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J van Gijn

Publications and source records attributed to J van Gijn.

At least 19 recordsLinked to original sources

Spinal dural arteriovenous fistulas: a congestive myelopathy that initially mimics a peripheral nerve disorder.

Spinal dural arteriovenous fistula (SDAVF) is a rare and enigmatic disease entity. The clinical features and structural changes have been recognized since 1926, and the pathophysiology and the essentials of treatment since 1974, but up to the present day it is unknown why these fistulas develop. The fistula between a radicular artery and the corresponding radicular vein within the dural root sleeve leads to congestion of the venous outflow of the spinal cord and eventually ischaemia. Patients, who are mostly middle-aged men, develop a progressive myelopathy, which at the early stages of the disease often mimics a polyradiculopathy or anterior horn cell disorder. By the time involvement of upper motoneurons or sacral segments makes the diagnosis of SDAVF inescapable, patients suffer from considerable neurological deficits. The diagnosis relies on MRI, which shows swelling of the spinal cord, with a centrally located hyperintense signal on T2-weighted images, and with hypointense 'flow void' phenomena dorsal to the cord, representing enlarged and tortuous veins. Catheter angiography is required to determine the exact location of the fistula as well as the angio-architecture, on which the mode of treatment depends. If the arterial feeder of the fistula is a tributary of the anterior spinal artery, embolization is not possible. After embolization recanalization may occur, but this is rarely seen after filling of the draining vein with glue. Alternatively, operation is a safe and permanent mode of treatment. No prognostic factors have been reliably established. Muscle strength and gait disturbances respond better to treatment than pain and symptoms related to damage of sacral segments. In any middle aged male patient with ascending motor or sensory deficits in the legs, SDAVF should be considered in order to prevent irreversible handicap.

Central Nervous System Vascular Malformations↗

Randomized controlled trial of acetylsalicylic acid in aneurysmal subarachnoid hemorrhage: the MASH Study.

BACKGROUND AND PURPOSE: A previous systematic review of randomized trials suggested a positive effect of antiplatelet therapy in patients with aneurysmal subarachnoid hemorrhage (SAH). We performed a randomized controlled trial to assess whether acetylsalicylic acid (ASA) reduces the risk of delayed ischemic neurological deficit (DIND) in patients with SAH. METHODS: Criteria for inclusion were aneurysm treatment within 4 days after SAH. Trial medication (14 daily suppositories with 100 mg ASA or placebo) was started within 12 hours after aneurysm treatment. Analysis for the primary outcome event DIND was made according to the "on-treatment" principle and for the secondary outcome measures "poor outcome" and "nonexcellent outcome" according to the "intention-to-treat" principle. RESULTS: Inclusion was stopped after the second interim analysis, when 161 of the planned 200 patients were included, because by then the chances of a positive effect were negligible. At the final analysis, ASA did not reduce the risk of DIND (hazard ratio, 1.83; 95% CI, 0.85 to 3.9). The relative risk reduction for poor outcome was 21% (relative risk, 0.79; 95% CI, 0.38 to 1.6). CONCLUSIONS: ASA given after aneurysm treatment does not appreciably reduce the occurrence of DIND.

Aneurysm, Ruptured↗

Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin.

BACKGROUND: Patients with limited cerebral ischaemia of arterial origin have an annual risk of major vascular events between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with oral anticoagulants is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy. OBJECTIVES: To compare the efficacy and safety of oral anticoagulants and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (searched 16 September 2004). Authors of published trials were contacted for further information and unpublished data. SELECTION CRITERIA: Randomised trials examining long-term secondary prevention after recent ischaemic stroke of presumed arterial origin were selected. The oral anticoagulant therapy had to be of specified intensity with warfarin, phenprocoumon or acenocoumarol versus antiplatelet therapy. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed trial quality and extracted data. Subgroup analyses with treatment International Normalized Ratio (INR) 1.4 to 2.8 (low intensity), INR 2.1 to 3.6 (medium intensity) and INR 3.0 to 4.5 (high intensity) were performed. MAIN RESULTS: Five trials, with 4076 patients were selected. The data do not allow a robust conclusion on whether anticoagulants are more or less efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation relative risk (RR) 0.96, 95% confidence intervals (CI) 0.38 to 2.42; high intensity anticoagulation RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low or medium intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents. The relative risk for major bleeding complications for low intensity anticoagulation was 1.27 (95% CI 0.79 to 2.03) and for medium intensity anticoagulation 1.19 (95% CI 0.59 to 2.41). However, it was clear that high intensity oral anticoagulants with INR 3.0 to 4.5 were not safe, because they yielded a higher risk of major bleeding complications (RR 9.0, 95% CI 3.9 to 21). AUTHORS' CONCLUSIONS: For secondary prevention of further vascular events after limited ischaemic stroke of arterial origin, there is insufficient evidence to justify the routine use of medium-intensity oral anticoagulants; such treatment should only be used as part of a clinical trial. More intense anticoagulation is not safe and should not be used in this setting. Low-intensity anticoagulation is not likely to be more or less efficacious than aspirin.

Administration, Oral↗

Functional status and use of healthcare facilities in long-term survivors of transient ischaemic attack or minor ischaemic stroke.

BACKGROUND: Stroke may have a major effect on survivors and on the healthcare system. AIMS: To study the functional status and use of healthcare facilities in long-term survivors of a transient ischaemic attack (TIA) or minor ischaemic stroke (MIS) and evaluate associations with baseline and follow-up characteristics. METHODS: Follow-up of patients who had participated in the Dutch TIA Trial or the European Atrial Fibrillation Trial was extended to a mean period of 15.6 years. Patients were interviewed through a postal questionnaire (n = 468) and a sample of this group was also interviewed at home (n = 198). Demographic data, information on comorbidity, functional status (Barthel Index, Frenchay Activities Index and modified Rankin Scale) and use of healthcare facilities were recorded. RESULTS: About one third of the survivors interviewed at home experienced any residual disability and 26% were moderately to severely handicapped. Factors associated with poor functional status were advanced age and the presence of any infarct on a baseline computed tomography scan, the recurrence of a new major stroke or the presence of comorbidity of locomotion. One third of survivors used any kind of professional care, which was predominantly related to the functional status at follow-up. CONCLUSIONS: Recurrent stroke and the presence of comorbidity of locomotion are important determinants of long-term disability of survivors of a TIA or an MIS, which, in turn, is strongly associated with the long-term use of professional care. The need for measuring comorbidity with regard to functional status is recommended in research on stroke outcome.

Comorbidity↗

Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.

BACKGROUND: Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty. METHODS: We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070). FINDINGS: Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache. INTERPRETATION: The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.

Aged↗

Dipyridamole for preventing stroke and other vascular events in patients with vascular disease.

BACKGROUND: Patients with limited cerebral ischaemia of arterial origin are at risk of serious vascular events (4% to 11% annually). Aspirin reduces that risk by 13%. In one trial, adding dipyridamole to aspirin was associated with a 22% risk-reduction compared with aspirin alone. However, a systematic review of all trials of antiplatelet agents by the Antithrombotic Trialists' Collaboration showed that, in high-risk patients, there was virtually no difference between the aspirin-dipyridamole combination and aspirin alone. OBJECTIVES: To assess the efficacy and safety of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (searched November 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to November 2005) and EMBASE (1980 to November 2005). SELECTION CRITERIA: Randomised long-term secondary prevention trials with concealed treatment allocation, treatment for more than one month, starting within six months after presentation of an arterial vascular disease were selected. Treatment consisted of dipyridamole with or without other antiplatelet drugs compared with no drug or an antiplatelet drug other than dipyridamole. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, assessed trial quality and extracted data. Data were analysed according to the intention-to-treat principle. MAIN RESULTS: Twenty-seven trials were included, with 20242 patients, among whom 1399 vascular deaths and 3090 fatal and non-fatal vascular events occurred during follow up. Compared with control, dipyridamole had no clear effect on vascular death (relative risk (RR) 1.02, 95% confidence internal (CI) 0.90 to 1.17). This result was not influenced by the dose of dipyridamole or type of presenting vascular disease. In the presence of aspirin, dipyridamole appeared to reduce the risk of vascular events compared with control (RR 0.90, 95% CI 0.82 to 0.97), due to a single large trial in patients presenting with cerebral ischaemia. AUTHORS' CONCLUSIONS: For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug reduced the risk of vascular death, though it may reduce the risk of further vascular events. However, this benefit was found in only one single large trial and only in patients presenting after cerebral ischaemia. There was no evidence that dipyridamole alone was more efficacious than aspirin. Further trials comparing the effects of the combination of dipyridamole with aspirin versus aspirin alone are justified.

Anticoagulants↗

Type of stroke after transient monocular blindness or retinal infarction of presumed arterial origin.

BACKGROUND: Retinal infarction and transient monocular blindness (TMB) are associated with an increased risk of future ischaemic stroke. Little information is available on the type of subsequent ischaemic strokes that may occur (anterior or posterior circulation and small vessel or large vessel). AIM: To analyse the type of stroke after TMB. METHODS: Patients with transient or permanent retinal ischaemia were selected from three prospective studies: the Dutch TIA Trial, the Dutch Amaurosis Fugax Study and the European/Australian Stroke Prevention in Reversible Ischaemia Trial. On follow-up the type of stroke was classified according to the supply territory and the type of vessel involved. RESULTS: 654 patients were included. During a mean follow-up of 5.2 years, 42 patients were found to have had a cerebral or retinal infarct, of which 27 occurred in the carotid territory ipsilateral to the symptomatic eye, 9 in the territory of the contralateral carotid artery and 6 were infratentorial strokes. Thirty patients had a large-vessel infarct, four had a small-vessel infarct and eight had a retinal infarct. Characteristics associated with a notable increased risk for subsequent stroke or retinal infarction were age > or = 65 years, a history of stroke, a history of intermittent claudication, diabetes mellitus, Rankin score > or = 3, more than three attacks of retinal ischaemia and any degree of ipsilateral carotid stenosis on duplex ultrasonography observation. CONCLUSION: Ischaemic strokes after TMB or retinal infarction were found to be mainly large-vessel infarcts in the territory of the ipsilateral carotid artery. TMB and retinal infarction are probably manifestations of large-vessel disease.

Aged↗

[Those who cannot remember the past are condemned to repeat it].

To the casual observer, the history of medicine seems one of continuous progress. In reality, for every therapeutic accomplishment that has withstood the test of time there have been several ineffective or even harmful treatments that are now forgotten; yet they were based on theories regarded as plausible at the time. Examples abound, also in the archives of the Dutch Journal of Medicine: treatments for poliomyelitis and sciatica provide striking illustrations. Even in the current era of controlled trials and meta-analyses, physicians need to be reminded that a logical theory in itself does not justify treatment decisions unless it is supported by experimental evidence. The essential difference between mainstream medicine and complementary medicine is not the plausibility of the underlying theories but the rigour in testing hypotheses. On the other hand, many decisions in medicine must be made without sufficient evidence. Logic is indispensable but should be part of an empirical cycle in which new thoughts lead to new experiments and vice versa.

Evidence-Based Medicine↗

Severity of cerebral white matter lesions and infarcts in patients with transient or moderately disabling cerebral ischaemia: reproducibility of grading by neurologists.

Diffuse or multifocal ischaemic white matter lesions increase the risk of intracranial haemorrhage in patients using oral anticoagulants for secondary prevention after cerebral ischaemia of arterial origin. We studied whether neurologists could reliably assess the presence of these white matter abnormalities. As part of the European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), the severity of white matter lesions and presence of ischaemic lesions were twice assessed in a consensus meeting of three neurologists (from a pool of nine) as absent, moderate or severe, in a sample of 126 randomly selected CT or MRI scans. The neurologists were not aware of the duplicate grading. The degree of agreement between the first and second observation was calculated with kappa statistics. The kappa value for agreement between the first and second assessment of white matter lesions was 0.58 (95% CI 0.40-0.76). The kappa value for the presence of clinically relevant and/or irrelevant ischaemic lesions was 0.68 (95% CI 0.58-0.78). Clinicians can assess the presence of white matter lesions with sufficient reliability. Such assessment may prevent unnecessary risk with oral anticoagulation in secondary prevention after cerebral ischaemia of arterial origin, of which the efficacy is currently being assessed in ESPRIT.

Brain Infarction↗

Early circulating levels of endothelial cell activation markers in aneurysmal subarachnoid haemorrhage: associations with cerebral ischaemic events and outcome.

OBJECTIVE: To investigate the relation of endothelial cell activation with delayed cerebral ischaemia (DCI) and outcome after subarachnoid haemorrhage (SAH). METHODS: Concentrations of soluble (s) intercellular adhesion molecule-1, sE-selectin, sP-selectin, ED1-fibronectin, von Willebrand Factor (vWf), and vWf propeptide were measured within three days of SAH onset. The associations with poor outcome were investigated at three months in 106 patients. In 90 patients in whom the occurrence of cerebral ischaemia could be dated accurately, two analyses were undertaken: one for all ischaemic events (n = 32), including those related to treatment, and another for spontaneous DCI (n = 11). Concentrations of markers were dichotomised at their medians. The associations of endothelial cell activation markers with outcome were expressed as odds ratios (OR) from logistic regression and those with ischaemic events as hazard ratios (HR) derived from Cox regression. RESULTS: Early vWf concentrations were associated with poor outcome (crude OR = 4.6 (95% CI, 2.0 to 10.9; adjusted OR = 3.3 (1.1 to 9.8). Early levels of vWf were also positively related to occurrence of all ischaemic events (crude HR = 2.3 (1.1 to 4.9); adjusted HR = 1.8 (0.8 to 3.9) and with occurrence of spontaneous DCI (crude HR = 3.5 (0.9 to 13.1); adjusted HR = 2.2 (0.5 to 9.8). None of the other markers showed any associations. CONCLUSIONS: Concentrations of sICAM-1, sP-selectin, sE-selectin, and ED1-fibronectin do not predict the occurrence of DCI or outcome. The positive associations of raised early vWf concentrations with ischaemic events and poor outcome after SAH may reflect a predisposition to further ischaemic injury through formation of microthrombi in the cerebral circulation.

Adult↗

[Probabilities cannot be calculated retrospectively--not even in the courtroom].

Chance events are part of everyday life, but coincidence of diseases often raises suspicions about hidden causes, for example when power lines are blamed for the geographical clustering of cancer. Recently, criminal procedures in the Netherlands have revolved around the question of whether statistical 'predictions' are a valid reason to hold a hospital nurse accountable for the occurrence of excess deaths during her duty hours, or a kindergarten employee for unexplained respiratory problems in several infants. In both cases, the appeals court judges did not accept the statistical 'argument' in the absence of other evidence. In the UK, however, Sally Clark's initial life sentence for the double murder of her 2 babies was largely based on 'probabilities in retrospect', put forward by the paediatrician Sir Roy Meadow as an expert witness. 4 years later she was acquitted, whereas Meadow was struck off the medical register on a charge of professional misconduct. There is no Bayesian or other mathematical solution to the problem of chance events. Only the detection of causal factors that are plausible and supported by new evidence can help to reinterpret coincidences as relationships. Scrupulous reasoning about probabilities is required, not only of physicians but also of judges and politicians.

Evidence-Based Medicine↗

Anticoagulation in ischemic stroke: opportunities in arterial disease.

In the acute phase of ischemic stroke, there is no evidence that anticoagulants provide any benefit in terms of death or dependency. A small reduction in the incidence of recurrent stroke is offset by an equally small increase in intracranial hemorrhage (ICH). In the secondary prevention of stroke, in patients with transient ischemic attacks (TIAs) and moderately disabling ischemic stroke, the relative risk reduction of major vascular events by aspirin is rather modest: 13% (or 19% in a systematic review of arterial disease in general). Anticoagulants might well offer stronger protection, since they provide a 35-50% risk reduction after myocardial infarction or in patients with TIAs or nondisabling ischemic stroke in the presence of atrial fibrillation. Meanwhile, it has become clear that anticoagulation with high intensity (INR 3.0-4.5) is associated with a high risk of ICH in patients with cerebral ischemia who are in sinus rhythm, while INR values around 1.9 do not offer protection against major vascular events. An international clinical trial of anticoagulation with INR values between 2.0 and 3.0 (ESPRIT) is still in progress. In cerebral venous sinus thrombosis, anticoagulant treatment is associated with a nonsignificant reduction of the risk of death or dependence, but the treatment has nevertheless become widely adopted because it seems safe: no increase in the proportion of patients with hemorrhagic transformation of infarction has so far been demonstrated.

Anticoagulants↗

Endovascular coiling versus neurosurgical clipping for patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: Patients who have had an aneurysmal subarachnoid haemorrhage (SAH) are at very high risk of rebleeding if the aneurysm is not treated. The standard treatment for several decades has been surgical clipping of the neck of the aneurysm. In recent years, an alternative, the introduction of detachable coils to occlude the aneurysm, has become more common. OBJECTIVES: To compare the effects of endovascular coiling versus neurosurgical clipping in patients with aneurysmal subarachnoid haemorrhage. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched in February 2005). In addition we searched MEDLINE (1966 to January 2004) and EMBASE (1980 to January 2004), and contacted trialists. SELECTION CRITERIA: We included randomised trials in which endovascular coiling of aneurysms was compared with neurosurgical clipping in patients with SAH who have proven aneurysm. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: We identified three randomised trials: two published and one unpublished. The trials included a total of 2272 patients (range per trial: 20 to 2143 patients). Most of the patients were in good clinical condition and had an aneurysm on the anterior circulation. After one year of follow up, the relative risk (RR) of poor outcome for coiling versus clipping was 0.76 (95% confidence interval (CI) 0.67 to 0.88). The absolute risk reduction was 7% (95% CI 4% to 11%). In the worst-case scenario analysis for poor outcome overall, the relative risk for coiling versus clipping was 0.81 (95% CI 0.70 to 0.92) and the absolute risk reduction was 6% (95% CI 2% to 10%). For patients with anterior circulation aneurysm the relative risk of poor outcome was 0.78 (95% CI 0.68 to 0.90) and the absolute risk decrease was 7% (95% CI 3% to 10%). For those with a posterior circulation aneurysm the relative risk was 0.41 (95% CI 0.19 to 0.92) and the absolute decrease in risk 27% (95% CI 6% to 48%). AUTHORS' CONCLUSIONS: The evidence comes mainly from one large trial. For patients in good clinical condition with ruptured aneurysms of either the anterior or posterior circulation we have firm evidence that, if the aneurysm is considered suitable for both surgical clipping and endovascular treatment, coiling is associated with a better outcome.

Aneurysm, Ruptured↗

Spinal dural arteriovenous fistulas--an underdiagnosed disease. A review of patients admitted to the spinal unit of a rehabilitation center.

BACKGROUND: Spinal dural arteriovenous fistulas (SDAVF) are rare and present with non-specific symptoms. The diagnosis is difficult and it is therefore conceivable that patients may not be recognized. METHODS: We reviewed the intake forms of patients who had been admitted to the spinal cord injury ward of a rehabilitation center in the period 1980-2004 to identify possible patients with an undiagnosed SDAVF. Clinical and radiological data were evaluated in selected cases. RESULTS: In 20 of 1429 newly admitted patients to the rehabilitation center (in 614 of whom trauma was not the cause), we restudied the CT myelograms, MRI scans or spinal angiograms and in two of these we found an undiagnosed SDAVF, and one cerebral dural arteriovenous fistula. One of these three was diagnosed with SDAVF 8 years after the admission to the rehabilitation center; the other two patients had never been diagnosed with SDAVF. In 9 patients a diagnosis of SDAVF had already been established by the time they were admitted to the spinal cord unit. In 20 other patients the admission diagnosis was a vascular lesion or 'progressive myelopathy' but appropriate radiological studies had been destroyed or had never been performed. CONCLUSION: Our results suggest that spinal dural arteriovenous fistulas are an underdiagnosed condition.

Aged↗

Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage.

BACKGROUND: Corticosteroids, particularly dexamethasone, are commonly used for treatments in patients with subarachnoid haemorrhage (SAH) and primary intracerebral haemorrhage (PICH) despite the lack of evidence. OBJECTIVES: This review aimed: (1) to determine whether corticosteroid therapy reduces the proportion of patients who die or have a poor outcome at one to six months after the onset of SAH or PICH; (2) to determine whether corticosteroid therapy reduces the frequency of delayed cerebral ischaemia (DCI) in patients with SAH; (3) to determine the frequency of adverse effects of corticosteroid therapy in patients with SAH or PICH within six months of the onset of the event. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched November 2003). In addition, we searched MEDLINE (1966 to March 2004) and EMBASE (1980 to March 2004), and searched reference lists of relevant studies identified. We also made an attempt to identify any relevant ongoing and published or unpublished studies by contacting trialists and pharmaceutical companies. SELECTION CRITERIA: We sought to identify all randomised or quasi-randomised clinical trials of corticosteroid therapy, in patients with SAH or PICH, that have a placebo or standard strategy arm as control. Patients of any age and either gender with clinically (bed-side) diagnosed PICH and cerebrospinal fluid documented SAH were included in the analysis. The data were analysed both separately and combined for computed tomography (CT)/magnetic resonance imaging (MRI)/autopsy/angiography verified patients. DATA COLLECTION AND ANALYSIS: Data extracted from eligible clinical trials included: (1) death and poor outcome (death, severe disability, or vegetative state) within the first one to six months of the event onset (primary outcomes); (2) development of delayed cerebral ischaemia (as defined by the trialists) in patients with SAH; and (3) adverse effects of the treatment during the scheduled treatment or follow-up period (secondary outcomes). A pooled estimate of the effect size was computed, and the test for heterogeneity between trial results was carried out using The Cochrane Collaboration's Review Manager software, RevMan 4.2. Intention-to-treat analysis was carried out whenever possible. MAIN RESULTS: Eight trials that fulfilled the eligibility criteria were identified, with a total of 256 randomised patients in three SAH trials, and 206 patients in five PICH trials. The studies differed substantially with regard to the study populations and drugs, and methodological quality. The number of patients allocated to either hydrocortisone or fludrocortisone acetate treatment in patients with SAH, or to dexamethasone treatment in patients with PICH, was too small to make any definitive conclusions (confidence intervals were wide for any of the outcome estimates). AUTHORS' CONCLUSIONS: Overall, there is no evidence of a beneficial or adverse effect of corticosteroids in patients with either SAH or PICH. Confidence intervals are wide and include clinically significant effects in both directions.

Adrenal Cortex Hormones↗

Timing of aneurysm surgery in subarachnoid haemorrhage--an observational study in The Netherlands.

BACKGROUND: There is still lack of evidence on the optimal timing of surgery in patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical trial has been done, which showed no difference between early and late surgery. Other studies were observational in nature and most had methodological drawbacks that preclude clinically meaningful conclusions. We performed a retrospective observational study on the timing of aneurysm surgery in The Netherlands over a two-year period. METHOD: In eight hospitals we identified 1,500 patients with an aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion criteria. We included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage. FINDINGS: We included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT RESULTS: Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition. CONCLUSIONS: In this observational study we found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling.

Adolescent↗

Non-adherence to aspirin or oral anticoagulants in secondary prevention after ischaemic stroke.

BACKGROUND: The effectiveness of medication is influenced by treatment adherence. After TIA or minor disabling stroke patients usually are advised to take antithrombotic medication. Stroke patients are an interesting group of patients with respect to adherence, since cardiovascular risk factors and stroke may (indirectly) negatively influence brain function, which can affect adherence. We investigated determinants of non-adherence in patients who used aspirin or oral anticoagulation after cerebral ischaemia of arterial origin. METHODS: Data of patients prospectively followed in two clinical trials (the Dutch TIA Trial and the Stroke Prevention In Reversible Ischaemia Trial) were analysed with Cox proportional hazards modelling. RESULTS: In the two trials 3796 patients were treated with aspirin. During a mean follow-up of 2.1 years, 689 patients (18%) prematurely stopped treatment, 305 (8 %) did so without a clear medical reason (non-adherence). Age >or= 65 years and the use of 300 instead of 30 mg of aspirin were independently associated with non-adherence. Diastolic blood pressure of >or= 90 mmHg and dizziness were associated with better adherence. Of 651 patients on oral anticoagulation, 143 patients (22 %) stopped after a mean follow-up of 1.0 year, 66 (10 %) did so because of nonadherence. No statistically significant determinants for non-adherence were identified. CONCLUSION: As found in the literature on nonadherence in general, age of >or= 65 years and a higher dose of aspirin (300 mg versus 30 mg) were independently associated with non-adherence with aspirin treatment that was prescribed for secondary prevention after cerebral ischaemia of arterial origin. Older patients may require extra encouragement to continue antithrombotic treatment. Lower doses of aspirin may improve treatment adherence.

Age Factors↗