Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Alcohol and Drug Consumption among Students from Pachuca, Hidalgo

OBJECTIVE. To determine the prevalence of alcohol and drug consumption and its relationship to sociodemographic variables, leisure activities, antisocial behavior, family norms and conflicts, among others. MATERIAL AND METHODS. Data derive from a representative survey of 1 929 students of junior high and high school, conducted in 1996 in the city of Pachuca, Hidalgo, Mexico. Of these, 44.9% were boys and 52.5% were girls; mean age was 14. A self-applied questionnaire, prepared by the WHO together with some countries, among them Mexico, was completed by the studied subjects, and included indicators of alcohol and drug consumption. RESULTS. Of the total sample, 47.9% had tried alcohol, and 12.6% had drunk large quantities -5 drinks or more per sitting- during the month previous to the survey. Preferred drinks are beer and coolers , which they buy at shops where no identification is required and drink at home or at friend\u27s homes. With respect to drugs, 5.1% had tried illegal or medical drugs without prescription, in particular inhalants, marihuana and tranquilizers. More boys consumed illegal drugs, and more girls medical drugs without prescription. Boys, who are also older, more frequently consumed alcohol and drugs and were more often employed during the previous year at part-time jobs. High alcohol level and drug consumers were characterized by their frequent report of being bored in their free time, drinking with friends and enrolling in antisocial behavior. With respect to family norms, they follow them less and show less interest in doing so. An elevated percentage informed that their parents fight frequently, that they have sought help for this reason and have intended separation. CONCLUSIONS. Groups who drink more alcohol and use other drugs, in contrast with non-users, presented more behavioral problems, more outdoors activities that included drinking with friends, more antisocial behavior, had a distant relationship with their families sharing few activities with them, an showed little interest in following family rules and perceiving conflicts within their families

Consumo de alcohol y drogas en estudiantes de Pachuca, Hidalgo. [Alcohol and drug use students from Pachuca, Hidalgo]

OBJETIVO. Determinar la prevalencia del consumo de drogas y bebidas alcohólicas entre estudiantes, así como la relación de este consumo con variables sociodemográficas, tiempo libre, actos antisociales, normas y conflictos familiares, entre otras. MATERIAL Y MÉTODOS. Los datos se derivan de una encuesta representativa de 1 929 estudiantes de enseñanza media y media superior de la ciudad de Pachuca, estado de Hidalgo, México, levantada en 1996, de los cuales 44.9% son hombres y 52.5% mujeres, con una media de edad de 14 años. Se utilizó un cuestionario autoaplicable, que incluye indicadores de consumo de drogas y alcohol elaborados por algunos países, entre ellos México, con la Organización Mundial de la Salud. RESULTADOS. El 47.9% ha probado bebidas alcohólicas; 12.6% bebieron cantidades considerables -cinco copas o más por ocasión- durante el mes anterior a la encuesta. Las bebidas preferidas son la cerveza y los coolers; el alcohol lo compraron principalmente en tiendas donde no les piden identificación y lo consumen en su casa o en la de otras personas. El 5.1% ha consumido drogas, sobre todo inhalables, mariguana y tranquilizantes. Una cifra mayor de varones consume drogas ilegales, y las mujeres, medicamentos sin prescripción. Un número superior de hombres toma más cantidades de alcohol y consume drogas, tienen mayor edad y trabajaron de medio tiempo durante el año anterior a la encuesta. Los consumidores de drogas y de altas cantidades de alcohol se distinguieron porque un número considerable informó que se aburría en su tiempo libre, se va a beber con sus amigos o ha cometido actos antisociales. Respecto a la familia, manifiestan cumplir menos con las normas parentales y muestran menor interés en hacerlo. Asimismo, un porcentaje más elevado informó que sus padres pelean con frecuencia, han pedido ayuda por esa razón y han intentado separarse. CONCLUSIONES. Los estudiantes que beben cantidades elevadas de alcohol y los consumidores de otras drogas, a diferencia de lo que sucede con los abstemios, presentaron más problemas al destinar su tiempo libre a actividades como irse a beber con amigos, exhibir más conductas antisociales y tener un distanciamiento de la familia que se refleja en la baja participación en actividades compartidas, en el desinterés por cumplir con sus normas y en la percepción de conflictos al interior de la misma.OBJECTIVE. To determine the prevalence of alcohol and drug consumption and its relationship to sociodemographic variables, leisure activities, antisocial behavior, family norms and conflicts, among others. MATERIAL AND METHODS. Data derive from a representative survey of 1 929 students of junior high and high school, conducted in 1996 in the city of Pachuca, Hidalgo, Mexico. Of these, 44.9% were boys and 52.5% were girls; mean age was 14. A self-applied questionnaire, prepared by the WHO together with some countries, among them Mexico, was completed by the studied subjects, and included indicators of alcohol and drug consumption. RESULTS. Of the total sample, 47.9% had tried alcohol, and 12.6% had drunk large quantities -5 drinks or more per sitting- during the month previous to the survey. Preferred drinks are beer and "coolers", which they buy at shops where no identification is required and drink at home or at friend's homes. With respect to drugs, 5.1% had tried illegal or medical drugs without prescription, in particular inhalants, marihuana and tranquilizers. More boys consumed illegal drugs, and more girls medical drugs without prescription. Boys, who are also older, more frequently consumed alcohol and drugs and were more often employed during the previous year at part-time jobs. High alcohol level and drug consumers were characterized by their frequent report of being bored in their free time, drinking with friends and enrolling in antisocial behavior. With respect to family norms, they follow them less and show less interest in doing so. An elevated percentage informed that their parents fight frequently, that they have sought help for this reason and have intended separation. CONCLUSIONS. Groups who drink more alcohol and use other drugs, in contrast with non-users, presented more behavioral problems, more outdoors activities that included drinking with friends, more antisocial behavior, had a distant relationship with their families sharing few activities with them, an showed little interest in following family rules and perceiving conflicts within their families

Consumo de alcohol y drogas en estudiantes de Pachuca, Hidalgo Alcohol and drug consumption among students from Pachuca, Hidalgo

OBJETIVO. Determinar la prevalencia del consumo de drogas y bebidas alcohólicas entre estudiantes, así como la relación de este consumo con variables sociodemográficas, tiempo libre, actos antisociales, normas y conflictos familiares, entre otras. MATERIAL Y MÉTODOS. Los datos se derivan de una encuesta representativa de 1 929 estudiantes de enseñanza media y media superior de la ciudad de Pachuca, estado de Hidalgo, México, levantada en 1996, de los cuales 44.9% son hombres y 52.5% mujeres, con una media de edad de 14 años. Se utilizó un cuestionario autoaplicable, que incluye indicadores de consumo de drogas y alcohol elaborados por algunos países, entre ellos México, con la Organización Mundial de la Salud. RESULTADOS. El 47.9% ha probado bebidas alcohólicas; 12.6% bebieron cantidades considerables -cinco copas o más por ocasión- durante el mes anterior a la encuesta. Las bebidas preferidas son la cerveza y los coolers; el alcohol lo compraron principalmente en tiendas donde no les piden identificación y lo consumen en su casa o en la de otras personas. El 5.1% ha consumido drogas, sobre todo inhalables, mariguana y tranquilizantes. Una cifra mayor de varones consume drogas ilegales, y las mujeres, medicamentos sin prescripción. Un número superior de hombres toma más cantidades de alcohol y consume drogas, tienen mayor edad y trabajaron de medio tiempo durante el año anterior a la encuesta. Los consumidores de drogas y de altas cantidades de alcohol se distinguieron porque un número considerable informó que se aburría en su tiempo libre, se va a beber con sus amigos o ha cometido actos antisociales. Respecto a la familia, manifiestan cumplir menos con las normas parentales y muestran menor interés en hacerlo. Asimismo, un porcentaje más elevado informó que sus padres pelean con frecuencia, han pedido ayuda por esa razón y han intentado separarse. CONCLUSIONES. Los estudiantes que beben cantidades elevadas de alcohol y los consumidores de otras drogas, a diferencia de lo que sucede con los abstemios, presentaron más problemas al destinar su tiempo libre a actividades como irse a beber con amigos, exhibir más conductas antisociales y tener un distanciamiento de la familia que se refleja en la baja participación en actividades compartidas, en el desinterés por cumplir con sus normas y en la percepción de conflictos al interior de la misma.OBJECTIVE. To determine the prevalence of alcohol and drug consumption and its relationship to sociodemographic variables, leisure activities, antisocial behavior, family norms and conflicts, among others. MATERIAL AND METHODS. Data derive from a representative survey of 1 929 students of junior high and high school, conducted in 1996 in the city of Pachuca, Hidalgo, Mexico. Of these, 44.9% were boys and 52.5% were girls; mean age was 14. A self-applied questionnaire, prepared by the WHO together with some countries, among them Mexico, was completed by the studied subjects, and included indicators of alcohol and drug consumption. RESULTS. Of the total sample, 47.9% had tried alcohol, and 12.6% had drunk large quantities -5 drinks or more per sitting- during the month previous to the survey. Preferred drinks are beer and "coolers", which they buy at shops where no identification is required and drink at home or at friend's homes. With respect to drugs, 5.1% had tried illegal or medical drugs without prescription, in particular inhalants, marihuana and tranquilizers. More boys consumed illegal drugs, and more girls medical drugs without prescription. Boys, who are also older, more frequently consumed alcohol and drugs and were more often employed during the previous year at part-time jobs. High alcohol level and drug consumers were characterized by their frequent report of being bored in their free time, drinking with friends and enrolling in antisocial behavior. With respect to family norms, they follow them less and show less interest in doing so. An elevated percentage informed that their parents fight frequently, that they have sought help for this reason and have intended separation. CONCLUSIONS. Groups who drink more alcohol and use other drugs, in contrast with non-users, presented more behavioral problems, more outdoors activities that included drinking with friends, more antisocial behavior, had a distant relationship with their families sharing few activities with them, an showed little interest in following family rules and perceiving conflicts within their families

Consumo de alcohol y drogas en estudiantes de Pachuca, Hidalgo

OBJETIVO. Determinar la prevalencia del consumo de drogas y bebidas alcohólicas entre estudiantes, así como la relación de este consumo con variables sociodemográficas, tiempo libre, actos antisociales, normas y conflictos familiares, entre otras. MATERIAL Y MÉTODOS. Los datos se derivan de una encuesta representativa de 1 929 estudiantes de enseñanza media y media superior de la ciudad de Pachuca, estado de Hidalgo, México, levantada en 1996, de los cuales 44.9% son hombres y 52.5% mujeres, con una media de edad de 14 años. Se utilizó un cuestionario autoaplicable, que incluye indicadores de consumo de drogas y alcohol elaborados por algunos países, entre ellos México, con la Organización Mundial de la Salud. RESULTADOS. El 47.9% ha probado bebidas alcohólicas; 12.6% bebieron cantidades considerables -cinco copas o más por ocasión- durante el mes anterior a la encuesta. Las bebidas preferidas son la cerveza y los coolers; el alcohol lo compraron principalmente en tiendas donde no les piden identificación y lo consumen en su casa o en la de otras personas. El 5.1% ha consumido drogas, sobre todo inhalables, mariguana y tranquilizantes. Una cifra mayor de varones consume drogas ilegales, y las mujeres, medicamentos sin prescripción. Un número superior de hombres toma más cantidades de alcohol y consume drogas, tienen mayor edad y trabajaron de medio tiempo durante el año anterior a la encuesta. Los consumidores de drogas y de altas cantidades de alcohol se distinguieron porque un número considerable informó que se aburría en su tiempo libre, se va a beber con sus amigos o ha cometido actos antisociales. Respecto a la familia, manifiestan cumplir menos con las normas parentales y muestran menor interés en hacerlo. Asimismo, un porcentaje más elevado informó que sus padres pelean con frecuencia, han pedido ayuda por esa razón y han intentado separarse. CONCLUSIONES. Los estudiantes que beben cantidades elevadas de alcohol y los consumidores de otras drogas, a diferencia de lo que sucede con los abstemios, presentaron más problemas al destinar su tiempo libre a actividades como irse a beber con amigos, exhibir más conductas antisociales y tener un distanciamiento de la familia que se refleja en la baja participación en actividades compartidas, en el desinterés por cumplir con sus normas y en la percepción de conflictos al interior de la misma

Safety and Efficacy of Radioimmunotherapy with 90Yttrium-rituximab in Patients with Relapsed CD20+ B cell Lymphoma: A Feasibility Study

info:eu-repo/semantics/publishe

Droplet digital PCR allows vector copy number assessment and monitoring of experimental CAR T cells in murine xenograft models or approved CD19 CAR T cell-treated patients

International audienceAbstract Background Genetically engineered chimeric antigen receptor (CAR) T lymphocytes are promising therapeutic tools for cancer. Four CAR T cell drugs, including tisagenlecleucel (tisa-cel) and axicabtagene-ciloleucel (axi-cel), all targeting CD19, are currently approved for treating B cell malignancies. Flow cytometry (FC) remains the standard for monitoring CAR T cells using a recombinant biotinylated target protein. Nevertheless, there is a need for additional tools, and the challenge is to develop an easy, relevant, highly sensitive, reproducible, and inexpensive detection method. Molecular tools can meet this need to specifically monitor long-term persistent CAR T cells. Methods Based on 2 experimental CAR T cell constructs, IL-1RAP and CS1, we designed 2 quantitative digital droplet (ddPCR) PCR assays. By targeting the 4.1BB/CD3z (28BBz) or 28/CD3z (28z) junction area, we demonstrated that PCR assays can be applied to approved CD19 CAR T drugs. Both 28z and 28BBz ddPCR assays allow determination of the average vector copy number (VCN) per cell. We confirmed that the VCN is dependent on the multiplicity of infection and verified that the VCN of our experimental or GMP-like IL-1RAP CAR T cells met the requirement (< 5 VCN/cell) for delivery to the clinical department, similar to approved axi-cel or tisa-cel drugs. Results 28BBz and 28z ddPCR assays applied to 2 tumoral (acute myeloid leukemia (AML) or multiple myeloma (MM) xenograft humanized NSG mouse models allowed us to quantify the early expansion (up to day 30) of CAR T cells after injection. Interestingly, following initial expansion, when circulating CAR T cells were challenged with the tumor, we noted a second expansion phase. Investigation of the bone marrow, spleen and lung showed that CAR T cells disseminated more within these tissues in mice previously injected with leukemic cell lines. Finally, circulating CAR T cell ddPCR monitoring of R/R acute lymphoid leukemia or diffuse large B cell lymphoma (n = 10 for tisa-cel and n = 7 for axi-cel) patients treated with both approved CAR T cells allowed detection of early expansion, which was highly correlated with FC, as well as long-term persistence (up to 450 days), while FC failed to detect these events. Conclusion Overall, we designed and validated 2 ddPCR assays allowing routine or preclinical monitoring of early- and long-term circulating approved or experimental CAR T cells, including our own IL-1RAP CAR T cells, which will be evaluated in an upcoming phase I clinical trial

Drotrecogin alfa (Activated) in adults with septic shock

There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock.In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization.At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81).DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.)

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified