Triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia - open-label trial.

OBJECTIVES: The objective of the study was to test the efficacy, safety and tolerability of triple therapy with deferiprone, idebenone and riboflavin in Friedreich's ataxia (FRDA) patients in a clinical pilot study. PATIENTS AND METHODS: Patients included in this study were 10 males and three females, 14-61 years of age (average 30.2 ± 12.1), diagnosed with FRDA with normal ventricular function. Patients were treated with triple therapy with deferiprone at 5-25 mg/kg/day, idebenone at 10-20 mg/kg/day and riboflavin at 10-15 mg/kg/day for 15-45 months. The efficacy of this triple therapy was assessed by change from baseline on the scale for the assessment and rating of ataxia (SARA) and by the change from baseline in echocardiogram parameters. RESULTS: Four patients discontinued due to adverse events (AEs) related with deferiprone. The annual worsening rate (AWR) was estimated in this series as 0.96 (CI 95%: 0.462-1.608) SARA score, whereas AWR for our FRDA cohort was estimated as 2.05 ± 1.23 SARA score. LVMI only decreased by 6.5 g/m(2) (6.2%) at the end of the first year of therapy. LVEF remained stable, except in case of three patients. CONCLUSION: Our results seem to indicate some uncertain benefit on the neurological and heart functions of this triple therapy in FRDA.

Off-hour effects on stroke care and outcome in stroke centres.

BACKGROUND AND PURPOSE: Poorer stroke care processes and outcomes have been reported for acute stroke patients arriving at centres during off hours and weekends. OBJECTIVE: To compare each step of the continuous specialized care that Stroke Centres (SC) provide according to time of admission and final outcome. METHODS: Observational study of consecutive stroke patients admitted to SC during 2008 and 2009. Patients were classified into two groups according to their arrival time: Work Hours (WH) and Off Hour (OH) (weekends and any time other than 8:00 am to 3:00 pm on weekdays). Differences in time to diagnostic procedures, tPA administration, stroke outcome [modified Rankin Scale, (mRS)] and in-hospital fatality rates were analysed. RESULTS: A total of 912 patients were admitted. Data from 674 patients fulfilling study criteria were analysed. A total of 434 (64.4%) patients arrived during OH. No differences in stroke severity were found when comparing OH and WH. Time to blood test results was higher for WH (median 67 min vs. 47 min; P < 0.01), but time to cranial CT scan was similar. Intravenous tPA was administered to 58 (16.4%) OH vs. 26 (13.1%) WH patients (P = 0.33). OH arrival was not associated with poorer outcome (mRS ≥ 3) at discharge (32.8% vs. 37%; P = 0.27), or at the 3-month follow-up (30.6% vs. 27.6%, P = 0.52). No differences were found for in-hospital fatality rates (5.8% vs. 5.4%, P = 1.00). CONCLUSIONS: The care provided by SC with neurologists on call 24/7 prevents differences in outcomes associated with time of admission and guarantees equal attention to stroke patients.

Bajo rendimiento del ecocardiograma, comparado con el Doppler transcraneal, en la detección de la comunicación derecha-izquierda / Low sensitivity of the echocardiograph compared with contrast transcranial doppler in right-to-left shunt

Introducción: El Doppler transcraneal con contraste (DTC-c) tiene una alta sensibilidad para la detección de comunicación derecha-izquierda (CDI), probablemente mayor que la del ecocardiograma transtorácico (ETT) y comparable con la del transesofágico (ETE). Objetivo: Evaluar la precisión del ecocardiograma (ETT y ETE) para detectar CDI, comparándolo con DTC-c. Material y métodos: Estudio observacional de pacientes <55 años con isquemia cerebral de origen indeterminado (2007-2009) a los que se les realizó una monitorización con DTC-c para detectar CDI, en reposo y tras maniobra de Valsalva (MV). El ETT y ETE se realizaron cuando estaba indicado según el protocolo de estudio cerebrovascular de nuestro centro. La precisión del ETT y ETE para detectar CDI fue calculada comparándolos con DTC-c. Resultados: Se incluyeron 115 pacientes a los que se les realizó monitorización con DTC-c. Edad media 43,3 (DE 10,3) años, 51,3% hombres. El ETT se realizó en 102 y el ETE en 81 pacientes. La detección de CDI fue mayor con DTC-c que con ETT (67,6 vs. 22,5%, p=0,001) o con ETE (77,8 vs. 53,1%, p=0,001). El ETT, comparado con DTC-c tras MV, mostró: sensibilidad 31,8%, especificidad 96,9%, valor predictivo positivo (VPP) 95,6%, valor predictivo negativo (VPN) 40,5% y precisión 52.9% para detectar CDI. El ETE, comparado con DTC-c tras MV, mostró: sensibilidad 63,4%, especificidad 83,3%, VPP 93%, VPN 39,4% y precisión 67,9%. La precisión del ETT y ETE se incrementó cuando se compararon con el DTC-c en reposo. Conclusiones: El ETT y ETE presentan un número elevado de falsos negativos para detección de CDI, cuando se comparan con el DTC-c. Los estudios clínicos deberían considerar al DTC-c como mejor técnica para diagnosticar CDI cuando se sospecha embolia paradójica (AU)

Background: Contrast transcranial Doppler (c-TCD) has a high sensitivity for detecting right-to-left shunt (RLS), and is probably higher than transthoracic echocardiography (TTE) and comparable with transesophageal echocardiography (TEE).Objective: To evaluate the accuracy of echocardiography (TTE and TEE) to detect RLS compared to c-TCD.Material and methods: Observational study of patients <55 years old with cerebral ischaemia of undetermined origin (2007-2009). All underwent c-TCD monitoring to detect RLS, at rest and after Valsalva manoeuvre (VM). The TTE and TEE were performed when indicated by our cerebrovascular protocol. The accuracy of TTE and TEE for detecting RLS was calculated by comparing them with c-TCD. Results: A total of 115 patients with c-TCD, mean age 43.3 (SD 10.3) years, 51.3% male. The TTE was performed in 102, and TEE in 81, patients. RLS detection was higher with c-TCD than with TTE (67.6% vs. 22.5%, P=.001) or TEE (77.8% vs. 53.1%, P=.001). The TTE, compared with c-TCD after MV showed: sensitivity 31.8%, specificity 96.9%, positive predictive value (PPV) 95.6%, negative predictive value (NPV) 40.5% and accuracy 52.9% to detect RLS. TEE, compared with c-TCD after MV showed: sensitivity 63.4%, specificity 83.3%, PPV 93%, NPV 39.4% and accuracy 67.9%. The accuracy of TTE and TEE improved when they were compared with c-TCD at rest. Conclusions: TTE and TEE show a considerable number of false negatives for RLS detection. Clinical studies should consider the c-TCD as the best technique to diagnose RLS when a paradoxical embolism is suspected (AU)

[Low sensitivity of the echocardiograph compared with contrast transcranial Doppler in right-to-left shunt]. / Bajo rendimiento del ecocardiograma, comparado con el Doppler transcraneal, en la detección de la comunicación derecha-izquierda.

BACKGROUND: Contrast transcranial Doppler (c-TCD) has a high sensitivity for detecting right-to-left shunt (RLS), and is probably higher than transthoracic echocardiography (TTE) and comparable with transesophageal echocardiography (TEE). OBJECTIVE: To evaluate the accuracy of echocardiography (TTE and TEE) to detect RLS compared to c-TCD. MATERIAL AND METHODS: Observational study of patients <55 years old with cerebral ischaemia of undetermined origin (2007-2009). All underwent c-TCD monitoring to detect RLS, at rest and after Valsalva manoeuvre (VM). The TTE and TEE were performed when indicated by our cerebrovascular protocol. The accuracy of TTE and TEE for detecting RLS was calculated by comparing them with c-TCD. RESULTS: A total of 115 patients with c-TCD, mean age 43.3 (SD 10.3) years, 51.3% male. The TTE was performed in 102, and TEE in 81, patients. RLS detection was higher with c-TCD than with TTE (67.6% vs. 22.5%, P=.001) or TEE (77.8% vs. 53.1%, P=.001). The TTE, compared with c-TCD after MV showed: sensitivity 31.8%, specificity 96.9%, positive predictive value (PPV) 95.6%, negative predictive value (NPV) 40.5% and accuracy 52.9% to detect RLS. TEE, compared with c-TCD after MV showed: sensitivity 63.4%, specificity 83.3%, PPV 93%, NPV 39.4% and accuracy 67.9%. The accuracy of TTE and TEE improved when they were compared with c-TCD at rest. CONCLUSIONS: TTE and TEE show a considerable number of false negatives for RLS detection. Clinical studies should consider the c-TCD as the best technique to diagnose RLS when a paradoxical embolism is suspected.