Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial.

OBJECTIVE: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial. METHODS: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017). RESULTS: Overall, 367 patients received niraparib 300 mg once daily. Dose reductions due to TEAEs were highest in month 1 (34%) and declined every month thereafter. Incidence of any-grade and grade ≥ 3 hematologic and symptomatic TEAEs was also highest in month 1 and subsequently declined. Incidence of grade ≥ 3 thrombocytopenia decreased from 28% (month 1) to 9% and 5% (months 2 and 3, respectively), with protocol-directed dose interruptions and/or reductions. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were reported in 2 and 6 niraparib-treated patients, respectively, and in 1 placebo patient each. Treatment discontinuations due to TEAEs were <5% in each month and time interval measured. CONCLUSION: These data demonstrate the importance of appropriate dose reduction according to toxicity criteria and support the safe long-term use of niraparib for maintenance treatment in patients with recurrent ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01847274.

Graphics for relatedness research.

Studies of relatedness have been crucial in molecular ecology over the last decades. Good evidence of this is the fact that studies of population structure, evolution of social behaviours, genetic diversity and quantitative genetics all involve relatedness research. The main aim of this article was to review the most common graphical methods used in allele sharing studies for detecting and identifying family relationships. Both IBS- and IBD-based allele sharing studies are considered. Furthermore, we propose two additional graphical methods from the field of compositional data analysis: the ternary diagram and scatterplots of isometric log-ratios of IBS and IBD probabilities. We illustrate all graphical tools with genetic data from the HGDP-CEPH diversity panel, using mainly 377 microsatellites genotyped for 25 individuals from the Maya population of this panel. We enhance all graphics with convex hulls obtained by simulation and use these to confirm the documented relationships. The proposed compositional graphics are shown to be useful in relatedness research, as they also single out the most prominent related pairs. The ternary diagram is advocated for its ability to display all three allele sharing probabilities simultaneously. The log-ratio plots are advocated as an attempt to overcome the problems with the Euclidean distance interpretation in the classical graphics.

Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR).

BACKGROUND: Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC). PATIENTS AND METHODS: Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m2/ days 1-3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization. The primary end point was progression-free survival (PFS) after 12 months. Overall survival (OS), response rate, toxicity, quality of life and treatment preference regarding standard treatment were defined as secondary end points. RESULTS: A total of 550 patients were recruited. The PFS rate after 12 months was 37.0% for TC compared with 40.2% in the standard combinations (P = 0.470). The overall response rate was 73.1% for TC versus 75.1% for standard combinations (P = 0.149). After a median follow-up of 20 months, the median PFS was 10 months [95% confidence interval (CI) 9.4-10.6] and did not differ between both arms (P = 0.414). The median OS was 25 months in the TC arm versus 31 months in the standard arm (95% CI: 22.4-27.6 resp. 26.0-36.0; P = 0.163). Severe hematologic toxicities (grade 3/4) were rare in the experimental arm (P < 0.001), with 17.4% leucopenia, 27.8% neutropenia and 15.9% thrombopenia. CONCLUSION: The combination of carboplatin and topotecan was well tolerated with significant lower rates of severe hematological toxicities but did not improve PFS or OS in platinum-sensitive relapsed ovarian cancer compared with established standard regimens.

Prevalence and immunological spectrum of temporal lobe epilepsy with glutamic acid decarboxylase antibodies.

BACKGROUND AND PURPOSE: High levels of glutamic acid decarboxylase (GAD)-ab were initially described in patients with stiff person syndrome, and have since also been observed in patients with other neurological diseases. Temporal lobe epilepsy (TLE) seems to be specially associated. Our purpose is to describe the prevalence of GAD-ab in patients with TLE, and to characterize the clinical-immunological profile of TLE patients with high levels of GAD-ab. METHODS: An immunological profile including GAD-ab and antinuclear, anti-DNA, anti-cardiolipin, anti-transglutaminase and antithyroid antibodies was determined in a consecutive series of patients with TLE. As adulthood onset is the least common onset in TLE + hipocampal sclerosis and febrile seizures, we selected patients whose onset was after 30 years of age, to expand the spectrum of aetiologies. Patients were divided into two groups: known aetiology, 19 patients (45%) and unknown aetiology, 23 (55%). The clinical-immunological study included TLE patients with high GAD-ab levels (>1000 IU). RESULTS: Amongst 42 patients, serum GAD-ab levels were positive in 5 (152-11, 963 IU/ml), all from the unknown aetiology group. Thus, GAD-ab levels were positive in 21.7% and high in 8.7% of the unknown aetiology group. The immunological profile study included nine patients (seven pharmacoresistant), of whom six were women (66%) with mean age 41 years. Three patients reported acute debut, four (44%) insulin-dependent diabetes mellitus, five (55%) other concomitant autoimmune diseases, four (44%) memory impairment and four moderate-to-severe mood disturbance. Intrathecal synthesis of GAD-ab was observed in seven patients (77%). CONCLUSIONS: Temporal lobe epilepsy with GAD-ab is not a rare condition. In the subgroup of patients with high titres, this epilepsy is often pharmacoresistant and associated with memory impairment, depression and other autoimmune diseases.

Actitud de los profesionales de Atención Primaria frente al tabaco / No disponible

OBJETIVOS. 1.o Cuantificar el número de fumadores entre los profesionales sanitarios (PS) de Atención Primaria(AP). 2.o Conocer el nivel de formación en el abordaje del fumador. 3.o Analizar los factores que pueden influir en dicho abordaje. DISEÑO. Estudio descriptivo-transversal. EMPLAZAMIENTO. Atención Primaria. PARTICIPANTES. Población diana (N): 1.250 profesionales. Población muestral (n): 297 (intervalo de confianza [IC]95%, e = 5%, p = 40%).MEDICIONES PRINCIPALES. Encuesta anónima (29ítems) y auto-cumplimentada. Variables: sociodemográficas, patrón-consumo, actitud ante su abandono, abordaje de la deshabituación. Análisis estadístico: descriptivo, t-Test, ANOVA, ji-cuadrado, regresión logística. RESULTADOS. El 56,8% son médicos (IC 95% 51,2-62%).Edad: 41,71 (IC 95% 41,1-42,3 años). El 28,7% son fumadores (17% fuma > 20 cigarrillos/día). Los fumadores (p =0,003), enfermeros/as (p = 0,007) y PS mujeres (p = 0,021)piensan que debe crearse un lugar en el centro de salud (CS) para fumadores (p = 0,003). El 17,2% no quiere abandonarlo. El 41,2% ha recibido formación en tabaco, estando más formado el médico (p = 0,0001) y el exfumador (31,8%; p =019), que es el que más recomienda el abandono a sus pacientes (24,3%; p = 0,017). La edad superior y el género masculino son los factores diferenciadores (y = -8,35+1,63 x género+ 0,69 x edad) (p = 0,0001). El 23% de los PS consideran fumar un hábito. El tabaquismo es poco valorado como factor de riesgo cardiovascular (p = 0,002). CONCLUSIONES. 1. Alto número de fumadores con consumo elevado. 2. El fumador valora la necesidad de tener un lugar para fumar. 3. El exfumador está más formado, aconseja y presenta mayor capacidad para abordar el tabaquismo. 4. Edad y género son los factores más determinantes en el abordaje del fumador

OBJECTIVES. 1. Measure number of smokers among primary health care professionals (PHCP). 2. Know the training level in the approach to the smoker. 3. Analyze the factors that may influence such approach. DESIGN. Descriptive-cross-sectional study. SITE. Primary Health Care. PARTICIPANTS. Target population (N): 1250 professionals. Sample population (N): 297 (95% CI, e = 5%, p = 40%).PRIMARY MEASUREMENTS. Anonymous survey (29items) and self-applied. Variables: sociodemographic, pattern-consumption; attitude to abandonment; de habituation approach. Statistical analysis: descriptive, T-test, ANOVA, chi-squared, logistic regression. RESULTS. 59.8% doctors (95% C 51.2%-62%). Age: 41.71(95% CI 41.1 - 42.3 years). 28.7% smokers (17% smoke > 20cig/day). Smokers (p = 0.003), ill subjects (p = 0.007) and female PHCP (p = 0.021) think that a site should be created for smokers (p = 0.003) in the health care sites (HCS). A total of 17.2% subjects do not want to quit and 41.2% have received education about smoking, it being the male doctor (p =0.0001) and ex-smoker (31.8%; p = 019), who most recommends their patient to quit smoking (24.3%; p = 0.017). Older age and male gender are the differentiating factors (y = -8.35+1.63 x gender + 0.69 x age) (p = 0.0001). A total of 23% PHCP consider that smoking is a habit. Smoking is not very evaluated as a cardiovascular risk factor (p = 0,002). CONCLUSIONS. 1. A high number of smokers with elevated consumption. 2. The smoker evaluates the need to have a place to smoke. 3. The ex-smoker is more trained, and recommends and has greater capacity to approach the smoking habit. 4. Age and gender are the most determining factors in the approach to the smoker

Xeroderma pigmentoso.Dos casos más en España / Xeroderma pigmentosum

No disponible

[Rational use of antibiotics in pediatrics: impact of a rapid test for detection of beta-haemolytic group A streptococci in acute pharyngotonsillitis]. / Empleo racional de los antibióticos en pediatría: impacto de la aplicación de un test rápido de detección de estreptococo beta-hemolítico del grupo A en la faringoamigdalitis aguda.

OBJECTIVES: To assess the reliability and validity of a rapid test for the identification of Streptococcus pyogenes in the pharyngeal exudate of children presenting with pharyngotonsillitis. To evaluate the impact of its use in outpatient clinics on antibiotic use, on the incidence of second medical visits and complications, and on the degree of parental satisfaction. PATIENTS AND METHODS: After a clinical diagnosis of acute pharyngitis was established and written informed consent obtained from the parents, dual throat swabs were collected from 430 children who attended the emergency department of our hospital or the pediatric offices of three health centers in our area. The first specimen was examined by the rapid test, QuickVue Flex Strep A, and the second one was sent to the laboratory for conventional culture. As a rule, antibiotics were indicated only when the rapid test was positive. Special emphasis was placed on explaining to parents that treatment was not necessary when the test was negative. Telephone follow-up was provided to the family during the next four weeks, after which a satisfaction survey was carried out. RESULTS: The sensitivity of the investigated rapid test was 91.2% (negative predictive value: 96.5%) and specificity was 96.2% (positive predictive value: 90.4%). Antibiotics were given to 41.9% of the patients, approximately half the expected rate in the absence of the rapid test. There was no significant difference in the number of second visits or hospitalizations between the groups of treated and non-treated subjects. Clinical evolution was good in all cases. The degree of parental satisfaction was very high, independent of the treatment given to the patients. CONCLUSIONS: The rapid test for the detection of group A streptococci is a reliable tool for the selection of patients able to benefit from antibiotic treatment. It is easy to handle and apply and its use allows a significant reduction in the administration of antibiotics in pharyngotonsillitis. Most users accept and are satisfied with this novel diagnostic and therapeutic procedure.

Amaurosis cortical transitoria por Metotrexato. A propósito de un caso / Transient cortical blindness due to Methotrexate. Report of a case

Propósito: Presentar un caso de amaurosis bilateral en el contexto de una encefalopotía metabólica en una paciente tratada por un linfoma de alto grado de malignidad mediante un esquema de poliquimioterapia que incluía Citarabina, Vincristina y Metotrexato como principales drogas neurotóxicas. Material y métodos: Paciente de 29 años que presentó una amaurosis cortical bilateral en el contexto de un síndrome de lisis tumoral tras administración de quimioterapia, comprometiéndose el aclaramiento plasmático de Metotrexato, citostático al que atribuimos la clínica neurológica que se describe y analiza. Resultado: La neurotoxicidad revirtió completamente tras el tratamiento de rescate con Leucovorin. Conclusiones: La amaurosis cortical es un tipo de toxicidad neurológica aguda del Metotrexato transitoria y reversible. Su tratamiento se basa en el soporte hemodinámico y el uso de Leucovorin (AU)

Empleo racional de los antibióticos en pediatría: impacto de la aplicación de un test rápido de detección de estreptococo beta-hemolítico del grupo a en la faringoamigdalitis aguda / Rational use of antibiotics in paediatrics: impact of a rapid test for detection of ß-haemolytic group A streptococci in acute pharyngotonsillitis

Objetivos: Analizar la fiabilidad y validez de un test rápido para la identificación de Streptococcus pyogenes en exudado faríngeo de niños con faringoamigdalitis aguda. Evaluar el impacto de su aplicación ambulatoria sobre la utilización de antibióticos, la incidencia de segundas visitas y complicaciones y el grado de satisfacción de los usuarios. Pacientes y métodos Tras proceder al diagnóstico clínico de faringitis aguda, informar a los padres y obtener su consentimiento escrito, se realizó frotis faringoamigdalar con 2 torundas a 430 niños atendidos en el servicio de urgencias de nuestro hospital o en las consultas de pediatría de 3 centros de salud de la zona. Con una muestra se efectuó el test rápido QuickVue(r) Flex Strep A, enviándose la otra al laboratorio para cultivo convencional. Salvo excepciones, se indicó tratamiento antibiótico sólo si el test rápido era positivo, haciéndose especial hincapié en explicar la ausencia de indicación de antibioterapia en el caso contrario. Se proporcionó seguimiento telefónico a los familiares durante 4 semanas, pasando al final una encuesta de satisfacción. Resultados La sensibilidad del test rápido fue del 91,2 por ciento (valor predictivo negativo 96,5 por ciento) y la especificidad 96,2 por ciento (valor predictivo positivo 90,4 por ciento). Recibió tratamiento antibiótico el 41,9 por ciento de los pacientes, aproximadamente la mitad de lo esperado en ausencia del test rápido. No se encontraron diferencias significativas en el número de segundas visitas ni de hospitalizaciones entre los grupos de tratados y no tratados. La evolución clínica fue favorable en todos los casos. El grado de satisfacción de los familiares resultó muy elevado entre los encuestados, independientemente de que el paciente hubiese recibido antibiótico o no. Conclusiones El test rápido citado tiene una sensibilidad y especificidad adecuadas para orientar sin riesgos el tratamiento. Es de fácil manejo y aplicación, y su uso permite una disminución significativa del empleo de antibióticos en esta patología. La gran mayoría de usuarios acepta y está satisfecha con esta nueva aproximación diagnóstico-terapéutica (AU)

Extracciones secuenciales de Cu y Cd en sedimentos de aguas de desecho

Empleando la técnica de Especiación o de las Extracciones Secuenciales, se midieron las diferentes fracciones en las que los metales Cd y Cu se asocian a los diferentes componentes cuyo origen está relacionado a aguas de desecho urbano e industrial

Determinación de cobre y cadmio en diferentes fracciones granulométricas en lodos de aguas de desecho

Se realizó un estudio del lodo proveniente de un lago que es nutrido con aguas pretratadas de desechos urbanos e industriales, midiéndose los totales de cadmio y cobre en tres etapas se muestreo; en paralelo se realizó el análisis por clase granulométrico de los metales, para determinar si existe alguna correlación en la determinación de cadmio y cobre con el tamaño de grano y la naturaleza del sedimento. Se halló que la mayor parte del Cu y del Cd se concentró en la fracción menor a 0.074 mn. El cobre total presentó un aumento notable en los meses de junio y setiembre, aumento que probablemente se haya debodo a que el lago no fuí limpiado, lo que contribuyó quizá a ello

Determinación de cobre y cadmio en diferentes fracciones granulométricas en lodos de aguas de desecho

Se realizó un estudio del lodo proveniente de un lago que es nutrido con aguas pretratadas de desechos urbanos e industriales, midiéndose los totales de cadmio y cobre en tres etapas se muestreo; en paralelo se realizó el análisis por clase granulométrico de los metales, para determinar si existe alguna correlación en la determinación de cadmio y cobre con el tamaño de grano y la naturaleza del sedimento. Se halló que la mayor parte del Cu y del Cd se concentró en la fracción menor a 0.074 mn. El cobre total presentó un aumento notable en los meses de junio y setiembre, aumento que probablemente se haya debodo a que el lago no fuí limpiado, lo que contribuyó quizá a ello

Extracciones secuenciales de Cu y Cd en sedimentos de aguas de desecho

Empleando la técnica de Especiación o de las Extracciones Secuenciales, se midieron las diferentes fracciones en las que los metales Cd y Cu se asocian a los diferentes componentes cuyo origen está relacionado a aguas de desecho urbano e industrial

Interaction of anthracyclines with nucleotides and related compounds studied by spectroscopy.

Interaction of the antitumour anthracyclines with mononucleotides and related compounds can be assessed through the perturbation of the spectral properties of the drugs. Purine-derived compounds induce spectral changes more efficiently than pyrimidine derivatives. No marked differences are observed when mono-, di- or triphosphate derivatives, deoxy forms, nucleosides or free nitrogen bases are used for the experiments. Visible absorbance data indicate the existence of a drug/purine nucleotide complex in solution. Assuming a simple equilibrium, this complex would be of low affinity (Keq 100 M-1). Circular dichroism spectra of daunomycin in the presence of ATP suggest that the resulting daunomycin/ATP complexes are not comparable to those formed by intercalation of the anthracycline into DNA. 31P-NMR of ATP in the presence of daunomycin does not support the notion that anthracycline/nucleotide complex formation involves interaction through the phosphate group(s) of the nucleotide. Analysis of the quenching of the drug's intrinsic fluorescence in the presence of nucleotides indicates a predominantly collisional, dynamic quenching mechanism. Values in the 2-6 mM and 85-100 mM range, respectively, are estimated for the reciprocal of the Stern-Volmer quenching constant for a variety of purine and pyrimidine derivatives. This indicates that purine derivatives are highly efficient quenchers of the fluorescence of anthracyclines, while pyrimidine derivatives are not. The fluorescence lifetime of daunomycin in the absence of quencher and the Stern-Volmer quenching constants obtained for different nucleotides are used to calculate the apparent bimolecular rate constants for collisions between fluorophore and quencher to occur. Values of (2-3) X 10(11) and 1 X 10(10) M-1 X s-1 are obtained, respectively, for purine and pyrimidine derivatives. This suggests a combination of static and dynamic quenching processes for purine compounds, which is consistent with the drug/purine nucleotide complex formation detected by visible absorbance. Because of the high intracellular concentration of certain nucleotides, particularly ATP, the above processes are predicted to be highly significant 'in vivo'.