Asimetría escapular por agenesia congénita de trapecio unilateral: a propósito de un caso / Case report: Scapular asymmetry caused by congenital unilateral absence of trapezius

La agenesia completa unilateral de trapecio es una afección infrecuente, reportada anteriormente en la literatura tras su hallazgo en muestras cadavéricas. Afecta a la estática, biomecánica y funcionalidad de la cintura escapular, por lo que es especialmente importante realizar una exhaustiva exploración física del paciente en consulta para descartarla o sospecharla. Presentamos el caso de un niño de 8 años con asimetría de la cintura escapular y escápula alada, remitido a la consulta de Rehabilitación por sospecha de distrofia facioescapulohumeral. La RM confirmó la agenesia de músculo trapecio derecho. No había alteración de la funcionalidad en el paciente. No se encontraron otras anomalías congénitas.(AU)

Congenital unilateral absence of trapezius is a rare condition, previously reported in cadaveric specimens. It can cause static shoulder asymmetry and affects the scapular biomechanics and functionality, so complete physical examination of the patient becomes important in order to dimiss or suspect an anomaly.We present a case of a 8 years old boy with asymmetry and scapular winging, who was referred to rehabilitation, suspected facioscapulohumeral dystrophy. An MRI scan of cervical spine and shoulder confirmed the absence of the right trapezius muscle. There were no functional disabilities. No other significant congenital anomalies were found.(AU)

[Case report: Scapular asymmetry caused by congenital unilateral absence of trapezius]. / Asimetría escapular por agenesia congénita de trapecio unilateral: a propósito de un caso.

Congenital unilateral absence of trapezius is a rare condition, previously reported in cadaveric specimens. It can cause static shoulder asymmetry and affects the scapular biomechanics and functionality, so complete physical examination of the patient becomes important in order to dimiss or suspect an anomaly. We present a case of a 8 years old boy with asymmetry and scapular winging, who was referred to rehabilitation, suspected facioscapulohumeral dystrophy. An MRI scan of cervical spine and shoulder confirmed the absence of the right trapezius muscle. There were no functional disabilities. No other significant congenital anomalies were found.

Workplace aggressions on hospital workers: A current and prevalent problem with a high demand for training.

BACKGROUND: Workplace aggressions on hospital workers is a very frequent and under-reported problem. OBJECTIVE: The novel objective of our study was to analyze the number of workplace aggressions per hospital worker. Other objectives of the study were to analyze the management knowledge and interest in receiving training on aggressions by hospital workers. METHODS: An anonymous survey was handed out among all professionals in a university hospital. RESULTS: A total of 1118 anonymous surveys were collected. The responders declared that throughout their working life they had suffered some sort of verbal aggression in the hospital in 766 cases (68.5%) and physical aggression in 393 cases (35.2%). Multiple logistic regression analyses found higher risk of receiving physical and verbal aggression in the nursing category and in the Emergency, Critical Care or Psychiatry Units, and a higher risk of receiving physical aggression in women. The score on the level of personal knowledge regarding the legal, physical, and psychological management of aggressions (score 0-10 for each of the 3 aspects) was 2.91±2.68 in legal management, 2.97±2.77 in psychological management and 2.91±2.76 in physical management. The opinion about the interest of receiving training (score from 0 to 10) on the legal management of hospital aggressions was 8.90±1.72, on psychological management was 8.85±1.78 and on physical management was 8.88±1.78. CONCLUSIONS: Workplace aggression on hospital workers mainly affects women, the nursing category and the Emergency, Critical Care or Psychiatry Units. Hospital workers showed little knowledge on the topic but a great interest in receiving training.

[Variability of the clinical expression of KCNB1 encephalopathy]. / Variabilidad de la expresión clínica de la encefalopatía KCNB1.

INTRODUCTION: The KCNB1 gene encodes a voltage-dependent potassium channel that regulates transmembrane currents in pyramidal neurons. Heterozygous variants have recently been associated with early-onset epileptic encephalopathies and intellectual disability, but their clinical characterisation has not yet been fully defined. AIM: To describe the clinical spectrum associated with variants of KCNB1 in paediatric patients. PATIENTS AND METHODS: Retrospective study of four patients from three families with KCNB1 encephalopathy, including an analysis of the clinical and electroencephalographic features of epilepsy, associated neurological manifestations and neurodevelopmental pattern. RESULTS: In two of them, the mutation in KCNB1 was de novo; the other two, who were sisters, inherited the variant from a parent with germline mosaicism. All had mild-to-moderate intellectual disability, two patients had autistic spectrum disorder and two had attention deficit hyperactivity disorder. Only case 2 displayed alterations in the MRI brain scan: progressive cortical atrophy. Three of them developed epilepsy (cases 1-3). Case 1: onset at 9.5 months with West syndrome that was well controlled with vigabatrine and zonisamide. Case 2: onset at 13 months with West syndrome, evolutionary development of polymorphic seizures (atonic, hypermotor, dysautonomic and tonic) that were refractory to 10 antiepileptic drugs and corticosteroids. Accompanied by a movement disorder characterised by ataxia, dyskinesias and tremor. Case 3: onset at 14.5 years with atonic seizures, multifocal EEG pattern and adequate control with levetiracetam. CONCLUSIONS: KCNB1 encephalopathy has a heterogeneous natural history, mainly with respect to epilepsy, ranging from patients with refractory epilepsy to patients without any epileptic seizures. All had neurodevelopmental disorders, such as intellectual disability or autism spectrum disorder, independent of epilepsy.

TITLE: Variabilidad de la expresión clínica de la encefalopatía KCNB1.Introducción. El gen KCNB1 codifica un canal de potasio dependiente del voltaje que regula corrientes transmembrana en las neuronas piramidales. Variantes en heterocigosis se han asociado recientemente con encefalopatías epilépticas de inicio precoz y discapacidad intelectual, pero su caracterización clínica no está completamente definida. Objetivo. Describir el espectro clínico asociado con variantes de KCNB1 en pacientes pediátricos. Pacientes y métodos. Estudio retrospectivo de cuatro pacientes procedentes de tres familias con encefalopatía KCNB1, analizando características clínicas y electroencefalográficas de la epilepsia, manifestaciones neurológicas asociadas y patrón de neurodesarrollo. Resultados. En dos, la mutación en KCNB1 fue de novo; las otras dos, hermanas, heredaron la variante de un progenitor con mosaicismo germinal. Todos presentaban discapacidad intelectual leve-moderada; dos pacientes, trastorno del espectro autista; y otros dos, trastorno por déficit de atención/hiperactividad. Sólo el caso 2 mostro´ alteraciones en la resonancia magnética cerebral: atrofia cortical evolutiva. Tres desarrollaron epilepsia (casos 1-3). Caso 1: inicio a los 9,5 meses con síndrome de West bien controlado con vigabatrina y zonisamida. Caso 2: inicio a los 13 meses con síndrome de West; desarrollo evolutivo de crisis polimorfas (atónicas, hipermotoras, disautonómicas y tónicas) refractarias a 10 fármacos antiepilépticos y corticoides. Asocio´ trastorno del movimiento caracterizado por ataxia, discinesias y temblor. Caso 3: inicio a los 14,5 años con crisis atónicas, patrón multifocal en el electroencefalograma y adecuado control con levetiracetam. Conclusiones. La encefalopatía KCNB1 presenta una evolución natural heterogénea, principalmente respecto a la epilepsia, y se observan desde pacientes con epilepsia refractaria hasta pacientes sin crisis epilépticas. Todos cursaron con alteraciones del neurodesarrollo, como discapacidad intelectual o trastorno del espectro autista, de forma independiente a la epilepsia.

Variabilidad de la expresión clínica de la encefalopatía KCNB1 / Variability of the clinical expression of KCNB1 encephalopathy

Introducción: El gen KCNB1 codifica un canal de potasio dependiente del voltaje que regula corrientes transmembrana en las neuronas piramidales. Variantes en heterocigosis se han asociado recientemente con encefalopatías epilépticas de inicio precoz y discapacidad intelectual, pero su caracterización clínica no está completamente definida.Objetivo: Describir el espectro clínico asociado con variantes de KCNB1 en pacientes pediátricos. Pacientes y métodos: Estudio retrospectivo de cuatro pacientes procedentes de tres familias con encefalopatía KCNB1, analizando características clínicas y electroencefalográficas de la epilepsia, manifestaciones neurológicas asociadas y patrón de neurodesarrollo. Resultados: En dos, la mutación en KCNB1 fue de novo; las otras dos, hermanas, heredaron la variante de un progenitor con mosaicismo germinal. Todos presentaban discapacidad intelectual leve-moderada; dos pacientes, trastorno del espectro autista; y otros dos, trastorno por déficit de atención/hiperactividad. Sólo el caso 2 mostro´ alteraciones en la resonancia magnética cerebral: atrofia cortical evolutiva. Tres desarrollaron epilepsia (casos 1-3). Caso 1: inicio a los 9,5 meses con síndrome de West bien controlado con vigabatrina y zonisamida. Caso 2: inicio a los 13 meses con síndrome de West; desarrollo evolutivo de crisis polimorfas (atónicas, hipermotoras, disautonómicas y tónicas) refractarias a 10 fármacos antiepilépticos y corticoides. Asocio´ trastorno del movimiento caracterizado por ataxia, discinesias y temblor. Caso 3: inicio a los 14,5 años con crisis atónicas, patrón multifocal en el electroencefalograma y adecuado control con levetiracetam. Conclusiones: La encefalopatía KCNB1 presenta una evolución natural heterogénea, principalmente respecto a la epilepsia, y se observan desde pacientes con epilepsia refractaria hasta pacientes sin crisis epilépticas...(AU)

Introduction: The KCNB1 gene encodes a voltage-dependent potassium channel that regulates transmembrane currents in pyramidal neurons. Heterozygous variants have recently been associated with early-onset epileptic encephalopathies and intellectual disability, but their clinical characterisation has not yet been fully defined. Aim: To describe the clinical spectrum associated with variants of KCNB1 in paediatric patients. Patients and methods. Retrospective study of four patients from three families with KCNB1 encephalopathy, including an analysis of the clinical and electroencephalographic features of epilepsy, associated neurological manifestations and neurodevelopmental pattern. Results: In two of them, the mutation in KCNB1 was de novo; the other two, who were sisters, inherited the variant from a parent with germline mosaicism. All had mild-to-moderate intellectual disability, two patients had autistic spectrum disorder and two had attention deficit hyperactivity disorder. Only case 2 displayed alterations in the MRI brain scan: progressive cortical atrophy. Three of them developed epilepsy (cases 1-3). Case 1: onset at 9.5 months with West syndrome that was well controlled with vigabatrine and zonisamide. Case 2: onset at 13 months with West syndrome, evolutionary development of polymorphic seizures (atonic, hypermotor, dysautonomic and tonic) that were refractory to 10 antiepileptic drugs and corticosteroids. Accompanied by a movement disorder characterised by ataxia, dyskinesias and tremor. Case 3: onset at 14.5 years with atonic seizures, multifocal EEG pattern and adequate control with levetiracetam.Conclusions: KCNB1 encephalopathy has a heterogeneous natural history, mainly with respect to epilepsy, ranging from patients with refractory epilepsy to patients without any epileptic seizures. All had neurodevelopmental disorders, such as intellectual disability or autism spectrum disorder, independent of epilepsy.(AU)

QSAR and molecular docking modelling of anti-leishmanial activities of organic selenium and tellurium compounds.

Leishmaniasis affects mainly rural areas and the poorest people in the world. A computational study of the antileishmanial activity of organic selenium and tellurium compounds was performed. The 3D structures of the compounds were optimized at the wb97xd/lanl2dz level and used in the quantitative structure-activity relationship (QSAR) analysis. The antileishmanial activity was measured by L. donovani ß carbonic anhydrase inhibition (Ki) and the half-maximal inhibitory concentration (IC50) against L. infantum amastigotes. The dataset was divided into training (75%) and test sets (25%) by using a k-means clustering algorithm. For pKi prediction, model M3 with seven 3D topographic descriptors was characterized by the following statistical parameters: r 2 = 0.879, Q 2 LOO = 0.822, and Q 2 ext = 0.840. For pIC50 prediction, model M12 with six attributes was characterized by the following statistical parameters: r 2 = 0.907, Q 2 LOO = 0.824, and Q 2 ext = 0.795. Both models met all the requirements of Tropsha´s test, which implies predictions of pIC50 and pKi activities with high accuracy. Concomitantly, favourable interactions of the sulphonamide group with the Zn atom in the protein were revealed by the docking analysis.

Pregnancy in autoimmune diseases in the sub-Saharan zone: the experience of the University Hospital of Libreville Department of Internal Medicine.

Autoimmune diseases are a group of heterogeneous conditions responsible for polymorphic clinical and biological manifestations. Because pregnancy activates them and promotes gestational complications, it is difficult for women with these diseases. Pregnancy and autoimmune diseases have rarely been studied in sub-Saharan Africa. We report the experience of the Internal Medicine Department of the University Hospital of Libreville. Conducted retrospectively for 2008 through 2011, and prospectively from 2012 through August 31, 2018, this descriptive and analytical study examined the records at the Department of Internal Medicine of the University Hospital Center of Libreville of women with a known autoimmune disease, receiving regular care there, and who became pregnant after the diagnosis. During pregnancy, women were monitored and manÂged simultaneously in the departments of obstetrics and internal medicine. Data considered for this study were demographic data (Âge, sex, social status), type of autoimmune disease, including the diagnosis, the therapies used, extent of disease control, and time from diagnosis to each pregnancy. Obstetric data include the number of fetuses, obstetric complications, gestational Âge at and route of delivery, fetal sex, and Apgar score to 5 minutes (normal ≥ 7). Women had the following autoimmune diseases : systemic lupus erythematosus (SLE) (n = 16), Sjögren's disease (n = 3), inflammatory myopathy (n = 2), rheumatoid arthritis (n = 1), primary antiphospholipid syndrome (APS) (n = 1), and Still disease (n = 1).The overall averÂge Âge at diagnosis was 26.6 years (range : 13-40). The 24 women had 32 pregnancies. The mean interval from diagnosis to first pregnancy was 3.3 years, to the second pregnancy also 3.3 years (n = 6), and to the third (n = 2), 5 years. Disease was controlled for at least 2 years (n = 23) except for one woman with primary APS. Therapeutically, corticosteroids were used alone (n = 2) or combined with other immunomodulatory therapies (n = 32). Gestational complications included spontaneous abortions in the first trimester (n =2), in utero deaths (n = 2), perinatal death on day 12 (n = 1), and eclampsia (n = 2), one of which was complicated by a pulmonary embolism in the first pregnancy. The mean gestational Âge at delivery was 37 weeks. Intrauterine growth restriction affected 11 fetuses, and preterm delivery 18. There were 11 cesarean deliveries and 16 vaginal. Mean birth weight was 2353.3 grams, Apgar was ≥ 7 for all neonates except in one case of dermatomyositis complicating a neonatal death. The sex ratio was 13 male infants per 17 females. Women with optimal disease control can become pregnant and have positive pregnancy outcomes. This possibility has been little explored in sub-Saharan Africa; mystical-religious notions of conceptions persist and can prevent women from attempting to become prégnant . This experience with a short series of viable fetuses of women with autoimmune diseases is therefore encouraging and deserves to be continued.

Trail Making Test: Normative data for the Latin American Spanish-speaking pediatric population.

OBJECTIVE: To generate normative data for the Trail Making Test (TMT) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 3,337 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the TMT as part of a larger neuropsychological battery. The TMT-A and TMT-B scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on both scores, such that as children needed less time to complete the test while they become older. TMT-A scores were affected by age2 for all countries except, Cuba, Guatemala, and Puerto. TMT-B scores were affected by age2 for all countries except, Guatemala and Puerto Rico. Models indicated that children whose parent(s) had a MLPE >12 years of education needed less time to complete the test compared to children whose parent(s) had a MLPE ≤12 years for Mexico and Paraguay in TMT-A scores; and Ecuador, Mexico, Paraguay, and Spain for TMT-B scores. Sex affected TMT-A scores for Chile, Cuba, Mexico, and Peru, in that boys needed less time to complete the test than girls. Sex did not affect TMT-B scores. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the TMT in pediatric populations.

Symbol Digit Modalities Test: Normative data for Spanish-speaking pediatric population.

OBJECTIVE: To generate normative data for the Symbol Digit Modalities Test (SDMT) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the SDMT as part of a larger neuropsychological battery. SDMT scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age in all countries, such that score increased linearly as a function of age. In addition, age2 had a significant effect in all countries, except in Honduras and Puerto Rico. Models indicated that children whose parent(s) had a MLPE >12 years of education obtained higher score compared to children whose parent(s) had a MLPE ≤12 years for Chile, Guatemala, Mexico, and Spain. Sex affected SDMT score for Paraguay and Spain. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate interpretation of the SDMT with pediatric populations.

Valoración de la capacidad predictiva de la calculadora Garvan del riesgo de fractura a 10 años en una población española / Assessment of the predictive capacity of the Garvan calculator of 10 year risk of fracture in a Spanish population

Introducción: En los últimos años se han desarrollado varias herramientas de cálculo o escalas para valorar el riesgo de fractura por fragilidad a largo plazo. La calculadora Garvan no ha sido validada en la población española. El objetivo de este estudio fue observar su capacidad predictiva en una muestra de la población canaria y, por tanto, de la española. Material y métodos: Se incluyó a 121 pacientes a los que se les realizó un seguimiento de 10 años en nuestras consultas. A todos se les valoró el riesgo de fractura usando la calculadora Garvan y basándonos en los datos obtenidos en la primera visita realizada. Resultados: De los 121 pacientes, 30 sufrieron al menos una fractura osteoporótica a lo largo de los 10 años de seguimiento. El grupo de pacientes fracturados tenían en la escala Garvan un valor medio de riesgo de sufrir cualquier fractura por fragilidad de 27%, frente al 13% de aquellos que no sufrieron fractura (p<0,001). El área bajo la correspondiente curva ROC fue de 0,718 (IC-95% = 0,613 ; 0,824). En base a ella, se estimó que el punto de corte óptimo para considerar un alto riesgo de fractura por fragilidad fue 18,5%. A este valor le correspondió una sensibilidad de 0,67 (IC-95% = 0,47 ; 0,83) y una especificidad de 0,67 (IC-95% = 0,56 ; 0,77). Conclusiones: Nuestros resultados muestran que la escala Garvan predice adecuadamente el riesgo de fractura osteoporótica a 10 años en nuestra población. Un valor inferior a 18,5% permitiría establecer un riesgo de fractura bajo, pudiendo ser utilizada como herramienta de cribado (AU)

Introduction: Several calculation tools or scales have been developed in recent years to assess the risk of fracture due to long-term fragility. The Garvan calculator has not been validated in the Spanish population. This study aims to observe their predictive capacity in a population sample of the Canary Islands and, therefore, of the Spanish population. Material and Methods: We included 121 patients who were followed up for 10 years in our consultations. All were assessed the risk of fracture using the Garvan calculator and based on the data obtained in the first visit. Results: Of the 121 patients, 30 suffered at least one osteoporotic fracture over the 10-year follow-up period. The group of patients with fractures had on the Garvan scale an average risk value to suffer any fracturing fracture of 27%, compared to 13% of those who did not suffer fracture (p<0.001). The área under the corresponding ROC curve was 0.718 (CI-95% = 0.613 ; 0.824). Based on this, the estimated optimal cut-off point to consider a high risk fracture was 18.5%. This value corresponded to a sensitivity of 0.67 (CI-95% = 0.47 ; 0.83) and a specificity of 0.67 (CI-95% = 0.56 ; 0.77). Conclusions: Our results show that the Garvan scale adequately predicts the risk of 10-year osteoporotic fracture in our population. A value lower than 18.5% would allow us to establish a low fracture risk and could be used as a screening tool (AU)

Hb Moncloa: A new variant of haemoglobin that interferes in the quantification of Hb A1c.

BACKGROUND: In most routine laboratories in Spain, the commonly used method for evaluating HbA1c is ion-exchange high performance liquid chromatography (HPLC). The presence of a variant of Hb may interfere with the quantification of HbA1c. AIMS: Here, we report a novel haemoglobin variant, named Hb Moncloa, which was found during a routine health check at the Hospital Clínico San Carlos in Moncloa (Madrid), Spain. METHODS AND RESULTS: Molecular characterization of ß gene identified a novel transversion mutation [ß80(EF4)Asn>Ser; HBB:c.242A>G]. CONCLUSIONS: When there is no correlation between clinical, glycemic status and glycated haemoglobin of the patient, the chromatogram of HbA1c should be carefully checked to detect the possible presence of variants that cause interference in their measurement.

Nine-year experience in Gaucher disease diagnosis at the Spanish reference center Fundación Jiménez Díaz.

BACKGROUND: Fundación Jiménez Díaz (FJD) is a reference center for genetic diagnosis of Gaucher disease (GD) in Spain. Genetic analyses of acid ß-glucosidase (GBA) gene using different techniques were performed to search for new mutations, in addition to those previously and most frequently found in the Spanish population. Additionally, the study of the chitotriosidase (CHIT1) gene was used to assess the inflammatory status of patients in the follow-up of enzyme replacement therapy (ERT). We present the genetic data gathered during the last nine years at FJD. METHODS: Blood samples from patients with suspected GD were collected for enzymatic and genetic analyses. The genetic analysis was performed on DNA from 124 unrelated suspected cases and 57 relatives from 2007 to 2015, starting with a mutational screening kit, followed by Sanger sequencing of the entire gene and other techniques to look for deletions. CHIT1 was also studied to assess the reliability of this biomarker. RESULTS: In 46 out of 93 GD patients (49.5%) the two mutant alleles were found. We detected 21 different mutations. The most common mutation was N370S (c.126A > G; p.Asp409Ser current nomenclature) (in 50.5% of patients), followed by L444P (c.1448T > C; p.Leu483Pro current nomenclature) (in 24.7%). The most common heterozygous compound genotype observed (18.3%) was c.1226A > G/c.1448T > C (N370S/L444P). Two novel mutations were found (del. Ex.4-11 and c.1296G > T; pW432C), as well as p.S146L, only once previously reported. Two patients showed the homozygous state for the duplication of CHIT1. CONCLUSION: N370S and L444P are the most common mutations and other mutations associated to Parkinson's disease have been observed. This should be taken into account in the genetic counseling of GD patients.

Inhibitor development after switching of FVIII concentrate in multitransfused patients with severe haemophilia A.

Switching between different therapeutic FVIII concentrate types has been postulated as a possible cause of inhibitor development in patient with haemophilia A. In this single-centre, retrospective study, the incidence, titre and duration of inhibitor development in multitransfused patients, defined as patients with more than 150 exposure days (ED), were analysed from January 1970 to December 2007 in relation to ED and the number of switches between different products. Inhibitor titre was assessed by Bethesda assay (before 1998) or Nijmegen assay (after 1998). Medical records of 167 patients were screened, of which 97 patients met the inclusion criteria. Fourteen products of plasmatic origin (different purities) and five recombinant (three generations) were used. Nine patients (9%) developed inhibitors, all transient, low-titre (1.41 ± 0.54 BU) after 323 ± 287 ED in average. Seventeen patients had no product switches of which four patients (23%) developed inhibitors (97 ED in average), whereas 13 patients (77%) did not (ED: 230). Fifty patients switched between plasmatic products only (median: 10 changes) of which five patients (10%) developed inhibitors (ED: 503), whereas 45 patients did not (ED: 932). Five patients switched between recombinant products only (seven changes) of which no patient developed inhibitors (748 ED). Twenty-five patients switched between plasmatic and recombinant products (13 changes) of which no patient developed inhibitors (ED: 1654). No statistically significant differences between patient groups were observed. Neither the number of different FVIII products administered nor the switching of products influenced the incidence of inhibitor in multitransfused patients.

Comparison of a new chemiluminescent immunoassay for von Willebrand factor activity with the ristocetin cofactor-induced platelet agglutination method.

Measuring von Willebrand factor (VWF) activity is essential for the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. A new automated chemiluminescent immunoassay VWF activity has recently become commercially available (HemosIL AcuStar von Willebrand Factor Ristocetin Cofactor Activity). The main objective of this study was to evaluate this new method and to compare it with the VWF:RCo assay as the reference method. We studied 91 samples, 18 healthy volunteers samples and 73 samples from patients (VWF:RCo level <50 IU dL(-1) ): 29 type 1 VWD, 13 type 2A, 5 type 2B, 5 type 2M, 3 type 2N, 5 type 3, 4 type 3 under treatment, 5 type 3 carriers and 4 samples with other pathologies. The HemosIL AcuStar VWF:RCo assay was 96% sensitive and 100% specific for detecting VWF abnormalities. The good analytical performance, and the sensitivity and specificity of HemosIL AcuStar VWF:RCo to detect VWF deficiency renders it a suitable method for VWD screening.

A clinical study assessing the pharmacokinetics, efficacy and safety of AlphaNine(®) , a high-purity factor IX concentrate, in patients with severe haemophilia B.

Effective treatment with factor IX (FIX) requires a thorough consideration of the properties of the concentrate to be used as replacement therapy, to date, the only available treatment for haemophilia B. The aim of the study was to determine the pharmacokinetics, clinical efficacy and safety in routine clinical use of AlphaNine(®) , a high-purity human FIX concentrate. This open, single-arm, multicentre, non-randomized trial included 25 subjects (age ≥ 12) with moderate/severe haemophilia B. Pharmacokinetics was assessed at baseline and after a 6-month follow-up. The degree of haemostasis control achieved was evaluated during a 12-month follow-up. Safety was evaluated in terms of tolerance, thrombogenicity, immunogenicity and viral safety. Mean recovery was 1.01 ± 0.19 IU dL(-1) per IU kg(-1) at baseline and 1.23 ± 0.34 IU dL(-1) per IU kg(-1) 6 months later. Terminal half-life was 34.5 ± 6.2 h and 33.7 ± 5.4 h, respectively. Ratios of each parameter between the two pharmacokinetic studies were all close to 1. A total of 1,576,890 IU AlphaNine(®) were administered in 889 infusions (mean dose per infusion: 1774 IU; 3.2 infusions per month per patient). The main reasons for infusion were mild/moderate bleeding (62.3%) and prophylaxis (20.5% continuous, 15.6% intermittent). Overall, 93.0% of the efficacy assessments were rated as excellent/good and 88.8% of bleedings resolved after the first infusion. Twenty-one adverse events were reported in eight patients, none of which was considered related to the study medication. AlphaNine(®) showed a pharmacokinetic profile in agreement with that of other plasma-derived FIX concentrates and provides safe and clinically effective substitution therapy for patients with haemophilia B.

Pharmacokinetic study of a high-purity factor IX concentrate (Factor IX Grifols) with a 6-month follow up in previously treated patients with severe haemophilia B.

Optimal replacement treatment in haemophilia B patients requires a good understanding of the pharmacokinetics of factor IX (FIX). The aim of this study was to compare the pharmacokinetic profile of Factor IX Grífols, a highly purified human FIX concentrate with two specific pathogen inactivation/removal steps, to that of available FIX preparations. The study was an open, non-randomized trial including 25 male subjects older than 12 years of age with severe haemophilia B. Pharmacokinetic profile of the FIX preparation regularly used by the subjects was determined as control. Pharmacokinetic profile of Factor IX Grifols was determined twice, one 7-15 days after control assessment and second after a 6 months period had elapsed. Results showed that all products had peak plasma levels of FIX:C within 30 min. Mean recovery was 1.3 +/- 0.3 IU dL(-1) per IU kg(-1) for Factor IX Grifols and 1.0 +/- 0.3 IU dL(-1) per IU kg(-1) for control products (P < 0.001). The mean terminal half-life (t(1/2)) for Factor IX Grifols was 26.7 h and 26.8 h for control product. Pharmacokinetic parameters after 6 months of treatment with Factor IX Grifols did not statistically differ from the parameters obtained with the first infusion. There were no adverse events related to Factor IX Grifols for the duration of the study. In conclusion, Factor IX Grifols has adequated pharmacokinetic properties comparable to the control plasma-derived FIX and these parameters remain stable after 6 months of treatment. Factor IX Grifols can be an effective and safe plasma-derived FIX concentrate for replacement therapy in haemophilia B patients.