L'exercice de la médecine générale à l'épreuve des crises sanitaires : de Lubrizol à la COVID.

INTRODUCTION: Following the fire of the chemical products stored by the Lubrizol (Seveso upper tier) and Normandie Logistique companies on 26 September 2019 in Rouen, a research group bringing together general practitioners (GP), anthropologists and sociologists has undertaken a multidisciplinary qualitative investigation of general practitioners. The initial objective was to study the practice of primary care health professionals following the event. Initiated in February 2020, this survey was strongly transformed by the COVID-19 pandemic. COVID-19 changed the object of this study, imposed a reflection and a link between the two crises, where GPs found themselves once again on the front line. PURPOSE OF RESEARCH: To analyze the practices of general practitioners in situations of uncertainty in the context of these extraordinary events, namely an industrial fire and a viral pandemic. METHODS: Eighteen general practitioners were interviewed between February and July 2019 in semi-structured interviews conducted by a pair of researchers (sociologist and GP). An analysis inspired by the grounded theory was carried out on three levels (individual thematic analysis, paired confrontation, and collective restitution). CONCLUSION: In the health crisis contexts studied, GPs were confronted with more recurrent complaints while they had relatively little robust knowledge on which to base their responses. Finally, physicians responded to these situations of high uncertainty by drawing in original ways on their personal experiences of these crises.

Quantitative assessment of dietary supplement intake in 77,000 French adults: impact on nutritional intake inadequacy and excessive intake.

BACKGROUND: Dietary supplements (DS) are largely consumed in Western countries without demonstrating their nutritional benefits and safety in the general population. The aims, in a large population-based study of French adults, were: (1) to compare the prevalence of nutrient intake inadequacy and the proportion of individuals exceeding tolerable upper intake levels (UL) between DS users and non-users, and (2) to quantify the extent of potentially "at-risk" DS use practices (e.g., DS/drugs contraindicated association or use of beta-carotene DS in smokers). METHODS: 76,925 participants, 47.6% men and 52.4% women, mean age 46.9 ± 16.3 years were enrolled to the NutriNet-Santé cohort and they completed a quantitative DS questionnaire and three 24 h dietary records. A composition database including > 8000 DS was developed. Variance reduction was applied to estimate usual intakes and analyses were weighted according to the French census data. RESULTS: Among DS users of the specific nutrient, DS contributed to 41% of total intake for vitamin D in men, 55% in women; and to 20% of total intake for pyridoxine in men, 21% in women. Compared to dietary intakes only, their prevalence of inadequacy was reduced by 11% for vitamin C, 9% for magnesium, 6% for pyridoxine in men, and 19% for calcium, 12% for iron, and 11% for magnesium in women (p < 0.0001). The proportion of subjects exceeding UL reached 6% for iron and 5% for magnesium in men, and 9% for iron in women. 6% of DS users had potentially "at-risk" practices. CONCLUSION: While DS use contributed to decrease the prevalence of insufficient intake for several nutrients, it also conveyed excessive intake of iron and magnesium. Besides, a substantial proportion of potentially "at-risk" DS use practices was reported.

Fasting and weight-loss restrictive diet practices among 2,700 cancer survivors: results from the NutriNet-Santé cohort.

Nutrition is often used by cancer survivors as a lever to take charge of their own health. However, some dietary behaviors are not currently recommended for patients without medical supervision. Our study aimed at evaluating weight-loss restrictive diets and fasting practices among cancer survivors of the NutriNet-Santé cohort, as well as related socio-demographic and lifestyle factors. In October 2016, 2,741 cancer survivors had completed a specific questionnaire about their practices. Fasting and non-fasting patients (respectively dieting and non-dieting) were compared using logistic regression models. Analyses were weighted according to the age, gender, and cancer location distribution of French cancer cases. 13.8% had already practiced weight-loss restrictive diet as their diagnosis. They were more likely to be women, professionally active, overweight/obese, to use dietary supplements and to have breast cancer (all p < 0.05). 6.0% had already fasted, 3.5% as their diagnosis. They were more likely to be younger, with higher educational level, higher incomes, professionally active, to have a healthy weight, and to use dietary supplements (all p < 0.05). Fasting was associated with the opinion that such practice could improve cancer prognosis (p < 0.0001). Patients who received nutritional information from health care professionals were less likely to practice fasting or weight-loss restrictive diet (0.42[0.27-0.66], p < 0.0001 and 0.49[0.38-0.64], p < 0.0001 respectively). Our study provided original results suggesting that weight-loss restrictive diets are widely practiced by cancer survivors. Fasting was less common in our study though non negligible. Sources of nutritional information received as cancer diagnosis seemed to be a key determinant of these practices.

Modifications in dietary and alcohol intakes between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort.

Postdiagnosis diet and alcohol consumption may be associated with cancer prognosis, recurrence and mortality. Our aim was to investigate food, nutrient and alcohol intake variations between before and after cancer diagnosis and their determinants in a prospective cohort. Subjects (n = 696) were incident cancer cases diagnosed in the NutriNet-Santé cohort between 2009 and 2016. Food, nutrient and alcohol intakes were prospectively collected using repeated nonconsecutive 24-hr dietary records since subjects' inclusion (i.e. an average of 2 y before diagnosis). Mean number of dietary records per subject was 5.9 before and 8.1 after diagnosis. All dietary data before and after diagnosis were compared by mixed models. Factors associated with the main dietary changes observed were also investigated using multivariable logistic regressions. We observed a decrease in intakes of vegetables (mean decrease in intake in patients who decreased their intake=-102.4 ± 79.8 g/d), dairy products (-93.9 ± 82.8 g/d), meat/offal (-35.5 ± 27.8/d), soy products (-85.8 ± 104.1 g/d), sweetened soft drinks (-77.9 ± 95.4 g/d), and alcoholic drinks (-92.9 ± 119.9 g/d), and an increase in broths (42.1 ± 34.9 g/d) and fats/sauces (18.0 ± 13.4 g/d). We observed a decrease in energy intake (-377.2 ± 243.5 kcal/d) and in intakes of alcohol (-7.6 ± 9.4 g/d) proteins (-17.4 ± 12.5 g/d), and several vitamins (p < 0.05) and micronutrients (p < 0.05). Conversely, lipid (19.4 ± 14.6 g/d), SFA (9.3 ± 7.0 g/d), MUFA (8.3 ± 6.3 g/d) and vitamin E (3.9 ± 3.3 mg/d) intakes increased after diagnosis. This large prospective study suggests that cancer diagnosis is a key period for nutritional changes. It highlights some healthy behaviors such as a decrease in alcohol and sweetened drink consumption, but also less favorable trends, such as a decrease in vegetable consumption and in many vitamin and mineral intakes. These results provide insights to identify and target recommendations to put forward for better nutritional care of cancer survivors.

Dietary supplement use among cancer survivors of the NutriNet-Santé cohort study.

Dietary supplements (DS) may influence cancer prognosis. Their use in cancer patients has been described in the United States, but data are largely lacking in Europe and notably in France. The present study's objectives were (1) to assess DS use and its sociodemographic, lifestyle, and dietary correlates in a large sample of French cancer survivors; (2) to evaluate the involvement of physicians in such DS use; and (3) to assess the extent of potentially harmful practices. Data were collected by self-administered web-based questionnaires among participants of the NutriNet-Santé cohort. Data on DS use was available for 1081 cancer survivors. DS users were compared to non-users with unconditional logistic regressions. DS use was reported by 62% of women and 29% of men. Vitamins D, B6, C and Mg were the most frequently consumed nutrients. 14% of cancer survivors initiated DS use after diagnosis. For 35% of the DS consumed, subjects did not inform their attending physician. DS use was associated with a healthier lifestyle (normal weight, never smoking and better diet) and substantially contributed to nutrient intake. 18% of DS users had potentially harmful DS use practices, such as the simultaneous use of vitamin E and anticoagulant/antiplatelet agents, the use of ß-carotene and smoking or the use of phyto-oestrogens in hormone-dependent cancer patients. The present study suggests that DS use is widespread among cancer survivors, a large amount of that use is performed without any medical supervision and a substantial proportion of that use involves potentially harmful practices. Physicians should be encouraged to more routinely discuss DS use with their cancer patients.

Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer.

Radiation therapy (RT) is an integral part of prostate cancer treatment across all stages and risk groups. Immunotherapy using a live, attenuated, Listeria monocytogenes-based vaccines have been shown previously to be highly efficient in stimulating anti-tumor responses to impact on the growth of established tumors in different tumor models. Here, we evaluated the combination of RT and immunotherapy using Listeria monocytogenes-based vaccine (ADXS31-142) in a mouse model of prostate cancer. Mice bearing PSA-expressing TPSA23 tumor were divided to 5 groups receiving no treatment, ADXS31-142, RT (10 Gy), control Listeria vector and combination of ADXS31-142 and RT. Tumor growth curve was generated by measuring the tumor volume biweekly. Tumor tissue, spleen, and sera were harvested from each group for IFN-γ ELISpot, intracellular cytokine assay, tetramer analysis, and immunofluorescence staining. There was a significant tumor growth delay in mice that received combined ADXS31-142 and RT treatment as compared with mice of other cohorts and this combined treatment causes complete regression of their established tumors in 60 % of the mice. ELISpot and immunohistochemistry of CD8+ cytotoxic T Lymphocytes (CTL) showed a significant increase in IFN-γ production in mice with combined treatment. Tetramer analysis showed a fourfold and a greater than 16-fold increase in PSA-specific CTLs in animals receiving ADXS31-142 alone and combination treatment, respectively. A similar increase in infiltration of CTLs was observed in the tumor tissues. Combination therapy with RT and Listeria PSA vaccine causes significant tumor regression by augmenting PSA-specific immune response and it could serve as a potential treatment regimen for prostate cancer.

Cranberry cocktail juice, cranberry concentrates, and proanthocyanidins reduce reovirus infectivity titers in African green monkey kidney epithelial cell cultures.

Studies were performed to investigate the effect of several cranberry and grape juice extracts on the inhibition of reovirus infectivity following cell culture inoculation. Infectivity testing was performed utilizing cranberry juice extracts NutriCran-100 and NutriCran-90. At 5% extract concentrations, titers were reduced by ca. 50%. Cranberry cocktail juice caused an infectivity loss of ca. 10%. We ascribe these data to higher concentrations of proanthocyanidins (PACs) in the cranberry extracts. Further testing was performed utilizing purified high and low molecular weight cranberry PAC fractions (CB HMW and CB LMW, respectively), a cranberry flavonol glycoside (CB EToAc), cranberry anthocyanins (CB CA), and a grape PAC extract. Reovirus titers were reduced to undetectable levels at PAC concentrations < or =0.2%. CB CA had no effect on the inhibition of infectivity titers. Loss of infectivity titers was in the order: GP PAC>CB HMW>CB LMW>CB EToAc. Probe homogenization of CB HMW enhanced the extract to efficacy levels equal to that of grape PAC. Reovirus dsRNA segments were undetectable 96-h postcranberry cocktail juice pretreatment of MA-104 cell cultures. This study indicates an inhibition of reovirus infectivity titers by cranberry or grape juices or their purified PAC extracts. Viral inhibition probably occurs at the host cell surface.

A national survey of HDR source knowledge among practicing radiation oncologists and residents: Establishing a willingness-to-pay threshold for cobalt-60 usage.

PURPOSE: Ir-192 is the predominant source for high-dose-rate (HDR) brachytherapy in United States markets. Co-60, with longer half-life and fewer source exchanges, has piloted abroad with comparable clinical dosimetry but increased shielding requirements. We sought to identify practitioner knowledge of Co-60 and establish acceptable willingness-to-pay (WTP) thresholds for additional shielding requirements for use in future cost-benefit analysis. METHODS AND MATERIALS: A nationwide survey of U.S. radiation oncologists was conducted from June to July 2015, assessing knowledge of HDR sources, brachytherapy unit shielding, and factors that may influence source-selection decision-making. Self-identified decision makers in radiotherapy equipment purchase and acquisition were asked their WTP on shielding should a more cost-effective source become available. RESULTS: Four hundred forty surveys were completed and included. Forty-four percent were ABS members. Twenty percent of respondents identified Co-60 as an HDR source. Respondents who identified Co-60 were significantly more likely to be ABS members, have attended a national brachytherapy conference, and be involved in brachytherapy selection. Sixty-six percent of self-identified decision makers stated that their facility would switch to a more cost-effective source than Ir-192, if available. Cost and experience were the most common reasons provided for not switching. The most common WTP value selected by respondents was <$25,000. CONCLUSIONS: A majority of respondents were unaware of Co-60 as a commercially available HDR source. This investigation was novel in directly assessing decision makers to establish WTP for shielding costs that source change to Co-60 may require. These results will be used to establish WTP threshold for future cost-benefit analysis.

Sociodemographic and economic factors are associated with weight gain between before and after cancer diagnosis: results from the prospective population-based NutriNet-Santé cohort.

PURPOSE: While many cancer patients are affected by weight loss, others tend to gain weight, which may impact prognosis and risk of recurrence and of second cancer. The aim of this prospective study was to investigate weight variation between before and after cancer diagnosis and socio-demographic, economic, lifestyle and clinical factors associated with moderate-to-severe weight gain. METHODS: 1051 incident cases of first primary cancer were diagnosed in the NutriNet-Santé cohort between 2009 and 2015. Weight was prospectively collected every 6 months since subjects' inclusion (i.e. an average of 2y before diagnosis). Mean weights before and after cancer diagnosis were compared with paired Student's t-test. Factors associated with moderate-to-severe weight gain (≥5% of initial weight) were investigated by age and sex-adjusted logistic regression. RESULTS: Weight loss was observed in men (-3.54±4.39kg in those who lost weight, p=0.0002) and in colorectal cancer patients (-3.94±4.40kg, p=0.001). Weight gain was observed in breast and skin cancers (2.83±3.21kg, p=0.04, and 2.96±2.75kg, p=0.04 respectively). Women (OR=1.75[1.06-2.87],p=0.03), younger patients (2.44[1.51-3.70],p<0.0001), those with lower income (OR=1.30[1.01-1.72],p-trend=0.007), lower education (OR=1.32[1.03-2.70],p-trend=0.03), excess weight before diagnosis (OR=1.64[1.12-2.42],p=0.01), lower physical activity (OR=1.28[1.01-1.64],p=0.04) and those who stopped smoking (OR=4.31[1.99-9.35],p=0.005]) were more likely to gain weight. In breast cancer patients, induced menopause was associated with weight gain (OR=4.12[1.76-9.67]), but no association was detected for tumor characteristics or treatments. CONCLUSION: This large prospective cohort provided original results on weight variation between before and after cancer diagnosis, highlighting different weight trajectories. Socio-demographic and economic factors appeared to influence the risk of weight gain, illustrating social inequalities in health.

Variations of physical activity and sedentary behavior between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort.

Physical activity (PA) but also reduced sedentary behavior may be associated with better prognosis and lower risk of recurrence in cancer patients. Our aim was to quantify the variations in PA and time spent sedentary between before and after diagnosis, relying on prospective data in French adults. We also investigated sociodemographic and lifestyle factors associated with these variations.Subjects (n = 942) were incident cancer cases diagnosed in the NutriNet-Santé cohort between 2009 and 2015. PA and sedentary behavior were prospectively collected with the 7-day short version of the IPAQ questionnaire every year since subjects' inclusion (i.e., an average of 2 year before diagnosis). All PA and sitting time points before and after diagnosis was compared by mixed model. Factors associated with decrease in PA and increase in sitting time were investigated using logistic regressions.Overall and vigorous PA decreased after diagnosis (P = 0.006, -32.8 ±â€Š36.8 MET-hour/week on average, in those who decreased their overall PA and P = 0.005, -21.1 ±â€Š36.8 MET-hour/week for vigorous PA, respectively), especially in prostate (-39.5 ±â€Š36.3 MET-hour/week) and skin (-35.9 ±â€Š38 MET-hour/week) cancers, in men (-40.8 ±â€Š46.3MET-hour/week), and in those professionally inactive (-34.2 ±â€Š37.1 MET-hour/week) (all P < 0.05). Patients with higher PA level before diagnosis were more likely to decrease their PA (odds ratio [OR]: 4.67 [3.21-6.81], P < 0.0001). Overweight patients more likely to decrease moderate PA (OR: 1.45 [1.11-1.89], P = 0.006) and walking (OR: 1.30 [1.10-1.70], P = 0.04). Sitting time increased (P = 0.02, +2.44 ±â€Š2.43 hour/day on average, in those who increased their sitting time), especially in women (+2.48 ±â€Š2.48 hour/day), older patients (+2.48 ±â€Š2.57 hour/day), and those professionally inactive (2.41 ±â€Š2.40 hour/day) (all P < 0.05). Patients less sedentary before diagnosis were more likely to increase their sitting time (OR: 3.29 [2.45-4.42], P < 0.0001).This large prospective study suggests that cancer diagnosis is a key period for change in PA and sedentary behavior. It provides insights to target the subgroups of patients who are at higher risk of decreasing PA and increasing sedentary behavior after cancer diagnosis.

A novel four-dimensional radiotherapy planning strategy from a tumor-tracking beam's eye view.

To investigate the feasibility of four-dimensional radiotherapy (4DRT) planning from a tumor-tracking beam's eye view (ttBEV) with reliable gross tumor volume (GTV) delineation, realistic normal tissue representation, high planning accuracy and low clinical workload, we propose and validate a novel 4D conformal planning strategy based on a synthesized 3.5D computed tomographic (3.5DCT) image with a motion-compensated tumor. To recreate patient anatomy from a ttBEV in the moving tumor coordinate system for 4DRT planning (or 4D planning), the centers of delineated GTVs in all phase CT images of 4DCT were aligned, and then the aligned CTs were averaged to produce a new 3.5DCT image. This GTV-motion-compensated CT contains a motionless target (with motion artifacts minimized) and motion-blurred normal tissues (with a realistic temporal density average). Semi-automatic threshold-based segmentation of the tumor, lung and body was applied, while manual delineation was used for other organs at risk (OARs). To validate this 3.5DCT-based 4D planning strategy, five patients with peripheral lung lesions of small size (<5 cm(3)) and large motion range (1.2-3.5 cm) were retrospectively studied for stereotactic body radiotherapy (SBRT) using 3D conformal radiotherapy planning tools. The 3.5DCT-based 4D plan (3.5DCT plan) with 9-10 conformal beams was compared with the 4DCT-based 4D plan (4DCT plan). The 4DCT plan was derived from multiple 3D plans based on all phase CT images, each of which used the same conformal beam configuration but with an isocenter shift to aim at the moving tumor and a minor beam aperture and weighting adjustment to maintain plan conformality. The dose-volume histogram (DVH) of the 4DCT plan was created with two methods: one is an integrated DVH (iDVH(4D)), which is defined as the temporal average of all 3D-phase-plan DVHs, and the other (DVH(4D)) is based on the dose distribution in a reference phase CT image by dose warping from all phase plans using the displacement vector field (DVF) from a free-form deformable image registration (DIR). The DVH(3.5D) (for the 3.5DCT plan) was compared with both iDVH(4D) and DVH(4D). To quantify the DVH difference between the 3.5DCT plan and the 4DCT plan, two methods were used: relative difference (%) of the areas underneath the DVH curves and the volumes receiving more than 20% (V20) and 50% (V50) of prescribed dose of these 4D plans. The volume of the delineated GTV from different phase CTs varied dramatically from 24% to 112% among the five patients, whereas the GTV from 3.5DCT deviated from the averaged GTV in 4DCT by only -6%±6%. For planning tumor volume (PTV) coverage, the difference between the DVH(3.5D) and iDVH(4D) was negligible (<1% area), whereas the DVH(3.5D) and DVH(4D) were quite different, due to DIR uncertainty (∼2 mm), which propagates to PTV dose coverage with a pronounced uncertainty for small tumors (0.3-4.0 cm(3)) in stereotactic plans with sharp dose falloff around PTV. For OARs, such as the lung, heart, cord and esophagus, the three DVH curves (DVH(3.5D), DVH(4D) and iDVH(4D)) were found to be almost identical for the same patients, especially in high-dose regions. For the tumor-containing lung, the relative difference of the areas underneath the DVH curves was found to be small (5.3% area on average), of which 65% resulted from the low-dose region (D < 20%). The averaged V20 difference between the two 4D plans was 1.2% ± 0.8%. For the mean lung dose (MLD), the 3.5DCT plan differed from the 4DCT plan by -1.1%±1.3%. GTV-motion-compensated CT (3.5DCT) produces an accurate and reliable GTV delineation, which is close to the mean GTV from 4DCT. The 3.5DCT plan is equivalent to the 4DCT plan with <1% dose difference to the PTV and negligible dose difference in OARs. The 3.5DCT approach simplifies 4D planning and provides accurate dose calculation without a substantial increase of clinical workload for motion-tracking delivery to treat small peripheral lung tumors with large motion.

Hyperthermia on immune regulation: a temperature's story.

Over the last decade the linkage between hyperthermia, heat shock proteins and fever with the body's immune system has been well investigated. The immunomodulatory function of hyperthermia has been found to be quite sensitively regulated by temperature, as different levels of heating can bring different modulatory effect on different sensitive targets. Understanding these intrinsic mechanisms could bring new inspirations on the design of clinical trials combining local tumor hyperthermia with immunotherapy in cancer patients. This review will attempt to tell the story about the effect of temperature on immune regulation, with special emphasis on the clinical application of hyperthermia and the feasibility of combining it with immunotherapy in the clinic.

Lack of effective MUC1 tumor antigen-specific immunity in MUC1-transgenic mice results from a Th/T regulatory cell imbalance that can be corrected by adoptive transfer of wild-type Th cells.

Glycoprotein tumor Ag MUC1 is overexpressed on the majority of epithelial adenocarcinomas. CTLs that recognize MUC1 and can kill tumor cells that express this molecule have been found in cancer patients, yet they are present in low frequency and unable to eradicate MUC1(+) tumors. Patients also make anti-MUC1 Abs but predominantly of the IgM isotype reflecting the lack of effective MUC1-specific Th responses. Mice transgenic for the human MUC1 gene (MUC1-Tg) are similarly hyporesponsive to MUC1. We used a vaccine consisting of dendritic cells loaded with a long synthetic MUC1 peptide to investigate the fate and function of MUC1-specific CD4(+) Th elicited in wild-type (WT) or MUC1-Tg mice or adoptively transferred from vaccinated WT mice. We show that hyporesponsiveness of MUC1-Tg mice to this vaccine is a result of insufficient expansion of Th cells, while at the same time their regulatory T cells are efficiently expanded to the same extent as in WT mice and exert a profound suppression on MUC1-specific B and T cell responses in vivo. Adoptive transfer of WT Th cells relieved this suppression and enhanced T and B cell responses to subsequent MUC1 immunization. Our data suggest that the balance between Th and regulatory T cells is a critical parameter that could be modulated to improve the response to cancer vaccines.