Brain lesion volume and capacity for consent in stroke trials: potential regulatory barriers to the use of surrogate markers.

BACKGROUND AND PURPOSE: European directives and legislation in some countries forbid inclusion of subjects incapable of consent in research if recruitment of patients capable of consent will yield similar results. We compared brain lesion volumes in stroke patients deemed to have capacity to consent with those defined as incapacitated. METHODS: Data were obtained from 3 trials recruiting patients primarily with cortical stroke syndromes. Patients were recruited within 24 hours of onset and used MRI based selection or outcome criteria. Method of recruitment was recorded with stroke severity, age, and brain lesion volumes on Diffusion Weighted Imaging. RESULTS: Of the 56 subjects included, 38 (68%) were recruited by assent and 18 (32%) by consent. The assent group had a median lesion volume of 18.35 cubic centimetres (cc) (interquartile range [IQR] 8.27-110.31 cc), compared to 2.79 cc (IQR 1.31-12.33 cc) when patients consented (P=0.0004). Lesions were smaller than 5 cc in 7/38 (18%) in the assent group and 11/18 (61%) in the consent group (P=0.0024). There was good correlation between neurological deficit by NIH stroke scale score and lesion volume (r=0.584, P<0.0001). Logistic regression demonstrated NIHSS or lesion volume predicted capacity to consent. CONCLUSIONS: Patients with acute stroke who retain capacity to consent have significantly smaller infarct volumes than those incapable of consent, and these are frequently below the limits where measurement error significantly compromises valid use of volumetric end points. Only a small proportion of patients with capacity to consent would be eligible for, and contribute usefully to, most acute stroke trial protocols.

Implementation of a stroke thrombolysis service within a tertiary neurosciences centre in the United Kingdom.

BACKGROUND: Intravenous alteplase is licensed for treatment of ischaemic stroke within 3 h of onset. Up to one-third of patients in the UK present to hospital within this time window but few are treated. AIMS: To examine the effect of a stroke thrombolysis protocol on service provision for an acute stroke service in the UK, jointly run by Neurology and Medicine for the Elderly providing a comprehensive stroke service to a local population of 370,000. DESIGN: Prospective observational study. METHODS: Data collected prospectively for all thrombolysis referrals over a 12-month period beginning July 2004. RESULTS: One hundred and eighty-eight patients were referred for potential thrombolysis, 129 transferred, 102 had an ischaemic stroke and 49 received intravenous thrombolysis. Referral rates from primary care and accident and emergency increased after guideline dissemination. Forty-three percent of the 49 patients treated with intravenous rt-PA achieved independence (modified Rankin Scale score 0-2) at 3months. CONCLUSION: A high proportion of ischaemic stroke patients can be treated with alteplase within 3 h of onset with organized hospital services and dissemination of a simple referral protocol to local primary and secondary care services.

Combined treatment with vessel dilator and kaliuretic hormone in persons with congestive heart failure.

Vessel dilator and kaliuretic hormone, two cardiovascular peptide hormones, enhance urine flow 2- to 13-fold and 4-fold, respectively, in persons with class III New York Heart Association congestive heart failure (CHF). The natriuresis and diuresis secondary to vessel dilator and kaliuretic hormone are not blunted as are atrial natriuretic peptide and brain natriuretic peptide effects in persons with CHF compared with healthy individuals. The present investigation determined if the two peptide hormones that do not have blunted effects in persons with CHF may have added beneficial effects when given simultaneously to individuals with class III CHF. Together with each at 100 ng/kg of body weight per minute, vessel dilator and kaliuretic hormone increased urine flow rate 3.5-fold (P < 0.05) compared with their 60-min baseline and control CHF subjects' urine flow rates. Combined, they enhanced the excretion rate of sodium a maximum of 3.6-fold (P < 0.05) with 2.5- and 2-fold enhancement 2 and 3 hrs after infusion. These data indicate that vessel dilator and kaliuretic hormone have diuretic and natriuretic effects when used in combination, but these effects are not additive over their individual effects in persons with CHF.