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.

[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.

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.

[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.

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.

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.

[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.

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.

[Evaluation of the new Canon HS-100 SD-OCT: Reproducibility of macular ganglion cell complex (GCC) thickness measurement in normal, hypertensive and glaucomatous eyes]. / Évaluation du nouvel OCT SD Canon HS-100: reproductibilité de la mesure de l'épaisseur du complexe cellulaire ganglionnaire maculaire pour des yeux normaux, hypertones et glaucomateux.

PURPOSE: To evaluate intra- and interobserver reproducibility of macular GCC thickness measurement by automated segmentation on the Canon HS-100 SD-OCT (Tokyo, Japan) in normal (N), hypertensive (OHT) and glaucomatous eyes. METHODS: A total of 179 eyes of 93 patients were included: 90 N, 28 OHT and 36 early glaucoma and 25 advanced glaucoma. All patients underwent a complete ophthalmologic exam, central corneal thickness and 24-2 standard automated perimetry (HFA SITA standard). Each of two observers performed three macular acquisitions with the Canon OCT HS-100. Acquisitions were analyzed with the Glaucoma 3D mode, which estimated the macular GCC thickness in global, superior and inferior hemisectors, and in eight separate macular areas. Reproducibility was assessed by intraclass correlation coefficient (ICC), coefficient of variation (CV) and test-retest variability (TRTV) calculated as 1.96 times the standard deviation. RESULTS: Mean GCC thickness was respectively 92.4 µm, 89.0 µm, 80.7 µm and 71.2 µm in N, OHT, early and advanced glaucomatous eyes. In all groups, intra- and interobserver reproducibility ranged respectively for ICC from 89.8 to 99.8% and from 90.2 to 99.4%, for CV from 0.43 to 1.95% and from 0.58 to 2.16% and for TRTV from 0.8 to 3.22 µm and from 1.04 to 3.53 µm. GCC thickness measurements using the new HS-100 SD-OCT were highly reproducible. However, in the advanced glaucoma group, while the reproducibility of GCC thickness measurement is good in the average, superior and inferior hemisectors of the macula, it was slightly less for the paracentral sectors, especially inferior. These sectors correspond generally to the areas most affected by glaucoma. CONCLUSION: The reproducibility of GCC thickness measurements using the new Canon HS-100 SD-OCT is high for normal, OHT, and glaucomatous eyes. It is thus a reliable and reproducible ancillary test available to the clinician for the examination of glaucomatous optic neuropathies.

Results of a cohort of 200 hormone-naïve consecutive patients with prostate cancer treated with iodine 125 permanent interstitial brachytherapy by the same multidisciplinary team.

PURPOSE: To report survival and morbidity of a cohort of 200 hormone-naïve consecutive patients with localized prostate cancer, treated by low-dose rate brachytherapy within the frame of multidisciplinary approach. PATIENTS AND METHODS: Between 2001 and 2011, 200 patients were treated by the same team with 125 iodine seeds: 167 low-risk and 33 intermediate risk according to the d'Amico classification; eligible patients had clinical stage T1/T2a-b, Gleason score 3+3 or 3+4, baseline prostate-specific antigen level below 15ng/mL, prostate volume less than 60cm(3). The median number of random biopsies was 12 (range 6-32) and the breakdown of positive cores was as follows: 1 (29%), 2 (35%), 3 or more (36%). Acute morbidity was assessed according to the Common Terminology Criteria for Adverse Events and late toxicity according to the EORTC/RTOG scale. Data were prospectively collected. RESULTS: The median follow-up was 69 months (range 16 to 135). The 5- and 10-year biochemical relapse free survivals were 95.6% (95% confidence interval [CI]: 91-98) and 89.7% (95% CI: 79.4-95.0). The 5-year and 10-year overall survival were respectively 96.4% (95% CI: 92-98.4) and 89.7% (95% CI: 80.8-94.6%) and the 10-year disease specific survival, 99.1% (95% CI: 93.0-99.9). The 5- and 10-year grade 3 acute toxicity cumulative rate were respectively 3.3% (95% CI: 1.4-6.6) and 4% (95% CI: 1.4-6.6) and the 5- and 10-year grades 3 cumulative late toxicity 2.5% (95% CI: 2.0-5.9) and 4% (95% CI: 2.0-5.9). CONCLUSION: Brachytherapy managed within the frame of a multidisciplinary approach - from diagnosis to evaluation - may offer optimized results with a reduced late toxicity rate, while remaining opened to dosimetry and technical improvements.

[Diagnostic use of macular layer analysis by SD-OCT in primary open angle glaucoma]. / Capacités diagnostiques de l'analyse des différentes couches maculaires par SD-OCT dans le glaucome primitif à angle ouvert.

PURPOSE: The purpose of this study is to evaluate the diagnostic ability of segmentation of the various internal macular layers by spectral domain optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec (CZM), Dublin, CA, USA) and to compare it to that of the peripapillary retinal nerve fiber layer (cpRNFL) in primary open angle glaucoma (POAG). MATERIALS AND METHODS: This study included 252 eyes diagnosed with primary open angle glaucoma (POAG) (164 early POAG, 44 moderate POAG and 44 advanced POAG) and 223 eyes of control subjects. All patients underwent visual field testing (Humphrey Field Analyser, SITA-Standard 24-2, CZM), and SD-OCT imaging (Cirrus HD-OCT) of the macular and optic nerve head regions (ganglion cell analysis (GCA), macular cube 200×200; optic disc cube 200×200). OCT macular scans were segmented into macular nerve fiber layer (mNFL), ganglion cell layer with inner plexiform layer (GCIPL), outer retinal layers, and ganglion cell complex (GCC) (mNFL+GCIPL). Glaucoma discriminating ability was assessed using the area under the receiver operator characteristic curve (AUC) for all macular parameters and mean circumpapillary retinal nerve fibre layer (cpRNFL). RESULTS: For the entire POAG population of this study, the minimum GCIPL index provided greater diagnostic ability than the other parameters studied, with a statistically significant difference in their AUC (minimum GCIPL [0.887], mean GCIPL [0.865], GCC [0.863], cpRNFL [0.823], mean mNFL [0.786] and minimum mNFL [0.742]). The results were similar in the early POAG group but without any statistically significant difference with the cpRNFL parameter. In the moderate POAG group, the diagnostic ability was similar for all indices, whereas in the advanced POAG group, minimum GCIPL and GCC gave the largest AUC indices. DISCUSSION AND CONCLUSION: The minimum macular GCIPL is a new index obtained with the GCA algorithm of the Cirrus HD-OCT. It appears to have an excellent ability to detect glaucoma at every stage and demonstrates performance comparable to that of the cpRNFL parameter, in combination with which it may provide important complementary information for clinical practice.

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.

[Analysis of macular ganglion cell complex (GCC) with spectral-domain optical coherence tomography (SD-OCT) in glaucoma]. / Analyse du complexe cellulaire ganglionnaire maculaire (GCC) en tomographie par cohérence optique (SD-OCT) dans le glaucome.

Early detection of ganglion cell loss is possible with new algorithms for the assessment of the Macular Ganglion Cell Complex (GCC) by SD-OCT. The various data acquisition protocols used by the various versions of software, as well as their accuracy and reproducibility, must be taken into account. Current results show similar ability to detect glaucoma as compared to Retinal Nerve Fiber Layer thickness (RNFL), with some limitations, possible artifacts, and interpretation pitfalls which must be taken into account. The role of the significance map and of various indices (Focal Loss Volume, Global Loss Volume, GCIPL minimum...); data obtained in the setting of various clinical entities (tilted disc, peripapillary atrophy, large and small optic discs, high myopia...); and detection of progression, especially in advanced glaucoma, underline the role of macular GCC analysis as a complementary method to peripapillary RNFL thickness. The diagnostic precision and better reproducibility of these new software protocols offer new perspectives in the detection and management of progression in various stages of the management of glaucomatous optic neuropathy.