International Guillain-Barré Syndrome Outcome Study: protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1–3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS

International Guillain-Barr\uc3\ua9 Syndrome Outcome Study: protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barr\uc3\ua9 syndrome

Guillain-Barr\uc3\ua9 syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1\ue2\u80\u933 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS

Regional variation of Guillain-Barré syndrome

Guillain-Barré syndrome is a heterogeneous disorder regarding the clinical presentation, electrophysiological subtype and outcome. Previous single country reports indicate that Guillain-Barré syndrome may differ among regions, but no systematic comparative studies have been conducted. Comparative studies are required to identify factors determining disease susceptibility, variation and prognosis, and to improve diagnostic criteria. The International Guillain-Barré Syndrome Outcome Study is a prospective, observational cohort study including all patients within the diagnostic spectrum, aiming to describe the heterogeneity of Guillain-Barré syndrome worldwide. The current study was based on the first 1000 inclusions with a follow-up of at least 1 year and confirmed the variation in clinical presentation, course and outcome between patients. The full clinical spectrum of Guillain-Barré syndrome was observed in patients from all countries participating in the International Guillain-Barré Syndrome Outcome Study, but the frequency of variants differed between regions. We compared three regions based on geography, income and previous reports of Guillain-Barré syndrome subtypes: ‘Europe/Americas’, ‘Asia’ (without Bangladesh), and ‘Bangladesh’. We excluded 75 (8%) patients because of alternative diagnoses, protocol violations, or missing data. The predominant clinical variant was sensorimotor in Europe/Americas (n = 387/562, 69%) and Asia (n = 27/63, 43%), and pure motor in Bangladesh (n = 74/107, 69%). Miller Fisher syndrome and Miller Fisher-Guillain-Barré overlap syndrome were more common in Asia (n = 14/63, 22%) than in the other two regions (Europe/Americas: n = 64/562, 11%; Bangladesh: n = 1/107, 1%) (P < 0.001). The predominant electrophysiological subtype was demyelinating in all regions (Europe/Americas: n = 312/573, 55%; Asia: n = 29/65, 45%; Bangladesh: n = 38/94, 40%). The axonal subtype occurred more often in Bangladesh (n = 34/94, 36%) than in Europe/Americas (n = 33/573, 6%) and other Asian countries (n = 4/65, 6%) (P < 0.001). In all regions, patients with the axonal subtype were younger, had fewer sensory deficits, and showed a trend towards poorer recovery compared to patients with the demyelinating subtype. The proportion of patients able to walk unaided after 1 year varied between Asia (n = 31/34, 91%), Europe/Americas (n = 334/404, 83%) and Bangladesh (n = 67/97, 69%) (P = 0.003). A similar variation was seen for mortality, being higher in Bangladesh (n = 19/114, 17%) than in Europe/Americas (n = 23/486, 5%) and Asia (n = 1/45, 2%) (P < 0.001). This study showed that factors related to geography have a major influence on clinical phenotype, disease severity, electrophysiological subtype, and outcome of Guillain-Barré syndrome

Current treatment practice of Guillain-Barré syndrome

ObjectiveTo define the current treatment practice of Guillain-Barre syndrome (GBS).MethodsThe study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account.ResultsWe excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE.ConclusionsIn current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations

Current treatment practice of Guillain-Barré syndrome

ObjectiveTo define the current treatment practice of Guillain-Barré syndrome (GBS).MethodsThe study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account.ResultsWe excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE.ConclusionsIn current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations

International Guillain-Barré Syndrome Outcome Study: protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)

International Guillain-Barré Syndrome Outcome Study: protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1–3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. © 2017 Peripheral Nerve Societ

Regional variation of Guillain-Barré syndrome

Guillain-Barré syndrome is a heterogeneous disorder regarding the clinical presentation, electrophysiological subtype and outcome. Previous single country reports indicate that Guillain-Barré syndrome may differ among regions, but no systematic comparative studies have been conducted. Comparative studies are required to identify factors determining disease susceptibility, variation and prognosis, and to improve diagnostic criteria. The International Guillain-Barré Syndrome Outcome Study is a prospective, observational cohort study including all patients within the diagnostic spectrum, aiming to describe the heterogeneity of Guillain-Barré syndrome worldwide. The current study was based on the first 1000 inclusions with a follow-up of at least 1 year and confirmed the variation in clinical presentation, course and outcome between patients. The full clinical spectrum of Guillain-Barré syndrome was observed in patients from all countries participating in the International Guillain-Barré Syndrome Outcome Study, but the frequency of variants differed between regions. We compared three regions based on geography, income and previous reports of Guillain-Barré syndrome subtypes: Europe/Americas', Asia' (without Bangladesh), and Bangladesh'. We excluded 75 (8%) patients because of alternative diagnoses, protocol violations, or missing data. The predominant clinical variant was sensorimotor in Europe/Americas (n = 387/562, 69%) and Asia (n = 27/63, 43%), and pure motor in Bangladesh (n = 74/107, 69%). Miller Fisher syndrome and Miller Fisher-Guillain-Barré overlap syndrome were more common in Asia (n = 14/63, 22%) than in the other two regions (Europe/Americas: n = 64/562, 11%; Bangladesh: n = 1/107, 1%) (P < 0.001). The predominant electrophysiological subtype was demyelinating in all regions (Europe/Americas: n = 312/573, 55%; Asia: n = 29/65, 45%; Bangladesh: n = 38/94, 40%). The axonal subtype occurred more often in Bangladesh (n = 34/94, 36%) than in Europe/Americas (n = 33/573, 6%) and other Asian countries (n = 4/65, 6%) (P < 0.001). In all regions, patients with the axonal subtype were younger, had fewer sensory deficits, and showed a trend towards poorer recovery compared to patients with the demyelinating subtype. The proportion of patients able to walk unaided after 1 year varied between Asia (n = 31/34, 91%), Europe/Americas (n = 334/404, 83%) and Bangladesh (n = 67/97, 69%) (P = 0.003). A similar variation was seen for mortality, being higher in Bangladesh (n = 19/114, 17%) than in Europe/Americas (n = 23/486, 5%) and Asia (n = 1/45, 2%) (P < 0.001). This study showed that factors related to geography have a major influence on clinical phenotype, disease severity, electrophysiological subtype, and outcome of Guillain-Barré syndrome

International Guillain-Barré Syndrome Outcome Study: protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1–3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS