Heena Olalde

Extending Acute Trials to Remote Populations: A Pilot Study During Interhospital Helicopter Transfer

Background and Purpose— Methods to increase recruitment into acute stroke trials are needed. The purposes of this study were to evaluate the safety and acceptability of initiating acute stroke trials during early helicopter evacuation and to test an intervention to facilitate informed consent. Methods— A randomized, controlled trial was done with patients with acute stroke who were transferred by helicopter to the University of Iowa Hospitals and Clinics from February 2007 to January 2008. The intervention to be evaluated was the use of fax and a telephone call to the patient/surrogate ahead of helicopter arrival at the outside emergency department. The aim was to improve the rate of subsequent consent (primary outcome) for a pilot trial of a potentially beneficial, low-risk medical intervention (ranitidine) to prevent aspiration pneumonitis. Consenting eligible patients received the infusion during the flight to University of Iowa Hospitals and Clinics. Results— One hundred patients were enrolled. Consent rate was 54% in the intervention group and 50% in the control group (P=0.69). However, the consent rate was higher (69%) when prearrival communications between the coinvestigator and potential subjects were successful (P=0.04). This approach resulted in an average gain of 59 minutes as compared with initiating recruitment on arrival to University of Iowa Hospitals and Clinics. Conclusions— Enrollment into stroke intervention trials is feasible during helicopter transportation from a community hospital emergency department to a tertiary stroke center. This underused resource may improve trial efficiency by enabling and expediting participation of remote populations currently excluded from research. Consent rates might be further improved by communication strategies that are more successful in reaching patients at outside emergency departments.

Previous Statin Use Is Not Associated With an Increased Prevalence or Degree of Gradient-Echo Lesions in Patients With Acute Ischemic Stroke or Transient Ischemic Attack

Background and Purpose— Microhemorrhages on gradient-echo T2*-weighted MRI sequences are often found in patients with cerebrovascular disease and are related to intracerebral hemorrhage. Because statin therapy is associated with increased risk of intracerebral hemorrhage, we investigated whether statin use was also associated with microhemorrhages in patients with acute ischemic stroke or transient ischemic attack. Methods— We performed a retrospective analysis on prospectively collected data from a stroke registry containing patients with acute ischemic stroke or transient ischemic attack. The primary and secondary outcome variables were the prevalence and degree of microhemorrhages as detected on gradient-echo MRI sequences and categorized as mild (1–2), moderate (3–10), or severe (>10). The location of the microhemorrhages was noted and rated by 2 neuroradiologists. Previous use of statins and other covariates were assessed as potential predictors. Results— Three hundred forty-nine patients were admitted from June 2008 to July 2009, and 300 of which were analyzed. Microhemorrhages were detected in 70 subjects (23%); 35 had only lobar lesions, 16 had only deep lesions, and 19 had both lobar and deep lesions. On univariate and multivariate analysis, statin therapy was not associated with the prevalence (OR, 0.73; 95% CI, 0.36–1.51; P=0.40) or degree of microhemorrhages modeled for lesser severity (OR, 2.31; 95% CI, 0.61–8.75; P=0.22). Conclusions— Previous statin therapy was not associated with the prevalence or degree of microhemorrhages in patients with acute ischemic stroke or transient ischemic attack. The association between statins and intracerebral hemorrhage does not appear to be mediated through microhemorrhages.

Effect of helicopter transport on neurological outcomes in a mouse model of embolic stroke with reperfusion: AIR-MICE pilot study

Background Patients often suffer a stroke at a significant distance from a center capable of delivering endovascular therapy, thus requiring rapid transport by helicopter emergency medical services while receiving a recombinant tissue plasminogen activator infusion that was initiated locally. But little is known about how a helicopter flight may impact the safety and efficacy of recombinant tissue plasminogen activator-induced reperfusion and patient outcomes. Aim To establish a new animal method to address with fidelity the safety and overall effect of helicopter emergency medical services during thrombolysis. Methods Prospective randomized open blinded end-point study of an actual helicopter flight exposure. Adult C57BL/6 male mice were treated with a 10 mg/kg recombinant tissue plasminogen activator infusion two-hours after an embolic middle cerebral artery occlusion. Mice were randomized in pairs to simultaneously receive the infusion during a local helicopter flight or in a ground hangar. Results Eighteen mice (nine pairs) were analyzed. The paired t-test analysis showed nonsignificant smaller infarction volumes in the helicopter-assigned animals (mean pair difference 33 mm3, P = 0.33). The amount of hemorrhagic transformation between the helicopter and ground groups was 4.08 vs. 4.56 μl, respectively (paired t-test, P = 0.45). Conclusions This study shows that helicopter emergency medical services do not have an inherent adverse effect on outcome in a mouse model of ischemic stroke with reperfusion. These results endorse the safety of the practice of using helicopter emergency medical services in stroke patients. The observed potential synergistic effect of helicopter-induced factors, such as vibration and changes in altitude, with reperfusion merits further exploration in animal experimental models and in stroke patients.

Lack of International Consensus on Ethical Aspects of Acute Stroke Trials

Acute stroke trials are becoming increasingly multinational. Working toward a shared ethical standard for acute stroke research necessitates evaluating the degree of consensus among international researchers. We surveyed all 275 coinvestigators and coordinators who participated in the AbESTT II study (evaluating abciximab vs placebo) about their experience with their local institutional review board (IRB) or equivalent, as well as, about their personal beliefs regarding the ethical aspects of acute stroke trials. A total of 90 coinvestigators from 15 different countries responded to our survey. Among the IRBs represented by the responding coinvestigators, only 18% allowed surrogate consent to be obtained over the phone. Although 52% allowed the participation of subjects with aphasia, only 5% allowed the participation of subjects with neglect/hemi-inattention. The National Institutes of Health Stroke Scale score was deemed adequate to establish decisional capacity based on language by 62% of the coinvestigators and 36% of the IRBs. A belief that IRB regulations cause unnecessary delays and fear in relatives/patients was reported by 67% of coinvestigators, and the belief that granting an exemption from informed consent under specific circumstances is appropriate was reported by 41%. There appears to be considerable international diversity in the ethical priorities and informed consent standards among different IRBs and investigators in stroke research. The stroke community should make an attempt to standardize the consent process used in research. Given the critical nature of the time to treatment in stroke care, these standards should be integrated into current frameworks of clinical care and research. The absence of an ethical consensus can become a barrier to advancing stroke treatment internationally.

Cerebral Microbleeds are an Independent Predictor of Hemorrhagic Transformation Following Intravenous Alteplase Administration in Acute Ischemic Stroke

BACKGROUND AND PURPOSE Intravenous alteplase (rt-PA) increases the risk of hemorrhagic transformation of acute ischemic stroke. The objective of our study was to evaluate clinical, laboratory, and imaging predictors on forecasting the risk of hemorrhagic transformation following treatment with rt-PA. We also evaluated the factors associated with cerebral microbleeds that increase the risk of hemorrhagic transformation. METHODS Consecutive patients with acute ischemic stroke admitted between January 1, 2009 and December 31, 2013 were included in the study if they received IV rt-PA, had magnetic resonance imaging (MRI) of the brain on admission, and computed tomography or MRI of the brain at 24 (18-36) hours later to evaluate for the presence of hemorrhagic transformation. The clinical data, lipid levels, platelet count, MRI, and computed tomography images were retrospectively reviewed. RESULTS The study included 366 patients, with mean age 67 ± 15 years; 46% were women and 88% were white. The median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range 3-15). Hemorrhagic transformation was observed in 87 (23.8%) patients and cerebral microbleeds were noted in 95 (25.9%). Patients with hemorrhagic transformation tended to be older, nonwhite, have atrial fibrillation, higher baseline NIHSS score, lower cholesterol and triglyceride levels, and cerebral microbleeds and nonlacunar infarcts. Patients with cerebral microbleeds were more likely to be older, have hypertension, hyperlipidemia, previous history of stroke, and prior use of antithrombotics. On multivariate analysis race, NIHSS score, nonlacunar infarct, and presence of cerebral microbleeds were independently associated with hemorrhagic transformation following treatment with rt-PA. CONCLUSIONS Presence of cerebral microbleeds is an independent predictor of hemorrhagic transformation of acute ischemic stroke following treatment with rt-PA.