-
[show abstract]
[hide abstract]
ABSTRACT: Object The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery-middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion. A recent publication documented the methodology of the COSS in detail and briefly outlined the major findings of the trial. The surgical results of the COSS are described in detail in this report. Methods The COSS was a prospective, parallel-group, 1:1 randomized, open-label, blinded-adjudication treatment trial. Participants, who had angiographically demonstrated complete occlusion of the ICA causing either a transient ischemic attack or ischemic stroke within 120 days and hemodynamic cerebral ischemia indicated by an increased OEF measured by PET, were randomized to either surgical or medical treatment. One hundred ninety-five patients were randomized: 97 to the surgical group and 98 to the medical group. The surgical patients underwent an STA-MCA cortical branch anastomosis. Results In the intention-to-treat analysis, the 2-year rates for the primary end point were 21% for the surgical group and 22.7% for the medical group (p = 0.78, log-rank test). Fourteen (15%) of the 93 patients who had undergone an arterial bypass had a primary end point ipsilateral hemispheric stroke in the 30-day postoperative period, 12 within 2 days after surgery. The STA-MCA arterial bypass patency rate was 98% at the 30-day postoperative visit and 96% at the last follow-up examination. The STA-MCA arterial bypass markedly improved, although it did not normalize, the level of elevated OEF in the symptomatic cerebral hemisphere. Five surgically treated and 1 nonsurgically treated patients in the surgical group had a primary end point ipsilateral hemispheric stroke after the 30-day postoperative period. No baseline characteristics or intraoperative variables revealed those who would experience a procedure-related stroke. Conclusions Despite excellent bypass graft patency and improved cerebral hemodynamics, STA-MCA anastomosis did not provide an overall benefit regarding ipsilateral 2-year stroke recurrence, mainly because of a much better than expected stroke recurrence rate (22.7%) in the medical group, but also because of a significant postoperative stroke rate (15%). Clinical trial registration no.: NCT00029146.
Journal of Neurosurgery 10/2012; · 2.96 Impact Factor
-
Neurosurgery 09/2012; 71(3):E772-6. · 2.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically.
To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia.
Parallel-group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002 to 2010.
Forty-nine clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers.
Patients with arteriographically confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. Of 195 patients who were randomized, 97 were randomized to receive surgery and 98 to no surgery. Follow-up for the primary end point until occurrence, 2 years, or termination of trial was 99% complete. No participant withdrew because of adverse events.
Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Antithrombotic therapy and risk factor intervention were recommended for all participants.
For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days after surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery, the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within 2 years of randomization.
The trial was terminated early for futility. Two-year rates for the primary end point were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%; 20 events) for the nonsurgical group (P = .78, Z test), a difference of 1.7% (95% CI, -10.4% to 13.8%). Thirty-day rates for ipsilateral ischemic stroke were 14.4% (14/97) in the surgical group and 2.0% (2/98) in the nonsurgical group, a difference of 12.4% (95% CI, 4.9% to 19.9%).
Among participants with recently symptomatic AICAO and hemodynamic cerebral ischemia, EC-IC bypass surgery plus medical therapy compared with medical therapy alone did not reduce the risk of recurrent ipsilateral ischemic stroke at 2 years.
clinicaltrials.gov Identifier: NCT00029146.
JAMA The Journal of the American Medical Association 11/2011; 306(18):1983-92. · 30.03 Impact Factor
-
01/2011: pages 151 - 216; , ISBN: 9781118033050
-
01/2011: pages 217 - 262; , ISBN: 9781118033050
-
01/2011: pages 441 - 460; , ISBN: 9781118033050
-
01/2011: pages 359 - 415; , ISBN: 9781118033050
-
01/2011: pages 417 - 439; , ISBN: 9781118033050
-
01/2011: pages 307 - 357; , ISBN: 9781118033050
-
01/2011: pages 119 - 149; , ISBN: 9781118033050
-
01/2011: pages 541 - 622; , ISBN: 9781118033050
-
01/2011: pages 509 - 540; , ISBN: 9781118033050
-
[show abstract]
[hide abstract]
ABSTRACT: In an ongoing multi-center randomized control clinical trial, the Carotid Occlusion Surgery Study (COSS), the study protocol specifies multiple interim analyses whose results will be reviewed by an independent DSMB to determine if the trial needs to be stopped early due to either efficacy or futility. Conditional power is used as the decision rule for the DSMB to recommend stopping the trial for futility. An aggressive rule for futility stopping sets a relatively high threshold for the conditional power which may result in significant loss of overall power of the study. A conservative rule using a lower threshold may not be able to stop the trial early when there is indeed no treatment efficacy.
The goal of this article is to develop a flexible futility monitoring plan with a time-varying conditional power boundary that maintains the overall power of the study well, but has a better chance to stop the trial earlier for futility compared to a futility stopping rule with a fixed value for the minimum conditional power to continue.
The conditional power boundary for futility is developed using the beta-spending function method for sequential test statistics and assuming no interim analysis for efficacy. It is then modified to account for the repeated interim analyses for efficacy.
Simulation studies that mirror the design of the COSS trial show that the proposed method with sample size calculated without considering interim analyses will maintain the designed size and power well when the designed effect size holds, but will have a better chance to exit the trial earlier if the true effect size is smaller than the designed size such that it is not clinically meaningful to conduct the trial.
The method is valid for sequential test statistics that constitute of a stochastic process which approximates the Brownian motion. It is not applicable to the monitored process that behaves quire differently from the Brownian motion.
The proposed conditional power method facilitates a flexible futility monitoring plan that can be easily implemented in long-term clinical trials where multiple interim analyses are required. It provides the DSMB an objective guideline to use in considering early stopping for futility. Clinical Trials 2010; 7: 209. http:// ctj.sagepub.com.
Clinical Trials 06/2010; 7(3):209-18. · 1.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial.
One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia (36 degrees C-37 degrees C) or hypothermia (32.5 degrees C-33.5 degrees C). Fever (> or =38.5 degrees C) and other complications (including infections) occurring between admission and discharge (or death) were recorded. Functional and neuropsychologic outcomes were assessed 3 months postoperatively. The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale (good outcome versus all others).
Fever was reported in 41% of patients. In 97% of these, fever occurred in the postoperative period. The median time from surgery to first fever was 3 days. All measures of outcome were worse in patients who developed fever, even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors (e.g., age, Fisher grade, initial neurological status). This demonstrated that fever continued to be significantly associated with most outcome measures, even when infection was added to the model. An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period (e.g., hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the loss of significance for dichotomized Glasgow Outcome Scale, but significant associations between fever and several other outcome measures remained. After adding postoperative delayed ischemic neurological deficits to the model, only worsened National Institutes of Health Stroke Scale score, Barthel Activities of Daily Living index, and discharge destination (home versus other) remained independently associated with fever.
These findings suggest that fever is associated with worsened outcome in surgical subarachnoid hemorrhage patients, although, because the association between fever and the primary outcome measure for the trial is dependent on the covariates used in the analysis (particularly operative events and delayed ischemic neurological deficits), we cannot rule out the possibility that fever is a marker for other events. Only a formal trial of fever treatment or prevention can address this issue.
Neurosurgery 05/2009; 64(5):897-908; discussion 908. · 2.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial.
METHODS: One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia (36°C-37°C) or hypothermia (32.5°C-33.5°C). Fever (≥38.5°C) and other complications (including infections) occurring between admission and discharge (or death) were recorded. Functional and neuropsychologic outcomes were assessed 3 months postoperatively. The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale (good outcome versus all others).
RESULTS: Fever was reported in 41% of patients. In 97% of these, fever occurred in the postoperative period. The median time from surgery to first fever was 3 days. All measures of outcome were worse in patients who developed fever, even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors (e.g., age, Fisher grade, initial neurological status). This demonstrated that fever continued to be significantly associated with most outcome measures, even when infection was added to the model. An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period (e.g., hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the loss of significance for dichotomized Glasgow Outcome Scale, but significant associations between fever and several other outcome measures remained. After adding postoperative delayed ischemic neurological deficits to the model, only worsened National Institutes of Health Stroke Scale score, Barthel Activities of Daily Living index, and discharge destination (home versus other) remained independently associated with fever.
CONCLUSION: These findings suggest that fever is associated with worsened outcome in surgical subarachnoid hemorrhage patients, although, because the association between fever and the primary outcome measure for the trial is dependent on the covariates used in the analysis (particularly operative events and delayed ischemic neurological deficits), we cannot rule out the possibility that fever is a marker for other events. Only a formal trial of fever treatment or prevention can address this issue.
Neurosurgery 04/2009; 64(5):897-908. · 2.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To test an interdisciplinary, multifaceted, translating research into practice (TRIP) intervention to (a) promote adoption, by physicians and nurses, of evidence-based (EB) acute pain management practices in hospitalized older adults, (b) decrease barriers to use of EB acute pain management practices, and (c) decrease pain intensity of older hospitalized adults.
Experimental design with the hospital as the unit of randomization.
Twelve acute care hospitals in the Midwest.
(a) Medical records (MRs) of patients > or =65 years or older with a hip fracture admitted before and following implementation of the TRIP intervention and (b) physicians and nurses who care for those patients.
Data were abstracted from MRs and questions distributed to nurses and physicians.
The Summative Index for Quality of Acute Pain Care (0-18 scale) was significantly higher for the experimental (10.1) than comparison group (8.4) at the end of the TRIP implementation phase. At the end of the TRIP implementation phase, patients in the experimental group had a lower mean pain intensity rating than those in the comparison group ( p<.0001).
The TRIP intervention improved quality of acute pain management of older adults hospitalized with a hip fracture.
Health Services Research 02/2009; 44(1):264-87. · 2.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate whether elevated intraoperative blood glucose concentrations are associated with an increased risk of long-term neurologic dysfunction in patients at risk for ischemic brain injury.
Data from 1000 patients were retrieved from the Intraoperative Hypothermia for Aneurysm Surgery Trial database. All patients were recruited between February 2000 and April 2003, and underwent surgery for aneurysm clipping within 14 days of subarachnoid hemorrhage. Gross neurologic and neuropsychological function was evaluated at 3 months after surgery using certified observers and standardized assessment instruments. Intraoperative blood glucose concentrations, measured once when the aneurysm clip was placed, were correlated with neurologic outcome using both univariable and multivariable logistic regression analyses.
Blood glucose concentrations at the time of aneurysm clipping ranged from 59 to 331 mg/dL. At 3 months after surgery, those with blood glucose concentrations of 129 mg/dL or more (upper 2 quartiles) were more likely to have impaired cognition (P=.03). Those with glucose concentrations of 152 mg/dL or more (upper quartile) were more likely to experience deficits in gross neurologic function assessed by the National Institutes of Health Stroke Scale (P<.05), but not other scoring scales. Length of stay in intensive care units was longer in those with glucose concentrations of 129 mg/dL or more, but there was no difference among glucose groups in the duration of overall hospital stay or the fraction of patients discharged to home.
In patients at high risk for ischemic brain injury, intraoperative hyperglycemia, of a magnitude commonly encountered clinically, was associated with long-term changes in cognition and gross neurologic function.
Mayo Clinic Proceedings 05/2008; 83(4):406-17. · 5.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: In health care and community-based intervention studies, cluster-randomised designs have been increasingly used because of administrative convenience, a desire to decrease treatment contamination, and the need to avoid ethical issues that might arise. While useful, cluster-randomised designs present challenges for data analysis. First, because of dependencies that exist among subjects within a cluster, methods that account for intra-class correlations have to be used. Second, on many occasions, because of unavailability of large numbers of clusters, lack of balance on baseline measures has to be carefully examined and appropriately controlled for. AIM/METHODOLOGY: Two strategies are presented that can be used when analysing data from a cluster-randomised design; both account for baseline differences. Examples of these challenges are provided by a pain management intervention study designed to promote the adoption of evidence-based pain management practices. One approach involves use of a mixed model via SAS PROC MIXED. The other approach involves use of a marginal model: Generalised estimating equations using SAS PROC GENMOD. IMPLICATIONS: In cluster-randomised design, one must adjust for intra-class correlation when evaluating the intervention effect. Although the parameter estimates and their standard errors might be comparable with both random effect and marginal strategies for certain link functions (identity link or log link only), the interpretations are quite different and the two approaches are suitable for indicating answers to different questions. If differences are present concerning baseline measures between experimental and control groups, accounting for baseline measures is important. The choice between a mixed model or marginal approach should be dictated by whether the primary interest is a population or individual.
Worldviews on Evidence-Based Nursing 02/2008; 5(2):95-101. · 1.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abnormalities in neurocognitive function are common after surgery for aneurysmal subarachnoid hemorrhage, even among patients with good functional outcomes. The time course of neurocognitive recovery, along with the long-term effects of mild intraoperative hypothermia (33 degrees C) and aneurysm location, is unknown. We determined these in a subset of subarachnoid hemorrhage patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST).
We performed a longitudinal, multicenter, prospective, blinded study of adult IHAST patients with a Glasgow Outcome Score=1 or 2 (independent function), 3 months postsurgery and a matched control group (n=45). Subjects were tested with a 5-test cognitive function battery and standard neurological evaluations at 3, 9 and 15 months postsurgery. The primary outcome measure was a composite score on cognitive test performance.
There were 303 IHAST patients available for inclusion: 218 eligible, 185 enrolled (89 hypothermic, 96 normothermic). Significant cognitive improvement was noted from 3 to 9 (P<0.001) and 3 to 15 (P<0.001) months in both hypothermic and normothermic groups, even after adjusting for practice effects observed in the control group. No significant change was identified between 9 and 15 months. Neither mild hypothermia nor aneurysm location (anterior communicating artery versus others) had a significant effect on recovery over time or frequency of cognitive impairment. Compared with control group, the frequency of cognitive impairment (Z score <-1.96) in all patients at 3, 9 and 15 months was 36%, 26% and 23%, respectively.
In this population, cognitive improvement continued beyond 3 months, with a plateau between 9 and 15 months. This was not affected by the use of intraoperative hypothermia or anatomical location of aneurysm.
Stroke 06/2007; 38(6):1864-72. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Subarachnoid hemorrhage and surgical obliteration of ruptured intracranial aneurysms are frequently associated with neurological and neuropsychological abnormalities. We reported that intraoperative cooling did not improve neurological outcome in good-grade surgical subarachnoid hemorrhage patients, as assessed by the Glasgow Outcome Scale score or other neurological and functional measures (National Institutes of Health Stroke Scale, Rankin Disability Scale, Barthel Activities of Daily Living). We now report the results of neuropsychological testing in these patients.
A total of 1,001 patients who bled < or = 14 days before surgery were randomly assigned to intraoperative hypothermia (t = 33 degrees C) or normothermia (37 degrees C). Outcome was assessed approximately 3 months after surgery. Patients underwent the Benton Visual Retention, Controlled Oral Word Association, Rey-Osterrieth Complex Figure, Grooved Pegboard, and the Trail Making tests. T-scores for each test were calculated from normative data. T-scores were averaged to calculate a Composite Score. A test result (or the Composite Score) was considered "impaired" if the T-score was two or more standard deviations below the norm. A Mini-Mental State Examination was also performed.
Neurological outcome data were available in 1,000 patients. Sixty-one patients died. Of the 939 survivors, 873 completed 3 or more tests (exclusive of the Mini-Mental State Examination). Patients with poor neurological outcomes were less likely to complete testing; only 3.9% of Good Outcome (Glasgow Outcome Scale score = 1) patients were untested, compared with 38.6% of patients with Glasgow Outcome Scale scores of 3 and 4. There were no prerandomization demographic differences between the two treatment groups. For hypothermic patients, 16.8% were impaired from their Composite Score versus 20.0% of patients in the normothermic group (p = 0.317). For patients in the hypothermic group, 54.5% were impaired on at least one test, compared with 55.5% of patients in the normothermic group (p = 0.865). Similar results were seen in patients with baseline WFNS scores = I. Mini-Mental State Examination scores in the hypothermic and normothermic groups were 27.4 +/- 3.8 and 26.8 +/- 4.5, respectively.
This is the largest prospective evaluation of neuropsychological function after subarachnoid hemorrhage to date. Testing was completed in a high fraction of patients, demonstrating the feasibility of such testing in a large trial. However, the frequent inability to complete testing in poor-outcome patients suggests that testing may be best used to refine outcome assessments in good-grade patients. Many patients showed impairment on at least one test, with global impairment present in 17 to 20% of patients (18-21% of survivors). This was true even among the patients with the best preoperative condition (WFNS = 1). There was no difference in the incidence of impairment between hypothermic and normothermic groups.
Annals of Neurology 11/2006; 60(5):518-27. · 11.09 Impact Factor
