The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial

10.1186/1471-2318-13-88BMC Geriatrics131

Polarized spectroscopy of aligned single-wall carbon nanotubes

Polarized resonant Raman and optical spectroscopy of aligned single-wall carbon nanotubes show that the optical transitions are strongly polarized along the nanotubes axis. This behavior is consistent with recent electronic structure calculations

Relationship between nitrate headache and outcome in patients with acute stroke: results from the efficacy of nitric oxide in stroke (ENOS) trial

IntroductionNitrate-induced headache is common and may signify responsive cerebral vasculature. We assessed the relationship between nitrate-headache and outcome in patients with acute stroke.Materials and MethodsPatients were those randomised to glyceryl trinitrate (GTN) versus no GTN in the Efficacy of Nitric Oxide in Stroke trial. Development of headache by end of treatment (day 7), and functional outcome (modified Rankin Scale, mRS, primary outcome) at day 90, were assessed. Analyses are adjusted for baseline prognostic factors and give odds ratio (OR) and mean difference (MD) with 95% confidence intervals (95% CI).ResultsIn 4011 patients, headache was more common in GTN than control (360, 18.0% vs. 170, 8.5%; 2

Effect of hyperacute administration (within 6 hours) of transdermal glyceryl trinitrate, a nitric oxide donor, on outcome after stroke

Background and Purpose — Nitric oxide donors are candidate treatments for acute stroke, potentially through hemodynamic, reperfusion, and neuroprotectant effects, especially if given early. Although the large Efficacy of Nitric Oxide in Stroke (ENOS) trial of transdermal glyceryl trinitrate (GTN) was neutral, a prespecified subgroup suggested that GTN improved functional outcome if administered early after stroke onset. Methods — Prospective analysis of subgroup of patients randomized into the ENOS trial within 6 hours of stroke onset. Safety and efficacy of GTN versus no GTN were assessed using data on early and late outcomes. Results — Two hundred seventy-three patients were randomized within 6 hours of ictus: mean (SD) age, 69.9 (12.7) years; men, 154 (56.4%); ischemic stroke, 208 (76.2%); Scandinavian Stroke Scale, 32.1 (11.9); and total anterior circulation syndrome, 86 (31.5%). When compared with no GTN, the first dose of GTN lowered blood pressure by 9.4/3.3 mm Hg (P<0.01, P=0.064) and shifted the modified Rankin Scale to a better outcome by day 90, adjusted common odds ratio, 0.51 (95% confidence interval, 0.32–0.80). Significant beneficial effects were also seen with GTN for disability (Barthel Index), quality of life (EuroQol-Visual Analogue Scale), cognition (telephone Mini-Mental State Examination), and mood (Zung Depression Scale). GTN was safe to administer with less serious adverse events by day 90 (GTN 18.8% versus no GTN 34.1%) and death (hazard ratio, 0.44; 95% confidence interval, 0.20–0.99; P=0.047). Conclusions—In a subgroup analysis of the large ENOS trial, transdermal GTN was safe to administer and associated with improved functional outcome and fewer deaths when administered within 6 hours of stroke onset

Associations between change in blood pressure and functional outcome, early events and death: results from the Efficacy of Nitric Oxide in Stroke trial.

OBJECTIVES: High blood pressure (BP) is associated with a poor outcome after acute stroke. Early reduction in BP may be associated with fewer early adverse events and deaths, and improved functional outcome. METHODS: Analyses used data from the Efficacy of Nitric Oxide in Stroke trial, a multicentre randomized single-masked and outcome-masked trial of glyceryl trinitrate vs. no glyceryl trinitrate in 4011 patients recruited within 48 h of an ischaemic or haemorrhagic stroke and with raised SBP (140-220 mmHg). Change in SBP from baseline to day 1 was categorized as: more than 15% decrease, 15-5% decrease, 5% decrease to 5% increase (no change - reference) and more than 5% increase. The primary outcome was functional outcome (modified Rankin scale) score at 90 days. RESULTS: Across all patients, both moderate (5-15%) and large (>15%) decreases in SBP were associated with beneficial shifts in the modified Rankin scale relative to patients with no change in BP: adjusted common odds ratio (OR) 0.81 [95% confidence interval (CI) 0.70-0.90] and OR 0.84 (95% CI 0.71-1.00), respectively. A moderate decrease in SBP was also associated with a lower risk of early adverse events, adjusted OR 0.69 (95% CI 0.52-0.90). CONCLUSION: Modest decreases in SBP in acute stroke appear to be associated with fewer early events and better long-term functional outcome

Continuing versus stopping prestroke antihypertensive therapy in acute intracerebral hemorrhage: a subgroup analysis of the efficacy of nitric oxide in stroke trial

Background and purpose: More than 50% of patients with acute intracerebral haemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Methods: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life. Results: Blood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45- 1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events. Conclusions: Among patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily

Effect of glyceryl trinitrate on haemodynamics in acute stroke: data from the Efficacy of Nitric Oxide in Stroke trial

Background and Purpose: Increased blood pressure (BP), heart rate and their derivatives (variability, pulse pressure, rate-pressure product [RPP]) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on haemodynamic parameters, and these on outcome in participants in the Efficacy of Nitric Oxide in Stroke trial.Methods: 4011 patients with acute stroke and raised BP were randomised within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral haemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as standard deviation) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale (mRS) and cognition as telephone mini-mental state examination (t-MMSE) at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference (MD) or odds ratios (OR) with 95% confidence intervals (CI).Results: Increased baseline BP (diastolic, variability), heart rate and RPP were each associated with unfavourable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in mRS (highest quintile adjusted OR 1.65, 95% CI 1.37 to 1.99), worse cognitive scores (t-MMSE: highest quintile adjusted MD -2.03, 95% CI -2.84 to -1.22) and increased odds of death at day 90 (highest quintile adjusted OR 1.57, 95% CI 1.12 to 2.19). GTN lowered BP and RPP, and increased heart rate at day 1; and reduced between-visit systolic BP variability.Conclusions: Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and RPP, GTN reduced between-visit systolic BP variability. Agents that lower BP variability in acute stroke require further study

Central adjudication of serious adverse events did not affect trial's safety results: Data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial

Background and Purpose: Central adjudication of serious adverse events (SAEs) can be undertaken in clinical trials, especially for open-label studies where outcome assessment may be at risk of bias. This study explored the effect of central adjudication of SAEs on the safety results of the Efficacy of Nitric Oxide in Stroke (ENOS) Trial. Methods: ENOS assigned patients with acute stroke at random to receive either transdermal glyceryl trinitrate (GTN) or no GTN and to Stop or Continue previous antihypertensive treatment. SAEs were reported by local investigators who were not blinded to treatment allocation. Central adjudicators blinded to treatment allocation, reviewed the investigators reports and used evidence available to confirm or re-categorise the classification of event, likely causality, diagnosis and expectedness of event. Results: Of 4011 patients enrolled in ENOS, 1473 SAEs were reported by local investigators; this was reduced to 1444 after the review by adjudicators, with 29 re-classified as not an SAE. There was fair agreement between investigators and adjudicators regarding likely causality, with 808 agreements and 644 disagreements (56% crude agreement, weighted kappa, κ = 0.31). Agreement increased upon dichotomisation of the causality categories, with 1432 agreements and 20 disagreements (99% crude agreement, kappa = 0.54). Repeating the main trial safety analysis with investigator reported events showed that adjudication had no effect on the main trial safety conclusions. Conclusions: In a large trial, with many SAEs reported, central adjudication of these events did not affect trial conclusions. This suggests that adjudication of SAEs in a clinical trial where the intervention already has a well-established safety profile may not be necessary. Potential efficiency savings (financial, logistical) can be made through not adjudicating SAEs

It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis

Background There is concern that blood pressure (BP) lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis. We assessed the effect of glyceryl trinitrate (GTN) in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke (ENOS) Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP (140–220 mm Hg) to transdermal GTN or no GTN within 48 hours of onset. Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days. The primary outcome was the modified Rankin Scale (mRS) at day 90. Ipsilateral carotid stenosis was split