Forecasted infliximab concentrations during induction predict time to remission and sustained disease control of inflammatory bowel disease.

BACKGROUND: Infliximab (IFX) exposure is established as a predictive factor of pharmacokinetic (PK) origin in inflammatory bowel disease (IBD), and expert consensus is to achieve adequate exposure during induction to achieve and sustain remission. METHODS: We retrospectively evaluated the performance of a Bayesian PK tool in IBD patients starting IFX. Trough IFX serum levels collected immediately before the third (at week 6) and fourth (at week 14) infusions were evaluated from 307 IBD patients (median age=17 years, 50 % females, 83 % with Crohn's disease). Forecasted IFX concentration at the fourth infusion were estimated using serum IFX, antibodies to IFX, albumin and weight determined immediately before the third infusion using population PK calculator with Bayesian prior. The outcome variable was a clinical & biochemical remission status achieved (CRP levels below 3 mg/L in presence of clinical remission). Statistics consisted of Kaplan Meier analysis with calculation of Hazard ratio (HR), and logistic regression. RESULTS: IFX concentration above 15 µg/mL immediately before the third infusion associated with shorter time to clinical & biochemical remission than concentration below 15 µg/mL without reaching significance (163±14 days vs 200±16 days, respectively; p=0.052). However, using PK parameters at the third infusion, forecasted IFX concentrations above 10 µg/mL immediately before the fourth infusion were significantly associated with a higher rate (HR=1.6 95 %CI: 1.1 to 2.1 p<0.01) and shorter time to remission (148±18 days vs 200±13 days p<0.01). In the presence of IFX concentration above 15 µg/mL at the third infusion, there was a significant 2.5-fold higher likelihood of sustained clinical & biochemical remission status during maintenance as compared to IFX concentrations below 15 µg/mL (p<0.01). Forecasted IFX level above 10 µg/mL at fourth infusion associated with significantly 3.9-fold higher likelihood of clinical & biochemical remission as compared to forecasted IFX concentrations below 10 µg/mL (p<0.01). CONCLUSIONS: These data further support that optimized IFX concentrations during induction are associated with enhanced disease control in IBD.

Viral Cultures for Coronavirus Disease 2019 Infectivity Assessment: A Systematic Review.

BACKGROUND: We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset. METHODS: We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up to 10 September 2020. We included studies attempting to culture or observe SARS-CoV-2 in specimens with RT-PCR positivity. Studies were dual-extracted and the data summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool. RESULTS: We included 29 studies reporting attempts at culturing, or observing tissue infection by, SARS-CoV-2 in sputum, nasopharyngeal or oropharyngeal, urine, stool, blood, and environmental specimens. The quality of the studies was moderate with lack of standardized reporting. The data suggest a relationship between the time from onset of symptom to the timing of the specimen test, cycle threshold (Ct), and symptom severity. Twelve studies reported that Ct values were significantly lower and log copies higher in specimens producing live virus culture. Two studies reported that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >14 days, but infectious potential declined after day 8 even among cases with ongoing high viral loads. Four studies reported viral culture from stool specimens. CONCLUSIONS: Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs, and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high Ct are unlikely to have infectious potential.

Ecological-level associations between highly processed food intakes and plasma phospholipid elaidic acid concentrations: results from a cross-sectional study within the European prospective investigation into cancer and nutrition (EPIC).

Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.

Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288,498 men and women.

BACKGROUND: The protective effect of physical activity (PA) on abdominal adiposity is unclear. OBJECTIVE: We examined whether PA independently predicted gains in body weight and abdominal adiposity. DESIGN: In a prospective cohort study [the EPIC (European Prospective Investigation into Cancer and Nutrition)], we followed 84,511 men and 203,987 women for 5.1 y. PA was assessed by a validated questionnaire, and individuals were categorized into 4 groups (inactive, moderately inactive, moderately active, and active). Body weight and waist circumference were measured at baseline and self-reported at follow-up. We used multilevel mixed-effects linear regression models and stratified our analyses by sex with adjustments for age, smoking status, alcohol consumption, educational level, total energy intake, duration of follow-up, baseline body weight, change in body weight, and waist circumference (when applicable). RESULTS: PA significantly predicted a lower waist circumference (in cm) in men (ß = -0.045; 95% CI: -0.057, -0.034) and in women (ß = -0.035; 95% CI: -0.056, -0.015) independent of baseline body weight, baseline waist circumference, and other confounding factors. The magnitude of associations was materially unchanged after adjustment for change in body weight. PA was not significantly associated with annual weight gain (in kg) in men (ß = -0.008; 95% CI: -0.02, 0.003) and women (ß = -0.01; 95% CI: -0.02, 0.0006). The odds of becoming obese were reduced by 7% (P < 0.001) and 10% (P < 0.001) for a one-category difference in baseline PA in men and women, respectively. CONCLUSION: Our results suggest that a higher level of PA reduces abdominal adiposity independent of baseline and changes in body weight and is thus a useful strategy for preventing chronic diseases and premature deaths.

Mediterranean dietary patterns and prospective weight change in participants of the EPIC-PANACEA project.

BACKGROUND: There is an association between a greater adherence to a Mediterranean diet and a reduced risk of developing chronic diseases. However, it is not clear whether this dietary pattern may be protective also against the development of obesity. OBJECTIVE: We assessed the association between the adherence to the Mediterranean dietary pattern (MDP), prospective weight change, and the incidence of overweight or obesity. DESIGN: We conducted a prospective cohort study [the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol Consumption, Cessation of Smoking, Eating Out of Home, and Obesity (EPIC-PANACEA) project] in 373,803 individuals (103,455 men and 270,348 women; age range: 25-70 y) from 10 European countries. Anthropometric measurements were obtained at recruitment and after a median follow-up time of 5 y. The relative Mediterranean Diet Score (rMED; score range: 0-18) was used to assess adherence to the MDP according to the consumption of 9 dietary components that are characteristic of the Mediterranean diet. The association between the rMED and 5-y weight change was modeled through multiadjusted mixed-effects linear regression. RESULTS: Individuals with a high adherence to the MDP according to the rMED (11-18 points) showed a 5-y weight change of -0.16 kg (95% CI: -0.24, -0.07 kg) and were 10% (95% CI: 4%, 18%) less likely to develop overweight or obesity than were individuals with a low adherence to the MDP (0-6 points). The low meat content of the Mediterranean diet seemed to account for most of its positive effect against weight gain. CONCLUSION: This study shows that promoting the MDP as a model of healthy eating may help to prevent weight gain and the development of obesity.

Meat consumption and prospective weight change in participants of the EPIC-PANACEA study.

BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.

Adherence to the Mediterranean diet is associated with lower abdominal adiposity in European men and women.

Given the lack of consistent evidence of the relationship between Mediterranean dietary patterns and body fat, we assessed the cross-sectional association between adherence to a modified Mediterranean diet, BMI, and waist circumference (WC). A total of 497,308 individuals (70.7% women) aged 25-70 y from 10 European countries participated in this study. Diet was assessed at baseline using detailed validated country-specific questionnaires, and anthropometrical measurements were collected using standardized procedures. The association between the degree of adherence to the modified-Mediterranean Diet Score (mMDS) (including high consumption of vegetables, legumes, fruits and nuts, cereals, fish and seafood, and unsaturated:saturated fatty acids ratio; moderate alcohol intake; and low consumption of meat and meat products and dairy products) and BMI (kg.m(-2)) or WC (cm) was modeled through mixed-effects linear regression, controlling for potential confounders. Overall, the mMDS was not significantly associated with BMI. Higher adherence to the Mediterranean diet was significantly associated with lower WC, for a given BMI, in both men (-0.09; 95% CI -0.14 to -0.04) and women (-0.06; 95% CI -0.10 to -0.01). The association was stronger in men (-0.20; 95% CI -0.23 to -0.17) and women (-0.17; 95% CI -0.21 to -0.13) from Northern European countries. Despite the observed heterogeneity among regions, results of this study suggest that adherence to a modified Mediterranean diet, high in foods of vegetable origin and unsaturated fatty acids, is associated with lower abdominal adiposity measured by WC in European men and women.

Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Plasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. OBJECTIVE: The objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. DESIGN: A cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in >3,000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. RESULTS: The most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n-3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. CONCLUSIONS: These findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of some food intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases.