Prospective association between adherence to the 2017 French dietary guidelines and risk of death, CVD and cancer in the NutriNet-Santé cohort.

Non-communicable diseases, such as cancers and CVD, represent a major public health concern, and diet is an important factor in their development. French dietary recommendations were updated in 2017, and an adherence score, the Programme National Nutrition Santé Guidelines Score (PNNS-GS2), has been developed and validated using a standardised procedure. The present study aimed to analyse the prospective association between PNNS-GS2 and the risk of death, cancer and CVD. Our sample consisted of French adults included in the prospective NutriNet-Santé cohort (n 67 748, 75 634 and 80 269 for the risk of death, cancer and CVD, respectively). PNNS-GS2 (range: -∞ to 14·25) was calculated from the 24-h dietary records of the first 2 years of monitoring. Association between PNNS-GS2 (in quintiles, Q) and the risk of death, cancer and CVD was studied using Cox models adjusted for the main confounding factors. The sample included 78 % of women, aged on average 44·4 years (sd 14·6) with on average 6·6 (sd 2·3) dietary records. Average PNNS-GS2 was 1·5 (sd 3·4) and median follow-up was 6·6 years for cancers and 6·2 years for CVD and deaths. PNNS-GS2 was significantly associated with the risk of death (hazard ratio (HR)Q5vsQ1: 0·77 (95 % CI 0·60, 1·00), 828 cases), cancer (HRQ5vsQ1 = 0·80 (95 % CI 0·69, 0·92), 2577 cases) and CVD (HRQ5vsQ1 0·64 (95 % CI 0·51, 0·81), 964 cases). More specifically, PNNS-GS2 was significantly associated with colorectal and breast cancer risks but not prostate cancer risk. Our results suggest that strong adherence to the 2017 French dietary recommendations is associated with a lower risk of death, cancer or CVD. This reinforces the validity of these new recommendations and will help to promote their dissemination.

Estimations of overdiagnosis in breast cancer screening vary between 0% and over 50%: why?

BACKGROUND: Published estimations of the extent of breast cancer overdiagnosis vary widely, and there have been heated debates around these estimations. Some high estimates have even been the basis of campaigns against national breast cancer screening programmes. Identifying some of the sources of heterogeneity between different estimates would help to clarify the issue. METHODS: The simple case of neuroblastoma-a childhood cancer-screening is used to describe the basic principle of overdiagnosis estimation. The more complicated mechanism of breast cancer overdiagnosis is described based on data from Denmark, taking into account the type of data used, individual or aggregated. FINDINGS: The type of data used in overdiagnosis studies has a meaningful effect on the estimation: no study based on individual data provides an estimate higher than 17%, while studies based on aggregated data often provide estimates higher than 40%. This is too systematic to be random. The analysis of two Danish studies, one of each kind, highlights the biases that come with the use of aggregated data and shows how they can lead to overdiagnosis. INTERPRETATION: Many estimates of overdiagnosis associated with breast cancer screening programmes are serious overestimations.

Screening for SARS-CoV-2 by RT-PCR: Saliva or nasopharyngeal swab? Rapid review and meta-analysis.

BACKGROUND: Diagnosis of COVID-19 in symptomatic patients and screening of populations for SARS-CoV-2 infection require access to straightforward, low-cost and high-throughput testing. The recommended nasopharyngeal swab tests are limited by the need of trained professionals and specific consumables and this procedure is poorly accepted as a screening method In contrast, saliva sampling can be self-administered. METHODS: In order to compare saliva and nasopharyngeal/oropharyngeal samples for the detection of SARS-CoV-2, we designed a meta-analysis searching in PubMed up to December 29th, 2020 with the key words "(SARS-CoV-2 OR COVID-19 OR COVID19) AND (salivary OR saliva OR oral fluid)) NOT (review[Publication Type]) NOT (PrePrint[Publication Type])" applying the following criteria: records published in peer reviewed scientific journals, in English, with at least 15 nasopharyngeal/orapharyngeal swabs and saliva paired samples tested by RT-PCR, studies with available raw data including numbers of positive and negative tests with the two sampling methods. For all studies, concordance and sensitivity were calculated and then pooled in a random-effects model. FINDINGS: A total of 377 studies were retrieved, of which 50 were eligible, reporting on 16,473 pairs of nasopharyngeal/oropharyngeal and saliva samples. Meta-analysis showed high concordance, 92.5% (95%CI: 89.5-94.7), across studies and pooled sensitivities of 86.5% (95%CI: 83.4-89.1) and 92.0% (95%CI: 89.1-94.2) from saliva and nasopharyngeal/oropharyngeal swabs respectively. Heterogeneity across studies was 72.0% for saliva and 85.0% for nasopharyngeal/oropharyngeal swabs. INTERPRETATION: Our meta-analysis strongly suggests that saliva could be used for frequent testing of COVID-19 patients and "en masse" screening of populations.

Effects of local laser treatment on vulvovaginal atrophy among women with breast cancer: a prospective study with long-term follow-up.

PURPOSE: Women with breast cancer (BC) often suffer from severe vulvovaginal atrophy (VVA) which ultimately leads to poor sexual and urinary quality of life. We conducted a prospective study among women with BC and VVA, in order to evaluate the long-term effect of laser therapy on VVA. METHODS: Women with BC and VVA were proposed to have fractional microablative CO2 laser therapy (MonaLisaTouch®, DEKA) once per month for 3 months. Efficacy of laser therapy was assessed at baseline, 6 months and 18 months after treatment, using Female Sexual Function Index (FSFI) score, Ditrovie score and vaginal pH. A pap smear was also performed and the epithelial maturation pattern was noted. Paired statistical tests were used to compare results between baseline, 6 months and 18 months. RESULTS: 46 women with BC (median age [interquartile range] 56.5 years [47.0 - 59.4]) were included between May and October 2018. PH level slightly decreased over time (mean Δ at 18 months -0.3, SD = 0.7, p = 0.02) whereas maturation pattern on pap smear did not change. Sexual quality of life was significantly improved at 6 months and 18 months (mean Δ at 6 months 8.3, SD = 6.2 (p < 0.0001) and mean Δ at 18 months 4.3, SD = 8.4 (p = 0.01)). Ditrovie total score improved at 6 months (mean Δ -1.2, SD = 2.7, p = 0.01) but returned to baseline afterwards. Side effects were very mild. Three women developed low (2)- and high (1)-grade HPV-linked cervical lesions during follow-up. CONCLUSION: Among women with BC, fractional microablative CO2 laser is effective on the long term on VVA symptoms and gynaecological quality of life. TRIAL REGISTRATION NUMBER: ID-RCB 2018-A01500-55.

Association between adherence to the French dietary guidelines and the risk of type 2 diabetes.

OBJECTIVE: French food-based dietary guidelines (FBDG) were updated in 2017. The objective of this prospective study was to estimate the associations between the Programme National Nutrition Santé-guidelines score 2 (PNNS-GS2), reflecting the level of adherence to the 2017 FBDG, and the risk of type 2 diabetes (T2D). METHODS: A total of 79 205 French adult participants (mean age: 41.5 y [SD = 14.5]; 78.5% were women; 65% were postgraduate) from the NutriNet-Santé cohort (2009-2019) were included. Dietary intakes were collected using repeated 24-h dietary records. The PNNS-GS2 (theorical range: -∞ to 14.25), including six adequacy components and seven moderation components as well as a penalization on energy intake, was computed. The association between the PNNS-GS2 (as quintiles [Q]) and T2D risk was estimated using multivariable Cox proportional hazard models accounting for sociodemographic, anthropometric, and lifestyle and health-related factors. RESULTS: During an average follow-up of 6.7 y (536 679 person-years), 676 T2D cases occurred. In the multiadjusted model, participants with the highest PNNS-GS2 (higher adherence to the 2017 FBDG), compared with those with the lowest (lower adherence to FBDG), exhibited a 49% reduction in risk of T2D (HRQ5 versus Q1: 0.51, 95% CI: 0.37, 0.69). Body mass index accounted for up to 27% of the main association. The healthy profiles of the cohort's participants may have reduced statistical power. CONCLUSIONS: In this large, prospective cohort study, a higher adherence to the French 2017 FBDG was strongly and inversely associated with the risk of developing T2D. Such analysis should be confirmed in other settings, but in terms of public health and nutritional policy, this study supports the relevance of the 2017 French FBDG.

Dose-intensive regimen treatment for small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT).

PURPOSE: Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a rare and rapidly lethal disease affecting young women. Cytoreductive surgery associated with chemotherapy followed by a high dose chemotherapy regimen (HDC) demonstrated improved outcomes in a unique prospective and several retrospective studies, and this report aimed to confirm these results in an independent and larger cohort. METHODS: Between 2006 and 2018, we conducted a multicentric prospective study on 44 women diagnosed with SCCOHT. Patients were treated homogeneously with optimal cytoreductive surgery and chemotherapy protocol for four to six cycles (PAVEP). In case of complete response, patients received HDC with stem-cell support, followed by pelvic radiotherapy. The primary endpoint was the event-free survival (EFS) in the per-protocol cohort. Secondary analysis explored the effect of HDC with outcomes. RESULTS: Mean age at diagnosis was 33 years old (range 13.8-75.8). 14 patients presented with stage FIGO I, 21 with stage III and 9 with stage IV. Median follow-up was 53.4 months. 38 patients underwent optimal surgery with up to 6 cycles of PAVEP. 30 received HDC, and 21 pelvic radiotherapy. 21 relapses were reported leading to death for 18 patients. Median EFS in the per-protocol cohort was 18.2 months, and 2-year EFS rate was 40%. HDC was significantly associated with better overall survival (p < .001). Grades 3/4 adverse events were frequent but, in most cases, manageable, although one grade-5 adverse-event occurred during HDC. CONCLUSION: Intensive regimen containing multidrug chemotherapy, HDC and pelvic radiotherapy, for the management of SCCOHT, demonstrated encouraging survival and should be proposed for all patients. However, the significant toxicity cost associated is of concern and it should be restricted to expert centers.

Patterns of first recurrence and outcomes in surgically treated women with vulvar cancer: results from FRANCOGYN study group.

OBJECTIVE: Cancer of the vulva recurrences vary considerably over time and are influenced by several pathological, surgical and adjuvant therapeutic prognostic factors. However, limited information is available about patterns of disease recurrence and prognosis. We analysed patterns of vulvar cancer recurrence based on a large French multicentre database. METHODS: Data of women with histologically proven squamous cell carcinoma (SCC) and other vulvar cancer treated between 1976 and 2016 were retrospectively abstracted from five institutions with prospectively maintained vulvar cancer databases in France. The endpoints were pattern of recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray's test) and competing risks regression analysis to estimate sub-distribution hazard ratios and 95% CIs. RESULTS: In the whole population, recurrences were observed in 188 of the 617 women (30%) with local-regional, distant and multifocal recurrences in 18% (109/617), 3% (17/617), 10% (62/617), respectively. The median time to recurrence with Interquartile Range (IQR) was 13 months IQR [8-30]. The overall respective 3-years OS and RFS were 78.5% (IC95%: 74.5-82.5) and 75.5% (IC95%: 71.1-80.0). According to FIGO stage, lymph node status and positive lympho-vascular invasion (LVSI), pattern and time of loco-regional and distant recurrence were significantly different. There wasn't interaction between FIGO stage and LVSI in OS neither RFS (p=0.08 and 0.9 respectively). CONCLUSION AND DISCUSSION: We report specific time and site patterns of first recurrence according to FIGO stage, lymph node status and lymphovascular invasion status. Positive LVSI is an important and independent prognostic factor. Defining patterns of recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches.

Adherence to the 2017 French dietary guidelines and adult weight gain: A cohort study.

BACKGROUND: The French dietary guidelines were updated in 2017, and an adherence score to the new guidelines (Programme National Nutrition Santé Guidelines Score 2 [PNNS-GS2]) has been developed and validated recently. Since overweight and obesity are key public health issues and have been related to major chronic conditions, this prospective study aimed to measure the association between PNNS-GS2 and risk of overweight and obesity, and to compare these results with those for the modified Programme National Nutrition Santé Guidelines Score (mPNNS-GS1), reflecting adherence to 2001 guidelines. METHODS AND FINDINGS: Participants (N = 54,089) were recruited among French adults (≥18 years old, mean baseline age = 47.1 [SD 14.1] years, 78.3% women) in the NutriNet-Santé web-based cohort. Mean (SD) score was 1.7 (3.3) for PNNS-GS2 and 8.2 (1.6) for mPNNS-GS1. Selected participants were those included between 2009 and 2014 and followed up to September 2018 (median follow-up = 6 years). Collected data included at least three 24-hour dietary records over a 2-year period following inclusion, baseline sociodemographics, and anthropometric data over time. In Cox regression models, PNNS-GS2 was strongly and linearly associated with a lower risk of overweight and obesity (HR for quintile 5 versus quintile 1 [95% CI] = 0.48 [0.43-0.54], p < 0.001, and 0.47 [0.40-0.55], p < 0.001, for overweight and obesity, respectively). These results were much weaker for mPNNS-GS1 (HR for quintile 5 versus quintile 1 = 0.90 [0.80-0.99], p = 0.03, and 0.98 [0.84-1.15], p = 0.8, for overweight and obesity, respectively). In multilevel models, PNNS-GS2 was negatively associated with baseline BMI and BMI increase over time (ß for a 1-SD increase in score [95% CI] = -0.040 [-0.041; -0.038], p < 0.001, and -0.00080 [-0.00094; -0.00066], p < 0.001, respectively). In "direct comparison" models, PNNS-GS2 was associated with a lower risk of overweight and obesity, lower baseline BMI, and lower BMI increase over time than mPNNS-GS1. Study limitations include possible selection bias, reliance on participant self-report, use of arbitrary cutoffs in data analyses, and residual confounding, but robustness was tested in sensitivity analyses. CONCLUSIONS: Our findings suggest that adherence to the 2017 French dietary guidelines is associated with a lower risk of overweight and obesity. The magnitude of the association and the results of the direct comparison reinforced the validity of the updated recommendations. TRIAL REGISTRATION: The NutriNet-Santé Study ClinicalTrials.gov (NCT03335644).

Prospective association between several dietary scores and risk of cardiovascular diseases: Is the Mediterranean diet equally associated to cardiovascular diseases compared to National Nutritional Scores?

BACKGROUND: Mediterranean diet has been consistently negatively associated with cardiovascular diseases (CVD) but the superiority compared to official nutritional guidelines has not been tested yet. Our objective was to prospectively investigate the association between several nutritional scores and incidence of cardiovascular diseases. METHODS AND FINDINGS: A total of 94,113 participants from the NutriNet-Santé cohort were followed between 2009 and 2018. The participants have completed at least three 24 h dietary records during the first two-years of follow-up to compute nutritional scores reflecting adherence to the Mediterranean diet (MEDI-LITE), American dietary guidelines (AHEI-2010) and French dietary guidelines (mPNNS-GS). Sex-specific quartiles (Q) of scores were computed. Multivariable Cox proportional hazards models were used to estimate the associations between scores and incidence of CVD, documented using Hazard Ratio (HR) and 95% confidence intervals (95%CI). Thus, 1399 incident CVD events occurred during the follow-up (mean follow-up = 5.4 years). Comparing Q4 versus Q1 quartile, HR for the MEDI-LITE and AHEI-2010 were 0.79 (95% CI: 0.67-0.93, P-trend = .004) and 0.75 (95% CI: 0.63-0.89, P-trend = .002) respectively. These associations remained similar when removing early cases of CVD, when analyses were restricted to participants with >6 dietary records and when considering transient ischemic attacks. In this last case, association between CVD' risk and mPNNS-GS become significant. CONCLUSIONS: A better nutritional quality of diet is overall associated with lower risk of CVD. The future version of the PNNS-GS, based on the updated version of the French dietary guidelines, should strengthen the CVD protective effect of French recommendations.

Programme National Nutrition Santé - guidelines score 2 (PNNS-GS2): development and validation of a diet quality score reflecting the 2017 French dietary guidelines.

Following the revision of the French dietary guidelines in 2017, the Programme National Nutrition Santé - guidelines score (PNNS-GS), built upon previous recommendations released in 2001, needed to be updated. This cross-sectional study thus aimed to develop and validate the PNNS-GS2, a predefined food-based dietary index based on the 2017-revised French nutritional guidelines. A total of 80 965 participants recruited among French adults (≥18 years old) in the NutriNet-Santé web-based prospective cohort were included. Collected data included repeated 24 h-dietary records over a 2-year period, sociodemographic and, for 16 938 subjects, clinical and biological data. Weighting and cut-offs of the PNNS-GS2 components were collegially arbitrated by nutrition experts who participated in the 2017 revision of the guidelines. Sociodemographic, nutritional and clinical and biological factors were investigated according to quintiles (Q) of PNNS-GS2 (theoretical ranging -17 to +13·5). Mean PNNS-GS2 was 2·1 (sd 3·1) in women and -0·3 (sd 3·6) in men. Higher PNNS-GS2 (higher adherence to 2017 dietary guidelines) was positively associated with (mean difference between Q5 and Q1 in women/men) age (+8·4/+4·7 years), education (+3·9/+7·4 % of university level), physical activity (+13·3/+3·5 % of ≥60 min/d) and non-smoking (+9·7/+13·7 %), and was negatively associated with mean blood pressure (-3·0/-2·8 mmHg), plasma LDL-cholesterol (-0·07/-0·06 g/l) and TAG (-0·10/-0·16 g/l) concentrations. Higher PNNS-GS2 was also associated with higher intake of favourable nutrients, e.g. n-3 PUFA (+0·2/+0·2 % of energy intake), fibres (+8·7/+10·7 g) and vitamin C (+36·6/+43·8 mg). Associations between PNNS-GS2 and sociodemographic and nutritional factors arguing for its validation are coherent. Further studies are needed to evaluate its association with mortality and morbidity.