Emergency Physician Treatment of Acute Stroke with Recombinant Tissue Plasminogen Activator: A Retrospective Analysis

Stroke teams are advocated for the rapid treatment of patients who have acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA). An alternate model uses existing ED resources with specialist consultation as needed. Objectives: To evaluate the treatment of AIS with rt-PA in this alternate ED model. Methods: A retrospective observational review was performed of consecutive patients with AIS treated with rt-PA at four hospitals affiliated with an emergency medicine residency. Emergency physicians (EPs) were directly responsible for the treatment of all patients according to predefined guidelines. Records were evaluated from the implementation of the guidelines through December 15, 1997. Results: 37 patients with AIS received rt-PA. Mean age ± SD was 63 ± 16 years (range 22-87), with 25 (68%) male. Patients presented 67 ± 29 minutes after stroke onset. After ED arrival, they were seen by the EP in 14 ± 13 minutes, had CT in 46 ± 22 minutes, and were treated in 97 ± 35 minutes. Neurologist consultation occurred in the department for nine patients (24.3%), and by telephone for 14 (37.8%). Symptomatic intracerebral hemorrhage (ICH) occurred in four (10.8%, 95% CI = 0.8% to 20.8%). There were two deaths, neither associated with ICH. Neurologic outcome at discharge compared with presentation in survivors was normal for four patients (11.4%), improved for 16 (45.7%), unchanged for ten (28.6%), and worse for five (14.3%). Conclusions: In this analysis, EPs, with specialty consultation as required, successfully identified patients with AIS and delivered rt-PA with satisfactory outcomes. Important elements of this model include early patient identification, preestablished protocols, and rapid access to CT scanning and interpretation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71596/1/j.1553-2712.1999.tb00416.x.pd

Propensity Score Matching in Randomized Clinical Trials

Cluster randomization trials with relatively few clusters have been widely used in recent years for evaluation of health-care strategies. On average, randomized treatment assignment achieves balance in both known and unknown confounding factors between treatment groups, however, in practice investigators can only introduce a small amount of stratification and cannot balance on all the important variables simultaneously. The limitation arises especially when there are many confounding variables in small studies. Such is the case in the  INSTINCT  trial designed to investigate the effectiveness of an education program in enhancing the tPA use in stroke patients. In this article, we introduce a new randomization design, the balance match weighted (BMW) design, which applies the optimal matching with constraints technique to a prospective randomized design and aims to minimize the mean squared error (MSE) of the treatment effect estimator. A simulation study shows that, under various confounding scenarios, the BMW design can yield substantial reductions in the MSE for the treatment effect estimator compared to a completely randomized or matched-pair design. The BMW design is also compared with a model-based approach adjusting for the estimated propensity score and Robins-Mark-Newey E-estimation procedure in terms of efficiency and robustness of the treatment effect estimator. These investigations suggest that the BMW design is more robust and usually, although not always, more efficient than either of the approaches. The design is also seen to be robust against heterogeneous error. We illustrate these methods in proposing a design for the  INSTINCT  trial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78638/1/j.1541-0420.2009.01364.x.pd

Percutaneous vascular interventions for acute ischaemic stroke.

peer-reviewedMost disabling strokes are due to blockage of a large artery in the brain by a blood clot. Prompt removal of the clot with intra-arterial thrombolytic drugs or mechanical devices, or both, can restore blood flow before major brain damage has occurred, leading to improved recovery. However, these so-called percutaneous vascular interventions can cause bleeding in the brain.PUBLISHEDpeer-reviewe

Treating the acute stroke patient as an emergency: current practices and future opportunities

Developments in acute stroke therapy have followed advances in the understanding of the evolving pathophysiology in both ischaemic stroke and intracerebral haemorrhage (ICH). In ischaemic stroke, rapid reperfusion of the ischaemic penumbra with thrombolysis within 3 h of symptom onset is of proven benefit, but few patients currently receive therapy, mainly due to the short-time window and lack of stroke expertise. In ICH, a recent study indicated that a haemostatic agent can limit ongoing bleeding and improve outcomes when administered within 4 h of stroke onset. These advances in acute stroke therapy underlie the concept that ‘time is brain’ and that urgent intervention can limit cerebral damage. Neuroprotective therapy could offer the prospect of a greater proportion of stroke patients receiving treatment, potentially before imaging and even in the ambulance setting. Virtually all stroke patients would benefit from receiving multidisciplinary care in acute stroke units

Ultrasound Enhanced Thrombolysis: Applications in Acute Cerebral Ischemia

Intravenous tissue plasminogen activator (TPA) improves patient chances to recover from stroke by inducing mostly partial recanalization of large intracranial thrombi. TPA activity can be enhanced with ultrasound including 2 MHz transcranial Doppler (TCD). TCD identifies residual blood flow signals around thrombi, and, by delivering mechanical pressure waves, exposes more thrombus surface to circulating TPA. The international multi-center CLOTBUST trial showed that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming multi-disciplinary experimental research conducted worldwide for the past 30 years

The roles of specialisation and evidence-based practice in inter-professional jurisdictions : a qualitative study of stroke services in England, Sweden and Poland

This paper investigates how the concepts of clinical specialisation and evidence influence the jurisdictional power of doctors, nurses and therapists involved in stroke care in Sweden, England and Poland. How stroke care has become a distinct specialism across Europe and the role that evidence has played in this development are critically analysed. Five qualitative case studies were undertaken across the three countries, consisting of 119 semi-structured interviews with a range of healthcare workers. The informants were purposively selected and their perspectives of evidence-based practice (EBP) within stroke care were explored. The data were analysed through thematic content analysis. The two key themes that emerged from the data were the health professionals' degrees of EBP and specialisation. The results illustrate how the two concepts of clinical specialisation and evidence are interrelated and work together to influence the different professions' degree of professional jurisdiction. It is concluded that doctors' professional dominance gives them full jurisdiction in stroke care and that nurses' and therapists' degrees of jurisdiction is dependent on their ability to specialise

The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective?

In the last two decades it has become apparent that thrombin has many extravascular effects that are mediated by a family of protease-activated receptors (PARs). PAR-1, -3 and -4 are activated via cleavage by thrombin. The importance of extravascular thrombin in modulating ischemic, hemorrhagic and traumatic injury in brain has recently become clear. Thus, in vitro , thrombin at low concentration protects neurons and astrocytes from cell death caused by a number of different insults. In vivo , pretreating the brain with a low dose of thrombin (thrombin preconditioning), attenuates the brain injury induced by a large dose of thrombin, an intracerebral hemorrhage or by focal cerebral ischemia. Thrombin may also be an important mediator of ischemic preconditioning. In contrast, high doses of thrombin kill neurons and astrocytes in vitro and cause disruption of the blood–brain barrier, brain edema and seizures in vivo . This review examines the role of thrombin in brain injury and the molecular mechanisms and signaling cascades involved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66277/1/j.1471-4159.2003.01268.x.pd