Patients' practices and experiences of using nebuliser therapy in the management of COPD at home.

How patients use their nebulisers at home is vital to ensure effective treatment and optimal health outcomes for patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to identify the practicalities and problems associated with nebuliser use by patients with COPD at home, which may impact on the safety and effectiveness of therapy

Assistance of family carers for patients with COPD using nebulisers at home: a qualitative study

Objective: For many patients with chronic conditions, such as chronic obstructive pulmonary disease (COPD), the assistance of family carers with medicines is vital for optimal treatment outcomes. The aim of this study was to identify the assistance carers provide to patients with COPD using nebuliser-delivered therapy at home, and the problems experienced that may impact on the safety and effectiveness of therapy and contribute to carer burden. Methods: A cross-sectional, qualitative descriptive study was conducted with participants recruited from primary and intermediate care. Home interviews were conducted with 14 carers who assisted a family member with COPD using a nebuliser. Qualitative procedures enabled analysis of nebuliser-related activities and problems experienced by carers. Results: The carer sample included 10 female and 4 male carers, with a mean age of 61 years: 11 spouses and 3 daughters. They had assisted patients with use of their nebuliser and associated medications for, on average, 4.5 years. Assistance ranged from taking full responsibility for nebuliser use to providing help with particular aspects only when required. Nebuliser-related activities included assembling and setting up equipment, mixing medicines, operating the device, dismantling and cleaning equipment. Difficulties were described with all aspects of care. Carers reported concerns about medication side effects and the lack of information provided. Conclusions: The study revealed the vital role of carers in enabling effective therapy. The wide-ranging responsibilities assumed by carers and problems experienced relate to all aspects of COPD management with nebulisers, and have a potential impact on treatment outcomes and carer burden. A systematic approach to addressing carers' needs and prioritising support would be anticipated to have positive consequences for patients, carers and health services

Pregnancy outcome in women with Gaucher disease type 1 who had unplanned pregnancies during eliglustat clinical trials

Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficient enzymatic activity of acid β-glucosidase, resulting in accumulation of its substrate glucosylceramide, leading to debilitating visceral, hematologic, and skeletal manifestations. Women with GD1 are at increased risk for complications during pregnancy, delivery, and postpartum. Treatment with enzyme replacement therapy is generally recommended before and during pregnancy to reduce risks. Eliglustat, an oral substrate-reduction therapy, is a first-line treatment for adults with GD1 adults who have extensive, intermediate, or poor CYP2D6-metabolizer phenotypes (>90% of patients). We report on pregnancy outcomes among women in eliglustat trials who had unplanned pregnancies and female partners of men in the trials. In four phase 2 and 3 eliglustat trials of 393 adults with GD1, women of childbearing potential were required to use contraception, have monthly pregnancy tests, and discontinue eliglustat promptly if pregnant. In phase 2 and 3 trials, 18 women had 19 pregnancies, resulting in 14 healthy infants from 13 pregnancies (one set of twins), three elective terminations, one ectopic pregnancy, one spontaneous abortion, and one in utero death. Median estimated eliglustat exposure duration during pregnancy was 38 days. In phase 1 trials (non-GD1 subjects), one woman had a spontaneous abortion. Partners of 16 eliglustat-treated men with GD1 had 18 pregnancies, all resulting in healthy infants. Eliglustat is not approved during pregnancy due to limited data. Guidelines for clinicians and patients with GD that address use of eliglustat in women of childbearing potential are needed

Enfermedad de Gaucher en Argentina: un informe del Registro Internacional de Gaucher y del Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher

La Enfermedad de Gaucher por su baja frecuencia está incluida dentro de las enfermedades huérfanas. En 1991 comenzó el ingreso de pacientes en el Registro Internacional de Gaucher. En 1992 se incorporaron los primeros dos pacientes de Latinoamérica. En 2006 se creó el Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher siendo sus objetivos principales el entendimiento de la prevalencia, presentación, manejo y tratamiento de la Enfermedad de Gaucher en Argentina. Hasta el 1 de febrero del 2013 ingresaron al Registro Internacional 5.986 pacientes provenientes de 60 países, de los cuales 133 (2.22%) fueron argentinos. El análisis de esta publicación fue realizado sobre 133 pacientes con Enfermedad de Gaucher. Esta es la primera publicación del Grupo Argentino de Diagnóstico y Tratamiento en base a los datos del Registro Internacional. La casuística argentina mostró un predominio femenino y la forma clínica más frecuente fue el tipo 1 (97.7%, n=128). El genotipo fue identificado en 57 pacientes (42.9%), siendo el más frecuente el N370S/ otro alelo (82.5%). Entre los pacientes con datos reportados, los síntomas basales predominantes, previos al inicio del tratamiento con Imiglucerasa que predominaron fueron la esplenomegalia (100%, n=13) y la hepatomegalia (88.9%, n=8) y como citopenias más frecuentes, la trombocitopenia (64.2%, n=34) y la anemia (45.9%, n=28). La infiltración de la médula ósea como un marcador específico de enfermedad ósea se encontró en el 50% de los pacientes. En total, el 85.7% de los pacientes argentinos reciben terapia de reemplazo enzimático con Imiglucerasa, lográndose las metas terapéuticas, en la mayoría de los casos, en la última evaluación. Las metas terapéuticas más frecuentemente alcanzadas resultaron: el control de las manifestaciones óseas (dolor óseo y crisis ósea, 81.9% y 99% respectivamente) y la normalización de la hemoglobina (86.5%). La terapia de reemplazo enzimática con Imiglucerasa, a largo plazo en la población argentina demostró ser una herramienta eficaz para mejorar los parámetros clínicos y bioquímicos de la Enfermedad de Gaucher tipo1.Fil: Drelichman, G.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Fernández Escobar, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Basack, Nora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Kohan, R.. Registro Argentino de Gaucher; ArgentinaFil: Watman, N.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Bolesina, M.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Elena, G.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Veber, S. E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Dragosky, M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Oncología Marie Curie; ArgentinaFil: Annetta, I.. Gobierno de la Ciudad de Buenos Aires. Hospital de Oncología Marie Curie; ArgentinaFil: Feliu, A.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sciuccati, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Cuello, María Fernanda. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fynn, Alcira. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Dodelson de Kremer, Raquel. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Angaroni, Celia Juana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Giner Ayala, Alicia. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Del Valle Oller, Ana María. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guelbert, Norberto Bernardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Delgado, María Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Becerra, Adriana Berónica. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Oliveri, María Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Larroudé, M.. Centro Médico TIEMPO; ArgentinaFil: Masllorens, F.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Nacional “Prof. Dr. A. Posadas"; ArgentinaFil: Szlago, M.. Fundación para el eEstudio de las Enfermedades Neurometabólicas; Argentina. Laboratorio de Neuroquímica “Dr. N. A. Chamoles”; ArgentinaFil: Schenone, A.. Laboratorio de Neuroquímica “Dr. N. A. Chamoles”; Argentina. Fundación para el eEstudio de las Enfermedades Neurometabólicas; Argentin

Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy

In the phase 3 trial of eliglustat in patients with Gaucher disease type 1 already stabilized with enzyme therapy (ENCORE), at one year, eliglustat was non-inferior to imiglucerase enzyme therapy in maintaining stable platelet counts, hemoglobin concentrations, and spleen and liver volumes. After this primary analysis period, patients entered a long-term extension phase in which all received eliglustat. Duration on eliglustat ranged from 2 to 5 years, depending on timing of enrollment (which spanned 2 years), treatment group to which patients were randomized, and whether they lived in the United States when commercial eliglustat became available. Here we report long-term safety and efficacy of eliglustat for 157 patients who received eliglustat in the ENCORE trial; data are available for 46 patients who received eliglustat for 4 years. Mean hemoglobin concentration, platelet count, and spleen and liver volumes remained stable for up to 4 years. Year to year, all four measures remained collectively stable (composite endpoint relative to baseline values) in ≥85% of patients, as well as individually in ≥92%. Mean bone mineral density Z-scores (lumbar spine and femur) remained stable and were maintained in the healthy reference range throughout. Eliglustat was well-tolerated over 4 years; 4 (2.5%) patients withdrew due to adverse events that were considered related to the study drug. No new or long-term safety concerns were identified. Clinical stability assessed by composite and individual measures was maintained in adults with Gaucher disease type 1 treated with eliglustat who remained in the ENCORE trial for up to 4 years.The ENCORE trial was funded and conducted by Sanofi Genzyme

Map-based navigation of an autonomous car using grid-based scan-to-map matching

© Copyright 2015 by ASME. This paper presents the map-based navigation of a car with autonomous capabilities using grid-based scan-to-map matching. The autonomous car used for demonstration is built based on Toyota Prius and can control the throttle, the brake and the steering by a computer. The proposed grid-based scan-to-map matching method represents a map with a finite number of grid cells, represents a scan and the map with scan points at each grid as normal distributions (NDs) and constructs a map by matching the scan NDs to the map NDs. The proposed method enables scan-based mapping at high speed while maintaining high accuracy. The representation of a grid cell of a map in terms of multiple NDs further enhances speed and accuracy. The accuracy analysis of the proposed method shows that a small robot with a wheel diameter of 8cm had yielded no loop closure error after the travel of 186m while the terminal position error by the GMapping was approximately 1m with the error growth of 1%. The application of the proposed method with the autonomous car has then demonstrated the ability of the proposed method for autonomous driving with varying and high speed and has also quantified the significance of speed for successful mapping in autonomous driving

Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes

Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (−308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (−174 G/C), and TGFB1 (+869 C/T and +915 G/C). The frequency of TNF and IL6 polymorphisms was different between patients and healthy controls (n = 131), suggesting a relatedness to MDS susceptibility in our population. Furthermore, the presence of each or both high-producing genotypes [TNF: p = 0.048, odds ratio (OR): 3.979; IL6: p = 0.001, OR: 6.835; both: p = 0.010, OR: 6.068] and thrombocytopenia at platelet counts of <50,000/μL (p = 0.004, OR: 4.857) were independently associated with an increased risk of manifesting a hemoglobin level of <8 g/dL at diagnosis. In particular, a severe bicytopenia was more frequently observed in patients with the TNF (high)_IL6 (high) combined genotype (p = 0.004, OR: 8.357), who consistently became transfusion dependent earlier (2.9 vs. 34.6 months; p = 0.001); and this likelihood was more evident in patients with lower bone marrow blast counts. The contribution of the remaining functional polymorphisms to the disease phenotype was less relevant. Our results demonstrate that TNF and IL6 gene polymorphisms, as underlying host features, are likely to play a key role in influencing the severity of the cytopenias in MDS and they may be instrumental for tailoring cytokine-target therapies.Fil: Bestach, Yesica Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Palau Nagore, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Flores, María G.. Hospital General de Agudos “C.G. Durand”; ArgentinaFil: González, Jacqueline. Hospital General de Agudos “C.G. Durand”; ArgentinaFil: Arbelbide, Jorge. Hospital Italiano; ArgentinaFil: Watman, Nora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Sieza, Yamila. Hospital Interzonal General de Agudos “Gral. San Martín”; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

La presencia del alelo -308 A del TNFa se asocia con anemia y plaquetopenia en pacientes con Síndromes Mielodisplásicos

Los Síndromes Mielodisplásicos (SMD) son un grupo heterogéneo de alteraciones hematológicas caracterizados, en parte, por la presencia de citopenias periféricas. El factor de necrosis tumoral alfa (TNFa) es una citoquina proinflamatoria con un rol predominante en la patofisiología de los SMD: niveles circulantes en plasma incrementados y una mayor expresión en células de médula ósea asociada con aumento en la tasa de apoptosis. El bloqueo del TNFa estimula la formación de colonias hematopoyéticas in vitro y mejora las citopenias periféricas in vivo. Objetivo: Analizar la presencia del polimorfismo de nucleótido simple (SNP) -308G/A del TNFa en pacientes con SMD de novo debido a que la presencia del alelo A se asocia con su mayor producción. Se estudiaron 107 pacientes (53 AR, 11 AS, 27 AREB, 2 AREBt y 14 LMMC), con una mediana de edad: 66 (14- 86) años, relación de sexos M/F=1,2 (59/48), mediana de sobrevida: 39,5 (1-170) meses. El SNP se analizó mediante amplificación por PCR y digestión con la enzima NcoI. Las frecuencias genotípicas halladas fueron: 0,74 G/G y 0,26 A/A+A/G en los pacientes vs 0,86 y 0,14 en los controles (n=94), respectivamente (p=0,0356; odds ratio-OR: 2,208). Los pacientes que portaban el alelo A presentaron un menor nivel de hemoglobina (8,7 vs 9,9 g/dL, p=0,0240), menor recuento de plaquetas (95000 vs 135000 /μL, p=0,0359) y menor edad (61 vs 68 años, p=0,0131) al diagnóstico. Además, se observó que estos pacientes presentaron un riesgo 4 veces aumentado de requerir transfusiones (78% vs 47%, p=0,0070, OR: 3,912). No se observaron diferencias estadísticas con otros parámetros clínicos analizados. Estos resultados fueron similares a los observados al excluir los pacientes con LMMC. El genotipo constitutivo asociado con alta expresión se encuentra 2 veces aumentado en los pacientes con SMD. La presencia del alelo -308 A se asoció con menor edad, mayor grado de anemia y trombocitopenia al diagnóstico. Estos resultados avalarían la hipótesis de que el TNFa podría actuar como un modificador de la severidad de la enfermedad. Estos pacientes se verían favorecidos, potencialmente, con terapias que bloqueen o modulen el TNFa.yelodysplastic Syndromes (MDS) constitute a heterogeneous group of clonal hematological diseases characterized by refractory cytopenia(s) as a result of an ineffective hematopoiesis. MDS patients show increased levels of Tumor Necrosis Factor alpha (TNFa) which is a multifunctional proinflammatory cytokine. The aim of this work is to examine the presence of -308G/A TNFα variants and to analyze whether it is associated with clinical parameters in a cohort of 107 Argentinean de novo MDS patients. The A/A+A/G genotype at TNFα -308 was overrepresented 2-fold in our population (p=0.0356, odds ratio-OR: 2.208). The presence of the high expressing -308A allele was associated with lower hemoglobin level (8.7 vs 9.9 g/dL; p=0.0240), reduced platelet counts (95000 vs 135000 /µL; p=0.0359) and younger age (61 vs 68 years; p=0.0131) at diagnosis. Also, these patients showed 4-fold higher risk of transfusion requirement (78% vs 47%, p=0.0070) during the follow up. In conclusion, the presence of an inherited -308A TNFα, which increases its transcription level, was associated with MDS phenotype in our cohort of Argentine MDS patients. And, an overexpression of TNFα may promote an underlying proinflammatory state that cooperates with intrinsic defects within MDS progenitors to increase the severity of certain phenotypic features of the disease.Fil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bestach, Yesica Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Flores, M. G.. Gobierno de la Ciudad de Buenos Aires. Hospital Interzonal de Agudos Dr. C. Durand; ArgentinaFil: Sieza, Y. Hospital Interzonal de Agudos Gral. San Martín, La Plata; ArgentinaFil: Gelemur, M.. Hospital Interzonal de Agudos Gral. San Martín, La Plata; ArgentinaFil: Venturini, C.. Instituto Privado de Hematología y Hemoterapia, Paraná; ArgentinaFil: Negri Aranguren, Pablo. Instituto Privado de Hematología y Hemoterapia, Paraná; ArgentinaFil: Watman, N.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Bengió, R.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

A reappraisal of Gaucher disease-diagnosis and disease management algorithms

Type 1 (non neuronopathic) Gaucher disease was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed and it has become a prototype for treatments for related orphan diseases. There are currently four treatment options available to patients with Gaucher disease, nevertheless, almost 25% of type 1 Gaucher patients do not gain timely access to therapy because of delays in diagnosis after the onset of symptoms. Diagnosis of Gaucher disease by enzyme testing is unequivocal, but the rarity of the disease and non-specific and heterogeneous nature of Gaucher disease symptoms may impede consideration of this disease in the differential diagnosis. To help promote timely diagnosis and optimal management of the protean presentations of Gaucher disease, a consensus meeting was convened to develop algorithms for diagnosis and disease management for Gaucher disease