Citizen science in environmental health research: A comparison with conventional approaches and creation of a guidance tool issued from the LILAS initiative.

CONTEXT: Public interest for citizen science (CS) in environmental health is growing. The goals of environmental health research projects are diverse, as are the methods used to reach these goals. Opportunities for greater implication of the civil society and related challenges differ at each step of such projects. These methodological aspects need to be widely shared and understood by all stakeholders. The LILAS initiative (acronym for "application of citizen science approaches such as LIving LAbS to research on environmental exposures and chronic risks") aimed to 1) favor a mutual understanding of the main issues and research methods in environmental health, of their stakes for different actors, but also of the requirements, strengths and limitations of these methods and to 2) identify expected benefits and points of attention related to stronger degrees of participation as part of environmental health research projects. METHODS: The LILAS initiative gathered institutional researchers, academics and civil society representatives interested in environmental exposures. Five meetings allowed to collectively identify different types of environmental health research studies and reflect about the benefits, limitations, and methodological issues related to the introduction of growing citizen participation as part of such studies. An analytic table matrix summarizing these aspects was co-created and filled by participants, as a tool devoted to help stakeholders with the definition of future CS research projects in environmental health. RESULTS: For different fields of research (e.g.: studies for assessment of environmental exposures, interventions on these exposures, quantitative risk assessment, epidemiological studies), the matrix lists expected benefits for various stakeholders, the fundamental principles of research methods and related practical constraints, but also advantages and limitations related to the use of CS or conventional research approaches. CONCLUSION: The LILAS initiative allowed to develop a tool which provides consolidated grounds for the co-creation of research projects on environmental exposures involving CS.

[Impact of patient testimony in the education of medicine and pharmacy students]. / Patients acteurs et formation en oncologie pour futurs médecins et pharmaciens.

The initiative from patients suffering from cancer or having had the disease in speaking about their illness to medical students during an internship in a cancer control center of the faculty of medicine and to pharmacy students at the university of Strasbourg was implemented in 2014. This action was coordinated by the French Cancer League as part of the National French cancer plan 3. After training, ten patients teachers were able to freely and spontaneously explain their diagnostic and therapeutic journey as well as their feelings about the disease and their relationship with their oncologists in front of 187 medical students and 131 pharmacy students. A moderator, often a former cancer teacher, helped coordinate the discussions. Questionnaires were given to students, patients teachers and moderators in order to assess the merits of the action and the expected benefits at the end of the training. A second questionnaire was sent to the students six months after the interviews. The assessment was made by an independent firm. The students' responses were very favorable and this training met their expectations in almost 98% of the cases and 1/3 of the students were destabilized by this training. Patients teacher were very satisfied with their intervention and felt that they were able to convey a message. Six months later, the 30% of student respondents said that these testimonies had or could have an impact on their practices. This is the first assessment of the interest of resource patients in teaching cancer patients about medical and pharmacy students.

Use of complementary and alternative medicine by children in Europe: published data and expert perspectives.

INTRODUCTION: Few data document the use of complementary and alternative medicine (CAM) in Europe, with even fewer investigating use by children. METHODS: A narrative, non-systematic review of CAM use in Europe was performed by combining data from published surveys with expert perspectives. Limitations created by a lack of representative studies, varying definitions of CAM use, and what qualifies as CAM in different countries was partially overcome by integrating local experts to summarise information available only in the national language and provide their perspectives about CAM availability, quality, use and popularity in their countries using a semi-structured questionnaire. Local and international published surveys were summarised, and the prevalence of CAM use was extrapolated. RESULTS: Data from 20 European countries were available, representing 69% of the European population. Some data about CAM use by the general population were available for 90% of the examined countries, whereas peer-reviewed published surveys were available for only 60%. We extrapolated that 56% (range: 10-90%, adjusted for population size) of the European population in general had used CAM at least once in the past year. Surveys in CAM use by children were available for 55% of the investigated countries. The extrapolated prevalence of CAM use by children in Europe was 52% (range: 5-90%, adjusted for population size). Paediatric CAM experts reported an increasing awareness for and use of CAM in healthcare institutions. CONCLUSION: This precursor for further surveys indicates that CAM appears to be popular not only among adults in Europe, but also for children. Development of a pan-European definition of CAM use and CAM therapies are required to achieve surveys comparable between European countries. Additionally, more research investigating the efficacy and potential adverse effects of CAM therapies is needed because of increasing CAM use by children in Europe.

Occupation and skin cancer: the results of the HELIOS-I multicenter case-control study.

BACKGROUND: Non-melanoma skin cancer (NMSC) is the most frequent tumour among Caucasian populations worldwide. Among the risk factors associated with this tumour, there are host-related factors and several environmental agents. A greater likelihood of high exposure to physical agents (with the exception of solar radiation) and chemical agents depends on the work setting. Our objective is to evaluate the role of occupational exposures in NMSC, with special emphasis on risk factors other than solar radiation and skin type. METHODS: We analysed 1585 cases (1333 basal cell carcinoma (BCC) and 183 squamous cell carcinoma (SCC)) and 1507 controls drawn from the Helios-I multicenter study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression mixed models. RESULTS: For NMSC as a whole (both histological types), miners and quarrymen, secondary education teachers, and masons registered excess risk, regardless of exposure to solar radiation and skin type (OR 7.04, 95% CI 2.44-20.31; OR 1.75, 95% CI 1.05-2.89 and OR 1.54, 95% CI 1.04-2.27, respectively). Frequency of BCC proved higher among railway engine drivers and firemen (OR 4.55; 95% CI 0.96-21.57), specialised farmers (OR 1.65; 95% CI 1.05-2.59) and salesmen (OR 3.02; 95% CI 1.05-2.86), in addition to miners and quarrymen and secondary education teachers (OR 7.96; 95% CI 2.72-23.23 and OR 1.76; 95% CI 1.05-2.94 respectively). The occupations that registered a higher risk of SCC (though not of BCC) were those involving direct contact with livestock, construction workers not elsewhere classified (OR 2.95, 95% CI 1.12-7.74), stationary engine and related equipment operators not elsewhere classified (OR 5.31, 95% CI 1.13-21.04) and masons (OR 2.55, 95% CI 1.36-4.78). CONCLUSION: Exposure to hazardous air pollutants, arsenic, ionizing radiations and burns may explain a good part of the associations observed in this study. The Helios study affords an excellent opportunity for further in-depth study of physical and chemical agents and NMSC based on matrices of occupational exposure.

Disclosure of competing financial interests and role of sponsors in phase III cancer trials.

Financial relationships between industry, researchers and academic institutions are becoming increasingly complex, raising concern about sponsors' involvement in the conduct of biomedical research. A review of published randomised trials (RCTs) in cancer research was performed to assess adherence to the 1997 disclosure requirements and to document the nature of the disclosed interests. Source(s) of study support, author-sponsor relationships and the role of the study sponsor were assessed for all RCTs published between 1999 and 2003 in 12 international journals. A total of 655 cancer RCTs were identified. Of these, 516 (78.8%) disclosed the source of sponsorship. The nature of the relationship between the authors and the study sponsor was included in 219 of the 227 industry-sponsored studies. The most commonly cited relationships were (131 studies had multiple relations): grants (93.6%); employment (39.2%); consultant/honorarium (12.7%) and stock ownership and participation in a speaker's bureau (12, 5.5% each). Only 41 (18%) of the 227 industry-sponsored RCTs reported the role of the sponsor. Of these, 20 explicitly stated that the sponsor had no role in the study. Twenty-one papers described the sponsor's role, the degree of sponsor involvement was variable and usually described vaguely. Among these papers, four stated that researchers had full access to all data, one that the researchers had no limits on publication and one that 'the decision to submit the paper for publication was determined by the study sponsor'. In conclusion, no researcher should be expected to produce 'findings' without full access to the data, freedom from interference in analysis and interpretation and liberty to publish all results, however disappointing to the stakeholder they may be. In the meantime, researchers do well to arm themselves with the rules for research partnerships and editors to take on the role of watchdog.

Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial.

PURPOSE: The French Adjuvant Study Group 05 (FASG-05) showed that fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2 (FEC 100) was superior to the same regimen with epirubicin 50 mg/m2 (FEC 50) in terms of disease-free survival (DFS) and overall survival (OS) in adjuvant treatment of early breast cancer. We report 10-year data on efficacy, and long-term side effects for FASG-05. PATIENTS AND METHODS: We randomly assigned 565 patients to treatment with FEC 50 or FEC 100 after surgery. Postmenopausal patients also received tamoxifen for 3 years, and almost all patients (96%) also received radiotherapy. RESULTS: Median follow-up was 110 months. The 10-year DFS was 45.3% (95% CI, 41.9% to 48.7%) with FEC 50 and 50.7% (95% CI, 47.3% to 54.1%) with FEC 100 (Wilcoxon P = .036; log-rank P = .08). The 10-year OS was 50.0% (95% CI, 46.7% to 53.3%) with FEC 50 and 54.8% (95% CI, 51.3% to 58.3%) with FEC 100 (Wilcoxon P = .038; log-rank P = .05). Delayed cardiac toxicity (before relapse) occurred in four patients (1.5%) in the FEC 50 arm and three patients (1.1%) in the FEC 100 arm. Cardiac toxicity after relapse occurred in six (4.3%) and five (4.1%) patients treated with FEC 50 and FEC 100, respectively. CONCLUSION: Treatment with adjuvant FEC 100 demonstrated superior DFS and OS versus FEC 50 at 10 years of follow-up. This survival advantage was not offset by long-term complications such as cardiac toxicity and second malignancy. Given the risk-benefit ratio, FEC 100 is a more optimal regimen for long-term survival in patients with poor prognosis.

[Burn out syndrome in oncology]. / Le point sur le syndrome d'épuisement professionnel des soignants ou burn out, en cancérologie.

SEPS or burnout syndrome was described among health care workers. Oncology care givers--physicians and nurses--can be concerned. Burnout is a chronical stress reaction. Emotional exhaustion and depersonalisation are more prevalent than low personal accomplishment. Burnout is essentially assessed by questionnaires. Oncologists report an higher level of burnout, than AIDS medical or palliative care staff. Causes of burn out are numerous: insufficient personal time, sense of failure,... followed by poorly management and difficulties in staff or institution relationships. Prevention and therapy of burn out can be considered on three levels: personal, (psychotherapy, advices on health way of life), team (improvement in communication) and institution (support meetings and talking groups).

[Methodological and ethical quality in phase III cancer trials: role of the cooperative group]. / Rôle des groupes coopérateurs dans la qualité éthique et méthodologique des essais de phase III en cancérologie.

Phase III clinical trials (CT) are carried out more and more often in a multicentric way, under the aegis of one or more cooperative groups (CG). The goal of this study was to analyze the influence of the GC on ethical quality (EQ) and methodological quality (MQ) in phase III cancer CT. EQ (Berdeu-score) and MQ (Jadad scale) were assessed for all CTs (n=231) published between 1999 and 2001 in 10 international journals. The impact of CG on EQ and MQ was evaluated with an univariate analysis. 140 ECR (60.6%) were carried out under the aegis of a CG. There was no improvement of the MQ and EQ for the trials carried out under the aegis of a CG. The methodological score (Jadad) was of 9.9 +/- 1.15 for the CT-CG (+) and of 9.8 +/- 1.28 for the CT-GC (-) (p=0.7). The ethical score (Berdeu) was of 0.43 +/- 0.14 for the CT-CG (+) and of 0.40 +/- 0.11 for the CT-CG (-) (p=0.08). Interim analysis, defined stopping rules and independent monitoring were more frequent for the CT-CG (+) and were respectively 37.8% vs 15.4%, 20.7% vs 8.8%, 19.3 vs 6.6%. 31.9% of the CT-CG (-) and 19.3% of the CT-CG (+) were financed by industry (p=0.03). The CG have a major role to play in the protection of the patient in CT, because they monitored trials from the conception to the publication and communication of results.

Disease-free survival advantage of weekly epirubicin plus tamoxifen versus tamoxifen alone as adjuvant treatment of operable, node-positive, elderly breast cancer patients: 6-year follow-up results of the French adjuvant study group 08 trial.

PURPOSE: To assess whether an epirubicin (EPI) -based chemotherapy plus hormonal regimen improves disease-free (DFS) in women older than 65 years, with node-positive, operable breast cancer (BC), relative to tamoxifen (TAM) alone. PATIENTS AND METHODS: A total of 338 patients were randomly assigned after surgery to receive TAM 30 mg/d for 3 years (TAM, n = 164), or EPI 30 mg on days 1, 8, and 15 every 28 days for six cycles plus TAM 30 mg/d for 3 years (EPI-TAM, n = 174). In both arms, patients received radiotherapy, delivered after chemotherapy (CT) in the EPI-TAM group. RESULTS: The 6-year DFS rates were 69.3% with TAM and 72.6% with EPI-TAM (P = .14). The multivariate analysis shows a relative risk of relapse of 1.93 (95% CI, 1.70 to 2.17) with TAM compared with EPI-TAM (P = .005). The 6-year OS, related to disease progression, was 79.1% and 79.8%, respectively (P = .41). Compliance with CT was good: 96.9% of patients received six cycles. The acute toxicity per patient was mild: grade 2 neutropenia in 5.9%, grade 2 anemia in 2.0%, grade 3 nausea or vomiting in 4.6%, and grade 3 alopecia in 7.2%. Five cases (in five patients) of decreased left ventricular ejection fraction occurred after CT: three after adjuvant CT, and two after anthracycline-based CT for relapse. One patient died as a result of dysrhythmia related to carcinomatous lymphangitis. No secondary leukemia occurred. CONCLUSION: This study conducted in node-positive elderly patients demonstrates a significant contribution of a weekly EPI regimen in terms of DFS. Moreover, this regimen is safe for hematologic, nonhematologic, and cardiac toxicities.

Randomized trial comparing six versus three cycles of epirubicin-based adjuvant chemotherapy in premenopausal, node-positive breast cancer patients: 10-year follow-up results of the French Adjuvant Study Group 01 trial.

PURPOSE: To evaluate the duration and dose intensity of epirubicin-based regimens in premenopausal patients with lymph node-positive breast cancer. PATIENTS AND METHODS: Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75). All patients in the three arms received chest wall irradiation at the end of the third cycle. RESULTS: After a 131-month median follow-up, the 10-year disease-free survival (DFS) was 53.4%, 42.5%, and 43.6% (P =.05) in the three arms, respectively. Pairwise comparisons demonstrate that 6 FEC 50 was superior both to 3 FEC 50 (P =.02) and to 3 FEC 75 (P =.05). The 10-year overall survival (OS) for the 6 FEC 50 arm was 64.3%, for the 3 FEC 50 arm it was 56.6%, and for the 3 FEC 75 arm, it was 59.7% (P =.25), respectively. Pairwise comparisons demonstrate that 6 FEC 50 was more effective than 3 FEC 50 (P =.10). Cox regression analysis demonstrates that OS was significantly better in the 6 FEC 50 than in the 3 FEC 50 arm (P =.046). No severe infections (grade 3 to 4), acute cardiac toxicity, or deaths from toxicity have been observed. Only five patients developed delayed cardiac dysfunctions, and three patients developed acute myeloblastic leukemia. CONCLUSION: After a long-term follow-up in an adjuvant setting, the benefit of six cycles of FEC 50 compared with three cycles, whatever the dose, is highly significant in terms of DFS. As regards OS, the group receiving six cycles of FEC 50 has significantly better results than the group receiving three cycles of FEC 50.

Reproducibility of skin characteristic measurements and reported sun exposure history.

BACKGROUND: The aim of the present study is to investigate the reproducibility of information on sun exposure, skin characteristics and sunburn collected through a standardized questionnaire used in the multi-centre South European case-control study on skin cancer, 'Helios'. We also intended to use results from reproducibility analysis for correcting odds ratio (OR) estimates from the original study. METHODS: We re-interviewed, with the same questionnaire, a sample of 115 cases of basal cell and squamous cell carcinoma of the skin and 119 population controls, 18-26 months apart, in four centres of Italy, Spain and France. The questionnaire included questions on skin characteristics, sunburns and sun exposure histories. We investigated agreement, studying the association between the difference of the two measures and a set of explanatory variables. According to the results of the reproducibility analysis we corrected OR estimates from the original study simultaneously adjusting for random measurement error. RESULTS: Hair and eye colour showed high agreement with intra-class correlation coefficients (ICC) of 0.81 and 0.74, respectively. Lifetime sun exposure showed substantial agreement with ICC ranging from 0.68 for time spent doing outdoor work to 0.79 for time spent outdoors during holidays and holidays at the beach. The poorest agreement was found for number of lifetime sunburns (ICC = 0.25), while sunburns during childhood showed a substantial agreement (Cohen's Kappa = 0.67). Lack of reproducibility was mainly associated with subjects' education, while no significant differences were observed between cases and controls. The corrected OR showed a moderate increase with a reinforcement of the effect of sun exposure and skin reaction to sun exposure. CONCLUSION: Overall, there was good reproducibility, particularly in the case of sun exposure histories, between answers given on two different occasions to a questionnaire administered by trained interviewers. However, since measurement error can substantially bias OR toward the null value, it should be taken into account in estimates of the effect of sun exposure on risk of skin cancer.

[Quality of life measurement in cancer survivors]. / Mesure de la qualité de vie chez le cancéreux guéri.

The quality of life (QOL) of cancer patients can be measured by semi structured interview or by validated QOL instruments. Late effect toxicity scales can be used but do not account for the different domains of QOL measured by the patient. Health related quality of life can be measured by health general questionnaire or by specific cancer questionnaires. These instruments add to a core questionnaire, modules according for the organ or the toxicity of the treatments developed to evaluate cancer treatments. Some questions can be added to evaluate special domain as medical expenses, personal insurance. Some specific questionnaires for long-term survivors are available, which explore patient's satisfaction according to this status for different domains of QOL or quote different aspects in comparison with a normal population and are transformed into an utility index. There is no gold standard to measure long-term survivors' quality of life. The use of proxy is limited by discrepancies observed in the evaluation of pain, psychological symptoms and general quality of life. QOL can be evaluated in a cohort of patients in a longitudinally study or better in a case control study. Examples of QOL evaluation of different cancers sites are given.

Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis.

PURPOSE: There is no consensus on the treatment strategy for adult patients with cerebral low-grade glioma. The diagnosis and primary treatment are usually undertaken by surgery. Some investigators doubt the efficacy of postoperative radiotherapy (RT), whereas others advise routine postoperative RT. We report the primary results of a multicenter randomized trial on this controversy. METHODS AND MATERIALS: From 24 European centers, 311 adult patients with low-grade glioma were randomized centrally after surgery from March 1986 through September 1997, between the two arms of the trial. The irradiated group received 54 Gy in 6 weeks. The other patients did not receive any treatment after surgery until the tumor showed progression, defined as clinical-neurologic deterioration and evidence of progressive tumor on imaging. RESULTS: Of 290 eligible and assessable patients (93%), the irradiated group showed a significant (log-rank p = 0.02) improvement in time to progression but not in overall survival, with a median follow-up of 5 years. The 5-year estimate was, respectively, 63% vs. 66% (overall survival) and 44% vs. 37% (time to progression) for the treated and control arms. Different treatment modalities, including RT, were undertaken for the 85 controls when a progressive tumor was noted. CONCLUSION: Early postoperative conventional RT such as that used for this protocol appears to improve the time to progression or progression-free survival, but not overall survival, for patients with low-grade glioma.

Assessment of response by breast helical computed tomography to neoadjuvant chemotherapy in large inflammatory breast cancer.

Breast helical computed tomography (CT) was evaluated for use in assessing response to neoadjuvant chemotherapy and residual tumor volume. Forty-three patients with large, inflammatory breast cancers (stage IIA, 12; IIB, 13; IIIA, 9; IIIB, 9), all histologically confirmed by core biopsy, were evaluated prior to and following neoadjuvant chemotherapy. The breast helical CT procedure involved patients in the prone position using single acquisition during quiet respiration following intravenous injection of nonionic contrast material. Helical CT results (3.2-mm slices and maximum intensity projections) were compared to clinical and mammographic evaluations, as well as to pathologic findings. All tumors were clearly visible by breast helical CT, showing important tumor enhancement. Helical CT evaluation of response to chemotherapy (using World Health Organization criteria) corresponded better with mammography (78%, Cohen's kappa statistic (kappa) = 0.65) than with clinical examination (53%, kappa = 0.30). Helical CT measurement of residual tumor volume after neoadjuvant chemotherapy and correlation with pathologic findings were globally satisfactory. The intraclass correlation coefficient was 0.69 (excellent for rounded opacities [0.97], but not as good for diffuse, scattered or multinodular opacities [0.60]). By contrast, clinical and mammographic correlations were globally unsatisfactory (0.49 and 0.28, respectively). Breast helical CT can be very useful in the quantitative assessment of response to neoadjuvant chemotherapy and preoperative determination of residual tumor volume. For this reason, it can be considered an alternative to breast magnetic resonance imaging because of its simplicity, rapidity, and accessibility.