Journal articles on the topic 'Risk management – France – History'

BackgroundGPs are confronted with therapeutic dilemmas in treating patients with multimorbidity and/or polypharmacy when unfavourable medication risk–benefit ratios (RBRs) conflict with patients’ demands.AimTo understand GPs’ attitudes about prescribing and/or deprescribing medicines for patients with multimorbidity and/or polypharmacy, and factors associated with their decisions.Design and settingCross-sectional survey in 2016 among a national panel of 1266 randomly selected GPs in private practice in France.MethodGPs’ opinions and attitudes were explored using a standardised questionnaire including a case vignette about a female treated for multiple somatic diseases, sleeping disorders, and chronic pain. Participants were randomly assigned one of eight versions of this case vignette, varying by patient age, socioprofessional status, and stroke history. Backward selection was used to identify factors associated with GPs’ decisions about drugs they considered inappropriate.ResultsNearly all (91.4%) responders felt comfortable or fairly comfortable deprescribing inappropriate medications, but only 34.7% decided to do so often or very often. In the clinical vignette, most GPs chose to discontinue symptomatic medications (for example, benzodiazepine, paracetamol/tramadol) because of unfavourable RBRs. When patients asked for ketoprofen for persistent sciatica, 94.1% considered this prescription risky, but 25.6% would prescribe it. They were less likely to prescribe it to older patients (adjusted odds ratio [AOR] 0.48, 95% confidence interval [CI] = 0.36 to 0.63), or those with a stroke history (AOR 0.55, 95% CI = 0.42 to 0.72).ConclusionIn therapeutic dilemmas, some GPs choose to prioritise patients’ requests over iatrogenic risks. GPs need pragmatic implementation tools for handling therapeutic dilemmas, and to improve their skills in medication management and patient engagement in such situations.

677 Background: Raltitrexed, indicated for palliative treatment of advanced colorectal cancer (CRC), may be useful for patients (pts) with cardiovascular (CV) risk factors, or cardiotoxicity/disease progression with prior chemotherapy (CT). The COMET study, conducted in France, described the characteristics of pts with metastatic CRC (mCRC) treated with raltitrexed, focusing on pts with cardiotoxicity or disease progression with prior 5-fluorouracil (5FU)/folinic acid. Methods: A national, multicentred, cross-sectional, non-interventional study to describe the profiles of pts with mCRC treated with raltitrexed. Pts (≥18 years) with mCRC, treated with raltitrexed as a single agent or in combination therapy, were included. Following patient consent, retrospective data were recorded during a single inclusion visit based on pt medical files; during the study, data were recorded prospectively. Results: 414 pts with mCRC were analysed; 84.8% had ≥1 prior CT, 60.9% had CV risk factors and 35.2% had CV history (angina: 11.8%; myocardial infarction: 11.8%). Overall, 79.5% of pts had received a prior 5FU-based CT. Reasons for switching to raltitrexed included short 15-min infusion duration (34.8%), treatment failure (49.8%) and acute cardiotoxicity with 5FU (8.9%). After switching, 57.2% of pts received raltitrexed as combination therapy. Mean initial dosage of raltitrexed was 2.6±0.6 mg/m2. Of those who had CV risk factors (n=73) or CV history (n=67), 69.0% and 72.7% received raltitrexed after CV toxicity, respectively. Of the pts treated with second-line raltitrexed and assessed with prior acute CV events (45/414), 88.9% (40/45) had no cardiac toxicity during treatment with raltitrexed. Of those (n=206) receiving raltitrexed due to treatment failure, 62.7% had received 5FU/folinic acid during their last CT. Of the pts assessed for tumour response (183/206), tumour progression was controlled with raltitrexed in 25.7% of cases (stable disease: 18.0%; partial response: 7.7%; progressive disease: 56.3%). Conclusions: Raltitrexed appears to be effective in heavily pretreated pts with mCRC and tumour progression after 5FU therapy and could be a safe therapeutic alternative to 5FU for pts with mCRC and prior cardiac toxicity.

The French inter-war steel cartels were characterized by contemporaries as powerful trusts, restricting output and raising steel prices. The cartels were cited as a cause for the length of the French depression, the low productivity of the 1930s, and the rapid rise in steel prices after 1936. This paper shows that the formation and development of the French steel cartels was problematic and argues that the French industry was not structurally conducive to widespread collusion and was further harmed by governmental policies. Steel cartels were unable to police their arrangements effectively among members and were unable to stop outsiders from undercutting prices. It is not at all clear that firms in the cartel achieved higher profits. The increase in prices that did occur after 1936 was not due to firms colluding and profiting from the increased demand for steel due to the anticipation of Nazi aggression; rather, these price increases occurred because of input price increases caused by government action that raised the costs of production.

(1) Background: One out of two pregnant women has a history of herpes infection. Initial infections have a high risk of neonatal transmission. Our objective was to analyse the professional practises of midwives regarding the management of herpes infections during pregnancy in France; (2) Methods: A national survey conducted via an online self-questionnaire, including clinical vignettes for which the midwives proposed a diagnosis, a drug treatment, a mode of birth, and a prognosis. These responses were used to evaluate the conformity of the responses to the guidelines, as well as the influence of certain criteria, such as mode of practise and experience; (3) Results: Of 728 responses, only 26.1% of the midwives reported being aware of the 2017 clinical practise guidelines. The midwives proposed taking the appropriate actions in 56.1% of the responses in the case of a recurrence, and in 95.1% of the responses in the case of a primary infection. For the specific, high-risk case of a nonprimary initial infection at 38 weeks of gestation, reporting knowledge of the recommendations improved the compliance of the proposed care by 40% (p = 0.02). However, 33.8% of the midwives underestimated the neonatal risk at term after a primary initial infection, and 43% underestimated the risk after a primary initial infection at term; (4) Conclusions: The majority of reported practises were compliant despite a low level of knowledge of the guidelines. The dissemination of guidelines may be important to improve information and adherence to appropriate therapeutic practise.

ObjectivesTo examine attitudes and practices in the management of attention-deficit/hyperactivity disorder (ADHD) among health professionals across seven European countries.MethodsThe web-based survey was developed by an international steering committee of ADHD experts and consisted of 64 multiple-choice questions relating to ADHD, covering the following topics: attitudes, diagnosis, referral, treatment and improving care. Health professionals working with ADHD were identified using a medical marketing database (Medical Marketing Service Inc., IL, USA) and invited via email to participate in the survey. No incentive was offered for participation and the survey was only available in English.ResultsOver 22 000 emails and postal invitations were sent. One hundred and thirty-four (0.6%) health professionals completed the survey. Results highlighted significant differences by profession and country. In general, ADHD is considered a clinically important and valid disorder (n = 111, 84%), with biological underpinnings (n = 82, 62%), continuing into adulthood (n = 123, 93%) and responsive to treatment. Respondents from France were less likely to be convinced about biological validity (n = 4, 27%) and those from Italy and France were more likely to be concerned about the risk of underdiagnosis (n = 9, 64% and n = 9, 60%, respectively). Psychologists were the specialty who most frequently reported not believing in the diagnostic validity of ADHD (n = 4, 19%). One-third (n = 25, 35%) of respondents recommended medical tests before prescribing medication, with differences emerging by country despite the lack of support for such routine assessments in the guidelines.ConclusionsDespite the very low response rate, intriguing country- and profession-specific differences emerged in this study and warrant further exploration.

Background. Helicobacter pylori (Hp) infection affects 30% to 40% of people in industrialized countries. Aim. This study aimed to synthesize knowledge on the diagnostic and therapeutic management of Hp infection in general practice in people under 40 years of age. Method. A narrative review of the literature with an inductive content analysis of the articles was performed. Results. The extracted data (22 articles out of 106 included after screening of 965 articles) determined three areas of analysis: indications for screening, methods of screening and diagnosis by non-invasive tests, and treatment modalities. Discussion. Targeted, easily performed screening with noninvasive tests is recommended for patients younger than 45 years of age with no family history of gastric cancer and symptoms of dyspepsia without warning signs. Given their proximity to the general population and their coverage of the territory, general practitioners are ideally positioned. Treatment modalities are well-codified and feasible in primary care. Simplifying the recommendations available to them would optimize the identification of patients at risk and the management of Hp infection. Informing, educating, involving, supporting, and promoting the control of Hp infection in primary care will be future goals. Further research is needed in primary care to evaluate the impact of new procedures on Hp control.

Objective This article describes the Personalized Reimbursement Model (PRM) program methodology, limitations, achievement and perspectives in using real-world data of cancer drugs use to improve and personalize drug pricing and reimbursement in France. Materials and methods PRM platform aggregates Electronic Pharmacy Records (EPR) data from French medical centers (PRM centers) to build retrospective cohorts of patients treated with injectable cancer drugs in a hospital setting. Data extracted on January 1st, 2020, from breast cancer (BC) patients who received trastuzumab, trastuzumab emtansin or pertuzumab since January 1st, 2011, and from lung cancer (LC) patients who received bevacizumab or atezolizumab since January 1st, 2015, enabled recovering their injectable cancer drugs history from diagnosis date until December 30th, 2019, and served as dataset for assessment. Results 123 PRM centers provided data from 30,730 patients (25,660 BC and 5,070 LC patients respectively). Overall, 20,942 (82%) of BC and 4,716 (93%) of LC patients were analyzed. Completion rate was above 98% for patients characteristics, diagnostic and treatment related data. PRM centers cover 48% and 33% of BC and LC patients in-hospital therapeutic management in France, respectively. Distribution of BC and LC patients therapeutic management, by medical center category and geographic location, was similar in PRM centers to all French medical centers, ensuring the representativeness of the PRM platform. Conclusion PRM Platform enabled building a national database generating on demand Real-World Evidence based on EPR. This enabled the first performance-based risk-sharing arrangements based on PRM data, between the CEPS and Roche, for atezolizumab cancer immunotherapy in metastatic non-small cell lung cancer indication.

Abstract The Breast Cancer Prevention Clinic: A Single Institution’s Experience Authors: Joe J. Stephenson MD1, LeAnn Perkins, FNP-BC, DipACLM1, Erinn Crowe, RN, BSN, OCN1, Regina Franco, MSN, NP-C, DipACLM1, Pamela Cloys, MSN, ANP-C1, Carmen Hancock, MSN, APRN, FNP-C, AOCNP1, Marie Smith, MS1 1Prisma Health Cancer Institute, Center for Integrative Oncology & Survivorship Background: Roughly 1 in 8 women will be diagnosed with invasive breast cancer in their lifetime1. Some women have higher risk for developing breast cancer due to numerous factors such as elevated risk modeling scores, a history of chest radiation therapy, a history of atypical cells on a breast biopsy or a pathogenic genetic mutation. Enhanced surveillance to detect cancers early and addressing modifiable lifestyle risks are helpful to mitigate risks. Methods: The Prisma Health’s Breast Cancer Prevention Clinic (BCPC) approaches prevention by monitoring non-modifiable risks with regular surveillance and education on optimizing lifestyle habits to decrease modifiable risks. Established in 2017, the BCPC team now includes multiple medical oncologists and nurse practitioners, allowing the clinic to be offered any day of the week. During the visit, patients receive a personal risk assessment. Recommendations are given for surveillance imaging, risk-reducing endocrine therapy, and risk-reducing lifestyle modifications such as diet, alcohol consumption, and exercise routines. Family history is also reviewed to recommend Genetic Counseling if appropriate. In March 2022, a statement was added to patient mammograms, generating referrals for those with calculated elevated risk (a calculated lifetime risk >20% using the Tyrer-Cuzick or International Breast Cancer Intervention Study model and/or a 5-year risk >1.7% using the National Cancer Institute Breast Cancer Risk Assessment Tool or Gail model). Results: In a 12-month period from June 1, 2021 through May 31, 2022, 56.2% of patients were referred based on family history, 26.9% for higher-risk breast pathology, 8.1% for calculated elevated risk, 4.4 % for a pathogenic genetic variant that increases breast cancer risk and 4.1% for mammographic identification risk modeling. Following the BCPC visit, referrals for patients may include imaging such as mammograms, MRIs, genetic counseling or testing, or surgical evaluations. Referrals for lifestyle modifications may include nutrition, exercise navigation, mindfulness classes, or Sexual Health Evaluations. From June 2021 through May 2022, 41.4% of patients were referred for a breast MRI, 26.6% were referred to genetic counselors for genetic testing recommendations, 11.1% were referred to nutrition or exercise services, 8.42% were referred for a Bone Density Scan (DXA), 4% were referred to a Breast Surgeon and 3.7% were referred to the Genetic Management Clinic. Additionally, 79.5% of patients were referred to the High-Risk Breast Lifetime Clinic for continued monitoring and surveillance for early detection of breast cancer, continued reinforcement of lifestyle modifications, and management of risk-reduction endocrine therapy. Conclusion: The unique structure of this model allows for enhanced surveillance through greater use of evidence-based cancer prevention, early detection methods, and increased education for lifestyle medicine practices with the overall goals of reducing breast cancer risk, earlier breast cancer detection, and increasing quality of life. Reference List 1. DeSantis C, Ma J, Gaudet, M, et al. Breast cancer statistics, 2019. CA: A Cancer Journal for Clinicians. 2019;69(6), 438-451. https://doi.org/10.3322/caac.21583. Citation Format: Joe Stephenson, LeAnn Perkins, Erinn Crowe, Regina Franco, Carmen Hancock, Pamela Cloys, Marie Smith. The Breast Cancer Prevention Clinic: A Single Institution’s Experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-07.

In 1930 Business Week alerted its interested readers to a new professional service: management consulting. As the writers at Business Week explained, the existing system of business professionals had become so complicated that, according to James McKinsey at the University of Chicago, a new type of professional was “increasing in numbers and influence . . . the adviser that tells business what other advisers to use and when.” Although Business Week would go on to chronicle the rise of management consulting over the next seventy years, consultants would continue to style themselves as an emerging profession through the end of the twentieth century.My dissertation title, “The World's Newest Profession,” plays off both the longstanding perception that consulting is an emerging profession and the widespread apprehension that consultants' advice is little more than corporate pandering. In response to these concerns, I address both the origins of management consultants and their influence on the strategies, structures, and operations of large bureaucratic organizations. Because the institutionalization and professionalization of management consulting occurred within firms, not among solo practitioners, I focus on management consulting firms like McKinsey & Company; Booz, Allen & Hamilton; and Arthur D. Little, Inc., which have advised large corporations since the 1920s. During the 1920s and 1930s these consulting firms were integral in reorganizing many of the largest companies in the United States, including General Motors, Swift, U.S. Steel, and Sears. By the 1960s the use of American management consultants had expanded beyond their initial domestic corporate clients to include international nonprofit organizations, businesses, and governments as diverse and influential as Air France, the Bank of England, Volkswagen, the University of Liberia, and the Government of Tanzania.

Abstract Objectives The objectives of the study were (1) to describe the clinical features of adult patients presenting with an immune thrombocytopenia (ITP), (2) to explore the predictors of chronicity and (3) to determine whether a family history of autoimmune disorder was a risk factor of ITP. Methods An observational prospective cohort study was conducted in France nationwide. During more than two years, 21 participating physicians from haematology centres recruited all consecutive adults of 18 years old or above, diagnosed with an incident episode of ITP. Data were collected at baseline and 12 months, regarding socio-demographic characteristics, personal and familial medical history, clinical and biological signs of ITP and its medical management, left at the discretion of each physician. Data were collected after 12 months clinical, biological signs of ITP and current medication, from which the outcome was derived: chronicity or recovery. Predictors of chronicity at baseline were explored using univariate logistic regression models, providing the Odds Ratio (OR) and their 95% Confidence Intervals (95%CI). To explore whether having a history of autoimmune disorder in first-degree relative was a risk factor of developing an ITP, referent-patients were drawn from a general practice setting database and matched to ITP-patients (10-1). The risk of developing an ITP was explored using univariate conditional logistic regression models, providing the OR and their 95%CI. Results 153 patients were included over a 28-month period: 94 (61%) patients were female, mean age was 48 years (SD=18.8), and 128 (84%) presented with bleeding symptoms at diagnosis. The median platelet count was 10×109/L. An initial treatment was required in nearly 90% of patients. After 12 months, only 36% of patients were cured without receiving any disease-modifying treatment. The baseline predictors of chronicity at 12 months were a lower platelet count (OR, 1.0; 95%CI, 1.0-1.2) and mucocutaneous bleeding (OR, 0.3; 95%CI, 0.1-1.0). No significant association was found between a history of autoimmune disorder in a first degree relative or the presence of anti-nuclear antibodies and the risk of developing a chronic ITP. Conclusions ITP in adults affects patients with a wide age range, mainly female. ITP is a serious disease in adults with a chronic evolution in a majority of patients that is in contrast with children. Low platelet count and severity of bleeding at the diagnosis were associated with a lower risk of chronic evolution. Disclosures Godeau: Roche: Research Funding; Amgen: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Grimaldi-Bensouda:LASER: Consultancy, Other: LASER provide consultancy to various pharma industry (virtually all). Abenhaim:LASER: Employment, Other: LASER provide consultancy to various pharma industry (virtually all). Haioun:Roche: Honoraria.

U.S. shipping to Bordeaux, France, once minimal, increased dramatically after 1793, the year that marked the beginning of the French Wars. The conflicts compelled merchants to adopt new patterns of trade, as the policies of the belligerent parties increasingly determined the evolution of neutral shipping. Merchants on both sides of the Atlantic strove for closer connections across political boundaries and tried to bypass the difficulties created by warfare. This examination of U.S. commerce with Bordeaux explores the impact of war on transatlantic trade and analyzes the strategies adopted by merchants of that period to minimize the impact of new risks. These merchants tended to rely on personal acquaintances, and they traveled frequently across the Atlantic in order to build and fortify relations of trust. Turning to older, established modes of doing business enabled them to respond rapidly to changes that occurred in the international situation and to anticipate the sudden shifts in policy that were inevitable in times of war.

AbstractThis keynote address, delivered in December 2015 at the International Federation of Workers’ Education Association General Conference in Lima, Peru, refutes the standard trope of labor movement decline and provides evidence for the global rise and feminization of labor movements worldwide. Trade union women’s commitment to emancipatory, democratic worker education helped spur these changes. The origins and effects of two historical examples are detailed: the Bryn Mawr Summer School for Women Workers held in the United States annually from 1921 to 1938 and the first International Women’s Summer School of the International Confederation of Free Trade Unions (ICFTU) held in France in 1953. The latter experiment, attended by women labor leaders from 25 countries, energized the Women’s Committee of the ICFTU. It led to the adoption of “The Charter of Rights of Working Women” by the ICFTU in 1965 and helped make possible the election of Sharan Burrow and other women to top office in the International Trade Union Confederation. The address concludes with a discussion of what the history of trade union women’s education teaches about strengthening future labor movements.

Abstract Abstract 3698 Background: Randomized trials had demonstrated that rituximab improved outcome in newly diagnosed follicular lymphoma (FL) and this anti-CD20 monoclonal antibody was approved in France since 2004 in combination of chemotherapy (CT) for LF in first line therapy. As these results were obtained in selected patients with strict inclusion and exclusion criteria used in clinical trials, whether the improvement of patient's outcome is valuable in unselected population of FL patients with various medical history, different CT regimens is questionable. We performed a retrospective analysis to evaluate if the management and the outcome of FL have significantly changed in our institution before and after rituximab approval in 2004. Patients and Methods: all adult patients referred for first line LF were included and separated into cohort 1 diagnosis between 1996 and 2003 (103 patients) and cohort 2 between 2004 and 2010 (144 patients). Baseline clinical and biological datas, Follicular Lymphoma International prognostic Index (FLIPI), type of therapy, treatment response, progression free survival (PFS) and overall survival (OS) were compared. Results: There were no statistical differences in patients' characteristics between the 2 cohorts, including FLIPI score. In cohort 2, 71% received in first line therapy a rituximab based regimen (19% in monotherapy and 52% with CT). In cohort 1, 58% of patients were treated with CT and 10% with rituximab, 2% in monotherapy and 8% in combination with CT. Response rate were significantly improved in cohort 2 compared to cohort 1: complete response rate was 74.3% versus 57.8%, P <.001. With a median follow-up of 115.5 and 46.5 months in cohort 1 and 2, the 2-year PFS was 67% for cohort 1 and 82% for cohort 2 (P =.0039), respectively. The 2-year OS was also improved between the two periods (98% versus 87%, P =.0007). We could confirm the prognostic value on OS of the FLIPI score in whole series, in cohort 1 before the rituximab era but not in cohort 2. In fact, the 2-year OS was respectively 100% in low risk, 98% in intermediate risk and 95% in high risk (P =.14)/ Conclusions: These datas confirms the improvement of FL patients' outcome observed in clinical trials after the approval of rituximab in first line therapy prescript in a context of daily practice whatever age, medical history, and type of CT. Disclosures: No relevant conflicts of interest to declare.

Background:Therapeutic decisions in patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX-IR) are complex. European guidelines position at the same level all biological disease-modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) for the treatment of RA(1,2). Furthermore, therapeutic decisions, or physician preferences, may be influenced by many factors related to patients and/or physicians.Objectives:To describe the therapeutic preferences of physicians involved in the management of RA after failure of a first-line strategy (including MTX) and the influence of predefined factors on these preferences.Methods:We planned to include 216 rheumatologists experienced in the management of RA in this cross-sectional multicenter study. A total of 64 hypothetical clinical cases (vignettes) were developed from a random combination of the following parameters: presence or absence of poor prognostic factors 1) RA-related autoantibodies, 2) structural damage progression on X-ray, 3) high or moderate disease activity, and presence or absence of a history of 4) infection, 5) pulmonary involvement, and 6) cardiovascular disease. Each participant was asked to complete 8 vignettes and were asked to choose the most and least appropriate therapeutic option (best-worst [BW] scaling method) from 3 of the following: replacing MTX by another conventional (c)sDMARD; adding one or more csDMARDs to MTX; adding a bDMARD (TNF inhibitor [TNFi], tocilizumab [TCZ], abatacept [ABA] or rituximab [RTX]). Each vignette was completed 10 times per participant. Physician preferences were assessed using discrete choice experiments methodology. Therapeutic option preference was expressed using a score – one point incremented when considered most appropriate; or removed when considered least appropriate. The therapeutic score was standardized for each vignette, ranging from -1 (more often chosen as the least appropriate) to +1 (more often chosen as the most appropriate). A normalized Best-to-Worst (BW) Score was then computed. The multiplication of vignettes and therapeutic options were used to elicit participants’ preferences without directly asking them to state their preferred options(3,4,5). Statistical analyses were carried out using SAS (version 9.4), or R (version 3.5.1).Results:A total of 211 French rheumatologists were recruited. Half of them had a hospital-only activity, 25% office-only activity and the rest had mixed activity. Each vignette was assessed by between 20 and 28 rheumatologists with a 94% completion rate. TNF inhibitors were the strategy of choice in 80% of the vignettes. ABA was the second preferred strategy in 75% of the vignettes; except in the 20% of patients with a history of infection and pulmonary comorbidity where it was the first choice. TCZ was chosen as a third strategy. All other strategies were associated with a negative BW score. Factors related to the prescribing physician appear to have no or only a limited impact on therapeutic decisions.Conclusion:This study provides information on the prescription habits of French rheumatologists in MTX-IR patients in RA, and reveals a conservative trend with TNFi the main therapeutic choice and ABA for patients with pulmonary involvement or high risk of infection. The study should be repeated in the future to include new therapeutic options.References:[1]Smolen J et al., EULAR 2019[2]Daien C et al., Joint Bone Spine 2019[3]Peabody JW et al., JAMA 2000[4]Fautrel et al., Arthritis Rheum 2009[5]Mühlbacher et al. Health Economics Review 2016Disclosure of Interests:Eric Senbel Consultant of: Nordic, Roche-Chugai, Lilly, Abbvie, Amgen, Pfizer, Sanofi, MSD, Biogen, UCB, frederick durand Shareholder of: Eli Lilly, Employee of: Lilly France, Baptiste Roux Grant/research support from: FAST4 company has received funding for research from Lilly, Pfizer, BMS, Vifor Pharma, Amgen, Novartis, Leo Pharma, Sanofi, Baxter, Abbvie, Astrazeneca, Novonordisk and Hac Pharma., Fatima Zohra Badaoui Employee of: Lilly France, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB

Background:JAKi (JAK inhibitors) seem simpler of use than injected biologic agents due to their oral administration route. Safety and adherence issues remain and may need to modify patients’ counseling.Objectives:To understand the influence of the DMARDs’ route of administration on these issues for both patients and physicians in order to update the Hiboot®education tool (ref1).Methods:Hiboot®is a free smartphone application developed by the French Society of Rheumatology to enhance the patient’s safety, adherence to treatment, self-assessment and to give periodic counseling messages (ref1). This ethnographic study involved i)18 patients with rheumatoid arthritis (RA) recruited by 3 rheumatologists considering diversity of clinical and sociological profiles. The panel included i) 14 women and 4 men, median age 56 years-old, median disease duration 10 years. Four patients were treated by methotrexate (MTX) monotherapy, 5 with MTX-bDMARDs or MTX-JAKi combo, 1 by bDMARDs monotherapy, 8 by JAKi monotherapy; ii) 9 rheumatologists with hospital or mixed hospital-private practice from 6 cities in France.The interviews were conducted by 2 anthropologists using in-depth semi directive and biographical methods (enough to reach saturation), registered and transcribed. The semi-directive interviews dealt with: i) the patient history with RA and its treatments, ii) the daily medication management, iii) the evolution of patients’ perceptions and knowledge over time.Results:For patients, adherence and safety behaviors were guided by their representations of 3 risks: disease-related, treatment-related, physician-related. When the disease-related risk was perceived greater than the treatment-related risk, patients tended to report better adherence. Beliefs on efficacy and safety depended more on the patient’s experience with RA over time (severity, activity, control) than on the route of administration (oral vs sub-cutaneous). However, patients treated with JAKi needed to update their lay knowledge and skills regarding their daily constraints and medication management.For rheumatologists, JAKi were considered a promising therapeutic option, but rarely prescribed so far due to a lack of personal experience. Owing to their recent introduction on the market (~2 years in France), JAKi were prescribed to patients with longer disease duration and after several DMARDs lines. The rheumatologists’ conservative attitude towards JAK-i depended on risk perceptions similar to the patients’: disease-related, treatment-related and patient-related i.e their perception of patients’ abilities to manage their care (presumed skills, autonomy…).This study confirms the importance of patients’ beliefs of the balance between medication necessity and risks regarding safety and adherence (ref2) which are shared with the rheumatologists. This study unexpectedly emphasized a doctor-related risk in patients as well as a patient-related risk in rheumatologists. One limitation is a bias in the recruitment of patients with long-standing RA.Conclusion:Rheumatologist-patient collaboration needs a shared vision of medication risks, independently of the route of administration. However new skills are needed for patients treated with JAKi. This qualitative study will serve to modify the Hiboot application to include the JAKi issues such as the reminders or daily life management.References:[1]Beauvais C et al EULAR 2019.[2]Neame R et al. Oxford Rheumatology. 2005.Acknowledgments:French Society of Rheumatology with institutional funding by Abbvie, Lilly, Pfizer.Disclosure of Interests:Guillaume Montagu: None declared, Sophie Gleizes: None declared, Thao Pham Speakers bureau: Novartis, Janssen, Lilly, Jérémie SELLAM: None declared, Catherine Beauvais Speakers bureau: Abbvie, MSD, Roche, UCB, Mylan, Sanofi

TPS1607 Background: The TP53 germline mutation carriers have a huge increase of cancer risk. The cancer spectrum is particularly broad (breast, sarcoma, brain tumour, leukaemia, …). The clinical management of these people is challenging, mainly concerning sarcoma screening. Moreover, some data let speculate that normal cells of these carriers are particular hypersensitive to X-rays. Among major breakthroughs in radiology, whole-body MRI (WBMRI) may contribute to TP53 carriers surveillance. In order to update the french guidelines on Li-Fraumeni families management, the LIFSCREEN study ( NCT01464086 ) was designed to assess its usefulness in France. Methods: This open, randomized, multicentric trial will evaluate the efficacy and tolerability of two screening schemes, avoiding irradiating exams. In the standard arm, people undergo clinical exam, abdominal sonography, brain MRI, Complete Blood Count, breast MRI, breast sonography, depending on the age) at inclusion, Month 12, Month 24, and a study visit at Month 36. In the experimental arm, people included undergo the same scheme, completed by a diffusion WBMRI at M0, M12, M24. At each round, quality of life and psychological impact will be assessed by self-questionnaires and semi-structured qualitative interviews. In an ancillary study, serums will be collected at each step. Subjects meeting these criteria are eligible: any TP53 germline mutation carrier, with or without personal cancer history, aged >5 and <71. A hundred people will be enrolled and randomized. The primary objective is to assess the efficiency of each scheme, evaluated by the cancer incidence at 3 years. Notably, sensitivity and specificity of each exam will be studied. As a secondary objective, the acceptability of each scheme will be assessed by quality of life / psychological questionnaires interpretation (SF-36, HADS, TAS 20, CBCL, CDI, R-CMAS, depending on subject’s age). Recruitment began in December, 2011. To date, 32 patients have been enrolled on 8 french study sites. The study will soon be implemented in another 12 sites. This academic study is, to our knowledge, the first randomized trial on this topic, and supported by the french “Ligue contre le cancer.” Clinical trial information: NCT01464086.

Abstract Introduction: In the last decades, the life expectancy of patients with hemophilia A (HA), hemophilia B (HB) and von Willebrand disease (VWD) has substantially improved. As a result, these patients experience age-related comorbidities, especially ischaemic heart disease. Safety and efficacy of antiplatelet drugs in patients with inherited bleeding disorders remain unclear, while there is no evidence-based guideline for the antithrombotic management in this population. The aims of our study were to describe the management of patients with HA, HB and VWD at the occurrence of ischaemic heart disease in our regional referral center; to compare this management to experts' recommendations; and to evaluate the safety and the efficacy of antiplatelet drugs in this population. Methods : The source of population was the 2008-2018 cohort of patients with HA (n=565), HB (n=115) and VWD (n=618) followed at Toulouse University hospital (France). Their follow-up is recorded in electronic medical files. We retrospectively identified the patients who experienced an ischaemic heart disease treated by antiplatelet therapy. Ischaemic heart disease included ST- and non-ST-segment elevation acute myocardial infarction, stable and unstable angina, and silent coronary artery disease. We described the reperfusion therapy, the use of antiplatelet drugs and replacement factors, and the occurrence of bleeding or thrombotic complications during the follow-up. Results: Eight patients had an ischaemic heart disease: 5 HA, 1 HB and 2 VWD patients. Four of the haemophilic patients had minor hemophilia; the two others had moderate hemophilia. VWD patients were one type 1 (FVIII 26%, VWF:Ag 13%) and one type 2B (FVIII 29%, VWF:Ag 75%, VWF :Act 24%, low platelet count). Age at the time of the cardiac event ranged from 49 to 80 years. All patients were men except the patient with type 2B VWD. Cardiovascular risk factors were frequent (overweight, n=5; hypercholesterolemia, n=4; smoking, n=4). Four patients were investigated because of cardiac symptoms (unstable angina, angina, dyspnea, palpitations, n=1 each), and one patient because of family history. The last 3 patients were investigated as part of a screening program including patients with a high cardiovascular risk estimation. The initial management was as follows: 4 patients underwent a percutaneous coronary intervention (PCI) and 4 had a triple coronary artery bypass grafting (CABG). All patients treated with PCI had dual antiplatelet therapy for one month, then low-dose aspirin. CABG patients were initiated with low-dose aspirin. FVIII exposure was lower in PCI patients than in CABG patients (13 ± 10.42 versus 19 ± 9.35 cumulative exposure days to FVIII). Four patients were managed with differences from current guidelines1-3: first, the woman with type 2B VWD was treated with two drug-eluting stents whereas bare-metal stents are recommended. Dual antiplatelet therapy was then initiated but stopped at one month because of microcytic anemia. She was then treated with acid acetylsalicylic, 160mg per day instead of 75mg, and presented a severe gastrointestinal bleeding. Second, the patient with HB (FIX 34%) received no replacement therapy during PCI and no proton pump inhibitors while treated by antiplatelet drug, but he experienced no bleeding. Third, a HA patient (FVIII 6%) had a trough level of FVIII slightly lower than recommended (FVIII 37% versus > 50%) at day 7 after CABG. He presented a hemopericardium the next day, complicated with cardiac tamponade. Lastly, a moderate HA patient had no long-term antiplatelet therapy after CABG. However, he did not experience any new cardiovascular event during the following 4 years. During the follow-up (median: 24,5 months), only one HA (FVIII 20%) patient had a new cardiovascular event: a critical lower limb ischemia complicated with an arterial ulcer at the age of 91 years, 11 years after CABG. In contrast, 3 patients experienced a severe bleeding while treated by dual or low-dose aspirin: one hemopericardium, one gastrointestinal bleeding and one intracranial bleeding at J7 post-CABG, 13 months and 11 years after the cardiac event, respectively. Conclusion: This series of 8 patients confirms the significant risk of severe bleeding complications when antiplatelet drug is initiated in patients with hemophilia or VWD. In 1/3 cases, the severe bleeding occurred despite strict adherence to current recommendations. Disclosures No relevant conflicts of interest to declare.

Introduction:Eltrombopag has been available in Europe for the treatment of chronic primary immune thrombocytopenia (ITP) since 2010. Since 2019, it has been indicated in patients with primary ITP, lasting 6 months or longer from diagnosis and who are refractory to other treatments, aged 1 year and above. However, data are lacking regarding the use, the efficacy and the safety of eltrombopag in clinical practice in Europe. The ELEXTRA study aimed to assess these questions in France. The intermediate results were presented at the 2019 ASH Annual Meeting. We present here the final results of the ELEXTRA study. Methods:Population source was the CARMEN-France registry. The CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013. Each investigator follows all adult patients (aged ≥18 years) newly diagnosed with ITP in routine visits or hospital stays, and detailed information on patients' characteristics and management of ITP are prospectively recorded. This registry has been implemented in other French centers since 2016, taking the name of CARMEN-France. ITP was defined by platelet count &lt;100 x 109/L and exclusion of other causes of thrombocytopenia. The study population consisted of all incident ITP adults included in the CARMEN-France registry from June 2013 to December 2019 who were exposed to eltrombopag during the disease course. We described the time from ITP diagnosis to first exposure to eltrombopag, and patients' characteristics. Efficacy was assessed in patients who had a platelet count &lt;30 x 109/L at eltrombopag initiation. Overall response was defined by platelet count ≥30 x 109/L and complete response by platelet count ≥100 x 109/L. Adverse drug reactions (ADRs) that occurred during eltrombopag exposure were collected and assessed according to the World Health Organization causality assessment scale. All ADRs with causality score assessed at least as "possible"were described. Results:Out of 795 patients included in the registry, 156 (19.6%) had been exposed to eltrombopag for a median duration of 100 days (range: 1-1427). Mean age was 60.2 years (standard deviation: 20.9) and 79 (50.6%) were males; 60 (38.5%) had at least one comorbidity of the Charlson Comorbidity Index score; 89 (57.1%) had at least one cardiovascular risk factor (not including age and sex) and 9 (5.8%) a history of venous thrombosis. At ITP diagnosis, the median platelet count was 8 x 109/L (range: 1-88 x 109/L) and 118 (75.6%) patients had bleeding. Median time from ITP onset to first exposure to eltrombopag was 3.3 months (range: 0.1-82.2): 74 (47.4%) patients were exposed before 3 months of ITP duration, 21 (13.5%) between 3 and 6 months and 61 (39.1%) after 6 months. Exposures to ITP treatments before eltrombopag initiation were: corticosteroids in 150 (96.2%) patients, intravenous immunoglobulin (IVIg) in 106 (67.9%), dapsone in 28 (17.9%), rituximab in 26 (16.7%), romiplostim in 12 (7.7%), hydroxychloroquine in 14 (9.0%), danazol in 8 (5.1%), vinblastine in 5 (3.2%), azathioprine in 2 (1.3%), ciclosporin in 1 (0.6%) and splenectomy in none. Eltrombopag was used as second-line agent in 52 (33.3%) patients and third-line in 56 (35.9%). Among the 156 patients, 75 (48.1%) had a platelet count &lt;30 x 109/L at eltrombopag initiation; among them, 65 (86.7%) achieved overall response and 53 (70.7%) complete response at any time during exposure to eltrombopag. Among the 65 patients who achieved overall response, 58 (89.2%) had a concomitant exposure to another ITP treatment at eltrombopag initiation (including steroids, n=42; IVIg during the past month, n=44; rituximab in the past 6 months, n=11). Overall, 47 ADRs were reported: the most frequent were: thrombocytosis (n=10), thrombosis (n=8: 6 pulmonary embolism, 1 deep and 1 superficial vein thrombosis), rash (n=4), hepatitis (n=3),and headache (n=3). Conclusion:In French real-world practice, eltrombopag is used early in the ITP course. Efficacy is similar to that observed in clinical trials. The safety profile identified in clinical trials is also confirmed. Disclosures Moulis: Grifols: Research Funding; Amgen: Other: meeting attendance grant; Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding. OffLabel Disclosure: Real-World use of eltrombopag in immune thrombocytopenia

Introduction: Eltrombopag has been marketed in Europe in 2010 for the treatment of chronic primary immune thrombocytopenia (ITP) lasting 12 months or longer from diagnosis, refractory to other treatments in splenectomized patients or patients who are contraindicated for splenectomy. Based on results of clinical trials, this marketing indication has been modified in 2019 for the treatment of patients aged 1 year and above with primary ITP lasting 6 months or longer from diagnosis and who are refractory to other treatments. However, data are lacking regarding the use, the efficacy and the safety of eltrombopag in the clinical practice in Europe. The ELEXTRA study was aimed at assessing these questions in France. Methods: Population source was the CARMEN-France registry. The CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013. Each investigator follows all adult patients (aged ≥18 years) newly diagnosed for ITP in routine visit or hospital stay and detailed information on patients' characteristics and management of ITP are prospectively recorded. This registry has been implemented in other French centers since 2016, taking the name of CARMEN-France. ITP was defined by platelet count <100 x 109/L and exclusion of other causes of thrombocytopenia. Study population consisted in all incident ITP adults included in the CARMEN-France registry from June 2013 to December 2018 and exposed to eltrombopag during the disease course. We described the time of exposure to eltrombopag from ITP diagnosis and patients' characteristics. Efficacy was assessed in patients who had a platelet count <30 x 109/L at eltrombopag initiation. Overall response was defined by platelet count ≥30 x 109/L and complete response by platelet count ≥100 x 109/L. Adverse drug reactions (ADRs) that occurred during exposure to eltrombopag were collected and assessed using the World Health Organization causality assessment scale. All ADRs at least "possible" were described. Results: Out of 552 patients included in the registry, 81 (14.7%) had been exposed to eltrombopag for a median duration of 92 days (range: 1-1523). Mean age was 60.9 years (standard deviation: 20.9) and 45 (55.6%) were males; 36 (44.4%) had at least one comorbidity of the Charlson Comorbidity Index score; 45 (55.6%) had at least one cardiovascular risk factor (not including age and sex) and 4 (4.9%) a history of venous thrombosis. At ITP diagnosis, median platelet count was 7 x 109/L (range: 1-88 x 109/L) and 67 (82.7%) patients had bleeding. Median time from ITP onset to first exposure to eltrombopag was 2.7 months (range: 0.2-72.2): 43 (53.1%) patients were exposed before 3 months of ITP duration, 8 (9.9%) between 3 and 6 months, 18 (22.2%) between 6 and 12 months and 12 (14.8%) after 12 months. Exposures to ITP treatments before eltrombopag initiation were: corticosteroids in 75 (92.6%) patients, intravenous immunoglobulin (IVIg) in 61 (75.3%), dapsone in 15 (18.5%), rituximab in 14 (17.3%), romiplostim in 10 (12.3%), hydroxychloroquine in 9 (11.1%), danazol in 5 (6.2%), vinblastine in 3 (3.7%), azathioprine in 1 (1.2%), ciclosporin in 1 (1.2%) and splenectomy in none. Eltrombopag was used as second-line agent in 24 (28.6%) patients and third-line in 20 (24.7%). Among the 81 patients, 39 (48.1%) had a platelet count <30 x 109/L at eltrombopag initiation; 34 (87.2%) achieved overall response and 31 (79.5%) complete response. These response rates were stable across disease duration phases (<3 months, 3-6 months and >6 months), age groups (<60 vs. ≥60 years), Charlson Comorbidity Index score (0, 1-2 and ≥3). Among the 34 patients who achieved overall response, 29 (85.3%) had a concomitant exposure to ITP treatment at eltrombopag initiation (including steroids, n=12; IVIg during the past month, n=15; rituximab in the past 6 months, n=5). Overall, 17 ADRs were reported: the most frequent were: rash (n=3), thrombosis (n=3: 1 deep vein thrombosis, 1 pulmonary embolism and 1 ischemic stroke), thrombocytosis (n=2), hepatitis (n=2) and bronchitis (n=2). Conclusion: In the French real-life practice, eltrombopag is used early in ITP course. Efficacy is similar to efficacy in clinical trials, and is stable by subgroups of patients. The profile of ADRs identified in clinical trials is also confirmed. Introduction: Eltrombopag has been marketed in Europe in 2010 for the treatment of chronic primary immune thrombocytopenia (ITP) lasting 12 months or longer from diagnosis, refractory to other treatments in splenectomized patients or patients who are contraindicated for splenectomy. Based on results of clinical trials, this marketing indication has been modified in 2019 for the treatment of patients aged 1 year and above with primary ITP lasting 6 months or longer from diagnosis and who are refractory to other treatments. However, data are lacking regarding the use, the efficacy and the safety of eltrombopag in the clinical practice in Europe. The ELEXTRA study was aimed at assessing these questions in France. Methods: Population source was the CARMEN-France registry. The CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013. Each investigator follows all adult patients (aged ≥18 years) newly diagnosed for ITP in routine visit or hospital stay and detailed information on patients' characteristics and management of ITP are prospectively recorded. This registry has been implemented in other French centers since 2016, taking the name of CARMEN-France. ITP was defined by platelet count <100 x 109/L and exclusion of other causes of thrombocytopenia. Study population consisted in all incident ITP adults included in the CARMEN-France registry from June 2013 to December 2018 and exposed to eltrombopag during the disease course. We described the time of exposure to eltrombopag from ITP diagnosis and patients' characteristics. Efficacy was assessed in patients who had a platelet count <30 x 109/L at eltrombopag initiation. Overall response was defined by platelet count ≥30 x 109/L and complete response by platelet count ≥100 x 109/L. Adverse drug reactions (ADRs) that occurred during exposure to eltrombopag were collected and assessed using the World Health Organization causality assessment scale. All ADRs at least "possible" were described. Results: Out of 552 patients included in the registry, 81 (14.7%) had been exposed to eltrombopag for a median duration of 92 days (range: 1-1523). Mean age was 60.9 years (standard deviation: 20.9) and 45 (55.6%) were males; 36 (44.4%) had at least one comorbidity of the Charlson Comorbidity Index score; 45 (55.6%) had at least one cardiovascular risk factor (not including age and sex) and 4 (4.9%) a history of venous thrombosis. At ITP diagnosis, median platelet count was 7 x 109/L (range: 1-88 x 109/L) and 67 (82.7%) patients had bleeding. Median time from ITP onset to first exposure to eltrombopag was 2.7 months (range: 0.2-72.2): 43 (53.1%) patients were exposed before 3 months of ITP duration, 8 (9.9%) between 3 and 6 months, 18 (22.2%) between 6 and 12 months and 12 (14.8%) after 12 months. Exposures to ITP treatments before eltrombopag initiation were: corticosteroids in 75 (92.6%) patients, intravenous immunoglobulin (IVIg) in 61 (75.3%), dapsone in 15 (18.5%), rituximab in 14 (17.3%), romiplostim in 10 (12.3%), hydroxychloroquine in 9 (11.1%), danazol in 5 (6.2%), vinblastine in 3 (3.7%), azathioprine in 1 (1.2%), ciclosporin in 1 (1.2%) and splenectomy in none. Eltrombopag was used as second-line agent in 24 (28.6%) patients and third-line in 20 (24.7%). Among the 81 patients, 39 (48.1%) had a platelet count <30 x 109/L at eltrombopag initiation; 34 (87.2%) achieved overall response and 31 (79.5%) complete response. These response rates were stable across disease duration phases (<3 months, 3-6 months and >6 months), age groups (<60 vs. ≥60 years), Charlson Comorbidity Index score (0, 1-2 and ≥3). Among the 34 patients who achieved overall response, 29 (85.3%) had a concomitant exposure to ITP treatment at eltrombopag initiation (including steroids, n=12; IVIg during the past month, n=15; rituximab in the past 6 months, n=5). Overall, 17 ADRs were reported: the most frequent were: rash (n=3), thrombosis (n=3: 1 deep vein thrombosis, 1 pulmonary embolism and 1 ischemic stroke), thrombocytosis (n=2), hepatitis (n=2) and bronchitis (n=2). Conclusion: In the French real-life practice, eltrombopag is used early in ITP course. Efficacy is similar to efficacy in clinical trials, and is stable by subgroups of patients. The profile of ADRs identified in clinical trials is also confirmed. Disclosures Moulis: Novartis pharma: Research Funding, Speakers Bureau; Amgen pharma: Research Funding, Speakers Bureau; CSL Behring: Research Funding. OffLabel Disclosure: Eltrombopag was used off-label in some patients in this real-life study

Abstract This article deals with the literature on the French nonprofit sector (NPS). A preliminary part is devoted to presenting and discussing the characteristics that shape the approaches to this sector in France. We stress the strong influence of legal categories on the sector’s definition and, in this context, the importance of the status inherited from the 1901 Act on contracts of association. This raises a problem for a more analytical approach to the sector, because the diversity of the nonprofit organizations (NPOs) regulated under this Act risks being overshadowed. Indeed, not all NPOs regulated under the 1901 Act are voluntary associations as understood by English-speaking people. The largest NPOs are voluntary agencies, usually with paid staff, and lacking memberships (Smith, 2015a, 2015b). In this first part, we also underline the primacy accorded in France to the concept of the social economy, which has today become the social and solidarity economy (SSE), over that of the nonprofit sector. The SSE, whose recognition from the public authorities has increased over the last few decades, includes, but is not limited to, the NPS, since cooperatives and mutuals (mutual aid groups) have to be added. In the second part, the article outlines some landmarks in the history of the French NPS. French NPOs were for many years objects of suspicion, arbitrariness and repression on the part of the public authorities and this persisted until the 1901 legislation on contracts of association was enacted. However, this hostile context did not prevent the sector from having a richer existence than is sometimes admitted. The 1901 Act marked a very significant moment in the history of the French NPS, since it finally enshrined freedom of association in French law. Although the history of the French NPS since this Act is yet to be written, our literature review highlights some aspects of its contemporary development and it addresses a topic that merits particular attention in France—namely the interpenetration between certain NPOs and the public authorities. Indeed, such an interpenetration may affect the autonomy of the former by rendering them instruments of the latter. The fear of an instrumentalization by government is a recurring problem among NPOs. This literature review also focuses on empirical studies of the sector, placing a particular emphasis on the more recent ones. These French studies basically adopt two types of approach. The first is concerned essentially with the NPOs and focuses its attention on their economic importance, whether measured in terms of financial resources, employment, or, less frequently, added value. This is undoubtedly the dominant approach in the literature on the subject. In doing so, a great deal of emphasis is placed on large organizations. Voluntary associations managed solely by volunteers are treated as insignificant and the less formal part of the NPS is unaddressed. The second approach investigates the kinds of individual participation the sector engenders by examining the various forms it takes, such as membership of NPOs or voluntary work. In this respect, research shows a relative stability of association membership over the past three decades but volunteering is still only partially documented, as are cash donations. This review ends with the analysis of the challenges that NPS faces in a context characterized by the increasing constraints on public funding, changes in the nature of such funding with a substitution of contracts for subsidies, an increased competition among NPOs as well as between NPOs and for-profit enterprises. Such a context has forced NPOs to increase their degree of organizational professionalization and certain NPOs increasingly use management instruments applied in for-profit enterprises. This raises questions about their specificities and their raison d’être, and these questions lead researchers to pay more attention to the governance systems of NPOs. The article concludes that, despite the advances in research on the French NPS, some aspects—like formal volunteering and the role of voluntary associations—are still understudied, while others—like informal groups and informal volunteering—are almost totally ignored.

The article justifies that the Mediterranean Basin in the broad sense (Mediterranean, Black, Azov and Marmara Seas) is a single ecosystem. The state of this ecosystem is affected by the rivers of this water intake basin, among them - the Nile, Tiber, Po, Rhone, Ebro, Danube, Don and others. The interconnection of the individual elements of the ecosystem is ensured through active water exchange and a sufficiently branched system of currents that turn the inland seas of the Mediterranean basin into communicating vessels. The paper analyzes the main anthropogenic factors, as well as the influence of climate changes on the ecological condition of the Mediterranean ecosystem. Within the framework of anthropogenic impact, special attention is paid to the negative impact of urbanization, the oil industry (production, transportation and oil refining), industrial and agricultural waste, as well as runoff waters. The problem of plastic, as well as contamination with dichlorodiphenyltrichloroethane (DDT) is discussed in detail. Analysis of DDT accumulations in the bottom sediments of the Mediterranean basin makes it possible to study the synchronization of anthropogenic processes and their long-term nature. Aridization (intensification of droughts) in the Mediterranean is shown as an important problem for the regional ecology, not directly related to the anthropogenic factor. The article reveals the disastrous effects of increasing droughts and climate change on Mediterranean basin countries. International cooperation to regulate transboundary environmental problems in the region is associated with a number of problems. Among them is the delimitation of sea zones between countries, first of all - the territorial claims of Turkey in the Eastern Mediterranean. The problem of the shelf around the Serpents Island in the Black Sea is also considered, as well as territorial disputes in the Western Mediterranean (France/Spain). The paper widely presents successful cases of cross-boundary cooperation: the 1976 RAMOGE Agreement, the 1975 Mediterranean Action Plan and the 1995 Barcelona Convention, as well as its seven protocols. The cases of PEGASO and 4GreenInn projects, as well as the BSEC environmental projects, are considered as successful examples of cross-border academic cooperation. Promising areas of cooperation are outlined and the conclusion is made about the importance of transboundary environmental risk management, despite the political differences between the Mediterranean countries and the EU sanctions restrictions on Russia after 2014.

Abstract Introduction: Patients with lymphoma and chronic lymphocytic leukemia (CLL) share immune-deficiencies due to the biological features of these diseases per se and to their treatments. They are at risk to develop severe and/or prolonged forms of Covid-19. The efficacy of vaccination against COVID in lymphoma/CLL patients also raises specific concerns: Antibody response to mRNA COVID-19 vaccine was shown to be negatively affected by CLL stage and its treatments, especially in case of previous administration of anti-CD20 antibodies (Herishanu et al). Therefore, the addition of a third dose of vaccine in immunosuppressed patients is currently recommended in France. Methods: To analyse the determinants of the antibody response after anti-SARS-Cov2 mRNA vaccines (Pfizer or Moderna), we conducted a retrospective monocentric study among adults with a past or current lymphoma/CLL who underwent serology 2 weeks or more after 2 or 3 previous injections. The decision of a third dose was at the discretion of each physician. Data were extracted from the patients' medical charts on their demographics, lymphoma history and detailed treatments, vaccinations and biological parameters (immunoglobulin (Ig) G dosage, lymphocytic, B-cell and T-cell counts) and serology (Elecsys ® Anti-SARS-CoV-2 S). Statistical tests were two-tailed and p-values &lt; 0.05 were considered significant. Multivariable analysis was conducted using independent variables having univariate significance below 0.1. This study was conducted in accordance with the Declaration of Helsinki, and approved by the ethics committee of our institution. Results: Ninety-one patients with non-Hodgkin's lymphomas (NHL) (n=48), CLL (32) or Hodgkin's lymphoma (11) were enrolled. With a median interval since last dose of 47 days (range 15-125), 48 patients (53%) had a negative serology (Table). Gender and age were not associated with antibody response. The proportion of seronegativity was 57% among patients with B-cell NHL, and 41% among those with CLL. Among the biological variables reflecting immune deficiency, lymphocytopenia (&lt;1.5G/L), low B-cell counts (&lt;0.2G/L) and IgG levels (&lt;6g/L) were significantly associated with a higher risk of seronegativity with odds-ratios (OR, [95% confidence interval]) of 5.1 [1.8-15.3], p&lt;7x10 -4 , 15.0 [3.0-147.9], p&lt;7x10 -5, and 15.3 [3.7-93.0], p&lt;9x10 ⁻6 respectively). Patients under watch and wait attitude and those who did not have a lymphoma/CLL treatment since at least 12 months before vaccination had a much lower risk of negative serology (OR: 0.08 [&lt;0.01 ; 0.4], p&lt; 2.10 -4). Among lymphoma/CLL therapies, chemotherapy overall or targeted therapy with BTK inhibitors or Venetoclax were not significantly associated with a lower risk of negative serology. In contrast, the administration of anti-CD20 therapy during the year before first dose of vaccine was associated with a higher risk of negative serology (OR: 4.5 [1.7; 12.1], p&lt;8.10 -4). Of note, this treatment was also significantly associated with both lymphocytopenia and low B-cell counts. There was no association between the number of vaccine doses and the risk of negative serology, 59% of the patients who received 3 doses remained seronegative.A multivariable analysis associating IgG level and treatment history showed that negative serology is significantly associated with a low level of IgG (OR: 25.74 [5.58; 201.14], p &lt; 10 -3) and anti-CD20 treatment (OR: 28.70 [4.14, 382.60], p = 3x10 -3). Conclusion: Overall, previous anti-CD20 therapy and low IgG levels are the main independent factors associated with a lack of serological response after anti-SARS-Cov2 mRNA vaccine. Administration of a third vaccine does not overcome their pejorative impact. This should contribute to the elaboration of guidelines for the management of lymphoma/CLL patients during the Covid-19 era. In particular, in all non-critical clinical situation, SARS-CoV-2 vaccination should be proposed before the onset of lymphoma/CLL therapy. Meanwhile, individuals with CLL/lymphoma should receive the Covid-19 vaccine, be informed that they are unlikely to be protected and continue social distancing and adhere to other proven mitigation strategies. Systematic vaccination of their proxies and hospital workers should also benefit directly to patients. Figure 1 Figure 1. Disclosures Rigaudeau: Takeda: Membership on an entity's Board of Directors or advisory committees.

The World Health Summit 2011 confirmed the epidemic-like occurrence of diabetes mellitus and obesity. In Germany, 62.7 % and 21.9 % of the population have a BMI of more than 25 kg/m² and more than 30 kg/m2, respectively. Currently, 10.5 obese people per 100 000 German inhabitants undergo bariatric surgery, while 86 and 114.8 per 100 000 in France and in Sweden, respectively, favor bariatric surgical interventions. Aim By means of a scientific case report, the instructive case of a young patient with morbid obesity is illustrated based on 1) selective references from the medical literature and 2) insights from the daily clinical practice in the case-specific medical and perioperative management after successful surgery for malformation in his childhood and, thus, the limited therapeutic options of metabolic surgery. Case report (case-, diagnostic-, and treatment-specific aspects) 35-year-old patient with morbid obesity. Medical history: Status after surgical intervention for gastroschisis as a newborn (surgery report not available). Clinical findings: Super obesity characterized by 234 kg and 174 cm (→ BMI: 77.3 kg/m²), hypogonadotrophic hypogonadism. Approach & course: Outcome (early postoperative and mid- to long-term): The patient tolerated the intervention well. Postoperative course was uneventful with regard to mobilization, beginning of oral nutrition, and wound healing; there was a subsequent weight reduction due to a “common channel” of 250 cm. Conclusion While the increase of obesity prevalence in adults has currently stopped, incidence in children and teenagers is rapidly rising. The consequence might be that children and young adults who have undergone bariatric surgery in childhood and adolescence can develop complications from these former interventions as adults. Therefore, it is reasonable to recommend follow-up investigations within specialized centers according to well-established standards. On the other hand, the increasing prevalence of obesity in childhood leads to the possibility that adults who underwent pediatric surgery because of embryonal malformations may require an appointment with a bariatric surgeon at some point. For these patients (as a representative example of the transition of care phenomenon), the risk of metabolic surgical intervention is increased; such operations require the appropriate knowledge and expertise of the bariatric surgeon on embryonal malformations and their approach by pediatric surgery.

According to one of the famous foundresses of the French Federation of Eclaireuses (FFE), Marguerite Walther, it had to a be a female movement where “any little French girl would be comfortable” – comfortable to learn about moral values and about freedom. The FFE was very successful during the 1930s, achieving a high number of enrolments which were maintained after World War II. But the 1960s resulted in some fatal consequences for the FFE due to several reasons. There were financial problems, personality clashes, changes of attitude, and, eventually, co-education. Nevertheless, undertaking the analysis ofthe impact ofthe Eclaireuses’ movement one may clearly see its contribution to women’s empowerment in France. The question is to determine the particularities of this kind of feminism and how the women participating in the movement became more engaged in civil society.

This volume of Frontiers: The Interdisciplinary Journal of Study Abroad offers a wide variety of approaches and topics in international education research. First, readers will note the geographic diversity that the articles represent; they examine study abroad topics in Africa, Argentina, Costa Rica, France, Nepal, Thailand, and Vietnam. Second, the articles cover a wide-range of issues, including language acquisition, risk management, recruitment of minority students for study abroad, evaluation of cultural integration, and financial inequities in study abroad. Third, this volume contains articles by a variety of authors, including U.S.-based study abroad administrators, faculty members, and on-site resident directors. Finally, the modes of inquiry are as varied as the topics and authors. Research approaches in this volume include survey instruments, interviews, participant observation, case studies, literature review, as well as analytical essays. This diversity of geography, issues, authors, and modes of inquiry has from the beginning characterized the content of Frontiers and been one of its chief strengths. When the first volume of Frontiers appeared in 1995, one was hard pressed to find many research-based and analytical studies in the field, let alone the diversity of such work that this volume represents. In this regard, Frontiers has matured along with the field of international education, and today, almost ten years later, this volume reflects the growing importance being placed on research on the critical aspects of our work. The opening article by Lilli Engle and John Engle, “Study Abroad Levels: Toward a Classification of Program Types,” offers a revolutionary perspective by which international educators may categorize and judge study abroad programs. Their proposed typology makes qualitative distinctions between study abroad program models based on their view of a spectrum of cultural immersion. Frontiers readers will find their analysis provocative, stimulating study abroad professionals to examine programming in useful ways. In “Women and Cultural Learning in Costa Rica: Reading the Contexts,” Adele Anderson reviews research on Costa Rica’s cultural context, student adjustment and tourism theory, relating them to American student experiences, and she includes data from ethnographic observations and interviews collected during three years as a resident director of short-term programs. Anderson introduces a tool that may be used by resident directors to guide student cultural adjustment more systematically. Mark Ritchie, an on-site resident director in Thailand, provides a very useful analysis of study abroad risk management in his article, “Risk Management in Study Abroad: Lessons from the Wilderness.” Ritchie draws upon the principles of wilderness education, especially as it is conducted in developing countries, in offering recommendations for study abroad risk management. Readers will appreciate his suggestions for reducing risk by applying the experiential techniques of wilderness education. J. Scott Van Der Meid’s study, “Asian Americans: Factors Influencing the Decision to Study Abroad,” examines the factors that influence Asian American students’ decision to study abroad, and provides useful suggestions for considering ways to increase study abroad participation among this population. As the field of study abroad continues to seek ways to increase minority participation in study abroad, Van Der Meid’s study offers a model for examining this question among all ethnic groups. In their analysis of an innovative Vietnam study abroad program, “History Lived and Learned: Students and Vietnam Veterans in an Integrative Study Abroad Course,” Raymond Scurfield, Leslie Root, and Andrew Wiest et al, analyze the collaborative learning experience of students and Vietnam veterans in a program that combined the teaching of Vietnam culture and military history with an exploration of the mental health aspects of combat and post-war recovery of the veterans. This article discusses the lessons learned from the experience of designing and implementing a study abroad program that integrates history education with therapeutic objectives. Jennifer Coffman and Kevin Brennan analyze the economic imbalance of African educational exchange with the United States in their article, “African Studies Abroad: Meaning and Impact of America’s Burgeoning Export Industry.” Coffman and Brennan recommend developing more equitable models of reciprocity by examining the economics of U.S. – African exchanges, and by reconsidering the ways in which African study abroad programs are conceived and implemented in light of their social and intellectual impact. “Development of Oral Communication Skills Abroad” by Christina Isabelli-Garcia examines the impact of a semester study abroad program in Argentina on the second language acquisition of three American university Spanish learners. Isabelli-Garcia’s study measures the development of two aspects of communications skills: first, fluency and performance in the oral functions of narration, and, second, description and supporting an opinion. Her study provides insight into the conditions of a study abroad program that best promote the acquisition of improved oral communication skills in a target language. In “Studying Abroad in Nepal: Assessing Impact,” Patricia Farrell and Murari Suvedi present the perceived impact of studying in Nepal on students’ academic program, personal development, and intellectual development. Using a survey instrument as well as interviews and case studies, the authors link the reported outcomes to the objectives of the study abroad program. We are pleased to include in this volume of Frontiers an essay by Patti McGill Peterson, “New Directions for the Global Century.” McGill Peterson’s analysis of the changing and challenging context for global education inspires us to meet the demands of the 21st century with determination, creativity, and enhanced global collaboration. This volume of Frontiers concludes with reviews of books of interest to international educators, each relating to diverse intellectual foundations of the field: Jean-Philippe Mathy’s Extrême-Occident: French Intellectuals and America, Louis Menand’s The Metaphysical Club: A Story of Ideas in America, and First Great Triumph: How Five Americans Made Their Country a World Power by Warren Zimmermann. We encourage our readers to continue to suggest books of interest, and to submit reviews for consideration. The update on the Forum on Education Abroad that appears at the back of this volume reflects the continuing fruitful collaboration between Frontiers and the Forum. Together with the Forum, Frontiers will continue to encourage and support research studies on study abroad topics, and to disseminate this research as widely as possible. The next volume of Frontiers, due to be published in November, 2004, will be our tenth anniversary volume. It is appropriate that this anniversary volume will be a Special Issue that focuses on the assessment of the learning outcomes of study abroad, a topic that reflects the maturation of a field that is now beginning to document the results of its activity. Other Special Issues that are in the planning stages include: curriculum integration and study abroad, the arts and study abroad, and student development and study abroad. Finally, I want to thank the new sponsors of Frontiers who, together with our existing sponsors, make the publication of this journal possible. The sponsors of Frontiers are institutions with a strong commitment to international education, and we are proud to be supported by them. The editorial board takes seriously its responsibility to provide the very best writing about and research on study abroad to our readers, and the support of our sponsors makes this mission possible. Brian J. Whalen Editor

There are two prominent motivations for why governments seek to promote the electric car: risk management and industrial policy. This article provides operational definitions of these two motivations and uses them to characterize the public policies of six political jurisdictions: California, China, the European Union, France, Germany, and the United States. The article finds that while the European Union is focused primarily on risk management, China, Germany and the United States are primarily engaged in industrial policy. California and France are intermediate cases with a substantial blend of industrial policy and risk management. Future research into the ramifications of industrial policy for liberalized international trade is recommended.

The objective of the article is to analyse the use of Humanities and Social Sciences (HSS) in public risk assessment and risk management organisations in France, Germany, the UK, the Netherlands, Canada and the United States based on more than a hundred interviews conducted with social sciences experts employed by or working for these organisations. If the added value brought by the integration of social scientists is recognised, the use of social sciences differs from one organisation to another. The article compares the different positions given to social scientists inside and outside the organisation, the various methods used and the different contents produced. The survey highlights a set of initiatives that are scattered, differentiated and ultimately have little in common – except that they often play a marginal role in the main activities of the agencies concerned.

Feminism as a movement is strongly connected with a political and philosophical reality which came after the French Revolution. The feminist movement in the 19th and early 20th century was focused on obtaining for women the right to vote and equal salary for work of equal value. The activists of this movement were called suffragettes. After their victory, the majority of feminists started to present abortion as a human right, thereby in fact refusing unborn children the right to life. The modern term „reproductive rights”, in contemporary feminist understanding of these words, means a right to decide about procreation both in morally acceptable and unacceptable way (e.g. allowing abortion). However, some feminist initiatives are worth to analyse as a way to protect human dignity, e.g. the prohibition of prostitution in France, which was supported by the French feminists. Finally, it should be said that feminism is a very differentiated movement and some feminists do not accept abortion. Also, not all women, or probably even not the majority of women, feel represented by the feminists.

1. Introduction This Special Issue (Part 2) expands upon the theme “Building Local Capacity for Long-term Disaster Resilience” presented in Special Issue Part 1 (JDR Volume 5, Number 2, April 2010) by examining the evolving concept of disaster resilience and providing additional reflections upon various aspects of its meaning. Part 1 provided a mixed set of examples of resiliency efforts, ranging from administrative challenges of integrating resilience into recovery to the analysis of hazard mitigation plans directed toward guiding local capability for developing resiliency. Resilience was broadly defined in the opening editorial of Special Issue Part 1 as “the capacity of a community to: 1) survive a major disaster, 2) retain essential structure and functions, and 3) adapt to post-disaster opportunities for transforming community structure and functions to meet new challenges.” In this editorial essay we first explore in Section 2 the history of resilience and then locate it within current academic and policy debates. Section 3 presents summaries of the papers in this issue. 2. Why is Resilience a Contemporary Theme? There is growing scholarly and policy interest in disaster resilience. In recent years, engineers [1], sociologists [2], geographers [3], economists [4], public policy analysts [5, 6], urban planners [7], hazards researchers [8], governments [9], and international organizations [10] have all contributed to the literature about this concept. Some authors view resilience as a mechanism for mitigating disaster impacts, with framework objectives such as resistance, absorption, and restoration [5]. Others, who focus on resiliency indicators, see it as an early warning system to assess community resiliency status [3, 8]. Recently, it has emerged as a component of social risk management that seeks to minimize social welfare loss from catastrophic disasters [6]. Manyena [11] traces scholarly exploration of resilience as an operational concept back at least five decades. Interest in resilience began in the 1940s with studies of children and trauma in the family and in the 1970s in the ecology literature as a useful framework to examine and measure the impact of assault or trauma on a defined eco-system component [12]. This led to modeling resilience measures for a variety of components within a defined ecosystem, leading to the realization that the systems approach to resiliency is attractive as a cross-disciplinary construct. The ecosystem analogy however, has limits when applied to disaster studies in that, historically, all catastrophic events have changed the place in which they occurred and a “return to normalcy” does not occur. This is true for modern urban societies as well as traditional agrarian societies. The adoption of “The Hyogo Framework for Action 2005-2015” (also known as The Hyogo Declaration) provides a global linkage and follows the United Nations 1990s International Decade for Natural Disaster Reduction effort. The 2005 Hyogo Declaration’s definition of resilience is: “The capacity of a system, community or society potentially exposed to hazards to adapt by resisting or changing in order to reach and maintain an acceptable level of functioning and structure.” The proposed measurement of resilience in the Hyogo Declaration is determined by “the degree to which the social system is capable of organizing itself to increase this capacity for learning from past disasters for better future protection and to improve risk reduction measures.” While very broad, this definition contains two key concepts: 1) adaptation, and 2) maintaining acceptable levels of functioning and structure. While adaptation requires certain capacities, maintaining acceptable levels of functioning and structure requires resources, forethought, and normative action. Some of these attributes are now reflected in the 2010 National Disaster Recovery Framework published by the U.S. Federal Emergency Management Agency (FEMA) [13]. With the emergence of this new thinking on resilience related to disasters, it is now a good time to reflect on the concept and assess what has recently been said in the literature. Bruneau et al. [1] offer an engineering sciences definition for community seismic resilience: “The ability of social units (e.g., organizations, communities) to mitigate hazards, contain the effects of disasters when they occur, and carry out recovery activities in ways that minimize social disruption and mitigate the effects of future earthquakes.” Rose [4] writes that resiliency is the ability of a system to recover from a severe shock. He distinguishes two types of resilience: (1) inherent – ability under normal circumstances and (2) adaptive – ability in crisis situations due to ingenuity or extra effort. By opening up resilience to categorization he provides a pathway to establish multi-disciplinary approaches, something that is presently lacking in practice. Rose is most concerned with business disruption which can take extensive periods of time to correct. In order to make resource decisions that lower overall societal costs (economic, social, governmental and physical), Rose calls for the establishment of measurements that function as resource decision allocation guides. This has been done in part through risk transfer tools such as private insurance. However, it has not been well-adopted by governments in deciding how to allocate mitigation resources. We need to ask why the interest in resilience has grown? Manyena [11] argues that the concept of resilience has gained currency without obtaining clarity of understanding, definition, substance, philosophical dimensions, or applicability to disaster management and sustainable development theory and practice. It is evident that the “emergency management model” does not itself provide sufficient guidance for policymakers since it is too command-and-control-oriented and does not adequately address mitigation and recovery. Also, large disasters are increasingly viewed as major disruptions of the economic and social conditions of a country, state/province, or city. Lowering post-disaster costs (human life, property loss, economic advancement and government disruption) is being taken more seriously by government and civil society. The lessening of costs is not something the traditional “preparedness” stage of emergency management has concerned itself with; this is an existing void in meeting the expanding interests of government and civil society. The concept of resilience helps further clarify the relationship between risk and vulnerability. If risk is defined as “the probability of an event or condition occurring [14]#8221; then it can be reduced through physical, social, governmental, or economic means, thereby reducing the likelihood of damage and loss. Nothing can be done to stop an earthquake, volcanic eruption, cyclone, hurricane, or other natural event, but the probability of damage and loss from natural and technological hazards can be addressed through structural and non-structural strategies. Vulnerability is the absence of capacity to resist or absorb a disaster impact. Changes in vulnerability can then be achieved by changes in these capacities. In this regard, Franco and Siembieda describe in this issue how coastal cities in Chile had low resilience and high vulnerability to the tsunami generated by the February 2010 earthquake, whereas modern buildings had high resilience and, therefore, were much less vulnerable to the powerful earthquake. We also see how the framework for policy development can change through differing perspectives. Eisner discusses in this issue how local non-governmental social service agencies are building their resilience capabilities to serve target populations after a disaster occurs, becoming self-renewing social organizations and demonstrating what Leonard and Howett [6] term “social resilience.” All of the contributions to this issue illustrate the lowering of disaster impacts and strengthening of capacity (at the household, community or governmental level) for what Alesch [15] terms “post-event viability” – a term reflecting how well a person, business, community, or government functions after a disaster in addition to what they might do prior to a disaster to lessen its impact. Viability might become the definition of recovery if it can be measured or agreed upon. 3. Contents of This Issue The insights provided by the papers in this issue contribute greater clarity to an understanding of resilience, together with its applicability to disaster management. In these papers we find tools and methods, process strategies, and planning approaches. There are five papers focused on local experiences, three on state (prefecture) experiences, and two on national experiences. The papers in this issue reinforce the concept of resilience as a process, not a product, because it is the sum of many actions. The resiliency outcome is the result of multiple inputs from the level of the individual and, at times, continuing up to the national or international organizational level. Through this exploration we see that the “resiliency” concept accepts that people will come into conflict with natural or anthropogenic hazards. The policy question then becomes how to lower the impact(s) of the conflict through “hard or soft” measures (see the Special Issue Part 1 editorial for a discussion of “hard” vs. “soft” resilience). Local level Go Urakawa and Haruo Hayashi illustrate how post-disaster operations for public utilities can be problematic because many practitioners have no direct experience in such operations, noting that the formats and methods normally used in recovery depend on personal skills and effort. They describe how these problems are addressed by creating manuals on measures for effectively implementing post-disaster operations. They develop a method to extract priority operations using business impact analysis (BIA) and project management based business flow diagrams (BFD). Their article effectively illustrates the practical aspects of strengthening the resiliency of public organizations. Richard Eisner presents the framework used to initiate the development and implementation of a process to create disaster resilience in faith-based and community-based organizations that provide services to vulnerable populations in San Francisco, California. A major project outcome is the Disaster Resilience Standard for Community- and Faith-Based Service Providers. This “standard” has general applicability for use by social service agencies in the public and non-profit sectors. Alejandro Linayo addresses the growing issue of technological risk in cities. He argues for the need to understand an inherent conflict between how we occupy urban space and the technological risks created by hazardous chemicals, radiation, oil and gas, and other hazardous materials storage and movement. The paper points out that information and procedural gaps exist in terms of citizen knowledge (the right to know) and local administrative knowledge (missing expertise). Advances and experience accumulated by the Venezuela Disaster Risk Management Research Center in identifying and integrating technological risk treatment for the city of Merida, Venezuela, are highlighted as a way to move forward. L. Teresa Guevara-Perez presents the case that certain urban zoning requirements in contemporary cities encourage and, in some cases, enforce the use of building configurations that have been long recognized by earthquake engineering as seismically vulnerable. Using Western Europe and the Modernist architectural movement, she develops the historical case for understanding discrepancies between urban zoning regulations and seismic codes that have led to vulnerable modern building configurations, and traces the international dissemination of architectural and urban planning concepts that have generated vulnerability in contemporary cities around the world. Jung Eun Kang, Walter Gillis Peacock, and Rahmawati Husein discuss an assessment protocol for Hazard Mitigation Plans applied to 12 coastal hazard zone plans in the state of Texas in the U.S. The components of these plans are systematically examined in order to highlight their respective strengths and weaknesses. The authors describe an assessment tool, the plan quality score (PQS), composed of seven primary components (vision statement, planning process, fact basis, goals and objectives, inter-organizational coordination, policies & actions, and implementation), as well as a component quality score (CQS). State (Prefecture) level Charles Real presents the Natural Hazard Zonation Policies for Land Use Planning and Development in California in the U.S. California has established state-level policies that utilize knowledge of where natural hazards are more likely to occur to enhance the effectiveness of land use planning as a tool for risk mitigation. Experience in California demonstrates that a combination of education, outreach, and mutually supporting policies that are linked to state-designated natural hazard zones can form an effective framework for enhancing the role of land use planning in reducing future losses from natural disasters. Norio Maki, Keiko Tamura, and Haruo Hayashi present a method for local government stakeholders involved in pre-disaster plan making to describe performance measures through the formulation of desired outcomes. Through a case study approach, Nara and Kyoto Prefectures’ separate experiences demonstrate how to conduct Strategic Earthquake Disaster Reduction Plans and Action Plans that have deep stakeholder buy-in and outcome measurability. Nara’s plan was prepared from 2,015 stakeholder ideas and Kyoto’s plan was prepared from 1,613 stakeholder ideas. Having a quantitative target for individual objectives ensures the measurability of plan progress. Both jurisdictions have undertaken evaluations of plan outcomes. Sandy Meyer, Eugene Henry, Roy E. Wright and Cynthia A. Palmer present the State of Florida in the U.S. and its experience with pre-disaster planning for post-disaster redevelopment. Drawing upon the lessons learned from the impacts of the 2004 and 2005 hurricane seasons, local governments and state leaders in Florida sought to find a way to encourage behavior that would create greater community resiliency in 2006. The paper presents initial efforts to develop a post-disaster redevelopment plan (PDRP), including the experience of a pilot county. National level Bo-Yao Lee provides a national perspective: New Zealand’s approach to emergency management, where all hazard risks are addressed through devolved accountability. This contemporary approach advocates collaboration and coordination, aiming to address all hazard risks through the “4Rs” – reduction, readiness, response, and recovery. Lee presents the impact of the Resource Management Act (1991), the Civil Defence Emergency Management Act (2002), and the Building Act (2004) that comprise the key legislation influencing and promoting integrated management for environment and hazard risk management. Guillermo Franco and William Siembieda provide a field assessment of the February 27, 2010, M8.8 earthquake and tsunami event in Chile. The papers present an initial damage and life-loss review and assessment of seismic building resiliency and the country’s rapid updating of building codes that have undergone continuous improvement over the past 60 years. The country’s land use planning system and its emergency management system are also described. The role of insurance coverage reveals problems in seismic coverage for homeowners. The unique role of the Catholic Church in providing temporary shelter and the central government’s five-point housing recovery plan are presented. A weakness in the government’s emergency management system’s early tsunami response system is noted. Acknowledgements The Editorial Committee extends its sincere appreciation to both the contributors and the JDR staff for their patience and determination in making Part 2 of this special issue possible. Thanks also to the reviewers for their insightful analytic comments and suggestions. Finally, the Committee wishes to again thank Bayete Henderson for his keen and thorough editorial assistance and copy editing support.

Purpose Enterprise risk management (ERM) is a risk management approach that calls for integrating all the organization-wide risks and takes a portfolio view point of managing organizational risks. The purpose of this paper is to investigate the factor that influence a firm’s decision to adopt ERM. Design/methodology/approach The authors employ a particular technique of survival data analysis, the Cox proportional hazards model, to investigate the factors that lead towards the decision of initiating an ERM programme. The authors constructed a unique sample of French firms derived from the information in 315 corporate news announcements for the hiring of a chief risk officer and information retrieved from publicly available annual reports to identify firms that initiated an ERM programme, over the period from year 1999 to 2008. Findings The results suggest that besides the growing international and local regulatory pressure, factors that are internal to the organizations like the expected probability of financial distress and its explicit and implicit costs, poor earnings performance and the existence of growth opportunities play vital role in motivating firms to adopt ERM. It was also found that corporate governance practices such as the independence of the board may also lead towards an initiation of the ERM. Originality/value This study makes theoretical and methodological contribution the ERM literature by employing a novel methodology and presenting empirical evidence based on data form French firms.

Abstract Abstract 4267 Introduction This multicenter, international, prospective registry is a longitudinal (5 year) assessment of diagnosis methods, management strategies, and outcomes for CML patients (pts) under ‘real world’ conditions. Pts were enrolled from Latin America (LA), United States (US), Asia Pacific (AP), Middle East and Africa (MEA), and Russia and Turkey (RT). This first, interim data summary reports baseline characteristics on the first 1001 enrolled pts. Methods Eligible pts were ≥ 16 yrs of age and entered the Registry within 6 months of CML diagnosis. Demographics, medical history, current disease status and management information are collected at baseline. Follow up data are collected at approximately 6-month intervals. Center practices in disease detection and monitoring are collected annually. Results 1001 patients from 148 sites worldwide were enrolled with a data cut-off of May 2009. Represented in this dataset: 165 (16.5%) from LA, 179 (17.9%) from US, 372 (37.2%) from AP, 84 (8.4%) from MEA, and 201 (20.1%) from RT. The majority of patients in LA (50%) were from government hospitals, US from private hospitals/practices (61.1%), AP and MEA from academic institutions (54.8% and 64.7% respectively), and RT from regional/community hospitals (55%). Overall, 953 (95.2%) pts were in chronic phase CML, with little variation across regions. Overall, 58.4% of pts were male (LA, 51.5%; US, 57.0%; AP, 67.7%; MEA, 53.6%; RT, 50.2%) and median age was 46 yrs (range, 15–91). Notably, median age in the AP region was just 40 yrs (LA, 48; US, 53; MEA, 41.5; RT, 52). Hematologic, bone marrow, and cytogenetic (Cy) assessments were used for CML diagnosis in most pts (88.7%, 84.4%, 82.6%, respectively). For Cy assessment, the method used varied widely by region. Most centers appeared to use both karyotype and fluorescence in situ hybridization (FISH), with FISH being used in a greater proportion of pts in the US and MEA (Table 1). Only 51.6% of pts had molecular assessments at diagnosis, ranging from 27.4% in RT to 70.2% in MEA. The majority (54.3%) of pts had no risk score assigned at diagnosis. Sokal score, assessed in 39.1% of pts, was the most common risk score used in all regions (LA, 46.7%; US, 5.6%; AP, 36.0%; MEA, 50.0%; RT, 63.7%). The most common comorbidity was cardiac disorders, in 211 (21.1%) pts, followed by diabetes in 74 (7.4%) pts. Pulmonary disorders were present in 33 (3.3%) patients. At the time of Registry enrollment, imatinib was the most commonly prescribed therapy. Most centers (83.1%) were not performing plasma drug monitoring of anti-leukemic therapy, primarily due to lack of availability (58.5%); 89.2% of those centers would consider performing plasma drug level testing if it were readily available. Conclusions The first interim results of this Registry reveal some regional differences in CML diagnosis and management. Notably, not all pts appear to be treated according to published disease management guidelines. For example, although only karyotyping can detect additional chromosomal abnormalities in Philadelphia chromosome-positive CML, approximately 20% of patients overall and 40% of patients in the US and MEA did not have karyotyping performed at diagnosis. Furthermore, molecular assessments were not universally performed at diagnosis. As these data mature, ongoing interim summaries from the WORLD CML Registry will continue to assess global trends in CML diagnostic methods, treatment approaches, adherence to disease management guidelines and response to treatment. Educational initiatives can thus be regionally tailored to optimize patient care in CML. Additional data summaries by center setting (private hospitals/practices, academic, etc) will also be available. Disclosures: Cortes-Franco: Novartis: Honoraria, Research Funding, Speakers Bureau; Wyeth: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau. Joske:Novartis Australia: Membership on an entity's Board of Directors or advisory committees; Novartis Pharma AG: Membership on an entity's Board of Directors or advisory committees. Mongay:Novartis: Employment. Eng:Novartis: Employment. Wang:Novartis: Employment. Hughes:Bristol-Myers Squibb: Advisor, Honoraria, Research Funding; Novartis: Advisor, Honoraria, Research Funding. Kim:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Wyeth: Research Funding.

In the EU the Flood Directive is part of the European legislation which is implemented in the domestic legal regimes of the Member States. The legal systems in which flood risks are managed are part of the domestic legal regimes. Floods in the European river basins of the the Scheldt and the Meuse are a special case, for they have transboundary consequences. Therefore, the flood risk management of the countries which are part of these river basins need to be compatible in order to prevent or mitigate transboundary floods risk. However, knowledge of the competences of relevant administrative authorities and the legal instruments for preventive flood risk management is lacking. Without this knowledge it is impossible for the member states to establish a balanced system in which transboundary flood risks are well managed . This article is the first step to provide a basis for such a cooperation by reducing this knowledge gap for the three countries which are part of the river Meuse and the Scheldt ± the Netherlands, Flanders and France. It offers a comparison of the consequences of policy making and implementation of specific measures by describing the actors and their legal instruments. The two specific aspects of flood risk management are selected because they form the core of the system in which flood risk management is implemented and are necessary for the realisation of measures to prevent or reduce flood risks.

Bubble and Speak was founded in 2016 as a small charity organization, inspired by the example of the Maisons vertes set up by Françoise Dolto in France, with the aim of welcoming children up to four years of age and their parents or carers, using a psychoanalytic approach. The ‘Bubble’ in our name indicates an emphasis on playing and the universe of childhood, while the verb ‘speak’ stands for our intention to focus on free expression, speaking and listening. This article presents the project's origins and its core concept, as well as two of our main challenges: the question of the families’ financial contribution and the principle of anonymity in our work.

Abstract What has changed in France in coastal flood risk management after Xynthia storm. One year after the Xynthia storm surge, which struck the Vendée and the Charente-Maritime counties of the French Atlantic Coast in the night of 27/28 February 2010, French authorities implemented a national plan for mitigation and management of the fl ash submersions (MEDDTL 2011). In this paper authors analyse partial results of this plan after almost three years of its effectiveness in the perspective of Xynthia catastrophic event, but also taking into account other dramatic coastal submersions, which occured during winter 2014 in the same region.