ABC of arterial and venous disease. Secondary prevention of transient ischaemic attack and stroke.
Explore the source record for details and available documents.
Anticoagulants↗
Biomedical subjects
P M Bath
Publications and source records attributed to P M Bath.
ABC of arterial and venous disease. Acute stroke.
Explore the source record for details and available documents.
Aspirin↗
Pentoxifylline, propentofylline and pentifylline for acute ischaemic stroke.
BACKGROUND: Methylxanthine derivatives are vasodilators. They also inhibit platelet aggregation and thromboxane A2 synthesis, decrease the release of free radicals and may be neuroprotective. OBJECTIVES: The objective of this review was to assess the effect of intravenous or oral methylxanthines (pentoxifylline, propentofylline, or pentifylline) in patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, Medline (from 1965), Embase (from 1981), ISI (from 1981) and the Ottawa stroke trials registry. We contacted drug companies. SELECTION CRITERIA: Randomised trials comparing pentoxifylline, propentofylline or pentifylline with placebo or control in patients with definite or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. Trial quality was assessed. MAIN RESULTS: Five trials were included. Four trials tested pentoxifylline in 763 people, and one tested propentofylline in 30 people. No trials of pentifylline were found. Early death (within four weeks) occurred in 34 of 408 patients given a methylxanthine drug compared with 49 of 385 given placebo (odds ratio 0.64, 95% confidence interval 0.41 to 1.02). This non-significant trend to less deaths was due mainly to one pentoxifylline trial that found a highly significant reduction in early deaths. Two trials reported early death or disability and found a non-significant reduction (odds ratio 0.49, 95% confidence interval 0.20 to 1.20). Late death (beyond four weeks) was reported in the propentofylline trial involving 30 patients, with no difference between treatment and placebo (odds ratio 0.70, 95% confidence interval 0.13 to 3.68). Data for neurological impairment and disability were not in a form suitable for analysis. Data on quality of life, stroke recurrence, thromboembolism and bleeding were not reported. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess the effectiveness and safety of methylxanthines after acute ischaemic stroke.
Brain Ischemia↗
Prostacyclin and analogues for acute ischaemic stroke.
BACKGROUND: Prostacyclin is an agent with a number of effects on platelets, blood vessels and nerve cells which might improve outcome after acute ischaemic stroke. OBJECTIVES: The objective of this review was to assess the effect of prostacyclin or analogues on survival in people with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched: March 1999), Medline (from 1965), Embase (from 1980) and ISI (from 1981). We contacted drug companies. SELECTION CRITERIA: Randomised trials comparing prostacyclin or analogues with placebo or control. Trials where people were entered within one week of stroke onset were included. DATA COLLECTION AND ANALYSIS: Trial quality was assessed. MAIN RESULTS: Five trials involving 191 people were included. Six early deaths (within four weeks) occurred with prostacyclin and nine with placebo (odds ratio of 0.63, 95% confidence interval 0.22 to 1.85). One trial of 32 patients reported late deaths (by 10 to 18 months) in 50% of patients in each group. REVIEWER'S CONCLUSIONS: Too few patients have been studied in randomised trials to allow conclusions to be drawn about the effect of prostacyclin treatment on survival of people with acute stroke.
Brain Ischemia↗
Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke.
BACKGROUND: Theophylline causes potent cerebral vasoconstriction which decreases blood flow in the non-ischaemic areas of the brain and increases collateral blood flow surrounding the ischaemic region. OBJECTIVES: The objective of this review was to assess the effect of theophylline and its analogues (aminophylline and caffeine) in people with confirmed or presumed acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched: March 1999), Medline (from 1965), Embase (from 1980), and ISI (from 1981). We contacted drug companies. SELECTION CRITERIA: Randomised trials of theophylline or an analogue compound compared with placebo or control in people with confirmed or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset. DATA COLLECTION AND ANALYSIS: Three reviewers applied the inclusion criteria, assessed trial quality and extracted data. MAIN RESULTS: Two trials involving 119 patients were included. Trial quality was good. Both of the trials tested aminophylline. Analysis was by intention-to-treat where possible. No difference was shown in early death (within four weeks) between aminophylline and placebo (odds ratio 1.12, 95% confidence interval 0.49 to 2.56). There was no significant difference for early mortality and deterioration (odds ratio 0.87, 95% confidence interval 0.41 to 1.88). Death or disability was not reduced by treatment based on 73 patients in one trial (odds ratio 0.64, 95% confidence interval 0.24 to 1.68). Data for late mortality and disability were not in a form suitable for analysis. No data on quality of life were available. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess whether theophylline or its analogues reduce mortality or morbidity, or are safe, in people with acute ischaemic stroke.
Aminophylline↗
Interventions for dysphagia in acute stroke.
BACKGROUND: It is unclear how dysphagic patients should be fed and treated after acute stroke. OBJECTIVES: The objective of this review was to assess the effect of different management strategies for dysphagic stroke patients, in particular how and when to feed, whether to supplement nutritional intake, and how and whether to treat dysphagia. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, Medline, Embase, ISI, and existing review articles. We contacted researchers in the field and equipment manufacturers. Date of the most recent searches: March 1999. SELECTION CRITERIA: Unconfounded truly or quasi randomised controlled trials in dysphagic patients with acute/subacute (within 3 months) stroke. DATA COLLECTION AND ANALYSIS: Three reviewers independently applied the trial inclusion criteria. Two reviewers assessed trial quality and extracted the data. MAIN RESULTS: Percutaneous endoscopic gastrostomy (PEG) versus nasogastric tube (NGT) feeding: two trials (49 patients) suggest that PEG reduces end-of-trial case fatality (Peto Odds Ratio, OR 0.28, 95% CI 0.09 to 0.89) and treatment failures (OR 0.10, 95% CI 0.02 to 0.52), and improves nutritional status, assessed as weight (Weighted Men Difference, WMD +4.1 kg, 95% CI -4.3 to +12.5), mid-arm circumference (WMD +2.2 cm, 95% CI -0.5 to +4.9) or serum albumin (WMD + 7.0 g/l, 95% CI +4.9 to +9.1) as compared with NGT feeding; two larger studies are ongoing. Timing of feeding: no completed trials; one large study is ongoing. Swallowing therapy for dysphagia: two trials (85 patients) suggest that formal swallowing therapy does not significantly reduce end-of-trial dysphagia rates (OR 0.55, 95% CI 0.18 to 1.66). Drug therapy for dysphagia: one trial (17 patients); nifedipine did not alter end-of-trial case fatality or the frequency of dysphagia. Nutritional supplementation: one trial (42 patients) found a non-significant trend to a lower case fatality, and significantly increased energy and protein intake; one large trial is ongoing and data is awaited from two other studies. Fluid supplementation: one trial (20 patients) found that supplementation did not alter the time to resolution of dysphagia. REVIEWER'S CONCLUSIONS: Too few studies have been performed, and these have involved too few patients. PEG feeding may improve outcome and nutrition as compared with NGT feeding. Further research is required to assess how and when patients are fed, and the effect of swallowing or drug therapy on dysphagia.
Deglutition Disorders↗
Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute ischaemic stroke.
BACKGROUND: Nitric oxide has several effects that may be beneficial in ischaemic stroke and useful in the management of hypertension in acute stroke. Some forms of nitric oxide synthase inhibition may also be beneficial. However, high concentrations of nitric oxide are likely to be toxic to brain tissue. OBJECTIVES: The objective of this review was to assess the effects of nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in people with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (July 1997), Medline (for trials from 1965), Embase (from 1980) and ISI (from 1981). We contacted drug companies and researchers in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in patients within one week of onset of confirmed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. MAIN RESULTS: No completed trials were found. One small placebo-controlled trial of glyceryl trinitrate patches is underway. REVIEWER'S CONCLUSIONS: There is currently no evidence from randomised trials on the effects of nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in patients with acute ischaemic stroke.
Arginine↗
Hypertension in patients presenting with stroke.
Hypertension is a major risk factor for stroke disease. There is now some international agreement on what constitutes hypertension, and at what level of blood pressure treatment is required. Large randomised controlled trials demonstrate the benefit of reducing blood pressure for the primary and secondary prevention of stroke disease. Studies have also demonstrated the benefit of particular classes of antihypertensive agents in certain patient groups. Research is beginning to elucidate the problems of hypertension in the acute phase of ischaemic stroke and the therapeutic strategies that may be helpful. Given the significant impact of stroke disease on all health services, it remains an important priority to determine the best management of hypertension in stroke.
Antihypertensive Agents↗
A trial of blood pressure reduction in acute stroke.
Explore the source record for details and available documents.
Acute Disease↗
Low-molecular-weight heparins and heparinoids in acute ischemic stroke : a meta-analysis of randomized controlled trials.
BACKGROUND AND PURPOSE: Low-molecular-weight heparins and heparinoids (LMWHs) are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism and acute coronary syndromes. We performed a systematic review of randomized controlled trials (RCTs) to examine the safety and efficacy of LMWH in acute ischemic stroke. METHODS: Randomized, controlled, and nonconfounded trials of LMWH in acute ischemic stroke were identified from the Cochrane Library (version 2, 1999), previous systematic reviews, and a review of publication quality relating to acute stroke trials. The authors each independently extracted data by treatment group and assessed trial quality using Cochrane Collaboration criteria. RESULTS: Eleven completed RCTs involving 3048 patients were identified; data were available from 10 of these. Four trials explicitly excluded patients with presumed cardioembolic stroke. Treatment with LMWH was associated with significant reductions in prospectively identified deep vein thrombosis (OR 0.27, 95% CI 0.08 to 0.96) and symptomatic pulmonary embolism (OR 0.34, 95% CI 0.17 to 0.69) and with increased major extracranial hemorrhage (OR 2.17, 95% 1.10 to 4.28). Nonsignificant increases in end-of-treatment (OR 1.20, 95% CI 0.86 to 1.69) and end-of-trial (OR 1.05, 95% CI 0.83 to 1.32) case fatality and symptomatic intracranial hemorrhage (OR 1.77, 95% CI 0. 95 to 3.31) were observed. End-of-trial death and disability was nonsignificantly reduced (OR 0.87, 95% CI 0.72 to 1.06). CONCLUSIONS: ++LMWHs reduce venous thromboembolic events in patients with acute ischemic stroke and increase the risk of extracranial bleeding. A nonsignificant reduction in combined death and disability and nonsignificant increases in case fatality and symptomatic intracranial hemorrhage were also observed. On the basis of the current evidence, LMWH should not be used in the routine management of patients with ischemic stroke.
Acute Disease↗
Optimising homeostasis.
There is a wealth of experimental and clinical information showing that hypertension, hyperglycaemia, hyperthermia and intracranial hypertension are each independent indicators of a poor prognosis after stroke, but there is an astonishing lack of evidence from randomised controlled trials to tell us how to manage these problems, bearing in mind their frequency in stroke patients. The therapeutic options will, in most cases, not involve patented drugs, and financial support for running the necessary randomised controlled trials will have to come from government or charity sponsors rather than from the pharmaceutical industry. It is vital that academic researchers now devise studies of appropriate design and size to answer these important questions. In the absence of randomised data, severe hyperglycaemia and pyrexia should be treated, whilst acute hypertension is probably best left untreated unless very severe or complicated by other medical conditions. The management of cerebral oedema remains an enigma.
Fever↗
Clinical application of asymptomatic embolic signal detection in acute stroke: a prospective study.
BACKGROUND AND PURPOSE: The detection of asymptomatic embolization with the use of Doppler ultrasound has a number of potential applications in patients with acute stroke. It may provide information on the stroke pathogenesis in individual cases, identify patients with continued embolization, and allow localization of the active embolic source. METHODS: We recruited 119 patients with acute anterior circulation infarction within 72 hours of stroke onset. Transcranial Doppler recordings were possible in 100 (84.0%). Bilateral 1-hour middle cerebral artery (MCA) recordings were made and saved on digital audiotape for blinded offline analysis. When embolic signals were detected during screening of the first recording, simultaneous recording was performed from the ipsilateral MCA and common carotid artery for an additional 30 minutes. In all patients with embolic signals at screening and in matched negative controls, recordings were repeated on days 4, 7, and 14. RESULTS: Embolic signals were detected in the symptomatic MCA in 16 patients (16%). They were more common in patients with carotid stenosis (P<0.0001), occurring in 50% of this group. They were rare in patients with cardioembolic stroke (4.5%) and were not detected in patients with lacunar stroke. In the 16 patients with embolic signals, the proportion with embolic signals fell over time (P=0. 0025), but they were still present in a third at 2 weeks. In 10 patients, localization of the embolic source was possible by simultaneous recording from the MCA and the ipsilateral common carotid artery. CONCLUSIONS: Continued asymptomatic embolization is common after stroke in patients with carotid artery disease and is still present in a significant proportion at 2 weeks. The technique may identify patients at risk of further stroke for more aggressive antiplatelet therapy; this needs to be tested in large prospective studies. The technique may also allow localization of the active embolic source.
Acute Disease↗
Platelets and stroke.
Platelets are anucleate cells with little or no capacity for de novo protein synthesis. Their potential haemostatic reactivity is established at or before thrombopoiesis by their precursor cell, the bone marrow megakaryocyte. In some pathologic conditions, the megakaryocyte-platelet-haemostatic axis (MPHA) becomes perturbed, resulting in the formation of hyperfunctional platelets which may contribute to the development of vascular disease or an acute thrombotic event such as ischaemic stroke or myocardial infarction. Laboratory measurements of platelet function have established that platelet reactivity is accentuated in acute ischaemic stroke, particularly following cortical rather than lacunar infarction. Whether accentuated platelet function is a cause or a consequence of stroke is not yet clear, but it is likely that patients with certain risk factor profiles have some degree of platelet activation preceding the stroke. Further work into the MPHA is required to establish whether enhanced post-stroke platelet reactivity can be referred to the megakaryocyte. The antiplatelet agents tested to date are effective in secondary but not primary prevention of stroke. This probably reflects the diverse pathophysiology of stroke: accentuated platelet function is only likely to be a significant factor in cortical stroke.
Animals↗
IST and CAST: some answers but more questions.
Explore the source record for details and available documents.
Acute Disease↗
Cerebroprotective effect of the nitric oxide synthase inhibitors, 1-(2-trifluoromethylphenyl) imidazole and 7-nitro indazole, after transient focal cerebral ischemia in the rat.
The novel neuronal nitric oxide synthase inhibitors, 1-(2-trifluoromethylphenyl)imidazole (TRIM) and 7-nitro indazole (7-NI), were used to investigate the role of nitric oxide in a model of transient focal cerebral ischemia in vivo. In halothane-anesthetized rats, the middle cerebral artery (MCA) was occluded for 2 hours using an intravascular thread and then reperfused for 22 hours before histologic evaluation. TRIM (10, 20, or 50 mg/kg), 7-NI (60 mg/kg), TRIM (50 mg/kg) plus L-arginine (300 mg/kg), or L-arginine (300 mg/kg) alone was administered intraperitoneally, either at 5 or 90 minutes after MCA occlusion. Immediate administration (5 minutes after MCA occlusion) of TRIM produced a dose-related reduction in lesion size, which was reversed with L-arginine coadministration. Similarly, delayed administration of TRIM (90 minutes after MCA occlusion, 50 mg/kg) decreased total lesion volume by 48.4% +/- 13.0% in comparison to a reduction of 39.3% +/- 10.9% when TRIM (50 mg/kg) was administered immediately (5 minutes) after occlusion. 7-NI (60 mg/kg) reduced the total lesion volume by 38.5% +/- 13.7% when administered immediately (5 minutes) after MCA occlusion, but had no effect when administration was delayed (90 minutes). Neither TRIM (50 mg/kg) nor 7-NI (60 mg/kg), administered 5 minutes after MCA occlusion, had any significant effect on mean arterial blood pressure throughout the ischemic period or for up to 10 minutes after reperfusion. These results indicate that immediate or delayed administration of the selective neuronal NOS inhibitor TRIM reduces the lesion volume after transient MCA occlusion. In contrast, only immediate administration of 7-NI reduces lesion volume.
Animals↗
Quality of full and final publications reporting acute stroke trials: a systematic review.
BACKGROUND AND PURPOSE: Several studies have shown that the quality of reporting of trials throughout medicine is variable and often poor. We report on the quality of the final reports of randomized controlled trials (RCTs) of drug therapies assessed in acute stroke. METHODS: English-language reports published up to the end of 1996 relating to completed RCTs in acute stroke were identified from electronic searches of the Cochrane Stroke Review Group database of stroke trials and the Cochrane Controlled Trials Register (CD-ROM issue 1, 1997, of the Cochrane Library). Report quality was assessed with the 33 criteria of the CONSORT statement and 53 additional factors relevant to acute stroke or trials in general. Trial quality was also assessed with a 7-point scale. RESULTS: Up to 1996, 114 RCTs were published which involved 20 536 patients (median, 80; range, 16 to 1267 per trial); 39 (35.5%) of these were published in Stroke. The median total report quality was 40/86 (range, 15 to 61) for all criteria and 19/33 (range, 9 to 29) for the CONSORT criteria alone. Although adequate information was given in the introduction and discussion sections of most reports, insufficient details were given on methods, assignment of patients to treatment groups, statistical analyses, the prevalence of risk factors, and assessment of outcomes. Report quality has improved between 1956 and 1996 (Spearman correlation coefficient [rs], 0.575; 95% confidence interval [CI], 0. 439 to 0.685) and was superior in large trials (rs=0.434; 95% CI, 0. 274 to 0.571). Although report quality was related to trial quality (rs=0.675; 95% CI, 0.563 to 0.763), it was not related to journal impact factor (rs=0.170; 95% CI, -0.015 to 0.344). Trials with a positive outcome tended to be less well reported than those with a neutral or negative outcome (rs=-0.192; 95% CI, -0.351 to -0.011). CONCLUSIONS: The overall quality of study reports for parallel group RCTs in acute stroke is poor but appears to be improving with time and in parallel with an increase in trial size. Reports often lack detailed information on the methods of randomization, concealment of allocation, and statistical analysis, all factors which can, if undertaken poorly, affect trial results and validity. It is vital that future trials are adequately reported; we believe that authors should follow the CONSORT guidelines and that referees and editors should ensure this happens.
Humans↗
Serum S-100 protein in acute stroke.
Explore the source record for details and available documents.
Cerebrovascular Disorders↗
Serum S-100 protein, relationship to clinical outcome in acute stroke.
The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0.27 (0.90) microgram/L, n = 68] and haemorrhagic stroke [0.43 (0.23 microgram/L, n = 13] compared to controls [0.11 (0.03) microgram/L, n = 51, P < 0.0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0.40 (0.22) microgram/L], and small vessel ('lacunar') infarcts concentrations having the lowest [0.20 (0.60) microgram/L, P < 0.0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disability and handicap scales (n = 81): modified Barthel index (rs = -0.285, P = 0.01), modified Rankin score (rs = 0.313, P = 0.004) and Lindley score (rs = 0.262, P = 0.018) with high values associated with poor clinical outcome. Similarly high values of serum S-100 protein were observed in patients who died or were discharged to an institution [median (SQR): 0.63 (0.29) microgram/L and 0.37 (0.13) microgram/L, respectively compared to those who were discharged home [0.26 (0.11) microgram/L, P = 0.13]. The present study suggests measurement of serum S-100 protein could be a useful prognostic marker of clinical outcome in acute stroke. Whether S-100 concentrations can be altered by therapeutic intervention in acute stroke remains to be elucidated.
Age Factors↗