemented over this period to improve dietary habits and physical activity patterns in children and adults. The periodic monitoring of dietary patterns through the INCA surveys is an essential part of the surveillance network in France.

Trends in food and nutritional intakes of French adults from 1999 to 2007: results from the INCA surveys.

Two independent cross-sectional dietary surveys (the Individual and National Food Consumption Surveys, INCA), performed in 1998-99 (INCA1) and in 2006-07 (INCA2) on nationally representative samples of French people, were used to analyse trends in the dietary habits and nutritional intake of French adults. Food consumption was recorded through 7-d dietary records, and nutritional intakes were assessed using the French food composition database. After exclusion of under-reporters, analyses were performed on 3267 adults, aged 18-79 years: 1345 from INCA1 and 1922 from INCA2. The trends highlighted over the 8-year period showed a decrease in consumption of dairy products, meat, bread, potatoes, pastries/croissant-like pastries/cakes/biscuits and sugar/confectionery. In contrast, the consumption of fruits and vegetables, rice, ice cream and chocolate increased. Other food groups, like fish and snacking foods, remained stable. Food choices were mostly age specific. These age differences remained consistent over the years and underlined two opposite dietary trends: a 'traditional' one mainly followed by the elderly, and a 'snacking and convenience' one mainly adopted by young adults. The overall trends in food consumption did not influence the mean energy intake, but did slightly modify the contribution of each macronutrient to energy intake. These repeated surveys highlighted the fact that trends in French food habits have moved towards an average European diet at the crossroads between Mediterranean and Northern diets, and that food consumption changes impacted, to a lesser extent, nutritional intake.

Impact of food consumption habits on the pesticide dietary intake: comparison between a French vegetarian and the general population.

This study aims to compare the pesticide residue dietary intake of the French general population and the vegetarian population, separated into five specific diets: omnivorous (OMN), lacto-vegetarian (LV), ovo-lacto-vegetarian (OLV), pesco-lacto-vegetarian (PLV) and vegan (VG). Theoretical Maximum Daily Intakes (TMDIs) based on Maximum Residue Levels (MRLs) were calculated as a percentage of the Acceptable Daily Intake (ADI). Among the 421 pesticides studied, only 48 had TMDI above ADI for at least one population subgroup. An excessive exposure was noticed for 44, 43, 42, 41 and 30 pesticides in the OLV, VG, OMN, LV and PLV groups, respectively, versus 29 in the general population. Meat and egg products consumption was responsible for higher intakes of organochlorine pesticides in the general population than in the vegetarian population (TMDI = 348% versus 146-183% ADI for aldrin). However, as the limited consumption of animal-origin commodities was largely offset by a higher fruit, vegetable and cereal intake in the vegetarian diets, vegetarians appear to be preferentially exposed to pesticides, for which fruit, vegetables and cereals are the main contributors, such as tri-allate, chlorpyrifos-methyl and diazinon. This study illustrates that consumption habits have a real impact on pesticide exposure in terms of intake levels, number and type of pesticides, representing a potential risk of dietary exposure. Except for organochlorine compounds, the vegetarian population may be more exposed to pesticide residues than the general population due to specific dietary habits. Thus, this population should be considered for risk assessment of pesticide residues.

School meals in French secondary state schools with regard to the national recommendations.

In 2001, a circular addressing both the composition of school meals and food safety issues was introduced in France to improve the nutrient composition of school meals and provided food-frequency guidelines to guarantee dietary balanced meals. The present study assesses the extent to which secondary state schools are familiar with and implement this circular. In 2005, a nationally representative sample of 1440 secondary state schools received a questionnaire on their catering service and the implementation of the circular's recommendations, and were requested to enclose all menus (lunches and dinners) served over 1 month. Menu analysis shows that progress is still required to achieve a meal composition in accordance with the food-group frequency guidelines appended to the circular. Some recommendations are followed by most of the schools, such as limiting high-fat products and providing plenty of raw fruits and vegetables, cooked vegetables and starchy foods. Other guidelines should be implemented further, especially with regard to the nutritional quality of main courses and dairy products, which are met by less than a third and a half of schools, respectively. Specific efforts are necessary for evening meals to ensure that the nutritional requirements of boarders are covered. Some recommendations, such as the food purchasing manager being trained in nutrition (38 % of schools) and the involvement of dietetic expertise when designing meals (6 %), seem to be linked to better dietary balance of meals. Implementation of the circular must therefore be promoted in schools and may require stronger regulatory nutrition standards and better cooperation between schools.

Dietary exposure estimates of 18 elements from the 1st French Total Diet Study.

To estimate the dietary exposure of the main minerals and trace elements from retail food typically consumed by the French population, samples were purchased and then prepared and cooked prior to analysis. A total of 1080 individual food composites samples were collected and analysed for 18 elements (arsenic, lead, cadmium, aluminium, mercury, antimony, chrome, calcium, manganese, magnesium, nickel, copper, zinc, lithium, sodium, molybdenum, cobalt and selenium). Intakes were calculated from different food consumption patterns found in France for average and high consumers among adults and children. Dietary exposures of those consumers estimated from the France 2000 Total Diet Study (FTDS) are reported, and compared with existing nutritional reference values (Lowest threshold Intake, LTI) or toxicological reference values (Provisional Tolerable Weekly Intake, PTWI or Upper Level, UL) of the respective element and from previous French studies. This study confirms for the populations concerned, the low probability of nutritional or health risks due to food consumption.