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Introduction The profile of nursing home (NH) residents has changed over the past decade with more dependency, more severe chronic diseases and more treatments prescribed. For residents, the major consequence is the higher risk of unplanned hospitalization. French guidelines recommend the development of interactive telemedicine (InT) in NHs in order to improve access to care, and to decrease the rate of avoidable unplanned hospitalizations. Methods and analysis: The aim of this study is to analyze the impact of an InT protocol delivered in NHs on the rate of unplanned hospitalizations, and on the quality of life at work and the organizational conditions of effectiveness of telemedicine in NHs. We will perform a mixed methods study combining a cluster non-randomized controlled trial in two matched parallel arms (telemedicine group and control group) and qualitative analysis of the evolution of organizational and professional contexts in NHs. Ethics and dissemination: The study protocol was approved and sponsored by the French Ministry of Health. The study received ethical approval from the Bordeaux University Hospital Institutional Review Board. We will communicate the final results to the public via conferences and results will also be submitted for publication in international peer-reviewed scientific journals. Trial registration number NCT03486977

International audience; The crystalline and magnetic properties of micron thick magnetron sputtered Co1−x Crx and Co1−x Nix alloy films are analyzed in the view of their implementation as semi-hard magnets. All of the tested films crystallize in an hcp lattice, at least up to 35 at% of alloying elements (Cr or Ni). The structural study shows that the ratio of hcp phase with [0001] axis orientated perpendicular to the film as compared with in-plane orientation increases (resp. decreases), when Ni (resp. Cr) concentration increases independently of the post-annealing temperature. The orientation of the magnetization results from the competition between the demagnetization field which tends to align the magnetization in plane and the crystalline anisotropy which tends to maintain the magnetization along the [0001] axis. Interestingly, we find that, although Co and Ni are very similar atoms, Co1−x Nix alloys crystalline anisotropy can be strongly increased and reach up to twice the anisotropy of the best Co1−x Crx alloy, while maintaining a magnetization at saturation above 1200 kA/m. The thermal stability of the structural and magnetic properties of both alloys is demonstrated for an annealing temperature up to 300 °C.

International audience; • FeO films were synthesized by pulsed-DC magnetron sputtering from metallic target. • The film oxidation was controlled with a plasma emission monitoring system. • Special attention was paid to the sample position relative to the target axis. • Structural features depend on the oxidation rate of the growing films. • FeO behaviors are tuned from hematite semiconductor to magnetite semimetal properties. A R T I C L E I N F O Keywords: FeO Reactive sputtering Plasma emission monitoring Hematite Magnetite A B S T R A C T Iron oxide films were synthesized by pulsed-DC magnetron sputtering from a metallic target in Ar and O 2 gas mixtures. Plasma emission monitoring was implemented to accurately control the metal-to-oxygen ratio in the coating through the chemical state of the iron target. The intensity of the Fe* emission line was maintained at a given value (setpoint) by regulating the introduced oxygen flow rate. In addition, the oxidation rate of the growing film was adjusted by controlling the oxidation-to-deposition rate ratio as a function of the position of the substrates relative to the magnetron axis. The iron oxide films were characterized by X-ray diffraction, UV-VIS spectrophotometry, electrical measurement and vibrating sample magnetometry. In addition to the crys-tallization of pure hematite and magnetite phases, both phases coexist in a transition domain for a short range of setpoint depending on the oxidation-to-deposition rate ratio. The electrical, optical and magnetic behaviors of the FeO x films suggest that the relative proportion of phases can be tailored in this range. The FeO x film behaviors can then be tuned from the hematite semiconductor properties to the semi-metallic magnetite properties .

International audience; Background: Chlamydia trachomatis can lead to a persistent infection in the lower gastrointestinal tract, suggesting a potential role of autoinoculation of cervical chlamydial infection from the rectal site, contributing to repeat infections. Moreover, around 75% of women with urogenital C. trachomatis have concurrent anorectal infection. Current treatment guidelines for urogenital C. trachomatis infection recommend either a single 1 g dose of azithromycin or doxycycline 100 mg twice daily for 7 days. Doxycycline appears to be more effective in treating anorectal infections as suggested in a population of men who have sex with men, but no randomized controlled trial (RCT) had directly compared azithromycin with doxycycline for the treatment of rectal infections. We propose an open-label RCT to compare the microbial cure obtained with a single 1 g dose of azithromycin versus 100 mg of doxycycline twice daily for 7 days, for the treatment of anorectal C. trachomatis infection concurrent to urogenital infection in women. Methods and study design: A total of 460 women with C. trachomatis urogenital infection will be enrolled in the study. Women will be asked to provide self-collected anorectal swabs and will be randomized to receive either a 1 g single dose of azithromycin or doxycycline 100 mg twice daily for 7 days. Clinical and biological data will be collected and patients will complete questionnaires about their sexual behavior. The primary outcome is the microbial cure rate, defined as a C. trachomatis negative nucleic acid amplification test (NAAT) result in the anorectal specimens 6 weeks after treatment initiation among women with a C. trachomatis positive urogenital and anorectal NAAT result at the baseline. The secondary outcome is autoinoculation from the rectum to the vagina, which will be evaluated based on the number of women with the same C. trachomatis genotype profile that will be identified in an anorectal-positive specimen obtained 6 weeks after treatment initiation and in a vaginal-positive specimen obtained four months after treatment. Discussion: The results of this trial will establish which treatment is more efficacious against anorectal infection and could affect recommendations for the treatment of urogenital C. trachomatis infection, taking into account concurrent anorectal infection. Trial registration numbers: EudraCT number: 2017-002595-15. ClinicalTrials.gov Identifier: NCT03532464. Date of registration: May 31, 2018. World Health Organisation International Clinical Trials Registry: NTC03532464. Secondary ID: CHUBX 2016/26. Date of registration: May 09, 2018.

The high temperature steam electrolysis (HTE) represents one of the most promising technologies for mass hydrogen production. A commercial K41X steel (AISI441) containing 18 wt. % of chromium was tested as interconnect for solid oxide electrolyser cells (SOEC). In a previous paper, it was shown that the uncoated alloy is not suitable for SOEC interconnect application at 800°C in O2-H2O atmosphere. It was also proved that the application of a LaNi0.6Fe0.4O3-δ coating on the surface by physical vapour deposition process improves the alloy electrical behaviour and reduces chromium species evaporation. For this study, the same coating was deposited on the alloy surface by screen-printing process. Moreover, two spinel-type oxides, Co2MnO4 and Co3O4, deposited by physical vapour deposition process, were also tested in O2-H2O atmosphere at 800°C. The electrical conductivity did not present any improvement, but the Cr species volatility was reduced, especially with the LaNi0.6Fe0.4O3-δ coating.

La 2 NiO 4 coatings were co-sputtered on rotating substrates from metallic La and Ni targets in the presence of a reactive argon–oxygen gas mixture. This material is a potential candidate as cathode material for Intermediate Temperature-Solid Oxide Fuel Cells. The structural and chemical features of these films have been determined by X-ray Diffraction and Scanning Electron Microscopy. Their electrical properties have been characterised using the four point probe method and by Complex Impedance Spectroscopy measurements. It is shown that the as-deposited coatings, initially amorphous, crystallise in the LaNiO 3 perovskite-type oxide or in the convenient K 2 NiF 4 structure as a function of their composition. The electrical measurements show a clear relation between resistivity and structure of the coatings. Despite electrical resistivity values close to the theoretical ones, the activation energy of a coating presenting the convenient K 2 NiF 4 structure is slightly higher than those given in the literature data.

K41X (AISI 441) stainless steel evidenced a high electrical conductivity after 3000 h ageing in H 2 /H 2 O side when used as interconnect for solid oxide electrolyser cells (SOEC) working at 800 °C. Perovskite (La 1 − x Sr x MnO 3 − δ ) and spinel (Co 3 O 4 ) oxides coatings were applied on the surface of the ferritic steel for ageing at 800 °C for 3000 h. Both coatings improved the behaviour of the steel and give interesting opportunities to use the K41X steel as interconnect for hydrogen production via high temperature steam electrolysis. Co 3 O 4 reduced into Co leading to a very good Area Specific Resistance (ASR) parameter, 0.038 Ω cm 2 . Despite a good ASR (0.06 Ω cm 2 ), La 1 − x Sr x MnO 3 − δ was less promising because it partially decomposed into MnO and La 2 O 3 during ageing in H 2 /H 2 O atmosphere.

International audience; High temperature water vapour electrolysis (HTE) is an efficient technology for hydrogen production. In this context, a commercial stainless steel, K41X (AISI 441), was chosen as interconnect. In a previous paper, the high temperature corrosion and the electrical conductivity were evaluated in both anode (O-2-H2O) and cathode (H-2-H2O) atmosphere at 800 degrees C. In O-2-H2O atmosphere, the formation of a thin chromia protective layer was observed. Nevertheless, the ASR parameter measured was higher than the maximum accepted value. These results, in addition with chromium evaporation measurements, proved that the K41X alloy is not suitable for HTE interconnect application. In this study, two perovskite-type oxides La0.8Sr0.2MnO3-delta and LaNi0.6Fe0.4O3-delta were tested as coatings in O-2-H2O atmosphere at 800 degrees C. Screen-printing and physical vapour deposition were used as coating processes. The high temperature corrosion resistance and the electrical conductivity were improved, especially with the LaNi0.6Fe0.4O3-delta coating. Cr specie volatility was also reduced. Copyright (C) 2013, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved

Nd2CuO4 and La2CuO4 are potential candidates as cathode material for intermediate temperature-solid oxide fuel cells. Nd–Cu and La–Cu oxides were co-sputtered on rotating substrates from metallic La, Nd and Cu targets in the presence of a reactive argon–oxygen gas mixture. Structural and chemical features of these films have been determined by X-ray diffraction and energy-dispersive spectroscopy. Their electrical resistivity was measured using the four-point probe method. As-deposited Nd–Cu based coatings are amorphous and, after annealing, crystallise in K2NiF4+ d -type structure for Nd/Cu atomic ratio of 2, with more or less Nd2O3 or CuO, depending on whether Nd or Cu is in excess, respectively. As-deposited La–Cu based coatings are also amorphous and crystallise in La2CuO4 for La/Cu >2 or in LaCuO3±d perovskite-type structure when Cu is in excess. The electrical measurements show a clear relation between resistivity and structure of the coatings. After annealing, crystallised neodymium-based coatings show higher resistivity than lanthanum-based ones. Finally, LaCuO3±d exhibit higher resistivity than La2CuO4.

Les procedes de depot physique en phase vapeur (PVD Physical Vapour Deposition) constituent un ensemble de techniques de synthese de revete-ments metallurgiques ou de films ceramiques trouvant leurs applications dans des domaines aussi divers que la mecanique, l'optique, l'electronique, les industries chimique et aeronautique, etc. D'un point de vue general, les revetements sont realises sous atmosphere rarefiee (< 10 Pa) suivant trois etapes: la creation d'une vapeur metallique a partir d'une source (ou cible), son transport au sein d'un reacteur et sa condensation a la surface d'un substrat a revetir. Si l'appellation PVD regroupe une quantite importante de procedes, on peut avantageusement les classer en trois grandes categories selon le mode d'obtention de la vapeur metallique: par effet thermique, on parle d'evaporation, tandis que par effet mecanique, c'est de pulverisation qu'il s'agit. Le cas de l'arc cathodique sous basse pression allie les deux effets pour la generation de la vapeur metallique. Un reacteur de depot physique assiste-plasma est constitue au minimum d'une chambre a vide secondaire, d'une source de vapeur metallique, d'un porte-substrat isole du reste de l'installation, d'une centrale de debitmetrie et des generateurs necessaires a la creation de la decharge electrique et a la polarisation des substrats. Nous nous interesserons ici specifiquement a une technique qui connait un essor industriel important, fruit des progres considerables realises au cours de ces vingt a trente dernieres annees dans la comprehension des mecanismes qui la gouvernent: la pulverisation cathodique magnetron. La premiere partie sera consacree a l'etude detaillee du procede de pulverisation cathodique magnetron. Apres un rappel de ses mecanismes physiques, nous nous attacherons a decrire les differents moyens d'obtention des revetements de metaux ou d'alliages metalliques en soulignant les relations entre les conditions d'elaboration et les caracteristiques metallurgiques des couches, ces dernieres conditionnant leurs proprietes d'emploi. Nous decrirons dans une seconde partie les phenomenes autorisant la synthese de revetements ceramiques en presence d'une atmosphere reactive. Les principales difficultes inherentes au procede de pulverisation cathodique magnetron en condition reactive et les methodes developpees pour les contourner seront egalement presentees. C'est dans ce contexte que nous proposerons finalement deux methodes spectroscopiques de diagnostic plasma et d'interferometrie optique autorisant le controle in situ du procede.

Abstract 685 Background: In 2004 we have shown that first-line intensive therapy plus transplantation of autologous hematopoietic stem cells lead to an improved EFS and OS over standard CHOP regimen in adults with disseminated aggressive lymphomas (NEJM 2004; 350: 1287). Then the rituximab era came. We have shown that the addition of R to the intensive therapy was feasible and might further improve the results (BBMT 2010; 16: 672). We present here the preliminary analysis of a multicenter randomized trial aiming at comparing the results of R- CHOP every 14 days to R- HDT in adults with untreated confirmed DLBCL (clinical trial.gov: NCT 00561379). Methods: The patients were 18 to 60 y.o. with CD20 + DLBCL Ann Arbor stage 1 or 2 with bulk >/= 7 cm or 3 and 4 were randomized at diagnosis (with a stratification according to age adjusted IPI) between R-CHOP every 14 days at standard doses (8 consecutive courses if a response was observed after the first 4 courses) and R-HDT. This program consisted of 2 courses of high-dose CHOP-like regimen, 15 days apart, with rituximab (375/mg/m2) on day 1 of each course, followed by rituximab on d 22, harvest of G-CSF mobilised peripheral blood stem cells on d 28,29, then rituximab on d 36 followed by a course of high-dose methotrexate with cytarabin. For patients who achieved at least a partial response after these 3 courses, a BEAM regimen started on d 66 to 80 followed by the infusion of stem cells. In each arm, the intermediate evaluation of response was assessed by means of standard CT Scan and PET. Patients not achieving a PR or a negative PET were proposed a salvage Tx followed in case of response by an autologous transplantation. The main objective of the study was the EFS with an event defined as insufficient intermediate response, progression, relapse or death. Analysis was performed on intent to treat basis. Results: 331 pts were included from 01/2005 to 05/2010. 305 patients were found eligible and 286 are fully evaluable at time of this abstract, 143 in each arm. The main characteristics of the pts in the 2 arms are strictly super imposable. Overall 56% had a bulk as defined, 72% had a 3 or 4 AA stage and 58% had an aa IPI 2 or 3. The treatment as scheduled in the protocol was completed in 71% in the R-CHOP arm and 60% in the R-HDT arm. The intermediate evaluation showed exactly the same rate of response with Standard CT scan (CR + CRu: 65% and 62% following 4 courses R-CHOP and first 3 courses of R-HDT respectively). PET remained significantly more often + after the first 3 courses of R-HDT (43% vs 30% following 4xR-CHOP; p=0.03). The ORR (CR + Cru) was 78% and 71% in the R-CHOP and R-HDT arms respectively (p=0.8). With a med FU of surviving patients of 25 m, the probability of survival for the whole group of patients is 88% and 74% at 2 and 5 years. There is no significant difference according to the treatment arm in any of the aaIPI strata. The EFS with the standard CT Scan as an intermediate evaluation is 74% and 66% at 2y and 5 y with no difference according to the treatment arm in any aaIPI strata. The EFS with PET scan as an intermediate evaluation is 49% and 45% at 2y and 5 y and is statistically worse with R-HDT for aaIPI 2 and 3 pts (p=0.01). Conclusion: Based on these results, one cannot recommend first-line R-HDT as performed in that trial for adult patients with DLBCL. R-CHOP 14 is as efficient, less toxic and spares resources. Disclosures: Milpied: Roche: Membership on an entity's Board of Directors or advisory committees.

The French group, GOELAMS, performed a multicenter phase III randomized open trial to evaluate whether adding androgens to post-remission induction therapy was associated with an improved outcome in elderly pts with de novo AML. All patients received the ICL induction protocol (idarubicin 8mg/m2 day1–5, cytarabine 100mg/m2 day1–7 & lomustine 200mg/m2 day1). Patients in complete or partial remission received maintenance therapy consisting in 6 reinduction courses (idarubicin 8mg/m2 day1, cytarabine 100mg/m2 day1–5.), once every 3 months, with a continuous regimen of methotrexate and 6-mercaptopurine in-between these. At diagnosis, patients were randomized to receive (AndroG arm) or not (Control arm) norethandrolone 10 to 20 mg per day, according to body weight. Androgen was started after recovery from aplasia, between day-20 and day-30 following induction chemotherapy, and was to be continued during the 2-year maintenance therapy period if a complete or partial remission was achieved following induction chemotherapy. The two arms were well-balanced for known prognostic factors. Between June 2002 and January 2005, 330 patients with de novo AML and age 60 y (median 70, range 60–86) were included. Pts with acute promyelocytic leukemia were not included. At diagnosis, ECOG was 0–1, 2, 3–4 in 270, 55, and 5 cases; WBC count was < 4 G/L, > 30 G/L, > 100 G/L in 141, 85, and 33 pts. Of note, 61% of the pts with a WBC count < 4 G/L were males, and 52% of males had a low WBC count vs 33% of females (p Results: Crude univariate analyses regarding the effect of androgen randomization on 5-year relapse incidence, LFS, EFS and OS are listed in Table 1. Table 1 Full time period from diagnosis HR, hazard ratio; CI, confidence interval; Cox p-val, p-value of Cox regression model. Endpoints Control AndroG Gray test p-val HR; 95%CI Cox p-val Relapse 66% 54% 0.21 -- -- LFS 23% 33% -- 0.79; 0.58–1.09 0.15 EFS 16% 22% -- 0.95; 0.75–1.22 0.69 OS 19% 26% -- 0.96; 0.74–1.23 0.72 Of note, the effect of norethandrolone on relapse incidence, LFS, EFS, and OS, was violating the proportional hazards assumption (scaled Schoenfeld residuals analysis). Since the 2 hazards rate functions crossed each other, which would result in ineffective comparisons if using log-rank tests, time-dependent models were considered. For all these endpoints, as estimates for the 2 arms were not significantly different during the first year, but diverged during the following years, favoring the AndroG arm (Table 2, Figure 1), a step-function at 1 year from diagnosis was considered. Table 2 Time period starting 1 year from diagnosis Endpoints Control AndroG Gray test p-val HR; 95%CI Cox p-val Relapse 55% 33% < 0.01 -- -- LFS 37% 54% -- 0.56; 0.33–0.94 0.028 EFS 32% 52% -- 0.57; 0.36–0.89 0.013 OS 37% 60% -- 0.63; 0.41–0.96 0.034 Figure Figure Thus, for pts alive and in complete remission at 1 year from diagnosis, relapse incidence was lower, while LFS, EFS and OS were higher in the AndroG arm, even after adjusting for other significant covariates (p=0.029 Relapse; p=0.038 LFS; p=0.028 EFS; p=0.029 OS). Moreover, the beneficial effect of norethandrolone was more pronounced in males, and in pts having WBC count < 4 G/L as shown in Figure 2 for the LFS. Figure Figure Conclusion: addition of low-dose norethandrolone to maintenance chemotherapy is associated with an improved outcome in elderly pts with AML; especially in those achieving CR and remaining in remission for at least a year. Improved outcome was observed with androgen in males and/or in pts with low proliferative disease.

In an attempt to improve the outcome of acute myeloid leukemia in older patients, we performed a multicenter randomized trial evaluating the possible benefit of androgens during post remission therapy. All patients received the ICL regimen as induction (Idarubicin, 8mg/m2 d1–5; Cytarabine, 100mg/m2 d1–7 and Lomustine, 200mg/m2 d1). All patients were randomized at the time of diagnosis to receive, after achieving CR or PR, a maintenance therapy including or not androgens. Maintenance therapy consisted of 6 courses of reinduction with idarubicin (8mg/m2 d1) and cytarabine (100mg/m2d1–5, subcutaneously) every 3 months, and, between these courses, a continuous regimen of methotrexate and 6-mercaptopurine. Patients randomized with androgens additionally received 10 to 20 mg according to body weigh of norethandrolone daily from CR/PR on, for up to 2 years. Between June 2002 and January 2005, 330 patients aged ≥ 60 years (median 70 yrs, range 60–86) were included. CR, PR, failure and death rates after induction were 69 %, 6%, 9% and 15% respectively. The median follow-up for the 330 patients was 26 months. Among the 249 patients who achieved remission, 119 had been randomized with norethandrolone and 130 without. The 2 arms were balanced according to age, sex-ratio, performance status, FAB, WBC as well as platelets counts, peripheral blood and bone marrow blasts counts and cytogenetic groups (low risk: t(8;21), inv(16); high risk: del(5), del(7), del(11q), complex karyotype; standard-risk: normal karyotype and other aberrations). Differences in CR rates were only related to the latter parameter of cytogenetic features (P = 0.005). For the whole cohort of patients DFS at 3-years was 23±3% (median 13 months) and OS at 3 years was 29±3% (median 15 months). For patients who achieved CR or PR and had been randomized, the addition of androgens did not influence either DFS (P = 0.6) or OS (P = 0. 9), even when considering age groups, high/low WBC, or cytogenetic features. In conclusion, the ICL regimen followed by six reinductions and two years maintenance therapy induce high CR rates and improve OS and DFS. However the addition of androgens did not decrease the relapse rate.

not Available.

Abstract 3110 Poster Board III-47 The aim of this study was to investigate the influence of the NPM1/FLT3-ITD status on outcome in relapsed/refractory AML patients with normal karyotype who received a salvage regimen using GO as monotherapy or in combination with other agents. For this purpose, we analyzed the outcome of 57 AML patients with normal karyotype treated between 2001 and 2009. Patients received GO as monotherapy or in combination with other chemotherapeutic agents at time of relapse (n=36) or in the setting of refractory disease (n=21). There were 26 males and 31 females with a median age of 52 (range, 20-70) years at time of leukemia diagnosis. The FAB distribution included 2, 13, 15, 11, 12 and 1 AML cases from the M0, M1, M2, M4, M5 and M6 subgroups, respectively. Three cases were considered as unclassified. In addition, 5 patients had secondary AML. All patients were CD33 positive with a median CD33 expression level of 98%. As salvage treatment, 46 patients received the MIDAM regimen (GO: 9 mg/m2 at day 4 + Cytarabine 1g/m2/12 hours day 1-5 + Mitoxantrone 12 mg/m2/day day 1-3).3 In 2 patients receiving the MIDAM regimen, Mitoxantrone was omitted to avoid cardiac toxicity. Four patients received GO as monotherapy at 9 mg/m2 (n=3) or at 6 mg/m2 (n=1). The 5 remaining patients received GO 3 to 9 mg/m2 combined with other chemotherapeutic agents (Cytarabine + VP16 + GO, n=2; Cytarabine + Idarubicine + GO, n=2; Cytarabine + Amsacrine + GO, n=1). After salvage therapy, 25 patients could proceed and receive consolidation with an allogeneic stem cell transplant. In this series, all patients could be screened in the blood or bone marrow for mutations in the NPM1 and in the FLT3 gene (ITD mutations) at diagnosis. Numbers of patients according to NPM1/FLT3-ITD status were as follow: (+/−): n=14, (+/+): n=9, (−/−): n=19, (−/+): n=15. The same proportion of refractory patients was observed in the favourable NPM1+/FLT3-ITD- sub-group as compared to the other sub-groups (36%, n=5/14 vs 37%, n=16/43). With a median follow-up of 23.3 (range, 2.3-94.5) months for surviving patients, OS was 46.5% (95%CI, 33.6-59.9%) at 2 years. CR, relapse and death rates according to NPM1/FLT3-ITD status were as follow: CR: (+/−): 85%, (+/+): 66%, (−/−): 47%, (−/+): 73%, P=NS; Relapses: (+/−): 33%, (+/+): 33%, (−/−): 33%, (−/+): 54%, P=NS; Deaths: (+/−): 28%, (+/+): 78%, (−/−): 58%, (−/+): 66%, P=0.02 Also, the death rate was significantly lower in FLT3-ITD- patients as compared to FLT3-ITD+ cases (45% vs. 71%, P=0.05). OS was significantly higher in the NPM1+/FLT3-ITD- sub-group as compared to other patients (78% vs. 36% at 2 years, P=0.026). In conclusion, and although this needs to be confirmed in a prospective setting, refractory/relapsed AML patients combining a normal karyotype and a NPM1+/FLT3-ITD- molecular status are likely to remain in a “favorable prognosis” category when receiving salvage therapy. Such information is of major interest for patients counselling and for the design of salvage therapy approaches. Disclosures No relevant conflicts of interest to declare.