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Papers by Thomas Hemmen

Stroke, 2007

We appreciate the importance of avoiding increased body temperature after stroke as treatment of ... more We appreciate the importance of avoiding increased body temperature after stroke as treatment of fever reduced poor neurological outcome after stroke. 1 We thank Dr den Hertog et al for pointing out that more evidence is needed to investigate the feasibility and efficacy of the various available cooling methods after stroke. We are currently testing the safety and feasibility of induced hypothermia and thrombolysis with tissue plasminogen activator until 6 hours after stroke. 2 The proof of neuroprotective efficacy after cardiac arrest has spurred an increased interest in neuroprotection through hypothermia after stroke and we greatly welcome this. 3,4 Most likely the neuroprotective effect is highest when treatment is initiated early, and we agree with the comments that delayed treatment is unlikely to yield success. Disclosures None.

Stroke, 2010

Background and Purpose— To assess the gender differences in patients with acute ischemic stroke t... more Background and Purpose— To assess the gender differences in patients with acute ischemic stroke treated with and without tissue plasminogen activator. The primary purpose is to evaluate for differences in baseline risk factors, treatment times, and 90-day outcomes. Data regarding gender differences in acute stroke treatment shows a delayed treatment and evaluation in women with stroke, associated with poorer outcome. Methods— Review of the University of California San Diego Specialized Program for Translational Research in Acute Stroke (SPOTRIAS) database from 2001 to 2009. All “code stroke” patients with the admitting diagnosis of acute ischemic stroke were classified based on gender and tissue plasminogen activator treatment (group 1 with tissue plasminogen activator, group 2 without). Results— A total of 848 patients were included, group 1: 294 patients, baseline median NIHSS and mean age in men was 10 and 67.6±16.5 years, in women 13 and 72.4±16.5 years. group 2: 554 patients, b...

Stroke, 2010

Mild hypothermia is an established neuroprotectant in the laboratory, showing remarkable and cons... more Mild hypothermia is an established neuroprotectant in the laboratory, showing remarkable and consistent effects across multiple laboratories and models of brain injury. At the clinical level, mild hypothermia has shown benefits in patients who have experienced cardiac arrest and in some pediatric populations experiencing hypoxic brain insults. Its role, however, in stroke therapy has yet to be established. Translating preclinical data to the clinical arena presents unique challenges with regard to cooling in patients who are generally awake and may require additional therapies, such as reperfusion. We review the state of therapeutic hypothermia in ischemic and hemorrhagic stroke and provide an outlook for its role in stroke therapy.

Stroke, 2011

Background and Purpose— Ongoing clinical trials are using early response to intravenous tissue-ty... more Background and Purpose— Ongoing clinical trials are using early response to intravenous tissue-type plasminogen activator (tPA) to stratify patients into endovascular therapies. Little is known about the likelihood of early recovery and its correlation with final stroke outcome. Methods— We analyzed the National Institute of Neurological Disorders and Stroke tPA dataset for patients with early improvement (EI), a change of ≥4, or score 0 on the 2-hour National Institutes of Health Stroke Scale (NIHSS) to predict good 90-day outcome. We adjusted for multiple confounders and divided the patients by baseline NIHSS score 0 to 10, 11 to 20, >20, and stroke type to analyze if EI predicted good outcome across stroke severities and types. We analyzed different EI thresholds to identify the best level of NIHSS change to predict good 90-day outcome using a receiver-operator characteristic curve. Results— In total, 183 of 624 (29.3%) patients had EI, 112 of 312 (35.9%) in the tPA group had ...

Neurocritical Care, 2012

Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action... more Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action. We demonstrated the feasibility of thrombolysis combined with endovascular hypothermia, but not all patients achieved effective cooling. We sought to identify the factors that determined effective cooling. Methods-In 26 patients who underwent endovascular hypothermia we computed 4 measures of effective cooling: time to reach target; Area-Under-the-Curve (AUC) 34 ratio; AUC-34; and AUC-35. Using multivariate regression, we examined the effects of age, weight, starting temperature, body mass index, body surface area (BSA) , gender, shivering, and total meperidine dose on the 4 outcome measures. Results-In univariate analyses, all 4 outcome measures were significantly influenced by BSA (p<0.01 in all univariate analyses). Time to reach target temperature was quicker in older patients (p<0.01). Shivering and meperidine dose were highly intercorrelated (r=0.6, p<0.01) and both marginally influenced all 4 outcome measures. In multivariate analysis, AUC ratio and time to reach target temperature were significantly influenced by BSA (p<0.01) and meperidine (p<0.05); AUC-34 was influenced only by BSA (p<0.01). The AUC-35 was influenced by BSA (p<0.01), shivering, and total meperidine dose (p<0.05). Conclusions-The most important determinant of effective cooling during endovascular hypothermia is BSA; larger patients are more difficult to cool and maintain in therapeutic range. Older patients cool more quickly. Shivering was well controlled by the combination of meperidine, buspirone, and surface counter-warming and only minimally influenced cooling

Journal of Stroke and Cerebrovascular Diseases, 2012

Journal of Stroke and Cerebrovascular Diseases, 2010

Journal of Stroke and Cerebrovascular Diseases, 2010

Background-In 1995 two studies by the NINDS showed that intravenous t-PA was superior to placebo ... more Background-In 1995 two studies by the NINDS showed that intravenous t-PA was superior to placebo in stroke patients when given less than 3 hours from stroke onset. The recently published ECASS III study introduced new patient selection criteria and treatment between 3 and 4.5 hours. Using these criteria, t-PA was shown effective at the later time window. Both analyses used the 3 month mRS as main primary outcome. We sought to study the effect of applying the ECASS III selection criteria to the original NINDS cohort. Methods-We analyzed the subgroup of patients from NINDS sample who matched the ECASSS III study criteria and examined 3-month outcomes adjusted and unadjusted for confounding factors. Results-The NINDS t-PA study included 624 patients. Two hundred in the t-PA treated and 199 in the placebo group were selected after applying ECASS III criteria. Of these selected patients, 52% in the t-PA group versus 31% had an mRS of 0 or 1 at 3 months (p<0.001). The unadjusted OR for t-PA treatment versus placebo on day 90 mRS 0-1 versus 2-6 was 2.45 (95% CI: 1.63-3.69) When adjusted for baseline NIHSS, smoking status, time to treatment and history of hypertension the OR was 2.14 (95% CI: 1.34-3.41) (p<0.001). Conclusion-Using the ECASS III patient selection in patient treated in less than 3 hours, 52% of t-PA treated patient had a favorable outcome at 3 months.

Journal of Stroke and Cerebrovascular Diseases, 2013

Background-More than a quarter of ischemic strokes (IS) are excluded from thrombolysis due to unk... more Background-More than a quarter of ischemic strokes (IS) are excluded from thrombolysis due to unknown time of symptom onset. Recent evidence suggests that a mismatch between DWI and FLAIR imaging could be used as a surrogate for the time of stroke onset. We compared used the DWI-FLAIR mismatch and the FLAIR/DWI ratio to estimate the time of onset in a group of patients with nocturnal strokes and unknown time of onset. Methods-We used a prospectively collected acute IS patient database with MRI as the initial imaging modality. Nineteen selected nocturnal stroke patients with unknown time of onset were compared with 22 patients who had an MRI within 6 hours from stroke onset (control A) and 19 patients who had an MRI between 6 and 12 hours (control B). DWI and FLAIR signal was rated as normal or abnormal. FLAIR/DWI ratio was calculated from independent DWI and FLAIR ischemic lesion volumes using semiautomatic software. Results-The DWI-FLAIR mismatch was different among groups (unknown 43.7%, control A 63.6%, control B 10.5%; FFH p=0.001). There were significant differences in FLAIR/DWI ratio among the 3 groups (unknown: 0.05±0.12, control A: 0.17±0.15, control B: 0.04±0.06; KW p<0.0001). Post-hoc pair wise comparisons showed that FLAIR/DWI ratio from the unknown group was significantly different from control B (p=0.0045), but not different from control A. DWI volumes were not different among the 3 groups. Conclusion-A large proportion of nocturnal IS patients with unknown time of stroke initiation have a DWI-FLAIR mismatch suggesting a recent stroke onset.

Journal of Stroke and Cerebrovascular Diseases, 2013

Background/Purpose-Intravenous Alteplase (t-PA) improves outcome in patients with acute ischemic ... more Background/Purpose-Intravenous Alteplase (t-PA) improves outcome in patients with acute ischemic stroke. Of those with full recovery, some may not have had ischemia. We analyzed the frequency and post-treatment outcomes of stroke code patients with no imaging evidence of stroke in order to establish the incidence of neuroimaging negative cerebral ischemia (NNCI) and stroke mimics treated with t-PA. In addition, we compared these patients to the group of stroke patients with imaging evidence of acute stroke to determine whether there was a difference in adverse events, and functional outcomes. Methods-We included all adult stroke patients treated with IV t-PA within 3 hours of stroke onset from the UCSD SPOTRIAS database through January 2013. The IPS group (Imaging Positive Stroke codes) was comprised of patients with neuroimaging evidence of acute ischemic stroke, while the INS group (Imaging Negative Stroke codes) included those patients without neuroimaging evidence of acute cerebral ischemia. All final diagnoses were reviewed by an adjudicating body. We reviewed medical records and neuroimaging; compared discharge diagnosis, 90-day mRS, and incidence of intracranial hemorrhage; and adjusted for age, admission NIHSS, pre-stroke mRS and diabetes in multivariable models. Results-We identified 106 patients; 74 IPS patients and 32 INS patients, who had similar baseline characteristics, except for baseline NIHSS (IPS 12.9±8.2, INS 8.0±5.6, p=0.002) and incidence of cardiac arrhythmias (IPS 32.4%, INS 12.5%, p=0.034). The diagnoses in the INS group were stroke (23, 72%)-representing NNCI, somatization (6, 19%), tumor (1, 3%), seizure (1, 3%), and migraine (1, 3%). All IPS patients were diagnosed with acute ischemic stroke. Adjusted for age, baseline NIHSS, pre-stroke mRS and diabetes, the INS patients had significantly higher rates (OR 3.04, p=0.036) of good functional outcome (90 day mRS 0-1). ICH was found in 24% of the IPS patients and was symptomatic in 6.8%. None of the INS patients had ICH.

Journal of Stroke and Cerebrovascular Diseases, 2014

The objective of this pooled analysis was to determine the level of agreement between central rea... more The objective of this pooled analysis was to determine the level of agreement between central read and each of 2 groups (spoke radiologists and hub vascular neurologists) in interpreting head computed tomography (CT) scans of stroke patients presenting to telestroke network hospitals. The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC and STRokE DOC-AZ TIME) trials were prospective, randomized, and outcome blinded comparing telemedicine and teleradiology with telephone-only consultations. In each trial, the CT scans of the subjects were interpreted by the hub vascular neurologist in the telemedicine arm and by the spoke radiologist in the telephone arm. We obtained a central read for each CT using adjudicating committees blinded to treatment arm and outcome. The data were pooled and the results reported for the entire population. Kappa statistics and exact agreement rates were used to assess interobserver agreement for radiographic contraindication to recombinant tissue plasminogen activator (rt-PA), presence of hemorrhage, tumor, hyperdense artery, acute stroke, prior stroke, and early ischemic changes. Among 261 analyzed cases, the agreement with central read for the presence of radiological rt-PA contraindication was excellent for hub vascular neurologist (96.2%, κ = .81, 95% CI .64-.97), spoke radiologist report (94.7%, κ = .64, 95% CI .39-.88), and overall (95.4%, κ = .74, 95% CI .59-.88). For rt-PA-treated patients (N = 65), overall agreement was 98.5%, and vascular neurologist agreement with central read was 100%. Both vascular neurologists and reports from spoke radiologists had excellent reliability in identifying radiologic rt-PA contraindications. These pooled findings demonstrate that telestroke evaluation of head CT scans for acute rt-PA assessments is reliable.

Stroke research and treatment, 2011

European Journal of Neurology, 2008

…, 1995

Rejection crises after kidney transplantation could be associated with individual variability of ... more Rejection crises after kidney transplantation could be associated with individual variability of pharmacokinetic parameters of steroids. We therefore investigated the individual pharmacokinetics of methylprednisolone on day 2 (60 mg intravenously) and day 4 (60 mg per os) in 40 patients after kidney transplantation. Methylprednisolone was determined in serum by HPLC. Within 6 months, all rejection episodes were recorded and confirmed by kidney transplant biopsy. Values are given as nonparametric medians with the 95% confidence interval (0.95 CI). The 7 patients with a rejection within the first 10 days had a methylprednisolone clearance of 437 ml/min (162-756) that was significantly higher than the 220 ml/min (121-604) in the 22 patients without a rejection episode (P = 0.04). In the complete group of 18 patients having a transplant rejection episode within 6 months, the methylprednisolone elimination half-life after oral dosage was 2.5 hr (1.6-3.9) and significantly shorter than 2.9 hr (1.7-4.0) in 22 patients without rejections (P = 0.03). No differences were seen for body weight, number of mismatches, cold ischemia time, immunosuppressive regimens, and other pharmacokinetic parameters of methylprednisolone (e.g. bioavailability, distribution volume, trough levels). We conclude that pharmacokinetic variability may contribute to the lack of immunosuppressive efficacy in patients with a short halflife of steroids. Therefore, a twice daily dose fraction might be useful for low-dose steroid regimens in kidney transplantation.

Journal of neurotrauma, 2009

Induced hypothermia after ischemic stroke is a promising neuroprotective therapy and is the most ... more Induced hypothermia after ischemic stroke is a promising neuroprotective therapy and is the most potent in pre-clinical models. Technological limitations and homeostatic mechanisms that maintain core body temperature, however, have limited the clinical application of hypothermia. Advances in intravascular cooling and successful trials of hypothermia after global cerebral ischemia, such as in cardiac arrest and neonatal asphyxia, have renewed interest in hypothermia for stroke.

Journal of neurology, 2004

Neuroprotective therapies have so far failed to provide improved neurological function and outcom... more Neuroprotective therapies have so far failed to provide improved neurological function and outcome after stroke. A recent focus on multimodal therapies, including the combination of neuroprotective medications with hypothermia, opens a promising new treatment strategy. Advances in hypothermia administration make it one of the most promising neuroprotective therapies available and an ideal candidate for combination with other neuroprotective approaches.

Stroke, 2007

We appreciate the importance of avoiding increased body temperature after stroke as treatment of ... more We appreciate the importance of avoiding increased body temperature after stroke as treatment of fever reduced poor neurological outcome after stroke. 1 We thank Dr den Hertog et al for pointing out that more evidence is needed to investigate the feasibility and efficacy of the various available cooling methods after stroke. We are currently testing the safety and feasibility of induced hypothermia and thrombolysis with tissue plasminogen activator until 6 hours after stroke. 2 The proof of neuroprotective efficacy after cardiac arrest has spurred an increased interest in neuroprotection through hypothermia after stroke and we greatly welcome this. 3,4 Most likely the neuroprotective effect is highest when treatment is initiated early, and we agree with the comments that delayed treatment is unlikely to yield success. Disclosures None.

Stroke, 2010

Background and Purpose— To assess the gender differences in patients with acute ischemic stroke t... more Background and Purpose— To assess the gender differences in patients with acute ischemic stroke treated with and without tissue plasminogen activator. The primary purpose is to evaluate for differences in baseline risk factors, treatment times, and 90-day outcomes. Data regarding gender differences in acute stroke treatment shows a delayed treatment and evaluation in women with stroke, associated with poorer outcome. Methods— Review of the University of California San Diego Specialized Program for Translational Research in Acute Stroke (SPOTRIAS) database from 2001 to 2009. All “code stroke” patients with the admitting diagnosis of acute ischemic stroke were classified based on gender and tissue plasminogen activator treatment (group 1 with tissue plasminogen activator, group 2 without). Results— A total of 848 patients were included, group 1: 294 patients, baseline median NIHSS and mean age in men was 10 and 67.6±16.5 years, in women 13 and 72.4±16.5 years. group 2: 554 patients, b...

Stroke, 2010

Mild hypothermia is an established neuroprotectant in the laboratory, showing remarkable and cons... more Mild hypothermia is an established neuroprotectant in the laboratory, showing remarkable and consistent effects across multiple laboratories and models of brain injury. At the clinical level, mild hypothermia has shown benefits in patients who have experienced cardiac arrest and in some pediatric populations experiencing hypoxic brain insults. Its role, however, in stroke therapy has yet to be established. Translating preclinical data to the clinical arena presents unique challenges with regard to cooling in patients who are generally awake and may require additional therapies, such as reperfusion. We review the state of therapeutic hypothermia in ischemic and hemorrhagic stroke and provide an outlook for its role in stroke therapy.

Stroke, 2011

Background and Purpose— Ongoing clinical trials are using early response to intravenous tissue-ty... more Background and Purpose— Ongoing clinical trials are using early response to intravenous tissue-type plasminogen activator (tPA) to stratify patients into endovascular therapies. Little is known about the likelihood of early recovery and its correlation with final stroke outcome. Methods— We analyzed the National Institute of Neurological Disorders and Stroke tPA dataset for patients with early improvement (EI), a change of ≥4, or score 0 on the 2-hour National Institutes of Health Stroke Scale (NIHSS) to predict good 90-day outcome. We adjusted for multiple confounders and divided the patients by baseline NIHSS score 0 to 10, 11 to 20, >20, and stroke type to analyze if EI predicted good outcome across stroke severities and types. We analyzed different EI thresholds to identify the best level of NIHSS change to predict good 90-day outcome using a receiver-operator characteristic curve. Results— In total, 183 of 624 (29.3%) patients had EI, 112 of 312 (35.9%) in the tPA group had ...

Neurocritical Care, 2012

Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action... more Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action. We demonstrated the feasibility of thrombolysis combined with endovascular hypothermia, but not all patients achieved effective cooling. We sought to identify the factors that determined effective cooling. Methods-In 26 patients who underwent endovascular hypothermia we computed 4 measures of effective cooling: time to reach target; Area-Under-the-Curve (AUC) 34 ratio; AUC-34; and AUC-35. Using multivariate regression, we examined the effects of age, weight, starting temperature, body mass index, body surface area (BSA) , gender, shivering, and total meperidine dose on the 4 outcome measures. Results-In univariate analyses, all 4 outcome measures were significantly influenced by BSA (p<0.01 in all univariate analyses). Time to reach target temperature was quicker in older patients (p<0.01). Shivering and meperidine dose were highly intercorrelated (r=0.6, p<0.01) and both marginally influenced all 4 outcome measures. In multivariate analysis, AUC ratio and time to reach target temperature were significantly influenced by BSA (p<0.01) and meperidine (p<0.05); AUC-34 was influenced only by BSA (p<0.01). The AUC-35 was influenced by BSA (p<0.01), shivering, and total meperidine dose (p<0.05). Conclusions-The most important determinant of effective cooling during endovascular hypothermia is BSA; larger patients are more difficult to cool and maintain in therapeutic range. Older patients cool more quickly. Shivering was well controlled by the combination of meperidine, buspirone, and surface counter-warming and only minimally influenced cooling

Journal of Stroke and Cerebrovascular Diseases, 2012

Journal of Stroke and Cerebrovascular Diseases, 2010

Journal of Stroke and Cerebrovascular Diseases, 2010

Background-In 1995 two studies by the NINDS showed that intravenous t-PA was superior to placebo ... more Background-In 1995 two studies by the NINDS showed that intravenous t-PA was superior to placebo in stroke patients when given less than 3 hours from stroke onset. The recently published ECASS III study introduced new patient selection criteria and treatment between 3 and 4.5 hours. Using these criteria, t-PA was shown effective at the later time window. Both analyses used the 3 month mRS as main primary outcome. We sought to study the effect of applying the ECASS III selection criteria to the original NINDS cohort. Methods-We analyzed the subgroup of patients from NINDS sample who matched the ECASSS III study criteria and examined 3-month outcomes adjusted and unadjusted for confounding factors. Results-The NINDS t-PA study included 624 patients. Two hundred in the t-PA treated and 199 in the placebo group were selected after applying ECASS III criteria. Of these selected patients, 52% in the t-PA group versus 31% had an mRS of 0 or 1 at 3 months (p<0.001). The unadjusted OR for t-PA treatment versus placebo on day 90 mRS 0-1 versus 2-6 was 2.45 (95% CI: 1.63-3.69) When adjusted for baseline NIHSS, smoking status, time to treatment and history of hypertension the OR was 2.14 (95% CI: 1.34-3.41) (p<0.001). Conclusion-Using the ECASS III patient selection in patient treated in less than 3 hours, 52% of t-PA treated patient had a favorable outcome at 3 months.

Journal of Stroke and Cerebrovascular Diseases, 2013

Background-More than a quarter of ischemic strokes (IS) are excluded from thrombolysis due to unk... more Background-More than a quarter of ischemic strokes (IS) are excluded from thrombolysis due to unknown time of symptom onset. Recent evidence suggests that a mismatch between DWI and FLAIR imaging could be used as a surrogate for the time of stroke onset. We compared used the DWI-FLAIR mismatch and the FLAIR/DWI ratio to estimate the time of onset in a group of patients with nocturnal strokes and unknown time of onset. Methods-We used a prospectively collected acute IS patient database with MRI as the initial imaging modality. Nineteen selected nocturnal stroke patients with unknown time of onset were compared with 22 patients who had an MRI within 6 hours from stroke onset (control A) and 19 patients who had an MRI between 6 and 12 hours (control B). DWI and FLAIR signal was rated as normal or abnormal. FLAIR/DWI ratio was calculated from independent DWI and FLAIR ischemic lesion volumes using semiautomatic software. Results-The DWI-FLAIR mismatch was different among groups (unknown 43.7%, control A 63.6%, control B 10.5%; FFH p=0.001). There were significant differences in FLAIR/DWI ratio among the 3 groups (unknown: 0.05±0.12, control A: 0.17±0.15, control B: 0.04±0.06; KW p<0.0001). Post-hoc pair wise comparisons showed that FLAIR/DWI ratio from the unknown group was significantly different from control B (p=0.0045), but not different from control A. DWI volumes were not different among the 3 groups. Conclusion-A large proportion of nocturnal IS patients with unknown time of stroke initiation have a DWI-FLAIR mismatch suggesting a recent stroke onset.

Journal of Stroke and Cerebrovascular Diseases, 2013

Background/Purpose-Intravenous Alteplase (t-PA) improves outcome in patients with acute ischemic ... more Background/Purpose-Intravenous Alteplase (t-PA) improves outcome in patients with acute ischemic stroke. Of those with full recovery, some may not have had ischemia. We analyzed the frequency and post-treatment outcomes of stroke code patients with no imaging evidence of stroke in order to establish the incidence of neuroimaging negative cerebral ischemia (NNCI) and stroke mimics treated with t-PA. In addition, we compared these patients to the group of stroke patients with imaging evidence of acute stroke to determine whether there was a difference in adverse events, and functional outcomes. Methods-We included all adult stroke patients treated with IV t-PA within 3 hours of stroke onset from the UCSD SPOTRIAS database through January 2013. The IPS group (Imaging Positive Stroke codes) was comprised of patients with neuroimaging evidence of acute ischemic stroke, while the INS group (Imaging Negative Stroke codes) included those patients without neuroimaging evidence of acute cerebral ischemia. All final diagnoses were reviewed by an adjudicating body. We reviewed medical records and neuroimaging; compared discharge diagnosis, 90-day mRS, and incidence of intracranial hemorrhage; and adjusted for age, admission NIHSS, pre-stroke mRS and diabetes in multivariable models. Results-We identified 106 patients; 74 IPS patients and 32 INS patients, who had similar baseline characteristics, except for baseline NIHSS (IPS 12.9±8.2, INS 8.0±5.6, p=0.002) and incidence of cardiac arrhythmias (IPS 32.4%, INS 12.5%, p=0.034). The diagnoses in the INS group were stroke (23, 72%)-representing NNCI, somatization (6, 19%), tumor (1, 3%), seizure (1, 3%), and migraine (1, 3%). All IPS patients were diagnosed with acute ischemic stroke. Adjusted for age, baseline NIHSS, pre-stroke mRS and diabetes, the INS patients had significantly higher rates (OR 3.04, p=0.036) of good functional outcome (90 day mRS 0-1). ICH was found in 24% of the IPS patients and was symptomatic in 6.8%. None of the INS patients had ICH.

Journal of Stroke and Cerebrovascular Diseases, 2014

The objective of this pooled analysis was to determine the level of agreement between central rea... more The objective of this pooled analysis was to determine the level of agreement between central read and each of 2 groups (spoke radiologists and hub vascular neurologists) in interpreting head computed tomography (CT) scans of stroke patients presenting to telestroke network hospitals. The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC and STRokE DOC-AZ TIME) trials were prospective, randomized, and outcome blinded comparing telemedicine and teleradiology with telephone-only consultations. In each trial, the CT scans of the subjects were interpreted by the hub vascular neurologist in the telemedicine arm and by the spoke radiologist in the telephone arm. We obtained a central read for each CT using adjudicating committees blinded to treatment arm and outcome. The data were pooled and the results reported for the entire population. Kappa statistics and exact agreement rates were used to assess interobserver agreement for radiographic contraindication to recombinant tissue plasminogen activator (rt-PA), presence of hemorrhage, tumor, hyperdense artery, acute stroke, prior stroke, and early ischemic changes. Among 261 analyzed cases, the agreement with central read for the presence of radiological rt-PA contraindication was excellent for hub vascular neurologist (96.2%, κ = .81, 95% CI .64-.97), spoke radiologist report (94.7%, κ = .64, 95% CI .39-.88), and overall (95.4%, κ = .74, 95% CI .59-.88). For rt-PA-treated patients (N = 65), overall agreement was 98.5%, and vascular neurologist agreement with central read was 100%. Both vascular neurologists and reports from spoke radiologists had excellent reliability in identifying radiologic rt-PA contraindications. These pooled findings demonstrate that telestroke evaluation of head CT scans for acute rt-PA assessments is reliable.

Stroke research and treatment, 2011

European Journal of Neurology, 2008

…, 1995

Rejection crises after kidney transplantation could be associated with individual variability of ... more Rejection crises after kidney transplantation could be associated with individual variability of pharmacokinetic parameters of steroids. We therefore investigated the individual pharmacokinetics of methylprednisolone on day 2 (60 mg intravenously) and day 4 (60 mg per os) in 40 patients after kidney transplantation. Methylprednisolone was determined in serum by HPLC. Within 6 months, all rejection episodes were recorded and confirmed by kidney transplant biopsy. Values are given as nonparametric medians with the 95% confidence interval (0.95 CI). The 7 patients with a rejection within the first 10 days had a methylprednisolone clearance of 437 ml/min (162-756) that was significantly higher than the 220 ml/min (121-604) in the 22 patients without a rejection episode (P = 0.04). In the complete group of 18 patients having a transplant rejection episode within 6 months, the methylprednisolone elimination half-life after oral dosage was 2.5 hr (1.6-3.9) and significantly shorter than 2.9 hr (1.7-4.0) in 22 patients without rejections (P = 0.03). No differences were seen for body weight, number of mismatches, cold ischemia time, immunosuppressive regimens, and other pharmacokinetic parameters of methylprednisolone (e.g. bioavailability, distribution volume, trough levels). We conclude that pharmacokinetic variability may contribute to the lack of immunosuppressive efficacy in patients with a short halflife of steroids. Therefore, a twice daily dose fraction might be useful for low-dose steroid regimens in kidney transplantation.

Journal of neurotrauma, 2009

Induced hypothermia after ischemic stroke is a promising neuroprotective therapy and is the most ... more Induced hypothermia after ischemic stroke is a promising neuroprotective therapy and is the most potent in pre-clinical models. Technological limitations and homeostatic mechanisms that maintain core body temperature, however, have limited the clinical application of hypothermia. Advances in intravascular cooling and successful trials of hypothermia after global cerebral ischemia, such as in cardiac arrest and neonatal asphyxia, have renewed interest in hypothermia for stroke.

Journal of neurology, 2004

Neuroprotective therapies have so far failed to provide improved neurological function and outcom... more Neuroprotective therapies have so far failed to provide improved neurological function and outcome after stroke. A recent focus on multimodal therapies, including the combination of neuroprotective medications with hypothermia, opens a promising new treatment strategy. Advances in hypothermia administration make it one of the most promising neuroprotective therapies available and an ideal candidate for combination with other neuroprotective approaches.