Digit preference and biased conclusions in cardiac arrest studies.

BACKGROUND: In cardiac arrest (CA), time is directly predictive of patients' prognosis. The increase in mortality resulting from delayed cardiopulmonary resuscitation has been quantified minute by minute. Times reported in CA management studies could reflect a timestamping bias referred to as "digit preference". This phenomenon leads to a preference for certain numerical values (such as 2, 5, or 10) over others (such as 13). Our objective was to investigate whether or not digit preference phenomenon could be observed in reported times of the day related to CA management, as noted in a national registry. METHODS: We analyzed data from the French National Electronic Registry of Cardiac Arrests. We analyzed twelve times-of-the-day corresponding to each of the main steps of CA management reported by the emergency physicians who managed the patients in prehospital settings. We postulated that if CA occurred at random times throughout the day, then we could expect to see events related to CA management occurring at a similar rate each minute of each hour of the day, at a fraction of 1/60. We compared the fraction of times reported as multiples of 15 (0, 15, 30, and 45 - on the hour, quarters, half hour) with the expected fraction of 4/60 (i.e. 4 × 1/60). MAIN RESULTS: A total of 47,211 times-of-the-day in relation to 6131 CA were analyzed. The most overrepresented numbers were: 0, with 3737 occurrences (8% vs 2% expected, p < 0.0001) and 30, with 2807 occurrences (6% vs 2% expected, p < 0.0001). Times-of-the-day as multiples of 15 were overrepresented (22% vs 7% expected, p < 0.0001). CONCLUSION: Prospectively collected times were considerably influenced by digit preference phenomenon. Studies that are not based on automatic time recordings and that have not evaluated and considered this bias should be interpretated with caution.

Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) and Cancer Risk in the Prospective NutriNet-Santé Cohort.

BACKGROUND: Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) have been shown to be involved in gastrointestinal disorders. In view of their proinflammatory potential and their interactions with the gut microbiota, their contribution to the etiology of other chronic diseases such as cancer has been postulated. However, to our knowledge, no epidemiologic study has investigated this hypothesis so far. OBJECTIVES: Our objective was to investigate the associations between FODMAP intake (total and by type) and cancer risk (overall, breast, prostate, and colorectal) in a large prospective cohort. METHODS: The study was based on the NutriNet-Santé cohort (2009-2020); 104,909 adult participants without cancer at baseline were included in our analyses (median follow-up time = 7.7 y, 78.7% women, mean ± SD age at baseline 42.1 ± 14.5 y). Baseline dietary intakes were obtained from repeated 24-h dietary records linked to a detailed food composition table. Associations between FODMAP intake (expressed in quintiles, Q) and cancer risks were assessed by Cox proportional hazard models adjusted for a large range of lifestyle, sociodemographic, and anthropometric variables. RESULTS: Total FODMAP intake was associated with increased overall cancer risk (n = 3374 incident cases, HR for sex-specific Q5 compared with Q1: 1.21; 95% CI: 1.02, 1.44; P-trend = 0.04). In particular, oligosaccharides were associated with cancer risk: a trend was observed for overall cancer (HR Q5 compared with Q1: 1.10; 95% CI: 0.97, 1.25; P-trend = 0.04) and colorectal cancer (n = 272, HR Q5 compared with Q1: 1.78; 95% CI: 1.13-2.79; P-trend = 0.02). CONCLUSIONS: Results from this large population-based study on French adults from the NutriNet-Santé cohort show a significant association between FODMAP intake and the risk of cancer development. Further epidemiologic and experimental studies are needed to confirm these results and provide data on the potential underlying mechanisms.

Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) and Cancer Risk in the Prospective NutriNet-Santé Cohort.

BACKGROUND: Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) have been shown to be involved in gastrointestinal disorders. In view of their proinflammatory potential and their interactions with the gut microbiota, their contribution to the etiology of other chronic diseases such as cancer has been postulated. However, to our knowledge, no epidemiologic study has investigated this hypothesis so far. OBJECTIVES: Our objective was to investigate the associations between FODMAP intake (total and by type) and cancer risk (overall, breast, prostate, and colorectal) in a large prospective cohort. METHODS: The study was based on the NutriNet-Santé cohort (2009-2020); 104,909 adult participants without cancer at baseline were included in our analyses (median follow-up time = 7.7 y, 78.7% women, mean ± SD age at baseline 42.1 ± 14.5 y). Baseline dietary intakes were obtained from repeated 24-h dietary records linked to a detailed food composition table. Associations between FODMAP intake (expressed in quintiles, Q) and cancer risks were assessed by Cox proportional hazard models adjusted for a large range of lifestyle, sociodemographic, and anthropometric variables. RESULTS: Total FODMAP intake was associated with increased overall cancer risk (n = 3374 incident cases, HR for sex-specific Q5 compared with Q1: 1.21; 95% CI: 1.02, 1.44; P-trend = 0.04). In particular, oligosaccharides were associated with cancer risk: a trend was observed for overall cancer (HR Q5 compared with Q1: 1.10; 95% CI: 0.97, 1.25; P-trend = 0.04) and colorectal cancer (n = 272, HR Q5 compared with Q1: 1.78; 95% CI: 1.13-2.79; P-trend = 0.02). CONCLUSIONS: Results from this large population-based study on French adults from the NutriNet-Santé cohort show a significant association between FODMAP intake and the risk of cancer development. Further epidemiologic and experimental studies are needed to confirm these results and provide data on the potential underlying mechanisms.

Fermentable Oligo-, Di-, and Mono-Saccharides and Polyols (FODMAPs) Consumption and Irritable Bowel Syndrome in the French NutriNet-Santé Cohort.

(1) Background: Specific foods, and more particularly, fermentable oligo-, di-, and mono-saccharides and polyols (FODMAPs) are often considered as triggers of digestive symptoms in Irritable Bowel Syndrome (IBS). Our aim was to study FODMAP consumption in controls and IBS participants in a large French population-based cohort; (2) Methods: Participants from the NutriNet-Santé cohort study completed the Rome IV and IBS-SSS questionnaire in a cross sectional study. Among them, 27,949 eligible participants had previously completed three 24-h recalls as well as anthropometrics, socio-demographical and lifestyle data. Total FODMAP intake (in g/day) was computed using a specific composition table. The association between FODMAPs and IBS was estimated through multivariable logistic regression models; (3) Results: Included participants were mainly women (75.4%) and the mean age was 43.4 ± 14.1 years. FODMAPs accounted for a mean daily intake of 19.4 ± 9.5 g/day. Overall 1295 participants (4.6%) were identified with an IBS. After adjusting for confounding factors, IBS participants had lower intakes in FODMAPs than non-IBS ones (aOR: 0.88, 95% CI: 0.82-0.95, p-value: 0.001). IBS severity was associated with more frequent low FODMAP intakes (<9 g/day); (4) Conclusions: Participants tended to consume 19 g of FODMAPs per day, but slightly less for IBS participants than for controls. In IBS participants, higher severity was associated with lower intakes.

FODMAP Consumption by Adults from the French Population-Based NutriNet-Santé Cohort.

BACKGROUND: Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are increasingly studied because they are suspected unfavorably to impact health (irritable bowel syndrome in particular). However, little is known about FODMAP intake in the general population, or which groups are more likely to consume them, because their intakes are usually assessed in inpatient settings. OBJECTIVES: This study aimed to describe FODMAP consumption in a large French cohort and its association with sociodemographic and lifestyle characteristics. METHODS: This cross-sectional study described FODMAP intakes in 109,362 volunteers (78.0% female, mean age 43.8 ± 14.7 y) from the French NutriNet-Santé cohort, using an ad hoc FODMAP composition table. Associations between FODMAP intakes and sociodemographic characteristics were investigated using χ2 tests or Kruskal-Wallis tests according to the qualitative or quantitative status of the variable, and multinomial logistic regressions were performed after adjusting for energy intake in sensitivity analyses. Eligible participants had completed ≥3 detailed 24-h food records. RESULTS: We observed a mean intake of 18.9 ± 9.5 g/d FODMAPs in this French cohort, and 11.7% of participants had intakes <9 g/d (i.e., low-FODMAP diets). Participants with FODMAP intakes <9 g/d were more likely to have lower caloric intakes (Δ = 383 kcal/d compared with participants with FODMAP intakes ≥16 g/d), to be smokers, to have lower incomes, and to have lower levels of physical activity. Total FODMAPs accounted for a mean intake of 18.9 ± 9.5 g/d, which was 3.7 ± 2.0% of total energy intake. The highest intake of FODMAPs was represented by lactose followed by excess fructose, fructans, polyols, and galacto-oligo-saccharides. CONCLUSIONS: FODMAP consumption by a large sample of adults from the general population is ∼19 g/d, with half of the population having a FODMAP intake >16 g/d.This trial was registered at www.clinicaltrials.gov as NCT03335644.

Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study.

Clinical features of COVID-19 have been mostly described in hospitalized patients with and without ICU admission. Yet, up to 80% of patients are managed in an outpatient setting. This population is poorly documented. In France, health authorities recommend outpatient management of patients presenting mild-to-moderate COVID-19 symptoms. The aim of this study was to describe their clinical characteristics. The study took place in an emergency medical dispatching center located in the Greater Paris region. Patients included in this survey met confirmed COVID-19 infection criteria according to the WHO definition. We investigated clinical features and classified symptoms as general, digestive, ear-nose-throat, thoracic symptoms, and eye disease. Patients were included between March 24 and April 6 2020. 1487 patients included: 700 (47%) males and 752 (51%) females, with a median age of 44 (32-57) years. In addition to dry cough and fever reported in more than 90% of cases, the most common symptoms were general symptoms: body aches/myalgia (N = 845; 57%), headache (N = 824; 55%), and asthenia (N = 886; 60%); shortness of breath (N = 479; 32%) and ear-nose-throat symptoms such as anosmia (N = 415; 28%) and ageusia (N = 422; 28%). Chest pain was reported in 320 (21%) cases and hemoptysis in 41 (3%) cases. The main difference between male and female patients was an increased prevalence of ear-nose-throat symptoms as well as diarrhea, chest pains, and headaches in female patients. General symptoms and ear-nose-throat symptoms were predominant in COVID-19 patients presenting mild-to-moderate symptoms. Shortness of breath and chest pain were remarkably frequent.

RF313, an orally bioavailable neuropeptide FF receptor antagonist, opposes effects of RF-amide-related peptide-3 and opioid-induced hyperalgesia in rodents.

Although opiates represent the most effective analgesics, their use in chronic treatments is associated with numerous side effects including the development of pain hypersensitivity and analgesic tolerance. We recently identified a novel orally active neuropeptide FF (NPFF) receptor antagonist, RF313, which efficiently prevents the development of fentanyl-induced hyperalgesia in rats. In this study, we investigated the properties of this compound into more details. We show that RF313 exhibited a pronounced selectivity for NPFF receptors, antagonist activity at NPFF1 receptor (NPFF1R) subtype both in vitro and in vivo and no major side effects when administered in mice up to 30 mg/kg. When co-administered with opiates in rats and mice, it improved their analgesic efficacy and prevented the development of long lasting opioid-induced hyperalgesia. Moreover, and in marked contrast with the dipeptidic NPFF receptor antagonist RF9, RF313 displayed negligible affinity and no agonist activity (up to 100 µM) toward the kisspeptin receptor. Finally, in male hamster, RF313 had no effect when administered alone but fully blocked the increase in LH induced by RFRP-3, while RF9 per se induced a significant increase in LH levels which is consistent with its ability to activate kisspeptin receptors. Altogether, our data indicate that RF313 represents an interesting compound for the development of therapeutic tools aiming at improving analgesic action of opiates and reducing adverse side effects associated with their chronic administration. Moreover, its lack of agonist activity at the kisspeptin receptor indicates that RF313 might be considered a better pharmacological tool, when compared to RF9, to examine the regulatory roles of RF-amide-related peptides and NPFF1R in reproduction.

Development of a peptidomimetic antagonist of neuropeptide FF receptors for the prevention of opioid-induced hyperalgesia.

Through the development of a new class of unnatural ornithine derivatives as bioisosteres of arginine, we have designed an orally active peptidomimetic antagonist of neuropeptide FF receptors (NPFFR). Systemic low-dose administration of this compound to rats blocked opioid-induced hyperalgesia, without any apparent side-effects. Interestingly, we also observed that this compound potentiated opioid-induced analgesia. This unnatural ornithine derivative provides a novel therapeutic approach for both improving analgesia and reducing hyperalgesia induced by opioids in patients being treated for chronic pain.