Unresectable hepatocellular carcinoma at dawn of immunotherapy era: real-world data from the French prospective CHIEF cohort.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma epidemiological data are limited in France. The Epidemio Liver Immunotherapy Tecentriq outcome research (ELITor) retrospective study, based on real-world data from the Carcinome HépatocellulaIrE en France (CHIEF) French cohort of hepatocellular carcinoma patients, aimed to get insight into the treatment patterns, the sociodemographic, clinical, biological, and etiological characteristics, and the quality of life of patients with unresectable hepatocellular carcinoma. METHODS AND RESULTS: Between 1 September 2019 and 4 December 2020, 367 patients from the CHIEF cohort received at least one locoregional (52.8%) chemoembolization or radioembolization or systemic treatment (88.3%) and were selected for ELITor. Most patients had a Barcelona Clinic Liver Cancer (BCLC) C (93.2%) hepatocellular carcinoma stage and were affected by cirrhosis (67.7%). Alcohol was confirmed as the main etiology both as a single etiology (29.1%) and in association with other risk factors (26.9%), mainly metabolic disorders (16.2%).Tyrosine-kinase inhibitors, mainly sorafenib, were the most administered systemic treatments in first line. Patients who received at least one combination of atezolizumab and bevacizumab during the study period ( N  = 53) had a better performance status and less portal hypertension frequency than the overall population and more hepatitis B virus infection and fewer metabolic disorders as single etiology. Overall, the global health score before treatment (62.3 ±â€…21.9) was in line with that of reference cancer patients and worsened in 51.9% of the cases after first-line palliative-intent treatment. CONCLUSION: This study provided real-life data on advanced hepatocellular carcinoma characteristics and treatment patterns and described the first patients to receive the atezolizumab-bevacizumab combination before it became the new standard of care for advanced hepatocellular carcinoma.

Occupational exposures in the rubber tire industry and risk of cancer: a systematic review.

OBJECTIVE: This study aimed at investigate the association between cancer and the rubber tire industry using indicators used to estimate exposure, such as duration or historical time period of exposure. METHODS: A systematic review using MEDLINE was carried out. The Preferred Reporting Items for Systematic Reviews (PRISMA) statement guided the systematic review. The Risk of Bias in Non-Randomized Studies of Exposures (ROBINS-E) was used to analyze biases in the selected studies. RESULTS: A total of 240 articles were initially selected. Of these, 17 were included in this systematic review of 15 different cohorts and one case-control study. Five cohorts were composed of rubber industry employees including some who worked in the rubber tire industry, whereas the other 10 cohorts were composed exclusively of rubber tire industry employees. An increased risk of lung/respiratory cancer is possible in the oldest time periods without duration of exposure showing any association according to the analysis. The work areas of mixing and milling as well as compounding seem to be more specifically associated with this risk, which could be expected because of the exposure to fumes containing carcinogenic agents. CONCLUSIONS: Having worked in the rubber tire industry in the past, especially in milling, mixing as well as compounding may be associated with an increased risk of lung/respiratory cancer.

[ISO 9001: 2015 certification of all research activities of a university hospital center]. / Certification ISO 9001 : 2015 de l'ensemble des activités de recherche d'un centre hospitalier universitaire.

INTRODUCTION: In France, the number of hospitals involved in clinical research and committed to a quality approach is increasing. The objective of such approaches is to ensure the safety of patients involved in research projects by improving quality. OBJECTIVE: The University Hospital of Amiens has chosen to certify all its clinical research activities in the same scope according to the ISO 9001: 2015 standard. METHODS: Action planning has been established and a head of quality management has been appointed to oversee this process. RESULTS: The activities in the five departments of our university hospital jointly certified in December 2019, are: activities related to internal and external sponsors, as well as methodology and monitoring of clinical research projects conducted in the Clinical Research and Innovation Department (CRID); help with clinical research investigations in the Clinical Research Center (CRC); management of the pathway of therapeutic units used in clinical research (excluding the manufacture of drugs) in the Clinical Trials Unit (CTU) of the Hospital Pharmacy; the conservation and provision of biological resources (tissues and fluids) for cancer research in the Tumor bank of Picardy; the collection, reception, preparation, quality control, conservation and provision of biological resources for research purposes. These activities fall within the framework of legal and regulatory activities and the provision of secure storage in the Biological Resources Center already ISO 9001 certified since 2004 and NF S96-900: 2011 certified since 2009. CONCLUSIONS: The choice of a common quality approach has brought together more than 70 persons from 5 departments involved in clinical research projects within a single certificate with the aim of continuous improvement.

Hospital-wide SARS-CoV-2 antibody screening of 4840 staff members in a University Medical Center in France: a cross-sectional study.

OBJECTIVES: Healthcare workers are more likely to be infected by SARS-CoV-2. In order to assess the infectious risk associated with working in a hospital, we sought to estimate the proportion of healthcare professionals infected with SARS-CoV-2 by screening staff in a University Medical Center in France. SETTING: A hospital-wide screening campaign (comprising a serological test and a questionnaire) ran from 18 May to 26 July 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The seroprevalence rate was analysed in a multivariate analysis according to sociodemographic variables (age, sex and profession), exposure to SARS-CoV-2 and symptoms. RESULTS: A total of 4840 professionals were included, corresponding to 74.5% of the centre's staff. The seroprevalence rate (95% CI) was 9.7% (7.0% to 12.4%). Contact with a confirmed case of COVID-19 was significantly associated with seropositivity (OR (95% CI: 1.43, (1.15 to 1.78)). The seroprevalence rate was significantly higher among nursing assistants (17.6%) than among other healthcare professionals. The following symptoms were predictive of COVID-19: anosmia (OR (95% CI): 1.55, (1.49 to 1.62)), ageusia (1.21, (1.16 to 1.27)), fever (1.15, (1.12 to 1.18)), myalgia (1.03, (1.01 to 1.06)) and headache (1.03, (1.01 to 1.04)).

Epidemiological impact of lung cancer screening by low dose CT scan in the French Department of the SOMME.

CONTEXT: Lung cancer is the leading cause of cancer death worldwide. In recent years, screening using low-dose CT scan has shown a reduction in lung cancer-related mortality and in all-cause mortality. The DEP KP80 study was implemented in the French department of the Somme with the aim of investigating lung cancer screening in practice. The results of the first round showed a prevalence of 2.7% for lung cancer, with the majority at localized stages (77%). The primary objective of our study was to compare the stage at diagnosis of patients with lung cancer screened as part of DEP KP80 and those who were not screened. The secondary objectives were to describe the epidemiological characteristics of lung cancer in the French department of the Somme for the period in question and to compare survival rates in screened and unscreened patients. METHODS: This retrospective cohort study compared from May 2016 to December 2017 the characteristics of patients with lung cancer screened as part of DEP KP80 and those who were not screened, using data from the Somme Cancer Registry. RESULTS: In total, 644 patients with lung cancer were included (18 in the screened group and 626 in the unscreened group). There was a significant inversion in the stage distribution at diagnosis, with a predominance of metastatic or locally advanced stages (69%) and a minority of early stages (31%) in unscreened patients, and a majority of early stages (77.8%) and a lower proportion of locally advanced or disseminated stages (22.2%) in screened patients (p < 0.01). In the screened group, there was a significant improvement in survival, a higher rate of surgical resection, and a longer time interval between first contact and treatment initiation. CONCLUSION: Lung cancer screening by low-dose CT scan in the French department of the Somme showed an impact on stage at diagnosis, with a majority of early stages in screened patients, allowing for curative treatment with a significant improvement in survival.

Cancer Among Adolescents and Young Adults Between 2000 and 2016 in France: Incidence and Improved Survival.

Purpose: This study was undertaken to determine cancer survival and describe the spectrum of cancers diagnosed among French adolescent and young adult (AYA) population. Methods: All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (18% of the French population), over the 2000-2016 period, were included. Age-standardized incidence rates, conventional annual percentage change (cAPC) of incidence over time, and 5-year overall survival (5yOS) were calculated. Results: We analyzed 2734 cancer diagnoses in adolescents and 4199 in young adults. Overall incidence rates were 231.9/106 in 15-19 year olds and 354.0/106 in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors (GCT), Hodgkin lymphoma (HL), and malignant melanoma and were HL, thyroid carcinoma, and malignant melanoma in females. Cancer incidence was stable over time with a cAPC of 0.8% (p = 0.72). For all cancers combined, 5yOS was 86.6% (95% CI: 85.8-87.4), >85% for HL, non-Hodgkin lymphomas (NHL), GCT, thyroid carcinomas, and malignant melanomas, and around 60% and lower for osteosarcomas, Ewing tumors, hepatic carcinomas, and rhabdomyosarcomas. The 5yOS has significantly improved from 2000-2007 to 2008-2015 for all cancers pooled, with a substantial gain of 4% for 15-19 year olds and 3% for 20-24 year olds. Conclusion: Notwithstanding the encouraging results for some cancers, and overall, persistent poorer survivals in AYA were shown compared to children for acute lymphoblastic leukemia, osteosarcoma, Ewing tumor, rhabdomyosarcoma, and malignant hepatic tumors. These disparities require further investigation to identify and address the causes of these inferior outcomes.

Association between renin-angiotensin system inhibitors and COVID-19 complications.

AIMS: To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. METHODS AND RESULTS: All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. CONCLUSIONS: We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes. METHODS: All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model. RESULTS: A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. CONCLUSIONS: Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.

The association between body mass index class and coronavirus disease 2019 outcomes.

BACKGROUND/OBJECTIVES: A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study's primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19. SUBJECTS/METHODS: Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis. RESULTS: In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77-3.24] and 2.58 [1.28-5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29-8.06]) and obesity (3.05 [1.25-7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment. CONCLUSIONS: Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.

Long-Term Natural History of Microscopic Colitis: A Population-Based Cohort.

OBJECTIVES: Data on long-term natural history of microscopic colitis (MC), including collagenous (CC) and lymphocytic colitis (LC), are lacking. METHODS: All new cases of MC diagnosed in the Somme area, France, between January 1, 2005, and December 31, 2007, were prospectively included. Colonic biopsies from all patients were reviewed by a group of 4 gastrointestinal pathologist experts to assess the diagnosis of CC or LC. Demographic and clinical data were retrospectively collected from diagnosis to February 28, 2017. RESULTS: One hundred thirty cases of MC, 87 CC and 43 LC, were included (median age at diagnosis: 70 [interquartile range, 61-77] and 48 [IQR, 40-61] years, respectively). The median follow-up was 9.6 years (7.6; 10.6). By the end of the follow-up, 37 patients (28%) relapsed after a median time of 3.9 years (1.2; 5.0) since diagnosis, without significant difference between CC and LC (30% vs 26%; P = 0.47). Twenty patients (15%) were hospitalized for a disease flare, and 32 patients (25%) presented another autoimmune disease. Budesonide was the most widely used treatment (n = 74, 59%), followed by 5-aminosalicylic acid (n = 31, 25%). The median duration of budesonide treatment was 92 days (70; 168), and no adverse event to budesonide was reported. Sixteen patients (22%) developed steroid dependency and 4 (5%) were corticoresistant. No difference in the risk of digestive and extradigestive cancer was observed compared with the general population. None of the death (n = 25) observed during the follow-up were linked to MC. In multivariate analysis, age at diagnosis (HR, 1.03; 95% confidence interval, 1.00-1.06; P = 0.02) and budesonide exposure (HR, 2.50; 95% confidence interval, 1.11-5.55; P = 0.03) were significantly associated with relapse. DISCUSSION: This population-based study showed that after diagnosis, two-third of the patients with MC observed long-term clinical remission. Age at diagnosis and budesonide exposure were associated with a risk of relapse.

Adolescent and young adult oncology patients in France: Heterogeneity in pathways of care.

BACKGROUND: In order to evaluate at the population level the impact of the actions developed in France since 2004 to organize the care of adolescents and young adults (AYAs) with cancer, we conducted the present study to provide an unbiased view of the pathway of care of these patients. METHODS: Using a population-based registry, we conducted a review of all cases of cancer diagnosed during 2012 and 2013 in 15- to 24-year-old patients living in nineteen French administrative areas. RESULTS: The median times for diagnosis and treatment of the 993 included AYAs were 9 weeks (3-22) and 1 day (0-20), respectively. Delays in diagnosis were significantly longer in young adults than in adolescents, especially for soft-tissue sarcomas (48.7 weeks vs. 15.4 weeks, P = 0.04) and bone tumors (21.4 weeks vs. 10.1 weeks, P = 0.04). The first physicians seen by patients were mostly general practitioners (67.4%). Most patients (77.5%) were treated in adult units. Management decisions were taken within the context of a multidisciplinary team (MDT) in 85.3% of cases. MDT meetings that involved both pediatric and adult oncologists were uncommon (15.7% of patients). Twenty-six percent of patients were included in randomized or nonrandomized clinical studies. The proportion of inclusion was significantly higher in adolescents (39.5%) than in young adults (16.8%). CONCLUSION: In France, pathways of care for AYAs are heterogeneous. It is necessary to organize a national network of expert centers with adequate medical skills and specific psychosocial support and facilities to provide the best possible care for these patients.

Building spatial composite indicators to analyze environmental health inequalities on a regional scale.

BACKGROUND: Reducing health inequalities involves the identification and characterization of social and exposure factors and the way they accumulate in a given area. The areas of accumulation then allow for prioritization of interventions. The present study aims to build spatial composite indicators based on the aggregation of environmental, social and health indicators and their inter-relationships. METHOD: Preliminary work was carried out firstly to homogenize spatial coverage, and secondly to study spatial variation of environmental (EI), socioeconomic (SI) and health (HI) indicators. The aggregation of the different indicators was performed using several methodologies for which results and decision-makers' usability were compared. RESULTS: Four methodologies were tested: 1) A simple summation of normalized HI, EI and SI indicators (IC), 2) the sum of the normalized HI, EI and SI indicators weighted by the first principal component of a Principal Component Analysis (IC PCA), 3) the sum of normalized and weighted indicators of the first principal component of Local Principal Component Analysis (IC LPCA), and 4) the sum of normalized and weighted indicators of the first principal component of a Geographically Weighted Principal Component Analysis (IC GWPCA). CONCLUSION: The GWPCA is particularly adapted to taking into account the spatial heterogeneity and the spatial autocorrelation between SI, EI and HI. This approach invalidates the basic assumptions of many standard statistical analyses. Where socioeconomic indicators present high deprivation and where they are associated with potential modifiable health determinants, decision-makers can prioritize these areas for reducing inequalities by controlling the socioeconomic and health determinants.

Risk assessment of second primary cancer according to histological subtype of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of diseases that are known to carry a considerable risk of second primary cancer (SPC). However, little attention has been paid to SPC risk assessment according to NHL subtypes. Data from 10 French population-based cancer registries were used to establish a cohort of 7546 patients with a first diagnosis of NHL (eight subtypes) between 1989 and 2004. Standardized incidence ratios (SIRs) of metachronous SPC were estimated. Among the 7546 patients diagnosed with a NHL, the overall SPC risk was 25% higher than that in the reference population (SIR = 1.25, 95% confidence interval 1.15-1.36). In univariate analysis, the SPC risk differed by lymphoma subtype. Interestingly, multivariate analysis showed that SPC risk did not differ significantly across NHL subtypes after adjustment for the other covariates (p = 0.786). Patients with NHL have an increased risk of SPC that is not influenced by the histological NHL subtype.

Effect of previous history of cancer on survival of patients with a second cancer of the head and neck.

OBJECTIVE: To provide head and neck squamous cell carcinoma (HNSCC) survival estimates with respect to patient previous history of cancer. MATERIALS AND METHODS: Data from ten French population-based cancer registries were used to establish a cohort of all male patients presenting with a HNSCC diagnosed between 1989 and 2004. Vital status was updated until December 31, 2007. The 5-year overall and net survival estimates were assessed using the Kaplan-Meier and Pohar-Perme estimators, respectively. Multivariate Cox regression models were used to assess the effect of cancer history adjusted for age and year of HNSCC diagnosis. RESULTS: Among the cases of HNSCC, 5553 were localized in the oral cavity, 3646 in the oropharynx, 3793 in the hypopharynx and 4550 in the larynx. From 11.0% to 16.8% of patients presented with a previous history of cancer according to HNSCC. Overall and net survival were closely tied to the presence, or not, of a previous cancer. For example, for carcinoma of the oral cavity, the five-year overall survival was 14.0%, 5.9% and 36.7% in case of previous lung cancer, oesophagus cancer or no cancer history, respectively. Multivariate analyses showed that previous history of cancer was a prognosis factor independent of age and year of diagnosis (p<.001). CONCLUSION: Previous history of cancer is strongly associated with survival among HNSCC patients. Survival estimates based on patients' previous history of cancer will enable clinicians to assess more precisely the prognosis of their patients with respect to this major comorbid condition.

[Alcohol, tobacco, cannabis, anxiety and depression among second-year medical students. Identify in order to act]. / Alcool, tabac, cannabis, anxiété et dépression des étudiants en 2(e) année de médecine. Repérer pour agir.

INTRODUCTION: Excessive alcohol consumption and illicit drug use among students have negative repercussions on their health, education and society in general. Medical students are no exception. METHODS: The objective of this study was to evaluate the consumption of alcohol, tobacco and cannabis as well as levels of anxiety and depression of students admitted to the second year of medical studies based on anonymous self-administered questionnaires containing the following tests: AUDIT, Fagerstrom, CAST and HAD. RESULTS: 198 of the 207 students involved agreed to participate. Excessive alcohol consumption was higher among women than among men (35% versus 22%), but fewer women were alcohol-dependent (2% versus 8%) (p < 0.05). 16% of students were tobacco smokers, with no signs of dependence in 80% of cases. 15% of students smoked cannabis and 52% of them presented problem use. 21% of women had a suspected anxiety disorder and 23% had a proven anxiety disorder, versus 17% and 6% of men, respectively (p = 0.002). 3% had a suspected depressive disorder and 0.5% had a proven depressive disorder. High-risk alcohol consumption was significantly correlated with high-risk cannabis use. No correlation was demonstrated between anxiety or depression and these consumptions. DISCUSSION: Doctors appear to be particularly affected by psychological disorders or addictions and medical students are paradoxically less likely than the general population to receive appropriate care. Universities must provide monitoring and support for students in order to improve their health, but also to enable them to provide care and appropriate educational messages to their patients.

Fighting violence against health workers: a way to improve quality of care?

Violence against health care workers impairs the quality of care. In one university medical center in France, 46% of the health care workers were physically assaulted at some point in the previous 12 months and 79% were verbally insulted. This article describes a participatory approach that was used to ensure health care workers take an active role in designing and implementing anti-violence measures. In each unit, a working group of health care professionals and managers developed an action plan for reducing violence-generating practices. This proactive approach is a powerful tool for motivating health care professionals to improve quality of care.

Spatial relationship quantification between environmental, socioeconomic and health data at different geographic levels.

Spatial health inequalities have often been analyzed in terms of socioeconomic and environmental factors. The present study aimed to evaluate spatial relationships between spatial data collected at different spatial scales. The approach was illustrated using health outcomes (mortality attributable to cancer) initially aggregated to the county level, district socioeconomic covariates, and exposure data modeled on a regular grid. Geographically weighted regression (GWR) was used to quantify spatial relationships. The strongest associations were found when low deprivation was associated with lower lip, oral cavity and pharynx cancer mortality and when low environmental pollution was associated with low pleural cancer mortality. However, applying this approach to other areas or to other causes of death or with other indicators requires continuous exploratory analysis to assess the role of the modifiable areal unit problem (MAUP) and downscaling the health data on the study of the relationship, which will allow decision-makers to develop interventions where they are most needed.

The effect of patient characteristics on second primary cancer risk in France.

BACKGROUND: Although cancer survivors are known to be at greater risk of developing second primary cancer (SPC), SPC incidence estimates in France are thus far lacking. We used a multivariate approach to compute these estimates and analyzed the effect of patient characteristics (gender, age at diagnosis, first cancer site, year of diagnosis and follow-up) on SPC risk. METHODS: Data from ten French population-based cancer registries were used to establish a cohort of all patients diagnosed with a first cancer between 1989 and 2004 and followed up until December 31, 2007. The person-year approach was used to estimate standardized incidence ratios (SIRs) and excess absolute risks (EARs) of metachronous SPC. Multivariate Poisson regression models were then used to model SIRs and EARs separately by gender, adjusting for age, year of diagnosis, follow-up and first cancer site. RESULTS: Among the 289,967 followed-up patients with a first primary cancer, 21,226 developed a SPC. The SIR was of 1.36 (95% CI, 1.35-1.38) and the EAR was of 39.4 excess cancers per 10,000 person-years (95% CI, 37.4-41.3). Among male and female patients, multivariate analyses showed that age, year of diagnosis, follow-up and first cancer site were often independently associated with SIRs and EARs. Moreover, the EAR of SPC remained elevated during patient follow-up. CONCLUSIONS: French cancer survivors face a dramatically increased risk of SPC which is probably related to the high rate of tobacco and alcohol consumption in France. Multivariate modeling of SPC risk will facilitate the construction of a tailored prediction tool to optimize SPC prevention and early detection strategies.

Finding a balance between patients' rights, responsibilities and obligations.

Patients' rights have developed over recent decades in many countries, resulting in improved access to high quality medical care. The alliance between patients and physicians is a moral obligation, backed up by patient rights. Poor patient compliance with medical recommendations constitutes a public health issue, illustrating the difficulty of obliging patients to comply with treatment. The legal recognition of patients' responsibilities is defined in a few legislative and regulatory texts, but is primarily based on jurisprudence. Patients, who despite being fully aware and informed about the risks adopt a behaviour that is harmful to their health, tend to be considered as being irresponsible. This judicial approach raises a number of questions, as it fails to take into account the complexity of the human factors involved in a behaviour with either positive or negative health effects.

The precautionary principle: is it safe.

The precautionary principle is generally acknowledged to be a powerful tool for protecting health but it was originally invoked by policy makers for dealing with environmental issues. In the 1990s, the principle was incorporated into many legislative and regulatory texts in international law. One can consider that the precautionary principle has turned into "precautionism" necessary to prove to the people, taking account of risk in decisions. There is now a risk that these abuses will deprive the principle of its meaning and value. When pushed to its limits, the precautionary principle can even be dangerous when applied to the healthcare field. This is why a critical analysis of the principle is necessary. Through the literature, it sometimes seems to deviate somehow from the essence of the precautionary principle as it is commonly used in relation to health. We believe that educational work is necessary to familiarize professionals, policy makers and public opinion of the precautionary principle and avoid confusion. We propose a critical analysis of the use and misuse of the precautionary principle.