Clinical profile of women diagnosed with Fabry disease non receiving enzyme replacement therapy / Perfil clínico de mujeres diagnosticadas de la enfermedad de Fabry no tratadas con sustitución enzimática

Introduction and objective: Fabry disease (FD) is an X-linked lysosomal storage disorder due to a deficiency of the alpha-galactosidase A enzyme. Although women were historically considered only carriers, many studies have contradicted this fact. The main aim of this work was to set the first Spanish study out of the on-going registries on health status and management of women diagnosed with FD who were not receiving enzyme replacement therapy (ERT). Material and methods: An epidemiological, cross-sectional, descriptive and multicentre study was assessed in women diagnosed for FD who were not receiving ERT. Assessments on symptomatology and severity were collected using several clinical questionnaires. Additionally, clinical information and lab tests were obtained from clinical records. Results: Thirty-three women with a mean age of 45.6±16.2 years were studied. Symptom onset was at a median age of 35.5 years old (range: 30.0-51.5), being diagnosed a median of 2 years later (range: 1.0-1.5). Missense mutations were the most prevalent mutation (n=22, 68.8%). Although 69% considered themselves as asymptomatic, 22 (66.7%) showed at least one FD-related clinical symptom. Using Mainz Severity Score index and Fabry International Prognosis Index neurological symptomatology obtained higher scores both for severity and prognostic. The EQ-5D questionnaire showed 42.2% patients referring to some anxiety or depression, and 30.3% thought that their life was somehow altered by the pain. 62.5% were not receiving any treatment and ERT was offered only to one patient (3.6%) who refused it. Conclusions: Although most of the heterozygous women for FD had not received ERT or either symptomatic treatment, they present symptoms of disease. Careful follow-up of female patients or some adjuvant treatment may be considered to delay progressive organ damage and improve patient quality of life

Introducción y objetivo: La enfermedad de Fabry (EF) es un trastorno de almacenamiento lisosómico hereditario, ligado al cromosoma X y derivado de una deficiencia de la enzima alpha-galactosidasa A. Aunque históricamente solo se ha considerado portadoras a las mujeres, esto ha sido contradicho por muchos estudios. El objetivo principal de este trabajo ha sido establecer un primer estudio español independiente de los registros actuales sobre la situación y seguimiento clínico de las mujeres diagnosticadas con EF que no recibían terapia de sustitución enzimática (TRE). Material y métodos: Se llevó a cabo un estudio epidemiológico, transversal, descriptivo y multicéntrico en mujeres diagnosticadas con EF que no recibían TRE. Las evaluaciones sobre la sintomatología y la gravedad fueron recopiladas mediante varios cuestionarios clínicos. Adicionalmente se obtuvo información clínica y resultados de pruebas de laboratorio de las historias clínicas. Resultados: Se estudiaron 33 mujeres con una edad media de 45,6±16,2 años. El inicio de los síntomas se produjo a una mediana de edad de 35,5 años (rango: 30,0-51,5), siendo diagnosticado en una mediana de 2 años después (rango: 1,0-1,5). Las mutaciones de sentido erróneo fueron las más frecuentes (n=22; 68,8%). Aunque el 69% se consideraron a sí mismas asintomáticas, 22 (66,7%) mostraron al menos un síntoma clínico relacionado con la EF. Utilizando el índice de severidad de Mainz y el índice pronóstico internacional de Fabry, la sintomatología neurológica obtuvo puntuaciones más altas tanto para la gravedad como para el pronóstico. El cuestionario de calidad de vida EQ-5D mostró que el 42,2% de las pacientes referían cierta ansiedad o depresión, y el 30,3% pensó que su vida estaba interferida de alguna manera por el dolor. El 62,5% no recibía ningún tratamiento y solo se ofreció TRE a una paciente (3,6%), que lo rechazó. Conclusiones: Aunque la mayoría de las mujeres heterocigotas para la EF no habían recibido TRE, ni tampoco ningún tratamiento sintomático, sí presentan síntomas de la enfermedad. Un seguimiento cuidadoso de las pacientes junto con alguna terapia adyuvante podría ser de interés para retrasar el daño progresivo de los órganos y mejorar la calidad de vida de las pacientes

Clinical profile of women diagnosed with Fabry disease non receiving enzyme replacement therapy.

INTRODUCTION AND OBJECTIVE: Fabry disease (FD) is an X-linked lysosomal storage disorder due to a deficiency of the α-galactosidase A enzyme. Although women were historically considered only carriers, many studies have contradicted this fact. The main aim of this work was to set the first Spanish study out of the on-going registries on health status and management of women diagnosed with FD who were not receiving enzyme replacement therapy (ERT). MATERIAL AND METHODS: An epidemiological, cross-sectional, descriptive and multicentre study was assessed in women diagnosed for FD who were not receiving ERT. Assessments on symptomatology and severity were collected using several clinical questionnaires. Additionally, clinical information and lab tests were obtained from clinical records. RESULTS: Thirty-three women with a mean age of 45.6±16.2 years were studied. Symptom onset was at a median age of 35.5 years old (range: 30.0-51.5), being diagnosed a median of 2 years later (range: 1.0-1.5). Missense mutations were the most prevalent mutation (n=22, 68.8%). Although 69% considered themselves as asymptomatic, 22 (66.7%) showed at least one FD-related clinical symptom. Using Mainz Severity Score index and Fabry International Prognosis Index neurological symptomatology obtained higher scores both for severity and prognostic. The EQ-5D questionnaire showed 42.2% patients referring to some anxiety or depression, and 30.3% thought that their life was somehow altered by the pain. 62.5% were not receiving any treatment and ERT was offered only to one patient (3.6%) who refused it. CONCLUSIONS: Although most of the heterozygous women for FD had not received ERT or either symptomatic treatment, they present symptoms of disease. Careful follow-up of female patients or some adjuvant treatment may be considered to delay progressive organ damage and improve patient quality of life.

Long-term graft function changes in kidney transplant recipients.

Background. Monitoring changes in glomerular filtration rate (GFR) is the recommended method for assessing the progression of kidney disease. The aim of this study was to assess the decline of graft function defined by the annualized change in GFR and the factors which affect it.Methods. Four thousand four hundred and eighty-eight patients, transplanted during the years 1990, 1994, 1998 and 2002 in 34 centres in Spain with allograft survival of at least 1 year, were included in the study. GFR was estimated using the four-variable equation of the Modification of Diet in Renal Diseases (MDRD) study. Linear mixed effects model was applied to determine the relation between the covariates and the annualized change in GFR after transplantation.Results. The average GFR at 12 months was 51.4 +/- 18.9 mL/min/1.73 m(2); most patients were in stage 3 of chronic kidney disease classification. The average patient slope, calculated in a linear model with varying-intercept and varying-slope without covariates, was -1.12 +/- 0.05 mL/min/year (slope +/- standard error). Some variables were related to both the 12-month GFR (intercept) and the slope: recipient gender, hepatitis C virus (HCV) status, estimated GFR (eGFR) at 3 months and proteinuria at 12 months. Some variables were only related to the slope of eGFR: time on dialysis, primary renal disease and immunosuppression. Others affected only the 12-month GFR: donor age, delayed graft function, acute rejection and systolic blood pressure at 12 months. Higher graft function at 3 months had a negative impact on the GFR slope. Cyclosporine-based immunosuppression had a less favourable effect on the rates of change in allograft function.Conclusions. There was a slow decline in GFR. Poor graft function was not associated with an increased rate of decline of allograft function. Immunosuppression with cyclosporine displayed the worst declining GFR rate.

A randomized trial of basiliximab with three different patterns of cyclosporin A initiation in renal transplant from expanded criteria donors and at high risk of delayed graft function.

This study assays therapy with basiliximab and different patterns of cyclosporin A (CsA) initiation in renal transplant (RT) recipients from expanded criteria donors (ECD) and at high risk of delayed graft function (DGF). A multicentre six-month open-label randomized trial with three parallel groups treated with basiliximab plus steroids, mycophenolate mofetil and different patterns of CsA initiation: early within 24 h post-RT at 3 mg/kg/d (Group 1; n = 38), and at 5 mg/kg/d (Group 2; n = 40), or delayed after 7-10 d at 5 mg/kg/d (Group 3; n = 36). There were no differences among groups in six months GFR (43.1 +/- 12, 48.0 +/- 14 and 47.2 +/- 17 mL/min, respectively), DGF (Group 1: 31%, Group 2: 37%, Group 3: 42%), nor biopsy-proven acute rejection, although clinically treated and biopsy-proven acute rejection was significantly higher in Group 3 (25%) vs. Group 1 (5.3%, p < 0.05). At six months no differences were observed in death-censored graft survival or patient survival. Induction therapy with basiliximab and three CsA-ME initiation patterns in RT recipients from ECD and at high risk of DGF presented good renal function and graft survival at six months. Late onset group did not achieve improvement in DGF rate and showed a higher incidence of clinically treated and biopsy-proven acute rejection.

[Validation of a rapid antigenic test in the diagnosis of pharyngitis caused by group a beta-haemolytic Streptococcus]. / Validación de una técnica antigénica rápida en el diagnóstico de la faringitis por estreptococo betahemolítico del grupo A.

OBJECTIVE: To determine the validity of the rapid antigen test (RAT) OSOM StrepA Genzyme for the diagnosis of acute pharyngitis caused by group A beta-haemolytic strep (GABHS). DESIGN: Diagnostic techniques survey. SETTING: Urban primary care centre, Spain. PARTICIPANTS: All patients over 14 years old seen in 6 surgeries with sore throat and 2 or more Centor criteria: pharyngotonsillar exudate, tender laterocervical nodes, absence of coughing, and/or history or presence of fever. PRINCIPAL MEASUREMENTS: Pharyngeal swabs were taken from all the patients, one for RAT and another to send for culture in the microbiology department. RESULTS: A total of 182 patients were evaluable, with a mean age of 30.6 (12.1) years of which 116 were women (63.7%); 63 patients had 2 Centor criteria; 83 had 3 and 36, the 4 criteria. The culture was positive in 102 patients (56%), with GABHS showing infection in forty (22%; 95% confidence interval [CI], 21.2-22.8). Group C Streptococcus was isolated in 26 patients (14.3%). GABHS was higher among patients with four Centor criteria (38.9% vs 25.3% observed among those with 3 criteria and 7.9% with 2 criteria; P<.001). Sensitivity of RAT was 95%, with a specificity of 93%, a positive predictive value of 79.2% and a negative predictive value of 98.5%. CONCLUSIONS: These results show the usefulness of RAT for diagnosing streptococcal pharyngitis. Its use should be spread to all primary care practices.

Validación de una técnica antigénica rápida en el diagnóstico de la faringitis por estreptococo betahemolítico del grupo A / Validation of a rapid antigen test in the diagnosis of pharyngitis caused by group A beta-haemolytic streptococcus

Objetivo. Determinamos la validez de latécnica antigénica rápida (TAR) OSOMStrepA Genzyme en el diagnóstico de lafaringitis aguda causada por estreptococobetahemolítico del grupo A (EBHGA).Diseño. Estudio de pruebas diagnósticas.Emplazamiento. Equipo urbano de atenciónprimaria.Participantes. Todos los pacientes mayoresde 14 años atendidos en 6 consultas consíntomas de odinofagia y 2 o más de loscriterios de Centor (exudado faringoamigdalar,adenopatías laterocervicales dolorosas,ausencia de tos y/o historia o presenciade fiebre).Mediciones principales. A todos los pacientesse les tomó una muestra faringoamigdalarcon 2 hisopos, uno para TAR y otro que fueremitido al servicio de microbiología pararealizar cultivo.Resultados. Fueron evaluables 182 sujetos,con una edad media de 30,6 ± 12,1 años,116 mujeres (63,7%). Presentaron 2, 3y 4 criterios de Centor 63, 83 y 36 sujetos,respectivamente. El cultivo fue positivo en102 casos (56%), observándose infección porEBHGA en 40 pacientes (22%; intervalode confianza [IC] del 95%, 21,2-22,8); en26 casos se aisló estreptococo del grupo C(14,3%). La infección por EBHGA presentóuna mayor prevalencia entre los pacientescon 4 criterios (un 38,9% frente a un 25,3%observado con 3 criterios y frente al 7,9%con 2 criterios; p < 0,001). La TAR tuvo unasensibilidad del 95%, una especificidad del93%, un valor predictivo positivo del 79,2%y un valor predictivo negativo del 98,5%.Conclusiones. Estos resultados demuestranla utilidad de la TAR para el diagnósticode la faringitis estreptocócica. Su uso deberíaextenderse a todas las consultas de atenciónprimaria

Objective. To determine the validity of therapid antigen test (RAT) OSOM StrepAGenzyme for the diagnosis of acutepharyngitis caused by group Abeta-haemolytic strep (GABHS).Design. Diagnostic techniques survey.Setting. Urban primary care centre, Spain.Participants. All patients over 14 years oldseen in 6 surgeries with sore throat and 2or more Centor criteria: pharyngotonsillarexudate, tender laterocervical nodes, absenceof coughing, and/or history or presence offever.Principal measurements. Pharyngeal swabswere taken from all the patients, one forRAT and another to send for culture inthe microbiology department.Results. A total of 182 patients wereevaluable, with a mean age of 30.6 (12.1)years of which 116 were women (63.7%); 63patients had 2 Centor criteria; 83 had 3 and36, the 4 criteria. The culture was positive in102 patients (56%), with GABHS showinginfection in forty (22%; 95% confidenceinterval [CI], 21.2-22.8). Group CStreptococcus was isolated in 26 patients(14.3%). GABHS was higher amongpatients with four Centor criteria (38.9% vs25.3% observed among those with 3 criteriaand 7.9% with 2 criteria; P<.001). Sensitivityof RAT was 95%, with a specificity of 93%,a positive predictive value of 79.2%and a negative predictive value of 98.5%.Conclusions. These results show theusefulness of RAT for diagnosingstreptococcal pharyngitis. Its use shouldbe spread to all primary care practices