Secondary stroke prevention with drugs: single or combined therapy?
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Anticoagulants↗
Biomedical subjects
J van Gijn
Publications and source records attributed to J van Gijn.
Initial loss of consciousness and risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. We studied the prognostic value for DCI of 2 factors: the duration of unconsciousness after the hemorrhage and the presence of risk factors for atherosclerosis. METHODS: In 125 consecutive patients admitted within 4 days after hemorrhage, we assessed the presence and duration of unconsciousness after the hemorrhage, the neurological condition on admission, the amount of subarachnoid blood, the size of the ventricles, and a history of smoking, hypertension, stroke, or myocardial infarction. The relationship between these variables and the development of DCI was analyzed by means of the Cox proportional hazards model. RESULTS: The univariate hazard ratio (HR) for the development of DCI in patients who had lost consciousness for >1 hour was 6.0 (95% CI 3.0 to 12.0) compared with patients who had no loss or a <1-hour loss of consciousness. The presence of any risk factor for atherosclerosis yielded an HR of 1.4 (95% CI 0.6 to 3.5). The HR for unconsciousness remained essentially the same after adjustment for other risk factors for DCI. The HR for a poor World Federation of Neurological Surgeons score (grade IV or V) on admission was 2.9 (95% CI 1.5 to 5. 5); that for a large amount of subarachnoid blood on CT was 3.4 (95% CI 1.6 to 7.3). CONCLUSIONS: The duration of unconsciousness after subarachnoid hemorrhage is a strong predictor for the occurrence of DCI. This observation may contribute to a better understanding of the pathogenesis of DCI and increased attention for patients at risk.
Arteriosclerosis↗
MR angiography as a screening tool for intracranial aneurysms: feasibility, test characteristics, and interobserver agreement.
OBJECTIVE: MR angiography may be an appropriate tool to screen for unruptured intracranial aneurysms. Feasibility, test characteristics, and interobserver agreement in evaluation of MR angiograms were assessed by members of the MARS (Magnetic resonance Angiography in Relatives of patients with Subarachnoid hemorrhage) Study Group. SUBJECTS AND METHODS: We screened 626 first-degree relatives of a consecutive series of 193 patients with subarachnoid hemorrhage examined at two institutions. We used MR imaging and MR angiography (three-dimensional time-of-flight imaging at both institutions and additional three-dimensional phase-contrast imaging at one institution). Three observers independently assessed the MR angiograms. Conventional angiography was performed in relatives with possible or definite aneurysms on MR angiography and was considered the standard of reference. RESULTS: Thirty-three aneurysms were found in 25 (4%; 95% confidence interval [CI], 3-6%) of 626 relatives. Thirteen (8%) of 169 relatives who refused screening had MR-related reasons; an additional six persons could not be screened because of contraindications for MR imaging (pregnancy, n = 1; claustrophobia, n = 5). The positive predictive value of MR angiography was 100% (95% CI, 79-100%) for "definite" aneurysms and 58% (95% CI, 28-85%) for "possible" aneurysms. Sensitivity of MR angiography was estimated at 83% (95% CI, 65-94%) and specificity at 97% (95% CI, 94-98%). Interobserver agreement in the evaluation of MR angiograms was poor (kappa < .30), probably because different diagnostic strategies used by individual observers resulted in different use of the assessment category "possible aneurysm." CONCLUSION: MR angiography is a feasible screening tool for detection of intracranial aneurysms. Positive predictive value, sensitivity, and specificity are acceptable when at least two neuroradiologists independently assess MR angiograms.
Adult↗
From therapeutic trials to current practice.
Ideally, there is continuous interaction between clinical reality and the methods of controlled clinical trials. The design of a proper trial ought to reflect the physician's and especially the patient's point of view, and conversely a familiarity with clinical trials improves the methods of daily practice. In other words, every methodological principle is rooted in clinical practice. Some examples are: randomisation (with constructive doubt as its practical equivalent), independence (a healthy mistrust of drug companies), informed consent (sharing uncertainty with patients), type I error (no false optimism after a single trial), type II error (no false pessimism after a single trial), choosing the right measure of outcome (relevance outweighs precision), the intention-to-treat principle (pragmatic analysis), and the dangers of subgroup analysis (the "my-last-patient syndrome").
Drug Industry↗
Antiplatelet therapy: views from the experts.
Antiplatelet therapy is recommended for stroke prevention in persons with a history of thromboembolic stroke or transient ischemic attack (TIA) that is not of cardiac origin. Aspirin was the first antiplatelet agent to be used in this context and is still the most frequently prescribed preventive treatment for ischemic stroke. However, because the results of clinical studies with aspirin have been inconsistent, the dose of aspirin required for stroke prevention in persons with cerebrovascular disease has been a subject of debate among stroke neurologists. In the present discussion, low-dose aspirin is generally regarded by the experts as equivalent in effectiveness to high-dose aspirin, and its higher tolerability has the potential to significantly increase compliance with long-term therapy. Higher aspirin doses may have clinical utility in particular settings, but this requires further study. Despite the controversy, aspirin is now recognized as the treatment standard against which other antiplatelet agents are compared. Antiplatelet agents that may be more effective than aspirin have now been developed. Although each of these agents has been directly compared with aspirin in a large, randomized clinical trial, the lack of direct comparisons among these alternative antiplatelet therapies complicates decisions regarding long-term care of patients with cerebrovascular disease. An international panel of stroke neurologists reports that their selection of antiplatelet therapies for patients with prior history of TIA or stroke depends most heavily on drug efficacy and safety issues and is limited by availability (approval status of alternatives).
Humans↗
[Roaming through methodology. IV. Causality].
If a factor A is often followed by an event B, it may erroneously be concluded that one causes the other. Actually B may have been brought about by a factor C (the true cause), A being only an epiphenomenon of C. If factors other than C (for example D or E) can cause the same effect B, none of those factors is a necessary cause. Causes often are multiple: a single causal factor is often not sufficient for a certain effect to ensue, whereas that effect can result from a number of factors acting together (simultaneously or consecutively).
Causality↗
[Reference manager: a personal database on literature for consultation and word processing].
The software programme Reference manager serves as a personal database for bibliographic references within a restricted field, especially journal articles (with abstracts). Yet it is more than a digital card index. References can be retrieved via author name, keyword, title word, year of publication, or name of periodical. During the preparation of a manuscript by means of a word processor, references can be simply indicated by one or more of these characteristics. Later Reference manager transforms these provisional references automatically into a bibliography and text references, according to the style of the journal in question. The personal database does not have to be built through laborious copying, but can be captured from Medline databases. Updating with recent references is possible by means of bibliographic services such as Current contents or Reference update.
Data Display↗
[Secondary prevention following cerebral ischemia: is monotherapy with acetylsalicylic acid still first choice?].
Acetylsalicylic acid (ASA) alone (at least 30 mg per day) in post-cerebral ischaemia patients reduces the relative risk of further vascular events by 13% compared with placebo. A meta-analysis of all studies shows that the combination of ASA with dipyridamole reduces the relative risk by 16% (95% confidence interval: 5-26%) compared with ASA alone, but confirmation by a major trial appears desirable, because of discrepant results of a recent trial and 4 previous ones. Clopidogrel might reduce the risk by 7% compared with ASA alone, but this drug is expected to be expensive. Anticoagulation therapy with an international normalized ratio (INR) of 2.0-4.0 is particularly efficacious for secondary prevention in patients with atrial fibrillation, but anticoagulation therapy with an INR of 3.0-4.5 is not safe in secondary prevention of cerebral ischaemia of presumed arterial origin. Finally, not all atherosclerotic vascular diseases are identical from the therapeutic point of view; the effect of treatment depends in part on the clinical manifestation form.
Anticoagulants↗
[Medical education: 'plus ça change, plus c'est la même chose'].
Medical curricula are being overhauled at increasingly short intervals. Fashion is one of the driving forces behind the changes, sometimes at the expense of reason. There is no scientific proof that one type of curriculum produces better doctors than an other. A caring and humanistic attitude in physicians is probably less dependent on specific training than on innate personality traits and the example of role models. The Dutch Journal of Medicine is launching two initiatives intended to contribute to the education of medical students: an almost free subscription is offered after the first year, and a (quarterly) student edition will appear from 1998.
Clinical Competence↗
Issues and answers in stroke care.
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Cerebrovascular Circulation↗
Mayo and NINDS scales for assessment of tendon reflexes: between observer agreement and implications for communication.
The purpose of this study was to assess the between observer reliability of two standard notation scales for grading tendon reflexes, The Mayo Clinic scale and the NINDS scale. In a university department of neurology two or three physicians judged the biceps, triceps, knee, and ankle tendon reflexes in two groups of 50 patients using either scale. The interobserver agreement was assessed by means of kappa statistics. The agreement among doctors was never better than "fair" for both scales (highest kappa value 0.35). A verbal description rather than a codified scale may improve communication among doctors.
Adult↗
Headache characteristics in subarachnoid haemorrhage and benign thunderclap headache.
One third of patients with aneurysmal subarachnoid haemorrhage (ASAH) present with headache only. A prompt diagnosis is crucial, but these patients must be distinguished from patients with non-haemorrhagic benign thunderclap headache (BTH). The headache characteristics and associated features at onset in subarachnoid haemorrhage and benign thunderclap headache were studied to delineate the range of early features in these conditions. In this prospective study, one of two observers interviewed 102 patients with acute severe headache by means of a standard questionnaire. The patients were alert on admission and had no focal deficits. ASAH was subsequently diagnosed in 42 patients, non-aneurysmal perimesencephalic haemorrhage (PMH) in 23 patients, and BTH in 37 patients. Headache developed almost instantaneously in 50% of patients with ASAH, 35% of patients with PMH, and 68% of patients with BTH and within 1 to 5 minutes in 19%, 35%, and 19%, respectively. Loss of consciousness was reported in 26% of patients with ASAH, 4% of patients with PMH and 16% of patients with BTH, and transient focal symptoms in 33%, 9%, and 22% respectively. Seizures and double vision had occurred only in ASAH. Vomiting and physical exertion preceding the onset of headache were more frequent in patients with ASAH (69% and 50%) and those with PMH (83% and 39%) than in those with BTH (43% and 22%). Headache developed almost instantaneously in only half the patients with aneurysmal rupture and in two thirds of patients with benign thunderclap headache. In patients with acute severe headache, female sex, the presence of seizures, a history of loss of consciousness or focal symptoms, vomiting, or exertion increases the probability of ASAH, but these characteristics are of limited value in distinguishing ASAH from BTH. Aneurysmal rupture should be considered even if focal signs are absent and the headache starts within minutes.
Acute Disease↗
Distribution of muscle weakness of central and peripheral origin.
According to the established clinical tradition about the distribution of weakness, the ratios of flexor/extensor strength of patients with upper motor neuron lesions are expected to be relatively high for the elbow and wrist and low for the knee. To assess the diagnostic value of these patterns of weakness, muscle strength of 70 patients with limb weakness of central or peripheral origin was measured with a hand held dynamometer. The ratios of flexor/extensor strength at the knee, elbow, and wrist did not differ significantly between patients with central or peripheral origin of muscle weakness. The examination of tendon jerks proved to be of more value as a localising feature. The traditional notion about the distribution of weakness in upper motor neuron lesions may be explained by an intrinsically greater strength in antigravity muscles, together with the effects of hypertonia.
Adult↗
Prevalence and risk of rupture of intracranial aneurysms: a systematic review.
BACKGROUND AND PURPOSE: The estimates on the prevalence and the risk of rupture of intracranial saccular aneurysms vary widely between studies. We conducted a systematic review on prevalence and risk of rupture of intracranial aneurysms and classified the data according to study design, study population, and aneurysm characteristics. METHODS: We searched for studies published between 1955 and 1996 by means of a MEDLINE search and a cumulative review of the reference lists of all relevant publications. Two authors independently assessed eligibility of all studies and extracted data on study design and on numbers and characteristics of patients and aneurysms. RESULTS: For data on prevalence we found 23 studies, totalling 56,304 patients; 6685 (12%) of these patients were from 15 angiography studies. Prevalence was 0.4% (95% confidence interval, 0.4% to 0.5%) in retrospective autopsy studies, 3.6% (3.1 to 4.1) for prospective autopsy studies, 3.7% (3.0 to 4.4) in retrospective angiography studies, and 6.0% (5.3 to 6.8) in prospective angiography studies. For adults without specific risk factors, the prevalence was 2.3% (1.7 to 3.1); it tended to increase with age. The prevalence was higher in patients with autosomal dominant polycystic kidney disease (relative risk [RR], 4.4 [2.7 to 7.2]), a familial predisposition (RR, 4.0 [2.7 to 6.0]), or atherosclerosis (RR, 2.3 [1.7 to 3.1]). Only 8% (5 to 11) of the aneurysms were >10 mm. For the risk of rupture, we found nine studies, totalling 3907 patient-years. The overall risk per year was 1.9% (1.5 to 2.4); for aneurysms = 10 mm, the annual risk was 0.7% (0.5 to 1.0). The risk was higher in women (RR, 2.1[1.1 to 3.9]) and for aneurysms that were symptomatic (RR, 8.3 [4.0 to 17]), >10 mm (RR, 5.5 [3.3 to 9.4]), or in the posterior circulation (RR, 4.1 [1.5 to 11]). CONCLUSIONS: Data on prevalence and risk of rupture vary considerably according to study design, study population, and aneurysm characteristics. If all available evidence with inherent overestimation and underestimation is taken together, for adults without risk factors for subarachnoid hemorrhage, aneurysms are found in approximately 2%. The vast majority of these aneurysms are small (=10 mm) and have an annual risk of rupture of approximately 0.7%.
Adult↗
Quality of life in patients and partners after aneurysmal subarachnoid hemorrhage.
BACKGROUND AND PURPOSE: Outcome after subarachnoid hemorrhage (SAH) is often graded as "poor," "fair," or "good." Such categories are usually based on physicians' assessments of physical abilities of patients rather than on how patients themselves perceive their physical, psychological, and social well-being. We assessed functional outcome and quality of life (QoL) in patients with SAH and their partners. METHODS: In a consecutive series of 64 patients and 51 partners studied 4 months after the SAH, we assessed functional outcome by means of the Rankin Scale, and QoL by means of the SF-36, the Sickness Impact Profile (SIP), and a visual analogue scale. Additionally, we asked two "simple questions" about dependency and recovery. All questionnaires were completed in an interview setting. The scores on the QoL instruments from patients and partners were stratified according to the Rankin grades of the patients and were compared with data from a Dutch reference population. RESULTS: Only patients who had no symptoms at all (Rankin grade 0) had no reduction in QoL compared with the reference population; some of these patients even indicated an improvement in QoL from before the SAH according to the visual analogue scale. Patients who had symptoms but were independent (Rankin grades 1 to 3) and therefore usually designated as having "good outcome" often had reductions in QoL, on both the physical and psychosocial subscores of the SIP and SF-36. The QoL of partners was considerably reduced in several psychosocial domains. CONCLUSIONS: SAH has a considerable impact on the QoL of patients and their partners. Only patients without residual symptoms (Rankin grade 0) have a good outcome in terms of physical performance and QoL.
Aneurysm, Ruptured↗
Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a systematic review.
BACKGROUND AND PURPOSE: It has been reported that nimodipine reduces the frequency of secondary ischemia and improves outcome after aneurysmal SAH, but definitive evidence concerning all available calcium antagonists is lacking. METHODS: Systematic overview of randomized trials that were completed by January 1996 compared calcium antagonists with control and started treatment within 10 days after onset of subarachnoid hemorrhage (SAH) was performed. All calcium antagonists studied thus far (nimodipine, nicardipine, and AT877) were included. RESULTS: We analyzed 10 trials totaling 2756 patients. The relative risk (RR) reduction of poor outcome (death or dependency) was 16% (95% CI, 6 to 27%) and that of case fatality was 10% (95% CI, -6 to 25%). To prevent one poor outcome, 19 (12 to 59) patients need to be treated. Calcium antagonists give a 33% (95%, CI 25 to 41) RR reduction in the frequency of ischemic neurologic deficit and a 20% (95% CI, 11 to 28) RR reduction in the frequency of CT-scan documented cerebral infarction. Eight (6 to 11) patients need to be treated to prevent one ischemic neurologic deficit. In the analyses for nimodipine only, treatment was associated with a 24% RR reduction of poor outcome (95% CI, 12 to 38). To prevent one poor outcome, 13 (8 to 30) patients need to be treated with nimodipine. The RR reduction of angiographically detected cerebral vasospasm was statistically significant for AT877 (38%; 95% CI, 17 to 54%) and nicardipine (21%; 95% CI, 6 to 34%) but not for nimodipine (9%; 95% CI, -2 to 19%). CONCLUSION: Calcium antagonists reduce the proportion of ischemic neurologic deficits and nimodipine improves overall outcome within 3 months of aneurysmal SAH; evidence for a reduction of poor outcome from all causes by nicardipine and AT877 is inconclusive. The intermediate factors by which nimodipine exerts its beneficial effect remain uncertain.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Transient monocular blindness and antiphospholipid antibodies in systemic lupus erythematosus.
BACKGROUND AND OBJECTIVE: Among patients with systemic lupus erythematosus (SLE), the presence of antiphospholipid antibodies (APA), notably the lupus anticoagulant, and anticardiolipin antibodies (aCL) characterizes a subset of patients with a thrombotic tendency. During the regular follow-up care of patients with SLE, we noticed that many described transient visual disturbances. Because a hypercoagulable state may cause transient monocular blindness (TMB), we determined the frequency of TMB and studied its relation to the presence of APA in patients with SLE. METHODS: We asked 175 unselected patients with SLE whether they had transient visual disturbances and reviewed their medical charts. All patients were examined with specific attention to the presence of livedo reticularis. Blood was examined for APA. RESULTS: Visual disturbances were recorded for 136 (78%) patients. According to predefined criteria, the symptoms were diagnosed as TMB for 10 (6%) patients and as visual disturbances associated with migraine for 18 (10%) patients. Five of the 10 patients with TMB had attacks in either eye. The 175 patients with SLE accrued a maximum total of 6,349 patient years in their lifetime. From this, the incidence of TMB can be calculated to be at least 158 per 100,000 per year. Lupus anticoagulant was detected in 3 of 10 patients with TMB and 41 of 165 patients without TMB (odds ratio, 1.3; 95% CI, 0.2 to 6.0). aCLs were found in 5 of 10 patients with TMB and 91 of 165 patients without TMB (odds ratio, 0.8; 95% CI, 0.2 to 3.7). CONCLUSIONS: The frequency of TMB among patients with SLE is at least 158 per 100,000 compared with the normal population (14 per 100,000 per year). However, among patients with SLE, no significant relation could be shown between TMB and the presence of APA or livedo reticularis.
Acute Disease↗
Leukoaraiosis and vascular dementia.
The emergence of sensitive techniques for brain imaging has drawn attention to the occurrence of diffuse or multifocal changes affecting the cerebral white matter. The white matter changes are usually termed periventricular leukoencephalopathy, or leukoaraiosis. Microscopic studies of affected areas in the deep white matter have shown mostly demyelination, reactive gliosis, and arteriolosclerosis, proportional to the degree of radiologic changes. Yet, many other disease conditions need to be ruled out. Risk factors for ischemic leukoaraiosis include arterial hypertension, a history of stroke, and age. In the hereditary disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), severe white matter changes occur in the absence of hypertension. In "ordinary" cases of leukoaraiosis, genetic factors might similarly determine the effect of risk factors on the aging brain and might explain, for example, why not all patients with severe hypertension develop leukoaraiosis. Not surprisingly, diffuse demyelination affects cognitive function. Although reduced speed of mental processes is the most characteristic sign, attention, concentration, and verbal and visual memory are also affected. Most importantly, less severe forms of cognitive impairment represent a silent and perhaps largely preventable epidemic among aged or even middle-aged subjects. They live independently, but mentally they perform on a level well below their previous capacities. Although being "a bit odd" does not lead to hospital admissions, it seriously affects quality of life of a large part of the community. Moderate grades of leukoaraiosis constitute a major public health problem and deserve the attention of the scientific community.
Brain↗