Second intravenous immunoglobulin dose in patients with Guillain-Barre syndrome with poor prognosis (SID-GBS):a double-blind, randomised, placebo-controlled trial

Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved

Attention-Deficit Hyperactivity Disorder (ADHD) Symptoms in Children Adopted from Poland and their Atypical Association Patterns : a Bayesian Approach

Although high rates of attention-deficit hyperactivity disorder (ADHD) symptoms have been observed among internationally adopted children, research on these symptoms in Polish adoptees is lacking. Therefore, we examined ADHD symptoms in Polish adoptees and their relationship to pre-adoptive risk factors, that is, time in institutional care, early deprivation, and prenatal alcohol exposure. We further compared the association patterns and gender distribution of ADHD symptoms in children adopted from Poland to those reported in the literature for ADHD symptoms in non-adopted children. Dutch adoptive parents of 121 Polish adoptees (52% boys; M age = 10.9 years, range 6.2–15.6; M ageadoption = 3.0 years, range 0.8–6.9) completed questionnaires regarding ADHD symptoms, pre-adoptive risk factors, attachment problems, conduct problems, and executive functioning deficits. Bayesian evaluation of informative hypotheses showed that Polish adoptees had increased levels of ADHD symptoms, compared to Dutch children in the general population. Time in institutional care, early deprivation, and prenatal alcohol exposure were not associated with ADHD symptoms. ADHD symptoms in Polish adoptees were more strongly associated with attachment problems and executive functioning deficits, but less strongly with conduct problems, compared to ADHD symptoms in non-adoptees. Furthermore, ADHD symptoms were more equally distributed among boys and girls than they are in non-adopted children. The findings indicate that Polish adoptees and their adoptive parents need special attention and support. The dissimilarities between ADHD symptoms in Polish adoptees and non-adoptees might indicate a different underlying causal mechanism, which may have important implications for clinical practice

Attention-Deficit Hyperactivity Disorder (ADHD) Symptoms in Children Adopted from Poland and their Atypical Association Patterns : a Bayesian Approach

Although high rates of attention-deficit hyperactivity disorder (ADHD) symptoms have been observed among internationally adopted children, research on these symptoms in Polish adoptees is lacking. Therefore, we examined ADHD symptoms in Polish adoptees and their relationship to pre-adoptive risk factors, that is, time in institutional care, early deprivation, and prenatal alcohol exposure. We further compared the association patterns and gender distribution of ADHD symptoms in children adopted from Poland to those reported in the literature for ADHD symptoms in non-adopted children. Dutch adoptive parents of 121 Polish adoptees (52% boys; M age = 10.9 years, range 6.2–15.6; M ageadoption = 3.0 years, range 0.8–6.9) completed questionnaires regarding ADHD symptoms, pre-adoptive risk factors, attachment problems, conduct problems, and executive functioning deficits. Bayesian evaluation of informative hypotheses showed that Polish adoptees had increased levels of ADHD symptoms, compared to Dutch children in the general population. Time in institutional care, early deprivation, and prenatal alcohol exposure were not associated with ADHD symptoms. ADHD symptoms in Polish adoptees were more strongly associated with attachment problems and executive functioning deficits, but less strongly with conduct problems, compared to ADHD symptoms in non-adoptees. Furthermore, ADHD symptoms were more equally distributed among boys and girls than they are in non-adopted children. The findings indicate that Polish adoptees and their adoptive parents need special attention and support. The dissimilarities between ADHD symptoms in Polish adoptees and non-adoptees might indicate a different underlying causal mechanism, which may have important implications for clinical practice

Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial

Background: Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barré syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barré syndrome with a predicted poor outcome. Methods: In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (≥12 years) with Guillain-Barré syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of ≥6) according to the modified Erasmus Guillain-Barré syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7–9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barré syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. This study is registered with the Netherlands Trial Register, NTR 2224/NL2107. Findings: Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barré syndrome disability score at 4 weeks was 1·4 (95% CI 0·6–3·3; p=0·45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13–24 weeks after randomisation). Interpretation: Our study does not provide evidence that patients with Guillain-Barré syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barré syndrome. Funding: Prinses Beatrix Spierfonds and Sanquin Plasma Products