Eficacia y seguridad de la profilaxis con emicizumab en la hemofilia A: estudio de 13 pacientes / Efficacy and safety of prophylaxis with emicizumab in hemophilia A: A study of 13 patients

Introducción: Emicizumab es el primer tratamiento no sustitutivo para profilaxis en hemofilia A grave. Objetivos: Describir los resultados de nuestros pacientes en profilaxis con emicizumab, según la práctica clínica habitual. Material y métodos: Seguimiento de 13 pacientes desde el inicio de la profilaxis, registro de hemorragias, cirugías, reacciones adversas y necesidad o no de tratamiento factorial. Se midieron los niveles plasmáticos en las visitas de seguimiento; la técnica ha sido coagulativa en una etapa, modificada mediante dilución 1:20. Resultados: La mediana de niveles plasmáticos fue de 52,2mg [30,7-71,9]. La profilaxis resultó segura y eficaz; solamente se contabilizó una hemorragia espontánea a lo largo del tiempo y no precisó tratamiento. No hubo episodios tromboembólicos ni reacciones graves de hipersensibilidad, anafilaxia o anafilactoides. La incidencia de reacciones en el lugar de la inyección fue del 8%. El abordaje perioperatorio en las intervenciones menores se llevó a cabo sin tratamiento factorial coadyuvante, en 2 cirugías mayores se precisó una dosis de concentrado de FVIII plasmático en el paciente con hemofilia A sin inhibidor y FVII en el paciente con inhibidor, y fue suficiente para parar la hemorragia. Conclusión: Este estudio demostró que la farmacocinética de emicizumab y su vida media aseguran niveles óptimos con tratamiento profiláctico a las dosis establecidas en la ficha técnica.(AU)

Introduction: Emicizumab is the first non-replacement therapy for prophylaxis in severe hemophilia A. Aims: The principal aim of this study is to describe the results of our patients in prophylaxis with emicizumab, according to the usual clinical practice. Material and methods: Follow-up of 13 patients from the start of prophylaxis, recording of bleeding, surgeries, adverse reactions and the need or not for factor therapy. Plasma levels were measured at follow-up visits, the technique was coagulative in one stage, modified by 1:20 dilution. Results: Median plasma levels were 52.2mg [30.7–71.9]. Prophylaxis was safe and effective; only one spontaneous haemorrhage was recorded over time and no treatment was required. There were no thromboembolic events or serious hypersensitivity, anaphylaxis or anaphylactoid reactions. The incidence of injection site reactions was 8%. Perioperative management in minor interventions was carried out without adjuvant factorial therapy, in 2 major surgeries a dose of plasmatic FVIII concentrate was required in the patient with hemophilia A without inhibitor and FVII in the patient with inhibitor, and it was sufficient to stop the bleeding. Conclusion: This study demonstrated emicizumab pharmacokinetics and its half life ensure optimal levels with prophylaxis treatment at doses established in the technical data sheet.(AU)

[Efficacy and safety of prophylaxis with emicizumab in hemophilia A: A study of 13 patients]. / Eficacia y seguridad de la profilaxis con emicizumab en la hemofilia A: estudio de 13 pacientes.

INTRODUCTION: Emicizumab is the first non-replacement therapy for prophylaxis in severe hemophilia A. AIMS: The principal aim of this study is to describe the results of our patients in prophylaxis with emicizumab, according to the usual clinical practice. MATERIAL AND METHODS: Follow-up of 13 patients from the start of prophylaxis, recording of bleeding, surgeries, adverse reactions and the need or not for factor therapy. Plasma levels were measured at follow-up visits, the technique was coagulative in one stage, modified by 1:20 dilution. RESULTS: Median plasma levels were 52.2mg [30.7-71.9]. Prophylaxis was safe and effective; only one spontaneous haemorrhage was recorded over time and no treatment was required. There were no thromboembolic events or serious hypersensitivity, anaphylaxis or anaphylactoid reactions. The incidence of injection site reactions was 8%. Perioperative management in minor interventions was carried out without adjuvant factorial therapy, in 2 major surgeries a dose of plasmatic FVIII concentrate was required in the patient with hemophilia A without inhibitor and FVII in the patient with inhibitor, and it was sufficient to stop the bleeding. CONCLUSION: This study demonstrated emicizumab pharmacokinetics and its half life ensure optimal levels with prophylaxis treatment at doses established in the technical data sheet.

Health-related quality of life in caregivers of community-dwelling individuals with disabilities or chronic conditions. A gender-differentiated analysis in a cross-sectional study.

BACKGROUND: Most care for people with chronic or disabling conditions living in the community is provided in the family context, and this care is traditionally provided by women. Providing informal care has a negative impact on caregivers' quality of life, which adds to existing health inequalities associated with gender. The aim of this study was to analyze factors associated with the health-related quality of life of caregivers and to determine their differences in a gender-differentiated analysis. METHODS: An observational, cross-sectional, multicenter study was conducted in primary healthcare. A total of 218 caregivers aged 65 years or older were included, all of whom assumed the primary responsibility for caring for people with disabling conditions for at least 6 months per year and agreed to participate in the CuidaCare study. The dependent variable was health-related quality of life, assessed with the EQ-5D. The explanatory variables tested were grouped into sociodemographic variables, subjective burden, caregiving role, social support and variables related to the dependent person. The associations between these variables and health-related quality of life were estimated by fitting robust linear regression models. Separate analyses were conducted for women and men. RESULTS: A total of 72.8% of the sample were women, and 27.2% were men. The mean score on the EQ-5D for female caregivers was 0.64 (0.31); for male caregivers, it was 0.79 (0.23). There were differences by gender in the frequency of reported problems in the dimensions of pain/comfort and anxiety/depression. The variables that were associated with quality of life also differed. Having a positive depression screening was negatively associated with quality of life for both genders: -0.31 points (95% CI: -0.47; -0.15) for female caregivers and -0.48 points (95% CI: -0.92; -0.03) for male caregivers. Perceived burden was associated with quality of life in the adjusted model for women (-0.12 points; 95% CI: -0.19; -0.06), and domestic help was associated in the adjusted model for male caregivers (-0.12 points; 95% CI: -0.19; -0.05). CONCLUSIONS: Gender differences are present in informal caregiving. The impact of providing informal care is different for male and female caregivers, and so are the factors that affect their perceived quality of life. It could be useful it incorporates a gender perspective in the design of nursing support interventions for caregivers to individualize care and improve the quality of life of caregivers. TRIAL REGISTRATION: NCT01478295 [ https://ClinicalTrials.gov ]. 23/11/2011.

Melatonin Improves Mood Status and Quality of Life and Decreases Cortisol Levels in Fibromyalgia.

BACKGROUND: Mood disturbances are implicated in the pathogenesis of fibromyalgia. The aim of this study was to assess the effect of different doses of melatonin on quality of life, mood status, pain, anxiety, and urinary cortisol levels in patients with fibromyalgia. METHODS: After a 10-day baseline period for the collection of data about participants' initial status, participants took different doses of melatonin for 10 consecutive days each, with placebo given during the 10 days either before or between melatonin doses. Participants' moods, quality of life, and pain levels were assessed using the Fibromyalgia Impact Questionnaire (FIQ), a Numerical Pain Scale (NPS), the State-Trait Anxiety Test (STAI), a Visual Analog Scale (VAS), and the Short Form-36 Health Survey (SF-36). Urinary cortisol levels were measured using enzyme-linked immunoassay. RESULTS: Doses of 9, 12, and 15 mg of melatonin were associated with decreases in the total score of the FIQ, NPS scores, and urinary cortisol levels. The State-Anxiety subscale of the STAI improved after the 12 mg dose. The scores on the VAS improved after the 9 mg dose. The dimensions evaluated in the SF-36 questionnaire improved after the 9 mg dose. CONCLUSION: Melatonin improved mood, anxiety levels, and quality of life while decreasing cortisol levels in patients with fibromyalgia.

Effectiveness of MiniMed 640G with SmartGuard® System for prevention of hypoglycemia in pediatric patients with type 1 diabetes mellitus. / Efectividad del sistema MiniMed 640G con SmartGuard® para la prevención de hipoglucemia en pacientes pediátricos con diabetes mellitus tipo 1.

INTRODUCTION/AIMS: Treatment with the MiniMed 640G-SmartGuard® system (640G-SG, sensor-augmented insulin pump system with low predicted glucose suspension feature) has been shown to decrease risk of hypoglycemia without altering metabolic control in patients with T1DM. The study purpose was to assess the impact of 640G-SG on hipoglycemia frequency and on metabolic control in a pediatric population with T1DM. PATIENTS/METHODS: A retrospective study on 21 children treated with 640G-SG. HbA1C, mean blood glucose (mg/dl), glucose variation coefficient, frequency of hypoglycemia (<70mg/dl) and hyperglycemia (>180mg/dl), daily capillary blood glucose measurements, ketosis/diabetic ketoacidosis, and severe hypoglycemic episodes were analyzed and compared before and during use of the system. Fasting blood glucose, frequency of sensor use and number and duration of system suspension events were also assessed in the last month of use of the system. RESULTS: All patients used the system continuously (5.0±2.1 months), with a median sensor use of 92%. Significant decreases were seen in hypoglycemia frequency (10.4±5.2% to 7.6±3.3%, p=.044) and number of capillary blood glucose measurements (11.3±2,2 to 8.1±2,1, p<.001), and there was no increase in hyperglycemia frequency (p=.65). Mean system suspension time was 3.1±1.2hours/day (37.3% of overnight stops). Changes in HbA1c, mean blood glucose, and variation coefficient were not significant. No patient experienced diabetic ketoacidosis or severe hypoglycemia. CONCLUSIONS: The sensor-augmented pump with the predictive low glucose suspension management system, as implemented in the 640G-SG system, can help avoid risk of hypoglycemia without significantly affecting metabolic control or causing diabetic ketoacidosis, and decrease the burden of additional capillary blood glucose measurements in our pediatric cohort.

Efectividad del sistema MiniMed 640G con SmartGuard(R) para la prevención de hipoglucemia en pacientes pediátricos con diabetes mellitus tipo 1 / Effectiveness of MiniMed 640G with SmartGuard(R) System for prevention of hypoglycemia in pediatric patients with type 1 diabetes mellitus

Introducción/objetivos: El tratamiento con el sistema MiniMed 640G-SmartGuard(R) (640G-SG, infusión subcutánea continua de insulina con sensor de monitorización continua de glucosa intersticial implementado con suspensión automática por predicción de hipoglucemia) ha demostrado en estudios previos, disminución del riesgo de hipoglucemia sin producir alteraciones en el control metabólico en pacientes con DM1. El objetivo del estudio fue evaluar la efectividad del sistema 640G-SG sobre la frecuencia de hipoglucemia y su impacto sobre el control metabólico en una población pediátrica con DM1. Pacientes/métodos: Estudio retrospectivo que incluyó 21 niños tratados con 640G-SG. Se analizaron previo y durante su uso: HbA1c, glucemia media (mg/dl), coeficiente de variación de glucosa, frecuencia de hipoglucemia (<70mg/dl) e hiperglucemia (>180mg/dl), controles de glucemia capilar/día, episodios de cetosis/cetoacidosis e hipoglucemias graves. En el último mes de uso: glucemia en ayunas, frecuencia de uso del sensor y número y duración de eventos de suspensión. Resultados: Los pacientes llevaron el sistema continuamente durante 5,0±2,1 meses con mediana de uso del 92%. Objetivamos disminución significativa de la frecuencia de hipoglucemia (10,4±5,2% a 7,6±3,3%, p=0,044) y del número de controles de glucemia capilar/día (11,3±2,2 a 8,1±2,1, p<0,001), sin aumento de hiperglucemia (p=0,65). Duración media de suspensión de infusión de insulina 3,1±1,2 h/día (37,3% suspensión nocturna). Sin cambios significativos en HbA1c, glucemia media, ni coeficiente de variación. Ningún paciente presentó cetosis/cetoacidosis ni hipoglucemia grave. Conclusiones: La suspensión automática de infusión de insulina por predicción de hipoglucemia implementada en MiniMed 640G-SmartGuard(R) ayuda a evitar el riesgo de hipoglucemia, sin empeorar el control metabólico ni provocar cetosis/cetoacidosis, y reduce la carga de controles adicionales de glucemia en nuestra cohorte pediátrica (AU)

Introduction/aims: Treatment with the MiniMed 640G-SmartGuard(R) system (640G-SG, sensor-augmented insulin pump system with low predicted glucose suspension feature) has been shown to decrease risk of hypoglycemia without altering metabolic control in patients with T1DM. The study purpose was to assess the impact of 640G-SG on hipoglycemia frequency and on metabolic control in a pediatric population with T1DM. Patients/methods: A retrospective study on 21 children treated with 640G-SG. HbA1C, mean blood glucose (mg/dl), glucose variation coefficient, frequency of hypoglycemia (<70mg/dl) and hyperglycemia (>180mg/dl), daily capillary blood glucose measurements, ketosis/diabetic ketoacidosis, and severe hypoglycemic episodes were analyzed and compared before and during use of the system. Fasting blood glucose, frequency of sensor use and number and duration of system suspension events were also assessed in the last month of use of the system. Results: All patients used the system continuously (5.0±2.1 months), with a median sensor use of 92%. Significant decreases were seen in hypoglycemia frequency (10.4±5.2% to 7.6±3.3%, p=.044) and number of capillary blood glucose measurements (11.3±2,2 to 8.1±2,1, p<.001), and there was no increase in hyperglycemia frequency (p=.65). Mean system suspension time was 3.1±1.2hours/day (37.3% of overnight stops). Changes in HbA1c, mean blood glucose, and variation coefficient were not significant. No patient experienced diabetic ketoacidosis or severe hypoglycemia. Conclusions: The sensor-augmented pump with the predictive low glucose suspension management system, as implemented in the 640G-SG system, can help avoid risk of hypoglycemia without significantly affecting metabolic control or causing diabetic ketoacidosis, and decrease the burden of additional capillary blood glucose measurements in our pediatric cohort (AU)

Impacto de la educación diabetológica en el control de la diabetes mellitus tipo 1 en la edad pediátrica / Impact of diabetes education on type 1 diabetes mellitus control in children

Introducción: En la diabetes mellitus tipo1 (DM1) la educación diabetológica es fundamental para lograr los objetivos de tratamiento. El objetivo de este estudio es determinar si el nivel de conocimientos diabetológicos de cuidadores/pacientes o los factores sociodemográficos afectan al control glucémico de niños y adolescentes con DM1. Pacientes y métodos: Se analiza el nivel de conocimientos de 105 cuidadores de niños y adolescentes con DM1 o de los pacientes adolescentes mediante una encuesta adaptada a la modalidad de tratamiento (múltiples dosis de insulina [MDI] o bomba de infusión subcutánea continua de insulina [ISCI]). Se considera la HbA1c media en el último año como marcador del control metabólico. Resultados: La media de HbA1c fue similar en ambos grupos de tratamiento (6,6±0,5 para MDI y 6,5±0,5% para ISCI, p=0,63), siendo discretamente más alta en niños mayores de 12años. Los pacientes con bomba tenían un mayor tiempo de evolución de la diabetes y obtuvieron peores resultados porque además la exigencia teórica de la encuesta fue superior por la mayor complejidad de manejo (p=0,005). Los cuidadores con nivel de estudios más bajos obtuvieron peores puntuaciones, si bien las cifras de HbA1c de sus hijos fueron más bajas, en probable relación con una mayor dedicación al cuidado de la enfermedad. Conclusiones: El nivel de conocimientos analizados fue alto, y esto se asoció con un buen control metabólico. Son necesarios estudios que evalúen la influencia de los conocimientos de los cuidadores en pacientes con diferentes grados de control metabólico (AU)

Introduction: Diabetes education is an essential tool to achieve treatment objectives in type1 diabetes mellitus (T1DM). The aim of this study was to determine if understanding of diabetes by caregivers/patients or sociodemographic factors affect blood glucose control in children and adolescents with T1DM. Patients and methods: The level of knowledge of 105 caregivers of children and adolescents with T1DM was assessed using a survey adapted to the type of treatment used (multiple dose insulin [MDI] or continuous subcutaneous insulin infusion [CSII]). Mean HbA1c levels in the previous year was considered as metabolic control marker. Results: Mean HbA1c levels were similar in both treatment groups, with slightly higher values in children over 12years of age. Patients on CSII had a longer time since disease onset and had poorer results, maybe because the items were more difficult due to the higher level of knowledge required for this treatment modality (P=.005). Caregivers with lower educational levels achieved poorer scores in the survey, but mean HbA1c levels of their children were lower, probably because of their greater involvement in disease care. Conclusions: The level of knowledge of caregivers and/or patients with T1DM was high, and this was associated to good metabolic control. Studies to assess the impact of caregiver knowledge on metabolic control of children are needed (AU)

Impact of diabetes education on type 1 diabetes mellitus control in children. / Impacto de la educación diabetológica en el control de la diabetes mellitus tipo 1 en la edad pediátrica.

INTRODUCTION: Diabetes education is an essential tool to achieve treatment objectives in type1 diabetes mellitus (T1DM). The aim of this study was to determine if understanding of diabetes by caregivers/patients or sociodemographic factors affect blood glucose control in children and adolescents with T1DM. PATIENTS AND METHODS: The level of knowledge of 105 caregivers of children and adolescents with T1DM was assessed using a survey adapted to the type of treatment used (multiple dose insulin [MDI] or continuous subcutaneous insulin infusion [CSII]). Mean HbA1c levels in the previous year was considered as metabolic control marker. RESULTS: Mean HbA1c levels were similar in both treatment groups, with slightly higher values in children over 12years of age. Patients on CSII had a longer time since disease onset and had poorer results, maybe because the items were more difficult due to the higher level of knowledge required for this treatment modality (P=.005). Caregivers with lower educational levels achieved poorer scores in the survey, but mean HbA1c levels of their children were lower, probably because of their greater involvement in disease care. CONCLUSIONS: The level of knowledge of caregivers and/or patients with T1DM was high, and this was associated to good metabolic control. Studies to assess the impact of caregiver knowledge on metabolic control of children are needed.

Spectromicroscopy study of intercalation and exfoliation in polypropylene/montmorillonite nanocomposites.

We present a combined study by X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and scanning transmission X-ray microscopy (STXM) of the successful formation of nanocomposites of polypropylene with montmorillonite by melt processing, providing a complete picture of the intercalation and exfoliation processes taking place. The nanocomposites contained 5 wt % of an organically modified montmorillonite, and different amounts of polypropylene-graft-maleic anhydride, used as a polar compatibilizer. Microscopy reveals a complex morphology, with partial intercalation/exfoliation, which depends on the concentration of compatibilizer. STXM spectromicroscopy provides direct information of the presence of different polymer components at the polymer-silicate interfaces and details on the intercalation mechanism.

Estudio comparativo de la capacidad de fluir entre distintos materiales de obturación en conductos laterales artificiales mediante la técnica System B / Comparative analysis of the flow capacity among different obturation materials in artificial lateral canals by means of the System B technique

Introducción y objetivo: El objetivo del presente trabajo es comparar la penetración de distintas marcas comerciales de gutapercha así como de Resilón® en los conductos laterales mediante el uso de la técnica de ola continua (System B).Material y métodos: Se han seleccionado bloques de resina con conductos principales simulados, teniendo cada uno un conducto lateral coronal y otro apical. Un tercer conducto lateral ha sido realizado entre los anteriores, con el fin de sustituir al apical. Un cono de gutapercha( Roeko®, Sybron Endo® y Maillefer®) o de Resilón® es termo plastificado en cada conducto lateral. Después de obtener la imagen radiográfica se realizaron las mediciones en un analizador de imagen y los datos se analizaron estadísticamente. Resultados y conclusiones: Más allá de 2 mm de la punta del System B no se ha observado penetración de ninguna de las presentaciones comerciales de gutapercha ni de Resilón®. Se han encontrado diferencias estadísticamente significativas en relación a la obturación del conducto lateral superior (p≤0,05), siendo el Resilón® el material que más ha penetrado (AU)

Introduction and objective: The objective of the study was to compare the penetration of different commercial brands of gutta-percha and Resilon® in the lateral canals using the continuous wave technique (System B).Material and methods: We selected blocks of resin with simulated main canals, each with a lateral coronal canal and apical canal. A third lateral canal was made between these two, with the purpose of substituting the apical canal. Agutta-percha cone (Roeko®, Sybron Endo® or Maillefer®) or Resilon® was thermoplastified in each lateral canal. After obtaining the radiograph, we took measurements in an image analyser and statistically analysed the data. Results and conclusions: Beyond the 2 mm of the System B point, none of the commercial presentations of gutta-percha or Resilon® demonstrated penetration. Statistically significant differences were found as regards the obturation of the upper lateral canal (p≤0.05), with Resilon® recording the highest penetration (AU)

Niveles de anticuerpos bactericidas frente a meningococo C tras la vacunación de niños de 2 a 6 años de edad en Andalucía / Levels of bactericidal antibodies against meningococcus C following the vaccination of children between 2 and 6 years of age in Andalusia

FUNDAMENTO: En 1997 el 18,5 por ciento de los casos de enfermedad meningocócica por serogrupo C en Andalucía fueron niños de 2 a 4 años de edad; edades donde respuesta inmune inicial y duración de la vacuna antimeningocócica de polisacárido capsular A+C, es menor que en edades superiores. Se diseñó una investigación para medir la respuesta inmune producida por esta vacuna, en niños de 2 a 6 años de edad, y compararla con la inmunidad natural presente en niños no vacunados. MÉTODOS: I.- Doble estudio de seguimiento: a) grupos de niños previamente vacunados y grupos control, b) grupo de niños que iba a ser vacunado, para análisis pre y postvacunal (1, 6 y 12 meses) y grupo control. II.- La actividad bactericida se midió según protocolo estandarizado del CDC frente a cepa de N. meningítidis C-11. Los sueros con título de actividad bactericida (TAB) ³ 1:8 se consideraron protectores. RESULTADOS: Al mes y a los 2 meses de vacunarse la proporción de TAB³ 1:8 era significativamente superior a la del grupo control (65,5 por ciento y 73,9 por ciento frente a 2,2 por ciento y 12 por ciento. En el prevacunal y en el postvacunal a los 6, 7, 12 y 13 meses no se observó diferencia significativa entre vacunados y controles. CONCLUSIONES: Las diferencias entre vacunados y no vacunados 1 y 2 meses después de la vacunación indican seroconversión en los vacunados. Para el grupo de edad de 2 a 6 años la actividad bactericida adquirida declina rápidamente, ya que a los 6 meses dejan de observarse diferencias con el grupo control (AU)