How do women comply with cancer screenings? A study in four regions of France.

BACKGROUND: This article looks at the behaviour of women facing different cancer screening options available to them from the age of 50 onward. The study was conducted in 2019 in four departments of the French territory with the objective of identifying the factors that influence acceptance of a population-based screening proposal. METHODS: A questionnaire was sent to women who had received three invitations to organised screenings (OS) for both breast and colorectal cancer. The categories of participants in both OS were designed from data from the regional cancer screening coordination centres in each department. Participation in opportunistic cervical cancer screening was evaluated as self-reported data. RESULTS: 4,634 questionnaires were returned out of the 17,194 sent, giving a global return rate of 27%. The highest rate of return (73.5%) was obtained from women who had participated at least once in both breast and colorectal cancer OS. An intermediate rate was obtained from women participating in breast cancer OS only (18.7%). Poor levels of return came from women who had participated in colorectal cancer OS only (3.6%) and from non-participants (4.1%). Our results suggest that women with lower educational levels tend to be the most regular attendants at OS (50.3%), compared to highly educated women (39.7%). 11.8% of women were overdue in their opportunistic cervical cancer screening. This percentage rose to 35.4% in the category of non-participants. In addition, women's comments provide a better understanding of the reasons for irregular attendance and non-participation. CONCLUSION: Overall, similar behaviours towards screening were observed in the four departments. Our analysis suggests that participation in one cancer OS increases the likelihood of participating in others. This adhesion could be an interesting lever for raising women's awareness of other cancer screenings.

Participation in breast cancer screening and its influence on other cancer screening invitations: study in women aged 56 years old in four French departments.

BACKGROUND: Today, women 50 years of age are offered three types of cancer screening in France. However, participation is not optimal. The aim was to describe (1) participation in organised breast cancer screening (OS) of women aged 56 years old, and the influence of this participation on colorectal and cervical cancer screening, (2) the reasons for non-participation in breast cancer OS, and (3) the reasons for screening before age 50. METHODS: A questionnaire was sent to 56-year-old women in four French departments to identify their participation behaviour in three breast cancer OS invitations and their reasons for non-participation. Three groups were determined according to the number of participations in breast cancer OS (3, 1-2 and 0). We described the quantitative responses and grouped the qualitative responses thematically. RESULTS: A total of 4634 women responded to the questionnaire. Seventy-six percent had undergone all three breast cancer OS, 16% irregular and 7% non-participant. Among women who irregularly perform breast cancer OS, 50.5% also irregularly perform colorectal cancer OS. Women who participated in all three invitations for the breast cancer OS performed more smear tests than women in the other groups. Many of the irregular participants or non-participants underwent opportunistic screening, often initiated before the age of 50. The reasons for non-participation in breast cancer OS were mainly medical or participation in opportunistic screening. CONCLUSION: There is no fundamental opposition to participation in breast cancer screening. However, it remains of the utmost importance that women should be better informed about OS and its benefits.

Termination of pregnancy for foetal indication in the French context analysis of decision-making in a Multidisciplinary Centre For Prenatal Diagnosis.

OBJECTIVE: In France, termination of pregnancy (TOP) for medical reasons is legal, regardless of the term, after authorisation by a Multidisciplinary Centre for Prenatal Diagnosis (MCPD). This study analyses the elements supporting the TOP decision-making process faced with a foetal pathology. STUDY DESIGN: Medical records of one MCPD were analysed for the period 2013 and 2014 and semi-structured interviews with MCPD members were conducted. RESULTS: Out of 265 files concerning foetal indications, all but one resulted in a decision for TOP. The main indications in number for TOP were malformations and chromosomal abnormalities. For indications such as trisomy 21, authorisations are generally given without discussion. Our results underline the importance that professionals attach to the collegiality of decisions, particularly in situations of uncertainty. CONCLUSION: This study provides information about the activity of MCPDs within the field of prenatal diagnosis and shows the importance of these structures in supporting women and couples whilst respecting their autonomy. At present, the role of the MCPD is in the process of evolving and could become an information and advisory board for women, based on collegial expertise to guide their decision-making.

Éthique et dépistages organisés des cancers en France.

Cancer screening has been among the priorities of the French Cancer Plans since 2003. However, participation in screening programs remains below expectations. The predominance of the value of autonomy in today's society may compromise the legitimacy of a public health action if it does not gain the adhesion of individuals. The Group of Reflection on the Ethics of Screening (GRED) set up by the French National Cancer Institute has brought together experts from different disciplines around this issue. The aim of the present article is to summarize the work of the group, which successively focused on breast and colorectal cancer screening programs, followed by reflection on the implementation of organized cervical cancer screening. Information and health education appear to be key levers to enable individuals to understand the collective interest of public health policies and thus to be able to adhere to the proposed actions in an informed manner. This should be made possible by providing complete and high quality information, addressing the limits of each screening including benefits and risks. Valuing the collective dimension of public health, which calls for solidarity, must make it possible to raise awareness of the proper use of public services.

[Ethical considerations in the evolution of organised cancer screening programs]. / Apport de la réflexion éthique dans l'évolution des programmes de dépistage organisé des cancers.

Ethical considerations in the evolution of organised cancer screening programs Since 2009, the French National Cancer Institute has set up a working group on the ethics of screening programs for breast, colon and cervical cancer. Collective and individual interest, equity and respect for autonomy are the values addressed in the respective reports. Ethical analysis has highlighted issues that are specific to each programme: the importance of the information provided by health professionals in a context of uncertainty for breast cancer screening; health professionals as a relay of information, access to test and support in the colorectal cancer screening process and, for cervical cancer screening, the implementation of an organisation adapted to women populations concerned. A public health policy whose efficiency depends on the public's adhesion of screening proposals must respect a fundamental ethical principle, namely the assessment of the benefit/risk balance.

Apport de la réflexion éthique dans l'évolution des programmes de dépistage organisé des cancers Depuis 2009, l'Institut national du cancer a mis en place un groupe de réflexion sur l'éthique des programmes de dépistage des cancers du sein, du côlon et du col de l'utérus. L'intérêt collectif et individuel, l'équité et le respect de l'autonomie sont les valeurs abordées dans les rapports respectifs. L'analyse éthique a fait émerger des enjeux spécifiques à chaque programme : l'importance de l'information délivrée par les professionnels de santé dans un contexte d'incertitude, pour le dépistage du cancer du sein ; les professionnels de santé comme relais d'information, d'accès au test et d'accompagnement dans le parcours de dépistage du cancer colorectal et pour le dépistage du cancer du col de l'utérus, la mise en place d'une organisation adaptée aux populations de femmes concernées. Une politique de santé publique dont l'efficience dépend de l'adhésion de la population aux propositions de dépistage doit respecter un principe éthique fondamental qui est l'évaluation de la balance bénéfices-risques.

Low participation in organized colorectal cancer screening in France: underlying ethical issues.

International studies have shown a significant reduction in colorectal cancer (CRC) mortality following the implementation of organized screening programs, given a sufficient participation rate and adequate follow-up. The French national CRC screening program has been generalized since 2008 and targets 18 million men and women aged 50-74 years. Despite broad recommendations, the participation rate remains low (29.8%), questioning the efficiency of the program. A panel of experts was appointed by the French National Cancer Institute to critically examine the place of autonomy and efficiency in CRC screening and propose recommendations. In this paper, we explore the ethical significance of a public health intervention that falls short of its objectives owing to low take-up by the population targeted. First, we analyze the reasons for the low CRC screening participation. Second, we examine the models that can be proposed for public health actions, reconciling respect for the individual and the collective good. Our expert panel explored possible ways to enhance take-up of CRC screening within the bounds of individual autonomy, adapting awareness campaigns, and new educational approaches that take into account knowledge and analysis of sociocultural hurdles. Although public health actions must be universal, target actions should nonetheless be developed for nonparticipating population subgroups.

[Participation to organized screening programs: Individual and collective stakes]. / Participation aux programmes organisés de dépistage des cancers : enjeu individuel, enjeu collectif.

The evaluation of the risk-benefit balance in public health is an ethical commitment, based on the imperative of not harming people. Screening is a probabilistic approach, which, in order to serve the needs of a few, involves the largest number to share the potential harmful effects. Improvement of scientific knowledge and opening of the societal debate modified the relation between collective and individual stakes over time. This article traces the evolution of the discourse surrounding cancer screening, particularly following the controversy surrounding breast cancer screening. Within the framework of a health policy, screening leads in the first place to a collective benefit and second, to an individual benefit. It describes how, within the French context, the debate has induced a complete re-examination of the modalities of information and consent leading to a shift from the promotion of screening to more balanced information on benefits and risks, so that people can decide whether to participate in a more informed way.

[Ethics of organized cancer screening in France] / Éthique et dépistages organisés des cancers en France.

Cancer screening has been among the priorities of the French Cancer Plans since 2003. However, participation in screening programs remains below expectations. The predominance of the value of autonomy in today's society may compromise the legitimacy of a public health action if it does not gain the adhesion of individuals. The Group of Reflection on the Ethics of Screening (GRED) set up by the French National Cancer Institute has brought together experts from different disciplines around this issue. The aim of the present article is to summarize the work of the group, which successively focused on breast and colorectal cancer screening programs, followed by reflection on the implementation of organized cervical cancer screening. Information and health education appear to be key levers to enable individuals to understand the collective interest of public health policies and thus to be able to adhere to the proposed actions in an informed manner. This should be made possible by providing complete and high quality information, addressing the limits of each screening including benefits and risks. Valuing the collective dimension of public health, which calls for solidarity, must make it possible to raise awareness of the proper use of public services.

Towards equity in organised cancer screening: the case of cervical cancer screening in France.

BACKGROUND: The French national cancer institute (INCa) conducted a series of studies to assist decision-making in view of the implementation of organised cervical cancer screening that will be launched in 2018. The programme will concern all women aged 25-65 and targeted interventions will be developed for underscreened populations. This is an evolution from an equality-based approach to a step-by-step strategy of equity aiming to tackle health cancer inequalities that are avoidable and represents unfair differences. Here we present the work of the expert-group in ethics drafted by INCa to review the ethical issues prior to the programme implementation. DISCUSSION: We discuss the value of such a strategy and presents reflections with regard to issues of stigmatization, respect for individual freedom and autonomy. Indeed, the balance has to be found between the search for beneficence and the potential occurrence of perverse effects, which should be considered with particular attention. CONCLUSION: Moving toward an equity-oriented policy under a strategy of proportionate universalism faces a number of challenges, thus an overview of ethics and social sciences must be an integral part of the process.

[The digital pill, between beneficence and vigilance: ethical stakes]. / Le médicament connecté, entre bienveillance et surveillance - Analyse des enjeux éthiques.

Since November 2017, the digital pill, which makes it possible to know whether a patient has achieved compliance or not with the treatment has become a reality. This drug can benefit the patients by helping them to better follow their treatment and avoid misuse. However, even though the use of this device requests patient consent, major questions arise regarding the respect for privacy and freedom of action. Evidently, the correct use of drugs is both a public health and economic issue, but through this digital tool, the temptation could be to implement measures to control citizens, in particular regarding the use of treatments that affect health expenditure. A too prescriptive conception of monitoring algorithms could alter the care relationship, denying the part of adaptation that a patient can legitimately claim in taking his treatment. The digital pill could be a helpful tool but it is necessary to evaluate its fair place in terms of respect for the person and adequacy with its liberties.

Partnering with patients in translational oncology research: ethical approach.

BACKGROUND: The research program CARPEM (cancer research and personalized medicine) brings together the expertise of researchers and hospital-based oncologists to develop translational research in the context of personalized or "precision" medicine for cancer. There is recognition that patient involvement can help to take into account their needs and priorities in the development of this emerging practice but there is currently no consensus about how this can be achieved. In this study, we developed an empirical ethical research action aiming to improve patient representatives' involvement in the development of the translational research program together with health professionals. The aim is to promote common understanding and sharing of knowledge between all parties and to establish a long-term partnership integrating patient's expectations. METHODS: Two distinct committees were settled in CARPEM: an "Expert Committee", gathering healthcare and research professionals, and a "Patient Committee", gathering patients and patient representatives. A multidisciplinary team trained in medical ethics research ensured communication between the two committees as well as analysis of discussions, minutes and outputs from all stakeholders. RESULTS: The results highlight the efficiency of the transfer of knowledge between interested parties. Patient representatives and professionals were able to identify new ethical challenges and co-elaborate new procedures to gather information and consent forms for adapting to practices and recommendations developed during the process. Moreover, included patient representatives became full partners and participated in the transfer of knowledge to the public via conferences and publications. CONCLUSIONS: Empirical ethical research based on a patient-centered approach could help in establishing a fair model for coordination and support actions during cancer research, striking a balance between the regulatory framework, researcher needs and patient expectations. Our approach addresses the concept of translational ethics as a way to handle the main remaining gap between combining care and research activities in the medical pathway and the existing framework.

Patient/family views on data sharing in rare diseases: study in the European LeukoTreat project.

The purpose of this study was to explore patient and family views on the sharing of their medical data in the context of compiling a European leukodystrophies database. A survey questionnaire was delivered with help from referral centers and the European Leukodystrophies Association, and the questionnaires returned were both quantitatively and qualitatively analyzed. This study found that patients/families were strongly in favor of participating. Patients/families hold great hope and trust in the development of this type of research. They have a strong need for information and transparency on database governance, the conditions framing access to data, all research conducted, partnerships with the pharmaceutical industry, and they also need access to results. Our findings bring ethics-driven arguments for a process combining initial broad consent with ongoing information. On both, we propose key item-deliverables to database participants.

Women's participation in breast cancer screening in France--an ethical approach.

BACKGROUND: Breast cancer is a major public health challenge. Organized mammography screening (OS) is considered one way to reduce breast cancer mortality. EU recommendations prone mass deployment of OS, and back in 2004, France introduced a national OS programme for women aged 50-74 years. However, in 2012, participation rate was still just 52.7%, well short of the targeted 70% objective. In an effort to re-address the (in) efficiency of the programme, the French National Cancer Institute has drafted an expert-group review of the ethical issues surrounding breast cancer mammography screening. DISCUSSION: Prompted by emerging debate over the efficiency of the screening scheme and its allied public information provision, we keynote the experts' report based on analysis of epidemiological data and participation rate from the public health authorities. The low coverage of the OS scheme may be partly explained by the fact that a significant number of women undergo mammography outside OS and thus outside OS criteria. These findings call for further thinking on (i) the ethical principles of beneficence and non-malfeasance underpinning this public health initiative, (ii) the reasons behind women's and professionals' behavior, and (iii) the need to analyze how information provision to women and the doctor-patient relationship need to evolve in response to scientific controversy over the risks and benefits of conducting mammographic screening. SUMMARY: This work calls for a reappraisal of the provision of screening programme information. We advocate a move to integrate the points sparking debate over the efficiency of the screening scheme to guarantee full transparency. The perspective is to strengthen the respect for autonomy allowing women to make an informed choice in their decision on whether or not to participate.

Ethical management in the constitution of a European database for leukodystrophies rare diseases.

BACKGROUND: The EU LeukoTreat program aims to connect, enlarge and improve existing national databases for leukodystrophies (LDs) and other genetic diseases affecting the white matter of the brain. Ethical issues have been placed high on the agenda by pairing the participating LD expert research teams with experts in medical ethics and LD patient families and associations. The overarching goal is to apply core ethics principles to specific project needs and ensure patient rights and protection in research addressing the context of these rare diseases. AIM: This paper looks at how ethical issues were identified and handled at project management level when setting up an ethics committee. METHODS: Through a work performed as a co-construction between health professionals, ethics experts, and patient representatives, we expose the major ethical issues identified. RESULTS: The committee acts as the forum for tackling specific issues tied to data sharing and patient participation: the thin line between care and research, the need for a charter establishing the commitments binding health professionals and the information items to be delivered. Ongoing feedback on the database, including delivering global results in a broad-audience format, emerged as a key recommendation. Information should be available to all patients in the partner countries developing the database and should be scaled to different patient profiles. CONCLUSION: This work led to a number of recommendations for ensuring transparency and optimizing the partnership between scientists and patients.

Arginine-supplemented enteral nutrition in critically ill diabetic and obese rats: a dose-ranging study evaluating nutritional status and macrophage function.

OBJECTIVE: Critically ill diabetic and obese patients are at high risk of complications. Arginine availability is lowered in diabetes and in stress situations, yet arginine is necessary for immune response, mainly by its action through nitric oxide (NO). These facts argue for arginine-supplemented diets in critically ill patients. However, studies have raised concerns about possible adverse effects of such diets in intensive-care patients. We therefore analyzed the metabolic and immunologic effects of an arginine-enriched diet in stressed diabetic-obese rats. METHODS: Zucker Diabetic Fatty rats (fa/fa) were made endotoxemic by an intraperitoneal injection of lipopolysaccharide and then fed 4-d enteral nutrition enriched with arginine (ARG group) or a non-essential amino acid mix (NEAA group). The two groups each were subdivided into three subgroups: the ARG subgroups received 0.5 g (ARG0.5), 2 g (ARG2), and 5 g (ARG5) of arginine per kilogram daily, and the NEAA groups were made isonitrogenous with the corresponding ARG subgroups (NEAA0.5, NEAA2, and NEAA5). Plasma and urinary biomarkers were measured. Cytokine and NO production levels and inducible NO synthase and arginase protein levels were determined from peritoneal macrophages. RESULTS: The survival rate was lower in the ARG5 and NEAA5 subgroups than in all the other subgroups. The nitrogen balance was higher in the ARG5 group than in the NEAA5 group. Plasma triacylglycerol levels were lower in the ARG2 group than in the NEAA2 group. Interleukin-6, tumor necrosis factor-α, and NO production in the macrophages decreased and arginase-1 was upregulated in the ARG-treated rats. CONCLUSIONS: In this model, mortality was increased by the nitrogen burden rather than by arginine per se. Arginine improved nitrogen balance and had an anti-inflammatory action on macrophages by regulating NO production, probably through arginase-1 expression.

Effects of a diabetes-specific enteral nutrition on nutritional and immune status of diabetic, obese, and endotoxemic rats: interest of a graded arginine supply.

OBJECTIVE: Obese and type 2 diabetic patients present metabolic disturbance-related alterations in nonspecific immunity, to which the decrease in their plasma arginine contributes. Although diabetes-specific formulas have been developed, they have never been tested in the context of an acute infectious situation as can be seen in intensive care unit patients. Our aim was to investigate the effects of a diabetes-specific diet enriched or not with arginine in a model of infectious stress in a diabetes and obesity situation. As a large intake of arginine may be deleterious, this amino acid was given in graded fashion. DESIGN: Randomized, controlled experimental study. SETTING: University research laboratory. SUBJECTS: Zucker diabetic fatty rats. INTERVENTIONS: Gastrostomized Zucker diabetic fatty rats were submitted to intraperitoneal lipopolysaccharide administration and fed for 7 days with either a diabetes-specific enteral nutrition without (G group, n=7) or with graded arginine supply (1-5 g/kg/day) (GA group, n=7) or a standard enteral nutrition (HP group, n=10). MEASUREMENTS AND MAIN RESULTS: Survival rate was better in G and GA groups than in the HP group. On day 7, plasma insulin to glucose ratio tended to be lower in the same G and GA groups. Macrophage tumor necrosis factor-α (G: 5.0±1.1 ng/2×106 cells·hr⁻¹; GA: 3.7±0.8 ng/2×106 cells·hr⁻¹; and HP: 1.7±0.6 ng/2×106 cells·hr⁻¹; p<.05 G vs. HP) and nitric oxide (G: 4.5±1.1 ng/2×106 cells·hr⁻¹; GA: 5.1±1.0 ng/2×106 cells·hr⁻¹; and HP: 1.0±0.5 nmol/2×106 cells·hr⁻¹; p<.05 G and GA vs. HP) productions were higher in the G and GA groups compared to the HP group. Macrophages from the G and GA groups exhibited increased arginine consumption. CONCLUSIONS: In diabetic obese and endotoxemic rats, a diabetes-specific formula leads to a lower mortality, a decreased insulin resistance, and an improvement in peritoneal macrophage function. Arginine supplementation has no additional effect. These data support the use of such disease-specific diets in critically ill diabetic and obese patients.

Arginine availability modulates arginine metabolism and TNFα production in peritoneal macrophages from Zucker Diabetic Fatty rats.

BACKGROUND & AIMS: Excess weight and type 2 diabetes lead to increased susceptibility to infections. Our aim was to investigate the role of diabetes-induced decreased arginine (Arg) availability and of a possible dysregulation of Arg metabolism in macrophages favoring inflammation and dysimmunity via altered nitric oxide (NO) and cytokine productions. METHODS: Isolated peritoneal macrophages from Zucker Diabetic Fatty (ZDF) or lean rats were incubated with increasing Arg concentration (0-2 mM) and Arg metabolism and regulatory properties were studied. RESULTS: Inducible NO synthase (iNOS) expression did not vary with Arg concentration while NO production reached a maximum at 0.5 mM Arg, being significantly lower in macrophages from ZDF rats. Arginase I and II protein levels reached a maximum between 0.25 and 0.5 mM Arg in controls; in macrophages from ZDF rats arginase I was significantly lower and progressively increased up to 2 mM Arg while arginase II was not affected by Arg concentration. In parallel, Arg downregulated TNFα production in both groups and IL-6 only in control. CONCLUSIONS: This in vitro study shows that Arg metabolism is impaired in macrophages from diabetic-obese rats and that improving Arg availability for these cells restores NO production and contributes to the regulation of the inflammatory process.

Arginine or citrulline associated with a statin stimulates nitric oxide production in bovine aortic endothelial cells.

Nitric oxide (NO) is an antiatherogenic vasodilator synthesized from arginine and, indirectly, from citrulline through argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL). Hypercholesterolemia-induced atherosclerosis is usually treated by statins, which decrease cholesterolemia and increase endothelial NO synthase (eNOS) activity. Therefore, a treatment associating a statin with arginine or citrulline could be more efficient than statin alone. The aim of this study was to optimize NO production in bovine aortic endothelial cells (BAEC) by a combination of simvastatin with arginine or citrulline and to identify the molecular mechanisms involved. NO production was measured after stimulation of BAEC in different conditions (simvastatin 0 to 10 µM associated with arginine or citrulline 0 to 5 mM) after 24-hour incubation. Intracellular levels of specific proteins were evaluated by Western-Blot analysis, and mRNA levels of eNOS, iNOS, caveolin-1, ASS and ASL were assessed by RT-PCR. Simvastatin co-administrated with arginine or citrulline increased NO production, but at simvastatin 10 µM, 1 mM arginine-induced NO production was significantly (P < 0.01) higher than 1 mM citrulline-induced NO production. Simvastatin induced an increase in eNOS mRNA expression and protein levels in the presence of arginine or citrulline. ASS and ASL mRNA levels were increased by simvastatin, whereas a high substrate concentration (1 mM) strongly decreased ASL mRNA levels. Combining statin with arginine or citrulline increased NO production in endothelial cells by increasing eNOS protein levels. These results form a strong rationale to evaluate the potential utilization of these in atherosclerosis prevention and treatment.