[French national overview of the inclusion of environmental criteria in the public purchasing of health products (drugs and sterile medical devices)]. / Prise en compte des critères environnementaux dans la commande publique des produits de santé.

OBJECTIVES: Healthcare products (HP) have a significant carbon footprint that must be included by regulation in the facility's purchasing policy. A national overview of the inclusion of environmental criteria (EC) in the public procurement (PP) of HP in hospitals has been carried out. METHODS: Thirty EC were identified in the literature. Two questionnaires were proposed: (i) for buyers that analyze the level of "importance" and "ease of application" for public tenders (PT), and (ii) for suppliers that declare their commitments and evidence. RESULTS: Six regional buyers and 28 suppliers participated. Buyers recognize the "importance" of sustainable development (SD) but are more reticent about the "applicability" of EC in PT. The environmental rating remains low: on average 4.38 (0.25-10.00) % of the total rating. Only 12 EC are integrated within some PT. Suppliers report a high and diversified commitment to SD: 18 suppliers sent 474 evidence. Buyers and suppliers converge on the optimization of primary packaging and the establishment of a minimum order or delivery group. CONCLUSIONS: Since the efficiency of PP is inevitable, EC that combines SD and savings should be prioritized. The integration of additional EC, simple and easily documented, allowing cost containment for both suppliers and buyers, is possible to promote sustainable purchasing.

Vaccination coverage in French 17-year-old young adults: an assessment of mandatory and recommended vaccination statuses.

We aimed to assess vaccination coverage (VC) in 17-year-old French young adults (YAs) participating in one mandatory Day of Defence and Citizenship (DDC). Between June 2010 and May 2011, YAs participating in 43 randomly selected mandatory sessions of the DDC programme in Poitou-Charentes (France) were asked to provide their personal vaccination record. Tetanus, diphtheria, polio, hepatitis B, Haemophilus influenzae b, pertussis, measles, mumps and rubella vaccination status were assessed at ages 2, 6, 13 and 17 years. Of 2610 participants, 2111 (81%) supplied documents for evaluation. Of these, 1838 (87%, M:F sex ratio 0·96) were aged 17 years (9% of the global population of this age in the area). The assessment of the 17-year-olds demonstrated the following rates of complete vaccination: diphtheria-tetanus-polio 83%; measles, mumps and rubella 83%; pertussis 69%; H. influenzae b 61%; human papillomavirus 47%; and hepatitis B 40%. At age 6 years, only 46% had received two doses of the vaccine against measles. The YAs were not aware of their status but were in favour of vaccination. VC in YAs is insufficient, particularly for hepatitis B, pertussis and measles. Combined vaccines and the simplification of vaccination schedules should improve VC. Preventive messages should focus on YAs.

Melanoma-associated retinopathy treated with ipilimumab therapy.

Melanoma-associated retinopathy (MAR) is a rare autoimmune syndrome in patients with melanoma characterized by visual disorders. MAR is induced by the degeneration of bipolar cells of the retina and the presence of serum autoantibodies against retina proteins. Ipilimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 antibody, improves survival in previously treated patients with metastatic melanoma, but is responsible for a spectrum of immune-related adverse events. Administration of ipilimumab to patients with autoimmune diseases (such as MAR or vitiligo) is actually not recommended. We report a patient presenting with MAR occurring during a melanoma relapse. Surgery and chemotherapy had no effect on visual acuity and melanoma increased. In the absence of alternative antitumoral treatment, we focused on the vital prognosis and treated the patient with ipilimumab. Two years after the treatment the patient is free from new metastasis but has presented with exacerbation of vitiligo and MAR. In the very rare case of melanoma with autoimmune disease without a therapy option, ipilimumab could be discussed, taking into account the fact that it can be effective on tumor burden but can also increase autoimmunity.

Trends in prescriptions for glaucoma and ocular hypertension in France between 2014 and 2019.

PURPOSE: To explore the national trend in prescriptions for glaucoma and ocular hypertension (OHT) in France between 2014 and 2019. METHODS: This is a retrospective descriptive study based on prescription data from the Primary Health Insurance Fund databases. All patients with a social security number who received one or more glaucoma/OHT prescriptions between 2014 and 2019 were identified. Figures for 2020 are not yet available as of the date of submission of this article. Demographic characteristics from Common Classification of Medical Acts information and from National Institute of Statistics and Economic Studies were analyzed. The data analysis was carried out using the R version 3.6.2.software from the available databases of the Information Systems Medicalization Program. RESULTS: Our results suggest an increase in the number of patients treated with glaucoma drugs, which cannot be explained simply by demographic growth. There is also a change in drug prescription habits, both in the class of medication used and in the use of fixed combinations. We also note the increasing use of SLT (Selective Laser Trabeculoplasty), a relatively newer tool in the therapeutic arsenal. Over the same time period, demographic characteristics remained stable; age and sex distribution for each year remained constant. In addition, the phenomenon of poor therapeutic compliance, which we attempted to explore, remained stable. DISCUSSION: This study updates the French epidemiologic data available on prescriptions for glaucoma and ocular hypertension, a true public health concern. CONCLUSION: On the one hand, prescribing practices have evolved over the study period. On the other hand, the number of patients treated has increased faster than the growth of the French population over the same period. These findings are consistent with trends observed in previous studies.

[A case report of wandering spleen]. / Le syndrome de la rate baladeuse : cas clinique.

INTRODUCTION: Wandering spleen is a rare condition that occurs when there is an acquired or congenital hypelaxity of the suspensory ligaments of the spleen, resulting in its migration to any abdominal or pelvic position. CASE REPORT: A 43-year-old woman presented with symptoms of acute abdominal pain. At physical examination, a splenomegaly was found in the left hypochondria, thereafter followed by a secondary migration of the lump to a periumbilical location. Computed tomography revealed a wandering spleen with vascular pedicle torsion. Splenopexia was perfomed. CONCLUSION: A wandering spleen is most frequently observed in children and young women. This rare diagnosis should be considered facing a recurrent abdominal pain syndrome, a splenomegaly accompanied with pain, or a pelvic lump. A wandering spleen may lead to torsion of the vascular pedicle of the spleen, a chronic volvulus with portal hypertension, or even a splenic infarction. The diagnosis is performed by computed tomography. Wandering spleen is treated surgically, by splenopexy or splenectomy.

Total body irradiation using helical tomotherapy: Set-up experience and in-vivo dosimetric evaluation.

PURPOSE: Helical Tomotherapy (HT) appears as a valuable technique for total body irradiation (TBI) to create highly homogeneous and conformal dose distributions with more precise repositioning than conventional TBI techniques. The aim of this work is to describe the technique implementation, including treatment preparation, planning and dosimetric monitoring of TBI delivered in our institution from October 2016 to March 2019. MATERIAL AND METHOD: Prior to patient care, irradiation protocol was set up using physical phantoms. Gafchromic films were used to assess dose distribution homogeneity and evaluate imprecise patient positioning impact. Sixteen patients' irradiations with a prescribed dose of 12Gy were delivered in 6 fractions of 2Gy over 3 days. Pre-treatment quality assurance (QA) was performed for the verification of dose distributions at selected positions. In addition, in-vivo dosimetry was carried out using optically stimulated luminescence dosimeters (OSLD). RESULTS: Planning evaluation, as well as results of pre-treatment verifications, are presented. In-vivo dosimetry showed the strong consistency of OSLD measured doses. OSLD mean relative dose differences between measurement and calculation were respectively +0,96% and -2% for armpit and hands locations, suggesting better reliability for armpit OSLD positioning. Repercussion of both longitudinal and transversal positioning inaccuracies on phantoms is depicted up to 2cm shifts. CONCLUSION: The full methodology to set up TBI protocol, as well as dosimetric evaluation and pre-treatment QA, were presented. Our investigations reveal strong correspondence between planned and delivered doses shedding light on the dose reliability of OSLD for HT based TBI in-vivo dosimetry.

Progastrin production transitions from Bmi1+/Prox1+ to Lgr5high cells during early intestinal tumorigenesis.

Progastrin is an unprocessed soluble peptide precursor with a well-described tumor-promoting role in colorectal cancer. It is expressed at small levels in the healthy intestinal mucosa, and its expression is enhanced at early stages of intestinal tumor development, with high levels of this peptide in hyperplastic intestinal polyps being associated with poor neoplasm-free survival in patients. Yet, the precise type of progastrin-producing cells in the healthy intestinal mucosa and in early adenomas remains unclear. Here, we used a combination of immunostaining, RNAscope labelling and retrospective analysis of single cell RNAseq results to demonstrate that progastrin is produced within intestinal crypts by a subset of Bmi1+/Prox1+/LGR5low endocrine cells, previously shown to act as replacement stem cells in case of mucosal injury. In contrast, our findings indicate that intestinal stem cells, specified by expression of the Wnt signaling target LGR5, become the main source of progastrin production in early mouse and human intestinal adenomas. Collectively our results suggest that the previously identified feed-forward mechanisms between progastrin and Wnt signaling is a hallmark of early neoplastic transformation in mouse and human colonic adenomas.

Radiotherapy quality assurance by individualized in vivo dosimetry: state of the art.

The quality insurance in radiotherapy in the frame of highly complex technical process as Intensity modulated radiotherapy (IMRT) needs independent control of the delivered dose to the patient. Actually, up to now, most of the radiotherapy treatments rely only on computed dosimetry through a rather complicated series of linked simulation tool. This dosimetry approach requires also qualified treatment means based on cautious quality insurance procedures. However, erroneous parameters could be difficult to detect and systematical errors could happen leading to radiotherapy accidents. In this context, in vivo dosimetry has a critical role of final control of the delivered dose. As many beam incidences and ports are used for any photontherapy treatment, external control could be very tedious and time consuming. Therefore, innovations are needed for in vivo dosimetry to provide ergonomic and efficient tools for these controls. This paper presents a review of technologies and products that can be used for in vivo dosimetry. It proposes also a reflection on the concepts to develop future devices suitable for this purpose. The technical means with their physical principles are reviewed, the clinical experiences demonstrating the feasibility of new techniques are then summarized and finally, the early clinical use and its impact on clinical practice is review.

[Report of the mission commissioned by the Ministry of Health to the French Society of Radiation Oncology]. / Rapport de la mission confiée par le ministère de la Santé à la Société française de radiothérapie oncologique.

Further to the Epinal events, Health Ministers P. Bas then R. Bachelot-Narquin have launched a plan of work devoted to radiotherapy; they have also committed the SFRO President, within the framework of a mission, to make proposals taking into account the demography of professionals and their level of competence, valorization of careers, cooperation with medical oncologists, delegations of authorities, mutualisation of human and material resources. Due to the numerous actions of the roadmap managed by the tutelages, the aim of the mission was focused on the modalities of work of the professionals linked to radiotherapy: radiation oncologists, radiographers and physicists.

Glaucoma progression analysis by Spectral-Domain Optical Coherence Tomography (SD-OCT).

Spectral domain optical coherence tomography (SD-OCT) provides an objective quantification of the lesions of various target tissue structures in glaucoma, with unprecedented resolution, which has now demonstrated its interest in controlling the progression of glaucomatous neuropathy, from early stages to late stages. A certain number of well-established proofs state that a progressive modification in OCT is a common predictor of functional loss, and that patients with rapid OCT changes have an increased risk of developing glaucomatous scotoma. Follow-up of the progression goes through three stages. It consists first of all in detecting the evolution of damage to the retinal nerve fiber layer (RNFL), then that of the macular ganglion cell complex (GCC), in order to better define this progression of the damage to the target structures and, thirdly, to complete its analysis by integrating it with the analysis of the functional impairment. We note today that there is a greater risk of developing a future functional deficit of the visual field in subjects with a RNFL loss slope greater than -1/year, for all clinical stages of glaucoma. The characteristics of GCC progression are much better specified. Often earlier than that of the progress of the thinning of the RNFL and much faster in the subjects considered as "progressors", its cartography is better defined, with a particular interest for the follow-up of diversion maps and "wide field" acquisitions offering better visibility of deficits and their progression. To date, a certain number of suspicious indicators of short-term progress can be retained, highlighting the essential precaution of having two or more basic measures and a confirmation of the change on at least one new OCT acquisition. Finally, if the interpretation of the progression must always be based on clinical examination data, and the macula in particular, it remains crucial to confront the progression of the RNFL with that of the GCC and with that of the visual field.

External radiation exposure and mortality in a cohort of French nuclear workers.

OBJECTIVE: To analyse the effect of external radiation exposure on the mortality of French nuclear workers. METHODS: A cohort of 29 204 workers employed between 1950 and 1994 at the French Atomic Energy Commission (Commissariat à l'Energie Atomique (CEA)) or at the General Company of Nuclear Fuel (COmpagnie GEnérale des MAtières nucléaires (Cogema, now Areva NC)) was followed up for an average of 17.8 years. Standardised mortality ratios (SMRs) were computed with reference to French mortality rates. Dose-effect relationship were analysed through trend tests and Poisson regression, with linear and log-linear models. RESULTS: The mean exposure to X and gamma radiation was 8.3 mSv (16.9 mSv for exposed worker population). A total of 1842 deaths occurred between 1968 and 1994. A healthy worker effect was observed, the number of deaths in the cohort being 59% of the number expected from national mortality statistics. Among the 21 main cancer sites studied, a statistically significant excess was observed only for skin melanoma, and an excess of borderline statistical significance was observed for multiple myeloma. A dose-effect relationship was observed for leukaemia after exclusion of chronic lymphoid leukaemia (CLL). The relative risk observed for non-CLL leukaemia, n = 20, was 4.1 per 100 mSv (90% CI 1.4 to 12.2), linear model and 2.2 per 100 mSv (90% CI 1.2 to 3.3), log-linear model. Significant dose-effect relationship were also observed for causes of deaths associated with alcohol consumption: mouth and pharynx cancer, cirrhosis and alcoholic psychosis and external causes of death. CONCLUSION: The risk of leukaemia increases with increasing exposure to external radiation; this is consistent with published results on other nuclear workers cohorts.

MEDOR, a didactic tool to support interpretation of bioassay data after internal contamination by actinides.

A didactic software, MEthodes DOsimètriques de REférence (MEDOR), is being developed to provide help in the interpretation of biological data. Its main purpose is to evaluate the pertinence of the application of different models. This paper describes its first version that is focused on inhalation exposure to actinide aerosols. With this tool, sensitivity analysis on different parameters of the ICRP models can be easily done for aerosol deposition, in terms of activity and particle number, actinide biokinetics and doses. The user can analyse different inhalation cases showing either that dose per unit intake cannot be applied if the aerosol contains a low number of particles or that an inhibition of the late pulmonary clearance by particle transport can occur which contributes to a 3-4 fold increase in effective dose as compared with application of default parameters. This underlines the need to estimate systematically the number of deposited particles, as well as to do chest monitoring as long as possible.

[Reliability and reproducibility of introcular pressure (IOP) measurement with the Icare® Home rebound tonometer (model TA022) and comparison with Goldmann applanation tonometer in glaucoma patients]. / Fiabilité et reproductibilité des mesures de la pression intraoculaire par le tonomètre Icare® Home (modèle TA022) et comparaison avec les mesures au tonomètre à aplanation de Goldmann chez des patients glaucomateux.

PURPOSE: The Icare® Home tonometer is a new rebound tonometer, developed for intraocular pressure (IOP) self-monitoring. The main objective of our study was to evaluate the reliability and reproducibility of measurements taken with the Icare® Home tonometer in glaucoma patients compared to the Goldmann applanation tonometer. A secondary objective was to investigate factors that could influence the reproducibility of these measurements. MATERIALS AND METHODS: Fifty-two glaucoma patients were included in this prospective, non-randomized, monocentric study. IOP measurements were performed on the right eye and then on the left eye in the following order (3 measurements of IOP for each method): air tonometer (T-Air), Icare® Home tonometer by the patient (RT-P), Icare® Home tonometer by an ophthalmologist (RT-O), Goldmann applanation tonometer (GAT). RESULTS: Forty-four patients (85%) managed to take their IOP on both eyes with the Icare® Home tonometer. Mean IOPs were 14.35±3.93mmHg (T-Air), 13.43±4.65mmHg (RT-P), 14.13±4.29mmHg (RT-O), 14.74±3.84mmHg (GAT). The intraclass correlation indices (ICC) on the 3 repeated IOP measurements were 0.924, 0.872, 0.947 and 0.957, respectively. Bland-Altman analysis found a mean difference (bias) between GAT and RT-P, between GAT and RT-O, and between RT-O and RT-P, respectively, of 1.31, 0.61 and 0.70mmHg, with a 95% confidence interval of -3.34 to 5.96, -3.91 to 5.14 and -3.44 to 4.84mmHg, respectively. The reproducibility of the measurements taken with the Icare® Home tonometer did not vary according to corneal thickness or age of the patients. CONCLUSION: The Icare® Home tonometer provides reliable and reproducible IOP values in glaucoma patients, although it appears to slightly underestimate the IOP measurements compared to the Goldmann applanation tonometer.

[Selective laser trabeculoplasty: Effect of number of preoperative topical glaucoma medications on pressure lowering and success rate]. / Trabéculoplastie sélective au laser : effet du nombre de traitements antiglaucomateux topiques préopératoires sur la baisse pressionnelle et le taux de succès.

PURPOSE: To evaluate the lowering of intraocular pressure (IOP) one year after SLT and to assess if differences are related to number of pre-SLT topical treatments in ocular hypertension (OHT) and primary open angle glaucoma (POAG) patients. METHODS: Retrospective review of 106 eyes of 13 OHT and 93 POAG patients treated by SLT for insufficient IOP control, allergy, discomfort or non-compliance to glaucoma medications, excluding patients with less than 1 year of follow-up after SLT. IOP was measured by applanation before and at 1, 6 and 12 months after SLT. RESULTS: Hundred and six eyes untreated (n=13), or treated with one (n=25), two (n=40) or three or more (n=28) glaucoma medications were included. Mean IOP decreased from 19.4±3.6mmHg preoperatively to 15.7±3.1mmHg at 12 months, which corresponds to an average decrease of 18.8%. At 1 year, 62.2% (n=66) were responders (IOP reduction≥3mmHg): 92.3% without medications (n=12), 68% with one (n=17), 57.5% with two (n=23) and 50% with three or more medications (n=14). Their average IOP decreased from 20.7±3.4 to 15.2±2.9mmHg (26.6%), respectively from 20.8±2.6 to 15.8±3.2 (25%) without medications, 20.6±3.2 to 14.9±3.7 (27.3%) with one, 20.8±4.1 to 15.5±3.3 (25.1%) with two and 20.7±3.2 to 14.4±2.4mmHg (29.7%) with three medications. CONCLUSIONS: The number of responders seems to be greater in OHT and POAG patients without or with few glaucoma medications, but the IOP reduction seems to be similar regardless of the number of glaucoma medications.

All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth.

Gastric carcinoma is the third leading cause of cancer-related death worldwide. This cancer, most of the time metastatic, is essentially treated by surgery associated with conventional chemotherapy, and has a poor prognosis. The existence of cancer stem cells (CSC) expressing CD44 and a high aldehyde dehydrogenase (ALDH) activity has recently been demonstrated in gastric carcinoma and has opened new perspectives to develop targeted therapy. In this study, we evaluated the effects of all-trans-retinoic acid (ATRA) on CSCs in human gastric carcinoma. ATRA effects were evaluated on the proliferation and tumorigenic properties of gastric carcinoma cells from patient-derived tumors and cell lines in conventional 2D cultures, in 3D culture systems (tumorsphere assay) and in mouse xenograft models. ATRA inhibited both tumorspheres initiation and growth in vitro, which was associated with a cell-cycle arrest through the upregulation of cyclin-dependent kinase (CDK) inhibitors and the downregulation of cell-cycle progression activators. More importantly, ATRA downregulated the expression of the CSC markers CD44 and ALDH as well as stemness genes such as Klf4 and Sox2 and induced differentiation of tumorspheres. Finally, 2 weeks of daily ATRA treatment were sufficient to inhibit gastric tumor progression in vivo, which was associated with a decrease in CD44, ALDH1, Ki67 and PCNA expression in the remaining tumor cells. Administration of ATRA appears to be a potent strategy to efficiently inhibit tumor growth and more importantly to target gastric CSCs in both intestinal and diffuse types of gastric carcinoma.

Development of educational image databases and e-books for medical physics training.

Medical physics education and training requires the use of extensive imaging material and specific explanations. These requirements provide an excellent background for application of e-Learning. The EU projects Consortia EMERALD and EMIT developed five volumes of such materials, now used in 65 countries. EMERALD developed e-Learning materials in three areas of medical physics (X-ray diagnostic radiology, nuclear medicine and radiotherapy). EMIT developed e-Learning materials in two further areas: ultrasound and magnetic resonance imaging. This paper describes the development of these e-Learning materials (consisting of e-books and educational image databases). The e-books include tasks helping studying of various equipment and methods. The text of these PDF e-books is hyperlinked with respective images. The e-books are used through the readers' own Internet browser. Each Image Database (IDB) includes a browser, which displays hundreds of images of equipment, block diagrams and graphs, image quality examples, artefacts, etc. Both the e-books and IDB are engraved on five separate CD-ROMs. Demo of these materials can be taken from www.emerald2.net.

[Diagnostic laser in glaucoma: scanning laser polarimetry (GDx VCC) and confocal scanning laser tomography (HRT)]. / Les lasers diagnostiques dans le glaucome: la polarimétrie à balayage laser (GDx VCC) et la tomographie confocale par balayage laser (HRT).

Automated structural measurements of retinal nerve fibers and optic nerve head are possible with new lasers providing objective and reproductible data for analysis. Scanning laser polarimetry (GDx VCC), based on retardation of polarized light, assesses peripapillary nerve fiber layer thickness. Confocal scanning laser tomography yields precise topographic maps of the optic disc and peripapillary retina. The advantages, applications for glaucoma detection, both in a screening setting as well as for monitoring progression, limitations and pitfalls need to be well known and results should be analyzed with clinical data.