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Please note that the content of this book primarily consists of articles available from Wikipedia or other free sources online. Chapters: AGOVV Apeldoorn, People from Apeldoorn, Wilhelm R ntgen, Piet de Jong, Het Loo Palace, Cornelis Hulsman, Demy de Zeeuw, 2009 attack on the Dutch royal family, Corine Dorland, Apeldoorn railway station, Arend Lijphart, Ans Schut, Patrick Bakker. Vandaag op het mooie bedrijf van melkveehouder Gijs en Jolanda van Eck op bezoek geweest, die een melkveebedrijf met een boederijcamping en natuurbeheer combineert. Daar ben ik op uitnodiging van. Background Immunosuppressed inflammatory bowel disease (IBD) patients are at increased risk to develop extra-intestinal malignancies. Immunosuppressed transplant patients show.

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MULTICENTER STUDY
Lancet 2015 July 4, 386 (9988): 46-55
25892679

BACKGROUND: Early mobilisation after stroke is thought to contribute to the effects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke.

METHODS: We did this parallel-group, single-blind, randomised controlled trial at 56 acute stroke units in five countries. Patients (aged ≥18 years) with ischaemic or haemorrhagic stroke, first or recurrent, who met physiological criteria were randomly assigned (1:1), via a web-based computer generated block randomisation procedure (block size of six), to receive usual stroke-unit care alone or very early mobilisation in addition to usual care. Treatment with recombinant tissue plasminogen activator was allowed. Randomisation was stratified by study site and stroke severity. Patients, outcome assessors, and investigators involved in trial and data management were masked to treatment allocation. The primary outcome was a favourable outcome 3 months after stroke, defined as a modified Rankin Scale score of 0-2. We did analysis on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000185561.

FINDINGS: Between July 18, 2006, and Oct 16, 2014, we randomly assigned 2104 patients to receive either very early mobilisation (n=1054) or usual care (n=1050); 2083 (99%) patients were included in the 3 month follow-up assessment. 965 (92%) patients were mobilised within 24 h in the very early mobilisation group compared with 623 (59%) patients in the usual care group. Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group (n=480 [46%] vs n=525 [50%]; adjusted odds ratio [OR] 0·73, 95% CI 0·59-0·90; p=0·004). 88 (8%) patients died in the very early mobilisation group compared with 72 (7%) patients in the usual care group (OR 1·34, 95% CI 0·93-1·93, p=0·113). 201 (19%) patients in the very early mobilisation group and 208 (20%) of those in the usual care group had a non-fatal serious adverse event, with no reduction in immobility-related complications with very early mobilisation.

INTERPRETATION: First mobilisation took place within 24 h for most patients in this trial. The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months. Early mobilisation after stroke is recommended in many clinical practice guidelines worldwide, and our findings should affect clinical practice by refining present guidelines; however, clinical recommendations should be informed by future analyses of dose-response associations.

FUNDING: National Health and Medical Research Council, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, UK Stroke Association, National Institute of Health Research.

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High-dose albumin treatment for acute ischaemic stroke (ALIAS) Part 2: a randomised, double-blind, phase 3, placebo-controlled trial.Lancet Neurology 2013, 12 (11): 1049-58
B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.Lancet Neurology 2010, 9 (9): 855-65
Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial.Lancet Neurology 2013, 12 (8): 768-76
Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial.Lancet 2011 November 12, 378 (9804): 1699-706
The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial.Lancet 2015 April 18, 385 (9977): 1519-26
Thrombolysis for acute ischaemic stroke.Cochrane Database of Systematic Reviews 2003, (3): CD000213
The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial.Lancet 2012 June 23, 379 (9834): 2352-63
Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial.Lancet Neurology 2010, 9 (8): 767-75
Telephone triage for management of same-day consultation requests in general practice (the ESTEEM trial): a cluster-randomised controlled trial and cost-consequence analysis.Lancet 2014 November 22, 384 (9957): 1859-1868
Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial.Lancet 2015 May 16, 385 (9981): 1966-74

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MULTICENTER STUDY
Lancet 2015 July 4, 386 (9988): 46-55
25892679

BACKGROUND: Early mobilisation after stroke is thought to contribute to the effects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke.

METHODS: We did this parallel-group, single-blind, randomised controlled trial at 56 acute stroke units in five countries. Patients (aged ≥18 years) with ischaemic or haemorrhagic stroke, first or recurrent, who met physiological criteria were randomly assigned (1:1), via a web-based computer generated block randomisation procedure (block size of six), to receive usual stroke-unit care alone or very early mobilisation in addition to usual care. Treatment with recombinant tissue plasminogen activator was allowed. Randomisation was stratified by study site and stroke severity. Patients, outcome assessors, and investigators involved in trial and data management were masked to treatment allocation. The primary outcome was a favourable outcome 3 months after stroke, defined as a modified Rankin Scale score of 0-2. We did analysis on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000185561.

FINDINGS: Between July 18, 2006, and Oct 16, 2014, we randomly assigned 2104 patients to receive either very early mobilisation (n=1054) or usual care (n=1050); 2083 (99%) patients were included in the 3 month follow-up assessment. 965 (92%) patients were mobilised within 24 h in the very early mobilisation group compared with 623 (59%) patients in the usual care group. Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group (n=480 [46%] vs n=525 [50%]; adjusted odds ratio [OR] 0·73, 95% CI 0·59-0·90; p=0·004). 88 (8%) patients died in the very early mobilisation group compared with 72 (7%) patients in the usual care group (OR 1·34, 95% CI 0·93-1·93, p=0·113). 201 (19%) patients in the very early mobilisation group and 208 (20%) of those in the usual care group had a non-fatal serious adverse event, with no reduction in immobility-related complications with very early mobilisation.

INTERPRETATION: First mobilisation took place within 24 h for most patients in this trial. The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months. Early mobilisation after stroke is recommended in many clinical practice guidelines worldwide, and our findings should affect clinical practice by refining present guidelines; however, clinical recommendations should be informed by future analyses of dose-response associations.

FUNDING: National Health and Medical Research Council, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, UK Stroke Association, National Institute of Health Research.

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Related Papers

High-dose albumin treatment for acute ischaemic stroke (ALIAS) Part 2: a randomised, double-blind, phase 3, placebo-controlled trial.Lancet Neurology 2013, 12 (11): 1049-58
B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.Lancet Neurology 2010, 9 (9): 855-65
Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial.Lancet Neurology 2013, 12 (8): 768-76
Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial.Lancet 2011 November 12, 378 (9804): 1699-706
The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial.Lancet 2015 April 18, 385 (9977): 1519-26
Thrombolysis for acute ischaemic stroke.Cochrane Database of Systematic Reviews 2003, (3): CD000213
The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial.Lancet 2012 June 23, 379 (9834): 2352-63
Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial.Lancet Neurology 2010, 9 (8): 767-75
Telephone triage for management of same-day consultation requests in general practice (the ESTEEM trial): a cluster-randomised controlled trial and cost-consequence analysis.Lancet 2014 November 22, 384 (9957): 1859-1868

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Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial.Lancet 2015 May 16, 385 (9981): 1966-74

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