Journal articles on the topic 'Toulouse county'
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Casanova, Maryse, and Jean-Louis Brousse. "The Comminges County from the 10th to the 15th century." EPJ Web of Conferences 244 (2020): 01007. http://dx.doi.org/10.1051/epjconf/202024401007.
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From the 10th to the 15th centuries, the counts of Comminges developed their important domain and resisted the ambitions of their powerful neighbors. Alliances, treaties, marriages, wars, everything has been good to preserve their goods. These counts played happily with their personalities, their strengths, their weaknesses, their malice. They supported the economic and social development. The population gradually migrated from the mountains to the plain, first with the help of the Church and the creation of the “sauvetés”. Then the liberality of the counts allowed the construction of numerous “bastides” in the 13th century. The county families provided the majority of the Commingeois bishops and reinforced the importance of the Secular Church. By their permanent support to the Regular Church, they favored the establishment of large monastic and templar domains, the development of as much farming land. The progressive close up with the raimondine city of Toulouse, placed the County under his protection after the crusade by the Albigensians in 1218. The war against the English, the devastations of the Black prince in 1355 opened the last page of this story, accompanied by calamities that left in 1453 a bloodless Comminges in the hands of the King of France.
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Aubrey, Elizabeth. "The dialectic between Occitania and France in the thirteenth century." Early Music History 16 (October 1997): 1–53. http://dx.doi.org/10.1017/s0261127900001686.
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The thirteenth century was a time of turmoil in Occitania, starting with the buildup to the Albigensian Crusade during the first decade and its eruption in the second and third, which resulted in the establishment of the university in Toulouse in 1229, the founding of the Order of Friars Preachers a short time later and the unleashing of several decades of inquisition led by these Dominicans, and ultimately the dissolution of the powerful county of Toulouse. France profited both economically and politically from this plundering of the rich culture to its south: the consolidation of power by the late Capetian monarchy owed much to the absorption of Occitania into its holdings. The inhabitants of the Midi continued to demonstrate their fierce independence from their conquerors in myriad ways, some overt, some subversive. But the tempestuous events in their homeland caused some trauma among the troubadours, and although this did not necessarily result in a general deterioration in the quality of the songs that they produced, it probably is at least partly to blame for a decline in the number of both songs and composers.
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Stutz, D. Dudley. "Papal Legates against the Albigensians: The Debts of the Church of Valence (1215–1250)." Traditio 68 (2013): 259–76. http://dx.doi.org/10.1017/s0362152900001677.
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In 1232 Pope Gregory IX (r. 1227–41) imposed a tenth of episcopal revenues on prelates of Occitania to subsidize the church of Valence, which owed 10,000 poundstournoisto various bankers of Vienne, Rome, Lyons, and Siena. In 1865 B. Hauréau first noted the event when he edited one of the main documents in theGallia christianavolume concerning the ecclesiastical province of Vienne. With the publication of Gregory IX's register from 1890–1908 most of the facts of the tax were more widely available. In 1910 Ulysse Chevalier briefly mentioned the tax in his monograph on the long tenure of John of Bernin, archbishop of Vienne (r. 1218–66). In 1913, Heinrich Zimmermann cited Hauréau's text in a note in his detailed treatment of early thirteenth-century papal legations. Recently Alain Marchandisse reviewed eight of the eleven papal letters pertaining to the tax in his study of William of Savoy (d. 1239) as bishop-elect of Liège. These scholars provided no reason for the debt or why the papacy would take such measures to ensure payment. Perhaps they did not study this tax further because a church indebted to moneylenders is not in itself surprising. It appears that the church of Valence acquired the debt, very large compared to the church's income, when bishop-elect William of Savoy (r. 1225–39) waged war against Adhémar II of Poitiers-Valentinois, count of the Valentinois (r. 1189–1239). Struggles between bishops and the local nobility occurred on a regular basis throughout the Middle Ages, so what in this unimportant Rhone-valley diocese interested the pope enough to impose taxes on prelates of Occitania over twenty years to ensure payment of this debt? Adhémar II faithfully supported Raymond VI (r. 1194–1222) and Raymond VII (r. 1222–49) of Saint-Gilles, counts of Toulouse, throughout their struggle with the papacy during and following the Albigensian crusades. Adhémar II was also their vassal for the Diois, which borders the Valentinois on the southeast and comprised the northern portion of the marquisate of Provence. These lands had been reserved for the church in the Treaty of Meaux-Paris (1229), which ended the Albigensian crusades. Thus William of Savoy as bishop-elect of Valence defended the papacy's claims on the marquisate of Provence, which the papacy deemed part of the larger struggle between the Roman church and the counts of Toulouse. The facts on the nature of the debts and the steps the papacy took to aid the diocese show that the local struggle between the bishop of Valence and the count of the Valentinois embodied a part of the larger struggle between the papacy and the counts of Toulouse over the marquisate of Provence, which began as early as 1215.
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Rosenwein, Barbara H. "Chapter 9 The Art of Speaking Well at the Court of the Counts of Toulouse." Essays in Medieval Studies 30, no. 1 (2014): 141–53. http://dx.doi.org/10.1353/ems.2014.0007.
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Barrett, Catherine Jean. "Origins of the French Bastides." Journal of Urban History 44, no. 3 (January 22, 2016): 421–56. http://dx.doi.org/10.1177/0096144215620620.
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The bastides of Languedoc form a significant sector of medieval urban history, yet their descriptions are often clouded by conflicting opinions and anachronistic views. This article aims to clarify some of the confusion about the word “bastide” through an etymological study and examination of charters in which the word was first used to designate new towns. The economic and political contexts preceding the bastide foundations are equally important. The bastides did not appear in southwestern France as an ex novo phenomenon ; rather, they followed on the heels of experiments in residential development and in a monetary economy that had been ongoing for two centuries by the counts of Toulouse.
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TACHE, SYLVIANE, MOUHSSINE BENKADDOUR, and DENIS E. CORPET. "Rotavirus Inhibitor and Recovery in Raw Bovine Milk." Journal of Food Protection 58, no. 4 (April 1, 1995): 434–38. http://dx.doi.org/10.4315/0362-028x-58.4.434.
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Milk could be a vector for viruses contaminating the human gut, but detection of rotavirus in raw bovine milk is prevented by the presence of a very active antiviral substance. Rotavirus inhibition by various milk samples and the nature of the inhibitor were examined, and an improved method for rotavirus detection in raw bovine milk was designed. Most milk samples from cows near Toulouse, France, could inhibit 5 × 106 PFU/ml of rotavirus, with wide variations among individuals and with time. The rotavirus inhibitor was bound on a protein G affinity column, and corresponded to the immunoglobulin G fraction (IgG) as shown by enzymatic immunoassay. The proposed method for rotavirus detection requires the action of HCl (pH 3) and dithiothreitol (0.01 M) for 10 min before PFU counts on cell cultures. This treatment improved the detection threshold 1,000-fold, and the recovery of rotavirus in raw bovine milk 300-fold.
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Coyne, Kenneth M. "The Oaths of Alexios I Komnenos and Count Raymond IV of Toulouse in Robert the Monk’s Historia Hierosolimitana." Nottingham Medieval Studies 66 (January 2022): 67–98. http://dx.doi.org/10.1484/j.nms.5.132194.
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Almeida, Evelyn Veronica, and Guido Vinicio Duque. "The Importance of Mediation in the Development of Entrepreneurial Minds." INNOVA Research Journal 2, no. 8.1 (September 11, 2017): 86–91. http://dx.doi.org/10.33890/innova.v2.n8.1.2017.343.
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The current unemployment of young adults in developing countries such as Ecuador is partially due to the collapse of the social security system, the increase in time of workers’ contributions to the retirement system, and the economic crisis. Assisting youth in creating their own labor market opportunities through developing entrepreneurial competencies is a possible partial remedy to the unemployement situation in the country. However, the main problem in establishing these competencies in business classes, where there is a gap between the theory of entrepreneurship and the simulation, and between the simulation and the entrepreneurial reality. To fill this gap, we are proposing a pedagogical model that merges students’ entrepreneurial traits and curiosities with guidance and experience from teachers and entrepreneurs to develop business projects, taking advantage of business opportunities to facilitate employability in the local area. This model draws upon Vygotsky’s (1978) concepts of Zone of Proximal Development and Mediation, Lantolf and Poehner´s (2011) concept of Dynamic Assessment, and Béchard and Toulouse´s (1991) Pedagogical Model in Entrepreneurship.
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Magnaval, Jean-François, Judith Fillaux, Sophie Cassaing, Alexis Valentin, Xavier Iriart, and Antoine Berry. "Human toxocariasis and atopy." Parasite 27 (2020): 32. http://dx.doi.org/10.1051/parasite/2020029.
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To assess the possible influence of atopy on the clinical picture of human toxocariasis, a retrospective study was carried out using file records for patients who attended the Outpatient Clinic of Parasitology in Toulouse University Hospitals. A total of 106 file records for patients who had been diagnosed with common/covert toxocariasis were extracted from the database. Forty-nine patients (20 females and 29 males) were considered atopic since they exhibited a long (≥ 1 year) history of various allergic issues along with a titer ≥ 0.7 kIU/L for specific IgE against at least two out of nine mixes of common inhalant allergens. Fifty-seven patients (42 females and 15 males) were designated nonatopic on the basis of a negative result (<0.35 kIU/L) of the test for specific IgE. Demographic (age and sex), clinical (20 signs or symptoms) and laboratory (blood eosinophil count, eosinophil cationic protein, serum total IgE, and specific anti-Toxocara IgE) variables were investigated by bivariate analysis followed by multivariate regression analysis using “atopy” as the outcome variable. On the basis of our results, the clinical or laboratory picture of toxocaral disease was not affected by the presence of an atopic status.
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Abravanel, Florence, Olivier Marion, Arnaud Del Bello, Thomas Beunon, Raphaelle Romieu-Mourez, Chloé Couat, Mélanie Pucelle, et al. "Humoral and Cellular Immune Responses of Solid Organ Transplant Patients on Belatacept to Three Doses of mRNA-Based Anti-SARS-CoV-2 Vaccine." Vaccines 10, no. 3 (February 24, 2022): 354. http://dx.doi.org/10.3390/vaccines10030354.
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Background: Two doses of anti-SARS-CoV-2 mRNA-based vaccines are poorly immunogenic in solid organ transplant recipients (SOT). Methods: In total, 68 belatacept-treated SOT recipients followed at the Toulouse University Hospital were investigated. They were given three injections of the BNT162b2 mRNA COVID-19 vaccine. Their humoral response was assessed by determining anti-spike antibodies and neutralizing antibodies. The T-cell responses were assessed using an enzyme-linked immunospot assay that measured the interferon-γ produced by specific SARS-CoV-2 T-cells in a subgroup of 17 patients. Results: Only 23.5% of these patients developed a detectable anti-spike response. Moreover, the cellular and the humoral responses were well correlated. Patients with no humoral response were also without a detectable cellular response. Those belatacept-treated patients who developed an Anti-SARS-CoV-2 humoral response were younger, had been transplanted for longer, and had a higher lymphocyte count and a better glomerular filtration rate than those with no response. Finally, patients on tacrolimus plus belatacept produced a lower immune response. Conclusions: Belatacept-treated SOT recipients have a reduced immune response to anti-SARS-CoV-2 mRNA vaccination. The vaccine should be given quite separately from the belatacept infusion to improve immunogenicity. Studies to assess whether switching to another immunosuppressive regimen can improve the post-vaccination immune response would be useful.
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Cuillandre, J. C., Y. Melliers, R. Murowinski, D. Crampton, G. Luppino, and R. Arsenault. "MOCAM: A 4k × 4k CCD Mosaic for the Canada-France-Hawaii Telescope Prime Focus." Symposium - International Astronomical Union 167 (1995): 213–20. http://dx.doi.org/10.1017/s0074180900056461.
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MOCAM is a wide field CCD camera, currently nearing completion, which will be offered to the Canada-France-Hawaii Telescope (CFHT) user community in 1995. The project is a collaboration between the CFHT, the Dominion Astronomical Observatory (DAO, Canada), the Institut des Sciences de l'Univers (INSU, France), Laboratoire d'Astrophysique de Toulouse (LAT, France) and the University of Hawaii (UH). In the interests of producing a reliable and effective camera in the shortest time, it was decided to use existing technologies rather than innovative ones. Two-edge buttable 2048 × 2048 15 μm pixel CCDs were obtained from the LORAL aerospace foundry, based on a mask designed by J. Geary at Smithsonian Astrophysical Observatory (SAO). They are mounted in a dewar designed by G. Luppino (UH); the focal plane mounting keeps the mosaic flat to within two pixels and the CCDs are aligned to within two pixels. A mechanical interface designed and fabricated by the DAO holds a 150 mm shutter and a filter wheel which has a positioning repeatability better than five μm.The four CCDs are operated in parallel by a San Diego GenIII controller adapted by LAT. The mosaic is read out in seven minutes and a single 33 Mb FITS file is generated to enable convenient on-line preprocessing. The user will control the system through a single CFHT Pegasus environment session. The camera field is 14′ × 14′ with a 0.″2 pixel sampling and the readout noise is less than seven electrons. The scientific goals of the initiators of the project are studies of distant clusters, deep galaxy counts and quasars surveys.
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Bétaille, David, François Peyret, and Maxime Voyer. "Applying Standard Digital Map Data in Map-aided, Lane-level GNSS Location." Journal of Navigation 68, no. 5 (March 31, 2015): 827–47. http://dx.doi.org/10.1017/s0373463315000132.
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Urban positioning using the Global Positioning System (GPS) is challenging because of multipath. Urban canyons limit open sky visibility, and cause signal reflection and diffraction, resulting in significant satellite range measurement errors. The investigations reported here have been carried out in a French project calledInturb(an acronym derived from integrity and urban positioning). So far, the project has had two phases: first, a simple Three-Dimensional (3D) geometrical city modelling, called “Urban Trench”, has been developed and engineered manually from data sets collected in different cities. Positioning improvement in terms of accuracy was quantified where the model could be applied. Second, this modelling has been automated, based on the standard national BD Topo ® map database for France, with promising results. This geometrical modelling makes it possible to distinguish between line-of-sight satellite signals and those from non-line-of-sight. The latter, apparentlybona fide, signals are caused by strong reflections, usually from buildings with a lot of steel and glass in their construction. A correction of the pseudo-range measurements of the latter is also computed and applied in the position estimator. Positioning accuracy is improved, whilst availability is kept at its maximum. In the study both manual and automatic 3D models are used in extensive experimental campaigns. Results are: first, the possibility to cover entirely any urban area in the country; second, the reduction of the median error in 3D by more than 50% on data collected in Nantes, Paris and Toulouse for a total duration of nearly ten hours; third, the compliance with standards used in most embedded maps and geographical information systems, including an assessment of the trade-off between the model simplicity and the positioning improvement.
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Comont, Thibault, Guillaume Moulis, Karen Delavigne, Pierre Cougoul, Olivier Parant, Beatrice Guyard Boileau, Christian Récher, Daniel Adoue, and Odile Beyne Rauzy. "Effect of Pregnancy in Women with a History of Primary Immune Thrombocytopenia Considered As Cured." Blood 128, no. 22 (December 2, 2016): 2552. http://dx.doi.org/10.1182/blood.v128.22.2552.2552.
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Abstract Immune thrombocytopenia (ITP) is an autoimmune disease that occurs in young women. Pregnancy is a well-known risk factor for developing newly diagnosed ITP as well as for inducing disease flares in patients with current ITP. However, the impact of pregnancy in women with an old history of ITP, considered as cured, has not been assessed. The aim of this study was to describe the course of ITP in pregnant women with an ITP in complete remission (platelets count >100x109/L and absence of bleeding symptoms) for at least 5 years without any ITP treatment. We retrospectively selected all pregnant women with delivery at Toulouse University Hospital, South of France, between 2010 and 2015 with a hospital discharge code of ITP (international classification of diseases; version 10 code D69.3). This code has a sensitivity of 81.2% and a positive predictive value of 89.8% in this database. All medical charts were reviewed to confirm the diagnosis of ITP. We included adult women (≥18 years) with a diagnosis of primary ITP according to French guidelines (platelet count <150 x 109 /L and exclusion of other causes of thrombocytopenia, especially other causes of thrombocytopenia during pregnancy) in complete remission for at least 5 years. We identified 50 pregnancies in 39 ITP patients during the study period. Eleven pregnancies occurred in 10 patients in long-term complete remission of ITP at the time of pregnancy onset. Baseline characteristics were: median age at ITP diagnosis: 21 years (range: 4-29); median age at pregnancy onset:32 years (range: 26-34; history of ITP during a previous pregnancy: 1; history of bleeding: 4 (36.4%); previous treatment for ITP: 8 (72.7%), corticosteroids-CS (5), CS and intravenously immunoglobulin-IVIg (3), splenectomy (4), dapsone (1); last median platelet count before pregnancy: 170x109/L (range: 118-363). Platelets count decreased below 100x109/L in 3 pregnancies (27.2%) from the first trimester for one patient, from the second trimester for one other and from the third trimester for the last one, with a nadir of 3, 39 and 87 (x109/L) respectively. One of them experienced a severe bleeding (grade 3 according to the International Working Group bleeding classification). All thrombocytopenic patients required treatment during pregnancy: CS+IVIg for 2 (one for bleeding and one to allow epidural analgesia) and IVIg for the other (to allow epidural analgesia). For these 3 women, the median platelet count at delivery was 128 (range: 38-159) and consequently only 2 of them could have epidural analgesia. No bleeding during delivery was observed. Transient thrombocytopenia occurred in 2 newborns. Primary ITP considered as cured may relapse during pregnancy and may induce severe bleeding requiring specific treatment. A tight monitoring should be proposed to all pregnant women with a history of primary ITP, even after several years of complete remission. Disclosures Récher: Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Walthall, John A. "Le Bison: Gibier et moyen de subsistance des hommes du Paléothihique aux Paléoindiens des Grandes Plaines (Actes du Colloque International, Toulouse, 6-10 juin, 1995). Jean-Philip Brugal, Francine David, James G. Enloe and Jacques Joubert, editors. 1999. Éditions APDCA, Antibes. 519 pp. $35.00 (paper), ISBN 2-904110-29-1 - Bison Hunters of the Western Prairies: Archaeological Investigations at the Dixon Site (13WD8), Woodbury County, Iowa. Richard L. Fishel, editor. 1999. Office of the State Archaeologist, The University of Iowa, Iowa City, xiv + 216 pp. $19.95 (paper), ISBN 0-87414-118-4." American Antiquity 67, no. 3 (July 2002): 590–92. http://dx.doi.org/10.2307/1593846.
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Etienne, Anne, Cecile Borel, Sarah Reutenauer, Sylviane Olschwang, Marie-Joelle Mozziconacci, Eric Delabesse, Cecile Demur, et al. "Prognostic Impact of Mutations in the Nucleophosmin (NPM1) and of the FMS-Related Tyrosine Kinase 3 (FLT3) Genes in Elderly Patients with Acute Myeloid Leukemia (AML) Treated with Intensive Chemotherapy." Blood 112, no. 11 (November 16, 2008): 2542. http://dx.doi.org/10.1182/blood.v112.11.2542.2542.
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Abstract AML is a heterogeneous disease and the actual most reliable prognostic factor is the karyotype. Mutations of NPM1 and FLT3 constitute the most frequent molecular genetic alterations in patients with AML. Their prognostic impact is now well recognized, especially in young patients with intermediate prognosis karyotype. However few studies have focused on elderly patients. We retrospectively studied the prevalence of NPM1 mutation and FLT3 internal tandem duplications (ITD) and its association with complete remission (CR) and survival in 86 patients aged 61 years or older treated between 1996 and 2007 for acute non promyelocytic leukemia with intermediate karyotype in the Institut Paoli-Calmettes, Marseille, and the university hospital of Toulouse. All patients received intensive induction chemotherapy (“3+7” regimen). Median age was 70 years (range, 61–79). The median follow-up of surviving patients was 34 months. 44 patients (51%) had NPM1 mutation and 21 had FLT3-ITD (24%). In the NPM1 mutated group, there were significantly more: female patients, absence of antecedent hematologic disorder, de novo AML, and low CD34 expression. In the FLT3-ITD group, there were significantly more: female patients, increased white blood cell counts and peripheral blood blasts. Overall CR rate was 67%; median disease free survival (DFS) and overall survival (OS) were 11 and 10 months, respectively. CR rate was negatively associated with a poor performans status and a high score previously described including assessment of comorbidities (Etienne et al., Cancer2007; 109(7):1376–83). CR rate was 57% versus 72% for patients with FLT3-ITD compared to patients with wild-type FLT3 (p 0.2), and 64% versus 71% for the NPM1 mutated group compared with the NPM1 non-mutated group (p 0.5). Median OS was 6 months versus 12 months for patients with FLT3-ITD mutation versus wild type patients (p = 0.04). Median OS was 9 months for patients with NPM1 mutation and did not differ from non-mutated patients. No significant difference in term of CR rate and OS was found between the 29 patients carrying NPM1 mutation without FLT3-ITD and the 57 other patients without NPM1 mutation or with FLT3-ITD. Median DFS was 21 months versus 9 months for these two groups, respectively (p 0.2). These results confirm the prognostic impact of FLT3-ITD in our series of old patients with AML. Unlike young patients, NPM1 mutated elderly patients have a similar outcome than NPM1 wild type patients. The absence of prognostic impact of NPM1 mutation without FLT3-ITD has to be validated on larger prospective cohort. FLT3 status should be taken into account for treatment choices in elderly patients.
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Maquet, Julien, Hélène Derumeaux, Maryse Lapeyre-Mestre, Laurent Sailler, and Guillaume Moulis. "Validation of Hemolytic Anemia Codes in the French Hospital Database." Blood 134, Supplement_1 (November 13, 2019): 3460. http://dx.doi.org/10.1182/blood-2019-124697.
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Introduction: Hemolytic anemia is a group of rare diseases. National databases are useful data sources to assess the epidemiology and the management of such diseases. The French national health database covers the entire French population (66 million inhabitants). It links sociodemographic data, out-hospital data including dispensing data and hospital data. As a consequence, this database is very useful for population-based studies on rare diseases. For instance, it has been used for epidemiological and pharmacoepidemiological studies on immune thrombocytopenia. Diseases are identified using the national hospital database (named PMSI) that contains discharge diagnoses for all hospital stays in all private and public hospitals in France. This study was aimed at assessing the positive predictive value (PPV) of hemolytic anemia diagnoses in the French hospital database. Methods: In the PMSI database, every hospital stay contains one primary diagnosis, and possibly one related and several associated diagnoses. They are coded using the International Classification of Diseases, 10th revision (ICD-10) by the physician in charge of the patient or trained nurses from the medical chart. We selected all hospital stays at Toulouse University Hospital, South of France (2860 beds) with a diagnosis of hemolytic anemia (D55.0-D59.9 ICD-10 codes) between January 2017 and December 2017. Medical charts and biological data were reviewed. Hemolytic anemia was defined by anemia with high reticulocyte count (>150 x 109/L), plus at least two of the three following signs of hemolysis: low serum haptoglobin level, hyperbilirubinemia and elevated serum lactate dehydrogenase level. PPVs and their 95% confidence intervals (CI) were calculated by categories of hemolytic anemia: autoimmune hemolytic anemia (AIHA; D59.1 ICD-10 code), enzyme deficiency (D55.0-D55.9 ICD-10 codes), hereditary spherocytosis (D58.0 ICD-10 code) and hemoglobinopathy (D56.0-D57.9 and D58.2 ICD-10 codes). AIHA was defined by positive direct antiglobulin test (DAT); enzyme deficiency was defined by low enzyme dosage and negative DAT; hereditary spherocytosis was defined by negative DAT and either positive flow cytometry osmotic fragility test either positive eosin-5'-maleimide binding test; hemoglobinopathy was defined by compatible blood count and positive hemoglobin electrophoresis. Results: During the study period, 54 patients had at least one hospital stay with a discharge diagnosis of AIHA, 12 with enzyme deficiency, 10 with hereditary spherocytosis, 92 with thalassemia and 285 with sickle cell disease. We further excluded 13 patients due to missing data, precluding disease classification. AIHA was confirmed in 49/53 patients; the PPV was 92.5% (95% CI: 85.3%-99.6%). Enzyme deficiency was confirmed in 8/12 patients (including G6PD deficiency: 7/9) and hereditary spherocytosis in 10/10 patients. Thalassemia was confirmed in 72/83 patients; the PPV was 86.7% (95% CI: 79.5%-94.0%); however, the code of thalassemia type was not adequately coded in most cases (PPV<30%). Sickle cell disease was confirmed in 279/284 patients; the PPV was 98.2% (95% CI: 96.7%-99.8%). Conclusions: Overall, this study confirms high PPV values for hemolytic anemia discharge diagnoses recorded in the French hospital database, allowing epidemiological studies using this source of data. Disclosures Moulis: CSL Behring: Research Funding; Amgen pharma: Research Funding, Speakers Bureau; Novartis pharma: Research Funding, Speakers Bureau.
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Comont, Thibault, Suzanne Tavitian, Laurent Bardiaux, Marylise Fort, Benedicte Debiol, Daniele Morere, Françoise Huguet, Christian Récher, and Sarah Bertoli. "Platelet Transfusion Refractoriness Following Induction Chemotherapy in Acute Myeloid Leukemia." Blood 128, no. 22 (December 2, 2016): 3987. http://dx.doi.org/10.1182/blood.v128.22.3987.3987.
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Abstract Platelet transfusion refractoriness (PTR) is defined by the repeated failure to appropriately increment platelet count after platelet transfusion. PTR represents a real concern in the management of patients (pts) who require iterative platelet transfusions, in particular those undergoing intensive treatment (Stanworth, Br J Haematol 2015). PTR can be secondary to non-immune and immune causes and is associated with adverse events including longer hospital stays, severe hemorrhages and increased risk of early deaths. After induction chemotherapy for acute myeloid leukemia (AML), intensive transfusion support is required during the 4-6 weeks of treatment-induced aplasia. There is few data regarding management and outcome of AML pts with PTR in this setting. This study included all consecutive pts treated by intensive chemotherapy for non-promyelocytic AML in Toulouse University Hospital between January 2001 and December 2014 who developed PTR during the induction phase. Platelet count is measured daily and transfusion of ABO-identical platelets is performed when <10.109/L according to standard guidelines. We pragmatically used a clinical definition of PTR, ie. persistent thrombocytopenia <10.109/L despite at least two successive daily platelet transfusions. Control patients were those treated by intensive chemotherapy without PTR. Intensive chemotherapy consisted in daunorubicin (60-90 mg/m² d1-3) or idarubicin (8 mg/m² d1-5) with cytarabine (100-200 mg/m² d1-7); lomustin being added in pts > 60y. We identified 41 cases of PTR among 897 pts in our database (4.8%; 2.9 patients/y). PTR patients were mostly women (78.1% vs 42.4% in non-PTR pts, p<0.0001), with a median age at diagnosis of 57y vs. 59y in non-PTR (table). PTR pts had more often splenomegaly which is a classical factor associated with PTR (22% vs 8.5%, p<0.009). PTR-AML were de novo in 73.2% of cases (only 10 pts had received platelet transfusions prior to initiation of the induction therapy [24.4%]), with cytogenetics and molecular abnormalities not significantly different to non-PTR AML (favorable/intermediate/adverse karyotype: 14.6/61/22% vs 9.1/68/20.4%,; NPM1 mutations: 33.3% vs 33%; FLT3-ITD mutations: 9.7% vs 22.8%). Anti-HLA antibodies were identified in 34/40 PTR pts (82.9%). The median time from chemotherapy initiation to PTR diagnosis was 10.5 days (IQR, 6-16.5). The median duration of thrombocytopenia (from PTR diagnosis to the first platelets count > 50.109/L) was 19 days (IQR 15 - 25.5). Management of PTR-pts was as follows: a twice-daily prophylactic transfusion strategy in 30 pts (73.2%) regardless of bleeding events, one or more HLA-matched platelet transfusion in 15 pts (83.3% of 18 patients with matched donors), corticosteroids (n=15, 36.6%), intravenous immunoglobulins (n=14, 34.2%), TPO agonists (n=10, 24.4%) or rituximab (n=1). Median time between PTR diagnosis and first HLA-matched platelet transfusion was 12.5 days (IQR, 6.5-15). There were 7 early deaths in the PTR group (17.1%) compared to 80 (9.3%) in the non-PTR group (p=0.1). Grade 3-4 bleeding events during induction, early death rate (before end of aplasia) by grade 3-4 bleeding and death rate by bleeding regardless of the phase of treatment (induction+consolidation) were significantly higher in the PTR group (respectively 22% vs 4.1%, p<0.0001, 12.2% vs 1.4%, p<0.0006 and 24.4% vs 5.3%, p<0.0001). However, there was no significant difference in 5-year overall survival between both groups (25.9% vs 33.7%, p= 0.35). HLA-matched transfusions have induced an increment in platelet count >10.109/L in 37% of cases.TPO agonists did neither shorten PTR duration (11.5 days with TPO agonists [IQR, 5.5-15] vs. 10.5 days [IQR, 6-16.5]), nor reduce severe bleeding or early death rate (40% and 20% with TPO agonists vs. 21.9% and 17.1% without). PTR during induction therapy for AML pts significantly increases the risk of early and late deaths by severe bleeding. While TPO agonists did not appear as a relevant strategy for PTR pts, the efficacy of both massive prophylactic and HLA-matched transfusion could have reduced the risk of severe bleeding but remains to be clearly established. Since steroids, immunoglobulins or even rituximab did not prove efficacy in this setting, a better understanding of platelet destruction is needed to design mechanism-based therapeutic strategies for this very high risk condition. Table Table. Disclosures Tavitian: Novartis: Membership on an entity's Board of Directors or advisory committees. Huguet:Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Récher:Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Felten, R., T. Fabacher, N. Sedmak, F. Berenbaum, B. Combe, J. Sibilia, C. Sordet, et al. "POS0533 REPURPOSING FIB-4 SCORE IN RHEUMATOID ARTHRITIS: DATA FROM THE ESPOIR COHORT." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 528.1–528. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2016.
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BackgroundThe Fibrosis-4 (FIB4) score, including age, transaminases and platelets, can detect severe fibrosis (F3-F4) in patients with Non Alcoolic Steato Hepatitis (NASH) and could be of interest in the follow-up of patients with RA. Indeed, platelets contribute to the pathophysiology of RA, transaminases are used in the liver monitoring of our treatments. In addition, retrospective data suggested the association between FIB4 and mortality in RA (1).ObjectivesWe aimed to evaluate the value of the FIB4 score as a prognostic factor in RA in the prospective ESPOIR cohort.MethodsPatients of the ESPOIR cohort diagnosed with RA according to ACR-EULAR criteria were included in our analysis. The formula for the FIB-4 score is as follows: [Age (years) × ASAT (U/L)] / [Platelet count (10^9/L) × ALT (U/L)1/2]. The analyses were based on linear mixed-effects models with a random effect on the subject to account for repeated measures throughout time.Results633 of the 813 patients included met the ACR/EULAR criteria for RA and had a calculable FIB4 score. Median FIB4 was 0.75 IQR (0.53-0.99) and 61 patients (9.6%) had a high FIB4 score at baseline. Baseline FIB4 was significantly higher in patients with a chronic alcohol consumption (p=0.021) or viral hepatitis (p<0.001). In multivariate analysis, including the main baseline prognostic factors for progression of RA (swollen Joint Count, CRP, Presence of ACPA, Rheumatoid Factor and modified Sharp score), FIB4 was not independently associated with progression of DAS28 during 10 years of follow-up, unlike baseline CRP and SJC. Baseline FIB4 was not associated with the modified Sharp score at 10-year follow-up unlike age and the presence of ACPA (Table 1). FIB4 was not associated with mortality (p=0.77) or major adverse cardiovascular events (p=0.22) during the 10-year follow-up. No significant change in FIB4 score over time was related to the use of NSAIDs, methotrexate, tocilizumab or other DMARDs.Table 1.Associations of FIB4 score with DAS28 and modified Sharp score evolutions in multivariate analysesVariableVariables included in modelp-valueDAS28Time<0.0001Age0.97Baseline number of swollen joints<0.0001Baseline Rheumatoid Factor0.51evolution over timeBaseline ACPA (presence)0.97Baseline CRP<0.0001Baseline modified Sharp score > 00.15Baseline FIB40.26Modified Sharp scoreTime0.052Age0.0005Baseline number of swollen joints0.38Baseline Rheumatoid Factor0.61evolution over timeBaseline ACPA (presence)0.012Baseline CRP0.84Baseline FIB40.25ConclusionOur study was the first to evaluate the value of FIB4 in a prospective cohort of RA patients. The present prospective cohort study with a 10-year follow-up did not find a prognostic role of FIB4 in RA, in contrast to previous retrospective studies. Reassuringly, FIB4 score was not increased by DMARD treatment after 10 years of follow-up, confirming the absence of long-term DMARD-related hepatotoxicity.References[1]Seung Up Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Yong-Beom Park, Kwang-Hyub Han & Sang-Won Lee (2018): Fibrosis-4 index at diagnosis can predict all-cause mortality in patients with rheumatoid arthritis: A retrospective monocentric study, Modern Rheumatology, DOI: 10.1080/14397595.2018.1558760Figure 1.Impact of baseline FIB4 score on DAS28, HAQ and total modified-Sharp score over time.AcknowledgementsAn unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. The French Society of Rheumatology, Pfizer, Abbvie, Lilly, Sanofi also supported the ESPOIR cohort study.We also wish to thank Nathalie Rincheval (CHU Montpellier and EA 2415) who did expert monitoring and data management and all the investigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine, MC. Boissier, Paris-Bobigny, A. Cantagrel, Toulouse, B. Combe, Montpellier, M. Dougados, Paris-Cochin, P. Fardellone et P. Boumier Amiens, B. Fautrel, Paris-La Pitié, RM. Flipo, Lille, Ph. Goupille, Tours, F. Liote, Paris- Lariboisière, O. Vittecoq, Rouen, X. Mariette, Paris Bicetre, P. Dieude, Paris Bichat, A. Saraux, Brest, T. Schaeverbeke, Bordeaux, J. Sibilia, Strasbourg) V. Devauchelle and C Lukas for expert X-ray reading.Disclosure of InterestsNone declared.
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Bories, Pierre, Sarah Bertoli, Françoise Huguet, Sophie Dobbelstein, Luc Fornecker, Odile Beyne Rauzy, Véronique Demas, Ana Berceanu, Eric Delabesse, and Christian Recher. "Efficacy of Frontline 5-Azacytidine in Older AML Patient Unfit for Chemotherapy." Blood 118, no. 21 (November 18, 2011): 2614. http://dx.doi.org/10.1182/blood.v118.21.2614.2614.
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Abstract Abstract 2614 Background: The efficacy of conventional treatment in older patients with acute myeloid leukemia remains unsatisfactory, with low remission rates and poor overall survival. Disappointing results of intensive chemotherapy in patient over 60y are explained by decreased bone marrow reserve and high chemoresistance rate. Novel treatment approaches for this age group are needed. Among these options, 5-azacytidine (AZA) have shown promising results, improving survival in high-risk myelodysplastic syndrome including patient with 20–29% marrow blast now considered WHO AML. Methods: AML patients (marrow blast≥20%) considered not candidates for ICT and treated frontline with only AZA in Toulouse University Hospital were retrospectively analyzed in this study. AZA 75 mg/m2/day was administered subcutaneously for 7 days every 4 weeks, which was defined as 1 cycle. Results: Ninety eight patients were registered between June 2007 and Dec 2010. In this period of time, a total of 470 AML patients older than 60 years were referred in our center. 234 received ICT, 98 AZA, and 138 LD-ARAC or BSC. Sex ratio M/F was 56/42 and median age was 76 (range 50–89). Eighty eight patients were >65y and 51 were >75y. Forty eight patients (48.9%) had de novo AML, 27 patients (27.5%) had prior history of WHO MDS, 5 patients (5.1%) had prior history of myeloproliferative disorder and 18 patients (18.3%) had therapy related AML. Median white blood cell (WBC) count was 2.2G/L (range 0.76–62) and median bone marrow (BM) blast was 35% (range 20–85). Karyotype (Medical Research Council classification) was intermediate in 48 patients (48.9%) including 36 normal and 6 trisomy 8, adverse in 44 patients (44.8%) including 24 -5/del5q, 28 -7/del7q, 35 complex karyotype and 21 monosomal karyotype, and failed in 6 patients (6.1%). Median follow up in survivors was 12.6 months. Patients received a median of 6 cycles of AZA (range 1–27). All patients received at least 1 cycle of AZA and were considered evaluable for response. Fifty patients (51%) presented a response to AZA. Overall response rate according to AML IWP criteria was documented in 24 patients (24.5%), including 13 CR, 5CRi (18CR/CRi 18.4%), and 6PR (6.1%). The median duration of remission for patients achieving CR or CRi was 9.5months. Among the 74 patients considered as failure according to AML-IWP criteria, 26 additional patients (26.5%) obtained hematological improvement HI (7 pts on 1 lineage, 13 pts on 2 lineages and 6 pts on the 3 lineages). Overall, 60 patients required hospitalization during treatment for neutropenic fever. The death rate during the first two months after AZA initiation was 18.3%, due to AML progression in 83% and to infection in 17% of cases. The unique prognosis factor that impacts the response rate in univariate and multivariate analysis was the cytogenetic risk group. We identified 18 CR/CRi/PR (37.5%) in the intermediate group and 6 CR/CRi/PR (13.6%) in the adverse group (p=0.02). Age, WBC count, BM blast, or secondary status of the AML were not statistically related to the response rate. However, it should be noted that only 14 patients had WBC>10G/L at diagnosis. In the entire cohort 1y OS was 50% and 2yOS was 28%. In univariate and multivariate analysis, intermediate karyotype was statistically linked to longer survival. Achievement of CR/CRi or PR translated in increased survival, and importantly in patient with no AML-IWP response, achievement of HI, even on 1 lineage only, translated in increased survival. Moreover when comparing patient treated with 1 or 2 courses, with patient receiving 3 or more courses, we noted a significant improve in survival while number of courses increased. Conclusion: AZA appears to be a valuable option for WHO AML patients considered unfit for chemotherapy and with a low WBC count. In this cohort of very old patients, response rates and more importantly survival rates with AZA are promising. Although, pretreatment prognosis factor such as high risk cytogenetic remains adverse factor, predictive factors of response are needed to guide therapeutic decision. Disclosures: Off Label Use: Azacytidine is approved by FDA and EMEA in the treatment of high risk MDS and AML up to 30% of bone marrow blast. In our study, Azacytidine use was supported by the published results of the French compasionate Azacytidine program in WHO AML patients with more than 30% blast. Recher:Celgene: Membership on an entity's Board of Directors or advisory committees.
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Claracq, Camille, Murielle Roussel, Benjamin Hébraud, Michel Attal, Herve Avet Loiseau, and Jill Corre. "Impact on Survival Outcomes of Bone Marrow Plasma Cells Percentage and Morphology Evaluation By Conventional Microscopy in Multiple Myeloma after High Dose Therapy." Blood 124, no. 21 (December 6, 2014): 3396. http://dx.doi.org/10.1182/blood.v124.21.3396.3396.
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Abstract Impact on Survival Outcomes of Bone Marrow Plasma Cells Percentage and Morphology Evaluation by Conventional Microscopy in Multiple Myeloma after High Dose Therapy. Background: The achievement of at least CR is a crucial step for a long-lasting response and prolonged survival after autologous stem cell transplantation (ASCT) in patients (pts) with multiple myeloma (MM). The current definition of complete remission (CR) or better in MM requires a negative serum and urine immunofixation (IF) and <5% bone marrow plasma cells (BMPCs). Additional prognostic tools are related to sFLC ratio, immunophenotypic and molecular evaluations, when possible. As BMPCs levels could differ if evaluated by BM biopsy or aspirate (the latter supposed to underestimate BMPCs count), we aim to determine a new threshold for PCs in BM aspirate and to determine whether it could be, in association with PCs morphology by standard microscopic evaluation, an easy and cheap surrogate marker for outcome, in the absence of sFLC assay and/or phenotypical-molecular analysis for MRD. Material and Methods: 191 de novo MM pts treated between 2003-2010 in Toulouse's myeloma and BMT center with adequate clinical and biological data were retrospectively studied. Responses were evaluated at day 100 after ASCT in all pts according to IMWG criteria. BM examination comprised PCs count, BM cellularity, and the presence of PCs dysmorphy. Progression free survival (PFS) was calculated from the start of therapy until progression, death or last follow-up. Overall survival (OS) was calculated from the start of therapy until death or last follow-up. The Kaplan-Meier method was used to estimate the survival distribution. Results: Baseline demographics and initial disease characteristics are summarized in table 1. Median follow-up is 6 years. At the completion of ASCT, 49 pts (26%) achieved CR, 89 (47%) VGPR and 41 (21%) PR; 57 pts (30%) had a negative serum IF (sIF). Overall, 151 pts relapsed and 68 died with median PFS and OS of 36 and 99 months, respectively. At D100, median PCs count was 1% (range 0-23%): 1% (0-3%) in CR pts, 1% (0-23%) in VGPR pts, and 1.5% (0-7%) in PR pts. Only 1 pt with negative sIF had 5% BMPCs and a positive urine IF, and was assessed as VGPR. Overall, 55 negative sIF pts had 2% or less BMPCs. The number of 2% of BMPCs was found to be predictive, irrespective of response. Median PFS was 39 vs 21 months if BMPCs is > 2% (p<.001) and median OS was 99 months vs 66 (ns). We further aimed to evaluate the impact of PCs dystrophy on survival outcomes in 176 evaluable pts. PCs dysmorphy was reported in 29 pts including 3 pts in CR, 9 VGPR and 13 PR, respectively. All except 2 pts relapsed, with a median PFS of 26 mo (vs 39, p=.002). Nineteen died with a median OS of 60 mo (vs 101, p=.003). For pts at least in VGPR, median PFS was 26 mo in case of PCs dysmorphy vs 40 mo (p=.004) and median OS was 59 mo vs not reached (p=.005). (see figures) Conclusion: conventional microscopy of BM aspirate is a useful and rapid tool to evaluate the percentage of PCs and their morphology as a first step to assess the residual tumor mass in patients with MM after ASCT, and it constitutes a good predictor for disease progression and survival outcome. These findings have to be confirmed and the exact threshold of PCs remains to be determinate in a large prospective study. Table Characteristics n=191 Sex: M/F, n 109/82 Median age, y (range) 57 (31–68) Isotype, n (%) IgG, IgA, LC 123 (64), 35 (18), 28 (15) ISS stage, n (%) n= 158 I, II, III 85 (54), 40 (25), 33 (21) Median bone marrow plasma cells, % (range) 23 (1-96) Median b2-microglobulin, mg/L (range) 3.1 (1.3–19.4) Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
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Bertoli, Sarah, Suzanne Tavitian, Emilie Berard, Noemie Gadaud, Audrey Sarry, Francoise Huguet, Eric Delabesse, and Christian Recher. "More Than 10% of NPM1-Mutated AML Relapses Occur after 5 Years from Complete Remission." Blood 132, Supplement 1 (November 29, 2018): 2802. http://dx.doi.org/10.1182/blood-2018-99-113109.
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Abstract The majority of relapses in acute myeloid leukemia (AML) patients occur in the first or second year following complete remission. In routine, AML patients are followed during five years because few relapses can occur after three or five years. These late or very late relapses remain poorly described, particularly at the molecular level, with only few consistent series in the literature. (Medeiros B et al., Leuk Lymphoma 2007; Verma D et al., Leuk Lymphoma 2010; Watts J et al., Leuk Res 2014). We retrospectively studied all AML relapses occurring after complete remission (CR) obtained with one or two induction cycles between 2000 and 2012 in Toulouse University Hospital, France. Our analyses focused on late relapses (LR, >3 years from CR) and very late relapses (VLR, >5 years from CR) in comparison to early relapses (ER, ≤3 years from CR). Between 2000 and 2012, out of 636 CR patients, 346 had morphological relapses (54.4%). The median time to relapse was 0.9 years (range, 0.1-11.9 years; interquartile range [IQR], 0.5-1.5 years). There were 198 relapses during the first year (57.2%), 82 during the second year (23.7%), 24 during the third year (6.9%) whereas 42 relapses occurred after 3 years (12.1%) and 16 after 5 years (4.6%). Characteristics at diagnosis, i.e., age, AML status, WBC count, karyotype, FLT3-ITD mutation, CEBPA mutation and induction regimen did not differ between ER and LR or VLR. However, NPM1 mutations were more frequent in LR (NPM1m at diagnosis in relapses >3 years: 46% vs. 28% in relapses <3 years, P=.0532), and in VLR (NPM1m at diagnosis in relapses >5 years: 67% vs. 27% % in relapses <5 years, P=.0070). Allogeneic stem cell transplantation (alloSCT) was more frequently performed in the LR group (24% vs. 14%, P=.0369) and in VLR group (31% vs. 14%, P=.0748). Second CR (CR2) rate and median overall survival from relapse date (OS2) were better in LR and VLR than in ER (CR2ER: 26%, CR2LR: 43%, CR2VLR: 50%; P=.0154; OS2ER: 4.6 months, OS2LR: 10.8 months, OS2VLR: 11.6 months; P=.0024). Among the 142 CR1 patients with NPM1m, 67 relapsed (47.2%). In patients with NPM1m, relapses occurred during the first year in 39 (58.2% of NPM1m relapses), during the second year in 14 (20.9%) and during the third year in 2 (3%) whereas 12 relapses occurred after 3 years (17.9%), 8 occurred after 5 years (11.9%) and 3 after 8 years (4.5%). In NPM1-wild type patients, LR and VLR were significantly less frequent (<3 years: 91.9%; >3 years: 8.1%; >5 years: 2.5%; >8 years: 0.6%; P=.0317, .0037 and .0783 respectively). NPM1m relapses represented one half of LR (48%) and two thirds of VLR (67%). Among them, genotype was NPM1m/FLT3-wild type in most patients (75% in LR and 88% in VLR patients). In LR and VLR, NPM1 mutational status had no impact on CR2 and OS2: CR2LR/NPM1m: 42% vs. CR2LR/NPM1-WT: 38% (P=.8702); CR2VLR/NPM1m: 50%vs. CR2LR/NPM1-WT: 50% (P=1.0000); OS2LR/NPM1m: 7.4 months vs. OS2LR/NPM1-WT: 19.4 months (P=.2019); OS2VLR/NPM1m: 7.8 months vs. OS2VLR/NPM1-WT: 29.8 months (P=.0917). Our data show that LR and VLR are not infrequent in AML patients with NPM1 mutations. Although this finding needs to be validated in updated multicentric cohorts with a very long follow-up, it strongly suggests that AML patients with NPM1 mutations should benefit from a prolonged follow-up beyond 5 years from CR. Table Table. Disclosures No relevant conflicts of interest to declare.
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Bertoli, Sarah, Emilie Bérard, Suzanne Tavitian, Anne Huynh, Cecile Borel, Sarah Guenounou, Isabelle Luquet, et al. "Survival Improvement for Acute Myeloid Leukemia Patients Treated in Routine Practice By Intensive Chemotherapy Between 2000 and 2014." Blood 128, no. 22 (December 2, 2016): 3996. http://dx.doi.org/10.1182/blood.v128.22.3996.3996.
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Abstract Acute Myeloid Leukemia (AML) is one of the hematological malignancies in which no key development in specific treatment has been achieved in opposition to B-cell malignancies or CML. Yet, few recent studies have reported an improvement in overall survival (OS) of adult AML patients (pts) (Sant, Lancet Oncol 2014; Derolf, Blood 2009; Pulte, Haematologica 2008). However, these studies are mainly based on registries or compilation of clinical trials and reasons for this improvement are not defined. We analyzed the outcome of AML pts treated between 2000 and 2014 by intensive chemotherapy in order to determine whether there has been an improvement in OS over time and independently of classic prognostic factors. From January, 1st, 2000 to December, 31st, 2014, 976 AML pts received intensive chemotherapy at the Toulouse University Hospital. With regards to routine practice evolution, voriconazole or caspofungin were used from 2003 as prophylaxis of fungal infections (Chabrol, Haematologica 2010), then posaconazole from 2008. Indications for alloSCT have evolved from geno to pheno-identical (Id) in first complete response (CR) and more recently to haplo-Id in high risk pts, whereas autologous-SCT was progressively abandoned. Molecular stratification for alloSCT indications based on NPM1, FLT3-ITD and CEBPA mutations started from 2006. A specific unit dedicated to acute leukemia was created in the Hematology department in 2005. Starting from 2010, dexamethasone was added to chemotherapy in pts with WBC>100 or >50 G/L with leukostasis. Since therapeutic strategies differed between younger and older pts, we analyzed separately the outcome of pts <60y (n=513) and pts 60y+ (n=463) according to 2000-2004, 2005-2009 and 2010-2014 periods. In pts <60y, there were no differences in median age (47.9, 47.3 and 50.5y), secondary AML (19.7; 18.2 and 15.7%), PS>1 (22.8, 10.5 and 24.2%), median WBC count (11, 13 and 9 G/l), favorable/unfavorable karyotypes (14.0/25.6, 15.5/22.7 and 11.5/21.0%), FLT3-ITD (23.7, 20.7 and 22.9%) or NPM1 mutations in intermediate-cytogenetic risk (24.5, 33.6, 33.3%) according to 2000-2004; 2005-2009 and 2010-2014 periods. Median FU of pts still alive was 67.4 months (84.0, 74.1 and 38.1 months for 2000-2004, 2005-2009 and 2010-2014, respectively). Patients were censored at 7 years. Table 1 shows response to induction, treatment distribution and outcome. There were no differences in term of cumulative incidence (CI) of death in CR1 or non-relapse mortality in allografted pts over time. However, multivariate analyses with regards to d60 death (HR 0.43, 95% CI, 0.17-1.13; p=0.089), CI of relapse (SHR 0.72, 95%CI 0.50-1.03; p=0.071) and disease-free survival (HR 0.76, 95%CI 0.54-1.06; p=0.104) showed a trend for better outcome in the 2010-2014 period than in 2000-2004. The period of time was significantly associated with a better OS (p=0.031) with HR of 0.92 (95%CI 0.70-1.20; p=0.536) and 0.68 (95%CI, 0.50-0.92; p=0.012) for 2005-2009 and 2010-2014 respectively, compared to 2000-2004. The 2010-2014 period effect was still significant in multivariate analysis when adjusted on age (≥50y), secondary AML, cytogenetics and WBC >50 G/L (HR 0.62, 95%CI 0.46-0.85; p=0.003). Characteristics of pts 60y+ were: median age (68.0, 68.7 and 66.9y), secondary AML (34.6; 20.2 and 25.7%), PS>1 (28.4, 20.0 and 21.7%), median WBC count (10.7, 8.3 and 11.2 G/l), favorable/unfavorable karyotypes (3.1/24.2, 3.8/21.3 and 4.8/19.8%), FLT3-ITD (12.0, 25.9 and 21.2%) or NPM1 mutations in intermediate-cytogenetic risk (41.3, 34.6, 32.8%) according to 2000-2004; 2005-2009 and 2010-2014 periods. Median FU of pts still alive was 52.5 months (84.0, 70.6 and 35.6 months for 2000-2004, 2005-2009 and 2010-2014, respectively). There was no difference in OS over time (table 2). However, there was a significant interaction between period of time and WBC in the multivariate analysis for OS meaning that the 2010-2014 period had an impact only in pts with WBC > 50 G/L (HR 0.41, 95%CI 0.24-0.71; p=0.002). The same interaction was also found for CR achievement (OR 3.90, 95%CI 1.30-11.7; p=0.015). Progresses have been made in each phase of the therapeutic course of younger AML pts (less early deaths, more alloSCT without increased NRM, less relapses, more second remissions) resulting in survival improvement. In older pts, though outcome of hyperleukocytic patients has improved, significant advances remain to be made. Disclosures Tavitian: Novartis: Membership on an entity's Board of Directors or advisory committees. Attal:sanofi: Consultancy; celgene: Consultancy, Research Funding; janssen: Consultancy, Research Funding; amgen: Consultancy, Research Funding. Huguet:Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Récher:Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Piel-Julian, Marie-Léa, Marie-Françoise Thiercelin-Legrand, Guillaume Moulis, Sophie Voisin, Ségolène Claeyssens, and Laurent Sailler. "Antithrombotic Therapy Management in Patients with Inherited Bleeding Disorders and Ischaemic Heart Disease: A Single-Center Experience." Blood 132, Supplement 1 (November 29, 2018): 1213. http://dx.doi.org/10.1182/blood-2018-99-117101.
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Abstract Introduction: In the last decades, the life expectancy of patients with hemophilia A (HA), hemophilia B (HB) and von Willebrand disease (VWD) has substantially improved. As a result, these patients experience age-related comorbidities, especially ischaemic heart disease. Safety and efficacy of antiplatelet drugs in patients with inherited bleeding disorders remain unclear, while there is no evidence-based guideline for the antithrombotic management in this population. The aims of our study were to describe the management of patients with HA, HB and VWD at the occurrence of ischaemic heart disease in our regional referral center; to compare this management to experts' recommendations; and to evaluate the safety and the efficacy of antiplatelet drugs in this population. Methods : The source of population was the 2008-2018 cohort of patients with HA (n=565), HB (n=115) and VWD (n=618) followed at Toulouse University hospital (France). Their follow-up is recorded in electronic medical files. We retrospectively identified the patients who experienced an ischaemic heart disease treated by antiplatelet therapy. Ischaemic heart disease included ST- and non-ST-segment elevation acute myocardial infarction, stable and unstable angina, and silent coronary artery disease. We described the reperfusion therapy, the use of antiplatelet drugs and replacement factors, and the occurrence of bleeding or thrombotic complications during the follow-up. Results: Eight patients had an ischaemic heart disease: 5 HA, 1 HB and 2 VWD patients. Four of the haemophilic patients had minor hemophilia; the two others had moderate hemophilia. VWD patients were one type 1 (FVIII 26%, VWF:Ag 13%) and one type 2B (FVIII 29%, VWF:Ag 75%, VWF :Act 24%, low platelet count). Age at the time of the cardiac event ranged from 49 to 80 years. All patients were men except the patient with type 2B VWD. Cardiovascular risk factors were frequent (overweight, n=5; hypercholesterolemia, n=4; smoking, n=4). Four patients were investigated because of cardiac symptoms (unstable angina, angina, dyspnea, palpitations, n=1 each), and one patient because of family history. The last 3 patients were investigated as part of a screening program including patients with a high cardiovascular risk estimation. The initial management was as follows: 4 patients underwent a percutaneous coronary intervention (PCI) and 4 had a triple coronary artery bypass grafting (CABG). All patients treated with PCI had dual antiplatelet therapy for one month, then low-dose aspirin. CABG patients were initiated with low-dose aspirin. FVIII exposure was lower in PCI patients than in CABG patients (13 ± 10.42 versus 19 ± 9.35 cumulative exposure days to FVIII). Four patients were managed with differences from current guidelines1-3: first, the woman with type 2B VWD was treated with two drug-eluting stents whereas bare-metal stents are recommended. Dual antiplatelet therapy was then initiated but stopped at one month because of microcytic anemia. She was then treated with acid acetylsalicylic, 160mg per day instead of 75mg, and presented a severe gastrointestinal bleeding. Second, the patient with HB (FIX 34%) received no replacement therapy during PCI and no proton pump inhibitors while treated by antiplatelet drug, but he experienced no bleeding. Third, a HA patient (FVIII 6%) had a trough level of FVIII slightly lower than recommended (FVIII 37% versus > 50%) at day 7 after CABG. He presented a hemopericardium the next day, complicated with cardiac tamponade. Lastly, a moderate HA patient had no long-term antiplatelet therapy after CABG. However, he did not experience any new cardiovascular event during the following 4 years. During the follow-up (median: 24,5 months), only one HA (FVIII 20%) patient had a new cardiovascular event: a critical lower limb ischemia complicated with an arterial ulcer at the age of 91 years, 11 years after CABG. In contrast, 3 patients experienced a severe bleeding while treated by dual or low-dose aspirin: one hemopericardium, one gastrointestinal bleeding and one intracranial bleeding at J7 post-CABG, 13 months and 11 years after the cardiac event, respectively. Conclusion: This series of 8 patients confirms the significant risk of severe bleeding complications when antiplatelet drug is initiated in patients with hemophilia or VWD. In 1/3 cases, the severe bleeding occurred despite strict adherence to current recommendations. Disclosures No relevant conflicts of interest to declare.
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Bertoli, Sarah, Suzanne Tavitian, Eric Delabesse, Audrey Sarry, Françoise Huguet, and Christian Récher. "Outcome of AML Patients with IDH1 or IDH2 Mutations from Diagnosis and Refractory/Relapse Phase of the Disease in Routine Practice." Blood 128, no. 22 (December 2, 2016): 1718. http://dx.doi.org/10.1182/blood.v128.22.1718.1718.
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Abstract Somatic mutations of isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) genes are found in 7-14% and 8-19% of AML. IDH1R132, IDH2R140 and IDH2R172mutations are most frequent in cytogenetically normal AML (25-30% of cases) and significantly associated with NPM1 mutations (except for IDH2R172). Their prognostic significance depends on mutational context (NPM1 and FLT3-ITD status) and on type of mutation: IDH1R132 has a possible adverse effect, IDH2R140 is associated with a favorable effect while the IDH2R172 effect remains controversial (Green C, Blood 2011; Papaemmanuil E, NEJM 2016). IDH1/2 mutations induce a neomorphic enzyme that overproduces the 2-hydroxyglutarate oncometabolite and thus have emerged as promising therapeutic targets. Indeed, AG-120 (IDH1 inhibitor) and AG-221 (IDH2 inhibitor) have shown encouraging activity in phase I trials including Rel/Ref AML pts though median OS are not yet reported. The prognosis of IDH mutated pts at this phase of the disease is not well described in routine practice outside clinical trials. The primary objective of this study was to describe characteristics and outcome of AML pts with IDH1/2 mutations treated in routine practice by intensive chemotherapy from both diagnosis and Rel/Ref phase of the disease. This study included 1603 pts admitted at the Toulouse University Hospital and/or registered in the Oncomip regional Network from January, 1st, 2000 to December, 31st, 2014. This database included all cases of AML pts treated by intensive chemotherapy since 2000 then, starting from 2007, all consecutive patients whatever their treatment (Bories P, Am J Hematol 2014; Bertoli S, Blood 2013). Molecular analyses were performed at diagnosis or retrospectively from stored samples. Only first relapses after standard intensive chemotherapy were considered for this analysis and refractory disease was defined as failure following one course of induction chemotherapy including or not a second course for patients with more than 5% bone marrow blasts at day 15. Treatment distributions were as follows: 984 pts received intensive chemotherapy, 224 azacitidine and 312 best supportive care. Mutational status of IDH1 and IDH2 was available for 465 pts of whom, 422 received intensive chemotherapy as first line therapy, 21 azacitidine and 20 BSC. The study focalized on pts treated by intensive chemotherapy: 349 IDH1/2wt (82%), 32 IDH1R132 (7.5%), 31 IDH2R140 (7.3%) and 11 IDH2R172 (2.6%). IDH2R140 (59y, IQR, 54-66.5) and IDH2R172 (60y, 42.5-64) pts were older than IDH1R132 (53y, 43.8-59.3) and IDHwt (52y, 39-62) pts. IDH2R172 pts had lower WBC count (2.1 G/l, 1.35-4.6) as compared to IDHwt (18 G/l, 4.3-66.9), IDH1R132 (14.7 G/l, 2.1-47.5) and IDH2R140 (21.5 G/l, 4.1-43). De novo AML was found in 85%, 94%, 74% and 73% of IDHwt, IDH1R132, IDH2R140 and IDH2R172 pts, respectively. Only 3 IDH1R132 and 3 IDH2R140 pts had unfavorable karyotype whereas 2 IDH2R140 pts had CBF-AML. Complete response was achieved in 80%, 91%, 74% and 100% of IDHwt, IDH1R132, IDH2R140 and IDH2R172 pts, respectively. Median overall survival (OS) from diagnosis was 23.6, 20.9, 35.8 and 41.1 months in IDHwt, IDH1R132, IDH2R140 and IDH2R172 pts, respectively. 185 Rel/Ref patients with IDH1/2-defined mutational status received salvage therapy with intensive chemotherapy (68%); azacitidine (18%) or other treatments (14%): 144 IDHwt (36 Ref/108 Rel), 18 IDH1R132 (3 Ref/15 Rel) and 23 IDH2R140/R172 (8 Ref/15 Rel). Complete response was achieved in 62 IDHwt (43%), 9 IDH1R132 (50%) and 12 IDH2R140/R172 (52%) pts, respectively. Median OS and 3-year OS from failure or relapse were: IDHwt: 7.6 months/19%; IDH1R132: 5.9 months/8% and IDH2R140/R172: 11 months/23%. Observational data should be considered complementary to that provided by randomized clinical trials. They provide data collected in a non-selected general population, while participants in clinical trials are generally under very restrictive eligibility criteria. In refractory or relapsed patients who received salvage therapy, substantial differences may be observed according to the subtype of mutations, IDH1R132 having the poorest prognosis. IDH2R172 appears to confer a more favorable outcome (3-year OS from diagnosis: 61%). Disclosures Tavitian: Novartis: Membership on an entity's Board of Directors or advisory committees. Huguet:Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Récher:Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Benamar, S., C. Lukas, C. Daien, C. Gaujoux-Viala, L. Gossec, A. C. Rat, B. Combe, and J. Morel. "OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 54.1–54. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3213.
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Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer
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Kaminski, Hannah, Julie Belliere, Laure Burguet, Arnaud Del Bello, Benjamin Taton, Stéphane Poirot-Mazères, Isabelle Accoceberry, et al. "Identification of Predictive Markers and Outcomes of Late-onset Pneumocystis jirovecii Pneumonia in Kidney Transplant Recipients." Clinical Infectious Diseases, October 23, 2020. http://dx.doi.org/10.1093/cid/ciaa1611.
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Abstract Background In the era of prophylaxis, Pneumocystis pneumonia (PCP) has become a late-onset opportunistic infection requiring indications for prolonged prophylaxis to be defined. The primary objective of our study was therefore to evaluate risk factors associated with late-onset PCP. The secondary objective was to assess the impact of this infection on graft and patient survival. Methods We conducted a French case-control study in Bordeaux and Toulouse center by matching 1 case to 1–2 controls from the same center based on the transplant date and the type of induction treatment. Results Seventy cases and 134 controls were included. PCP occurred at a median of 3 years after transplantation. The total lymphocyte count and CD4+ and CD8+ T-lymphocyte values were lower in the cases than in their matched controls on the day of infection and annually up to 4 years earlier. The covariables independently associated with PCP were the total lymphocyte count 1 year before Pneumocystis, mTOR inhibitors used as maintenance immunosuppressive drugs, and the administration of corticosteroid boluses used in acute rejection. A total lymphocyte count threshold <1000/µL offered the best predictive value for infection occurrence. PCP was associated with high incidence of graft loss and patient death (30% and 17% respectively, 3 years after PCP). Conclusions Pneumocystis pneumonia has dramatic consequences in kidney transplant recipients; a targeted prophylaxis based on simple criteria, such as chronic lymphopenia and/or history of corticosteroid boluses, could be useful to avoid life-threatening complications.
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de Souto Barreto, P., K. Pothier, G. Soriano, M. Lussier, L. Bherer, S. Guyonnet, A. Piau, P. J. Ousset, and B. Vellas. "A Web-Based Multidomain Lifestyle Intervention for Older Adults: The eMIND Randomized Controlled Trial." Journal of Prevention of Alzheimer's Disease, 2020, 1–9. http://dx.doi.org/10.14283/jpad.2020.70.
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Importance/Objective: To describe the feasibility and acceptability of a 6-month web-based multidomain lifestyle training intervention for community-dwelling older people and to test the effects of the intervention on both function- and lifestyle-related outcomes. Design: 6-month, parallel-group, randomized controlled trial (RCT). Setting: Toulouse area, South-West, France. Participants: Community-dwelling men and women, ≥ 65 years-old, presenting subjective memory complaint, without dementia. Intervention: The web-based multidomain intervention group (MIG) received a tablet to access the multidomain platform and a wrist-worn accelerometer measuring step counts; the control group (CG) received only the wrist-worn accelerometer. The multidomain platform was composed of nutritional advices, personalized exercise training, and cognitive training. Main outcomes and measures: Feasibility, defined as the proportion of people connecting to ≥75% of the prescribed sessions, and acceptability, investigated through content analysis from recorded semi-structured interviews. Secondary outcomes included clinical (eg, cognitive function, mobility, health-related quality of life (HRQOL)) and lifestyle (eg, step count, food intake) measurements. Results: Among the 120 subjects (74.2 ±5.6 years-old; 57.5% women), 109 completed the study (n=54, MIG; n=55, CG). 58 MIG subjects connected to the multidomain platform at least once; among them, adherers of ≥75% of sessions varied across multidomain components: 37 people (63.8% of 58 participants) for cognitive training, 35 (60.3%) for nutrition, and three (5.2%) for exercise; these three persons adhered to all multidomain components. Participants considered study procedures and multidomain content in a positive way; the most cited weaknesses were related to exercise: too easy, repetitive, and slow progression. Compared to controls, the intervention had a positive effect on HRQOL; no significant effects were observed across the other clinical and lifestyle outcomes. Conclusions and Relevance: Providing multidomain lifestyle training through a web-platform is feasible and well-accepted, but the training should be challenging enough and adequately progress according to participants’ capabilities to increase adherence. Recommendations for a larger on-line multidomain lifestyle training RCT are provided.
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Takeda, C., S. Guyonnet, P. J. Ousset, M. Soto, and B. Vellas. "TOULOUSE ALZHEIMER’S CLINICAL RESEARCH CENTER RECOVERY AFTER THE COVID-19 CRISIS: TELEMEDICINE AN INNOVATIVE SOLUTION FOR CLINICAL RESEARCH DURING THE CORONAVIRUS PANDEMIC." Journal of Prevention of Alzheimer's Disease, 2020, 1–4. http://dx.doi.org/10.14283/jpad.2020.32.
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In the context of the COVID-19 pandemic (1)(2) declared by the World Health Organization in March 2020, the French government decided to lockdown the entire country on March 17th. Consequently, the ongoing recruitment of participants for the INSPIRE study (3, 4) was temporarily interrupted on March 16th and the 123 future participants programmed until April 30th were postponed (5). In France, only emergencies were allowed to be physically seen. As an alternative for the other patients, Telemedicine has become essential. France authorized the reimbursement of these new techniques by the National Health Insurance; allowing rapid deployment of online consultations to be used to maintain the level of care (6).
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Schietzel, Simeon, Patricia O. Chocano-Bedoya, Angelique Sadlon, Michael Gagesch, Walter C. Willett, Endel J. Orav, Reto W. Kressig, et al. "Prevalence of healthy aging among community dwelling adults age 70 and older from five European countries." BMC Geriatrics 22, no. 1 (March 2, 2022). http://dx.doi.org/10.1186/s12877-022-02755-8.
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Abstract Background To compare the prevalence of healthy aging among adults age 70 and older from 5 European countries recruited for the DO-HEALTH clinical trial. Participants were selected for absence of prior major health events. Methods Cross-sectional analysis of DO-HEALTH baseline data. All 2,157 participants (mean age 74.9, SD 4.4; 61.7% women) were included and 2,123 had data for all domains of the healthy aging status (HA) definition. HA was assessed based on the Nurses` Health Study (NHS) definition requiring four domains: no major chronic diseases, no disabilities, no cognitive impairment (Montreal Cognitive Assessment, MoCA ≥25), no mental health limitation (GDS-5 <2, and no diagnosis of depression). Association between HA and age, BMI, gender, and physical function (sit-to-stand, gait speed, grip strength) was assessed by multivariate logistic regression analyses adjusting for center. Results Overall, 41.8% of DO-HEALTH participants were healthy agers with significant variability by country: Austria (Innsbruck) 58.3%, Switzerland (Zurich, Basel, Geneva) 51.2%, Germany (Berlin) 37.6%, France (Toulouse) 36.7% and Portugal (Coimbra) 8.8% (p <0.0001). Differences in prevalence by country persisted after adjustment for age. In the multivariate model, younger age (OR = 0.95, 95% CI 0.93 to 0.98), female gender (OR = 1.36, 95% CI 1.03 to 1.81), lower BMI (OR = 0.94, 95% CI 0.91 to 0.96), faster gait speed (OR = 4.70, 95% CI 2.68 to 8.25) and faster performance in sit-to-stand test (OR = 0.90, 95% CI 0.87 to 0.93) were independently and significantly associated with HA. Conclusions Despite the same inclusion and exclusion criteria preselecting relatively healthy adults age 70 years and older, HA prevalence in DO-HEALTH varied significantly between countries and was highest in participants from Austria and Switzerland, lowest in participants from Portugal. Independent of country, younger age, female gender, lower BMI and better physical function were associated with HA. Trial registration DO-HEALTH was registered under the protocol NCT01745263 at the International Trials Registry (clinicaltrials.gov), and under the protocol number 2012–001249-41 at the Registration at the European Community Clinical Trial System (EudraCT).