Biomedical subjects
Publications and source records attributed to L B Goldstein.
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The efficacy of endarterectomy for patients with symptomatic high-grade stenosis of the extracranial carotid artery has been firmly established. Those with asymptomatic carotid disease may also be candidates for the operation. A thorough understanding of the benefits and risks of the operation for the individual patient is necessary in determining whether to recommend the operation.
Pharmacological studies in laboratory animals show that systemically administered drugs that modulate the levels of specific central neurotransmitters can influence post brain injury behavioral recovery. Several lines of evidence support an important role of central norepinephrine. Selective lesions of central noradrenergic pathways impair recovery after a subsequent injury to the cerebral cortex. Drugs that deplete central norepinephrine, block alpha 1-adrenergic receptors, or decrease norepinephrine release (alpha 2-adrenergic receptor agonists) impede recovery whereas drugs that increase norepinephrine release (alpha 2-adrenergic receptor antagonists) or sympathomimetics (amphetamine) facilitate recovery. These studies also provide insights into the potential neurobiological processes underlying these drug effects.
Studies in laboratory animals clearly show that the rate and extent of functional recovery after focal brain injury can be modulated by drugs affecting certain neurotransmitters in the central nervous system. Preliminary clinical studies suggest that similar drug effects occur in humans recovering from stroke. Understanding these pharmacological effects is important because several of the classes of drugs that impair recovery in laboratory experiments are used to treat coincident medical problems in patients who have had a stroke.
Intracranial vasculitis, or primary angiitis of the central nervous system (PACNS), is an uncommon, often fatal disorder that frequently responds to aggressive immunosuppressive therapy. Magnetic resonance imaging (MRI), cerebral angiography, and brain biopsy are diagnostic modalities that vary in invasiveness and diagnostic accuracy. The purpose of this study was to determine whether certain clinical or radiologic features were predictive of a diagnostic biopsy. Thirty consecutive patients undergoing brain biopsy to "rule out vasculitis" were studied. Nine patients demonstrated granulomatous or lymphocytic vasculitis, 1 had lymphocytic vasculitis and encephalitis secondary to arbovirus infection, 5 had thickened vessels consistent with hypertensive changes, 5 had amyloid angiopathy and/or changes of Alzheimer disease, 5 demonstrated no pathologic abnormalities, and 1 each had acute infarct, vascular malformation, aneurysm, acellular fibrinoid necrosis, and demyelination. The spectrum of MRI and angiographic changes associated with PACNS were nonspecific, overlapping extensively with changes of chronic hypertension and amyloid deposition. The predictive values of brain biopsy (90-100%) were significantly higher than those of angiography (37-50%) or MRI (43-72%). In this study, morbidity associated with aggressive immunosuppression was significantly greater than that associated with cerebral angiography or brain biopsy. Thus, wedge biopsy of cortical and leptomeningeal tissues is central to the multi-disciplinary approach to a patient with clinical suspicion of PACNS.
BACKGROUND AND PURPOSE: North Carolina is situated in the "stroke belt" region of the United States, an area of the country with a particularly high incidence of cerebrovascular disease. The North Carolina Stroke Prevention and Treatment Facilities Survey was carried out to determine the availabilities of a variety of stroke prevention and treatment services throughout the state. The purpose of the present study was to determine how widely recombinant tissue-type plasminogen activator (rtPA) has been adopted for the treatment of patients with acute ischemic stroke and to determine the characteristics of the medical facilities in the state offering this therapy. METHODS: A single-page survey was mailed to the medical center directors of each inpatient medical facility in North Carolina. Data collected included questions related to the availability of selected basic and advanced diagnostic tests and procedures, stroke prevention and treatment programs and services (community stroke awareness program, acute stroke identification program, acute stroke team, stroke rtPA protocol, stroke care map, neurologist), and facilities (Stroke Acute Care Unit or equivalent). RESULTS: Responses were obtained from all 125 inpatient medical facilities in North Carolina. rtPA stroke protocols were adopted in 54 facilities located in 46 of the state's 100 counties. Seventy-four percent of the state's population resides in counties with hospitals providing rtPA treatment. Compared with facilities not offering rtPA, those with rtPA protocols more commonly sponsored stroke community awareness programs (41% versus 17%, P=0.003) and more frequently had an organized stroke team (31% versus 8%, P=0. 001), used stroke care maps (56% versus 17%, P<0.001), had rapid stroke identification programs (33% versus 6%, P<0.001), or had a Stroke Acute Care Unit or its equivalent (33% versus 7%, P<0.001). Neurologists were available in 78% of the facilities offering rtPA compared with 38% in facilities without rtPA protocols (P<0.001). CONCLUSIONS: These data show that this new therapy for ischemic stroke is potentially available to a high proportion of the state's citizens based on their county of residence. However, other services that may improve outcomes and reduce stroke-related costs (eg, stroke teams, stroke units, care maps) are not being widely used, even in centers providing treatment with rtPA. The simple methodology used in this study is potentially applicable in other states and permits targeting of selected centers for development of stroke treatment capabilities.
BACKGROUND AND PURPOSE: The benefit of carotid endarterectomy is highly dependent on surgical risk. However, little data are available concerning factors affecting the risk of endarterectomy performed for asymptomatic carotid artery stenosis outside the setting of a randomized controlled trial. The purpose of this study was to analyze the impact of potential preoperative risk factors on the frequency of postoperative complications in patients undergoing the operation for asymptomatic disease in academic medical centers. METHODS: Data regarding postoperative complications were systematically abstracted from the medical records of a random sample of patients who underwent carotid endarterectomy at 12 academic medical centers. RESULTS: Of 1160 procedures reviewed, 463 (40%) were performed for asymptomatic disease. Postoperative stroke or death occurred in 13 (2.8%), and myocardial infarction occurred in 8 (1.7%). The rate of postoperative stroke or death was lower in asymptomatic patients than in those with a history of cerebrovascular symptoms in a different vascular distribution, but the difference was not significant (1.8% versus 4.2%; P=.21). There were no significant differences in these rates based on race, a history of angina, recent myocardial infarction, chronic obstructive pulmonary disease, hypertension, the degree of stenosis of the contralateral or ipsilateral carotid artery, or the presence of angiographically recognized ulceration, intraluminal thrombus, or siphon stenosis in the ipsilateral vessel (chi(2); P>.05). Postoperative stroke or death was more frequent in women (5.3% versus 1.6% in men; P=.02), in those aged 75 years or older (7.8% versus 1.8% in those younger than 75 years; P=.01), and in those with a history of congestive heart failure (8.6% versus 2.3% in those without a history of congestive heart failure; P=.03). The risk of stroke or death was higher in the 16 patients who had carotid endarterectomy performed in combination with coronary artery bypass surgery than in those who had only endarterectomy (18.7% versus 2.1%; P<.001). CONCLUSIONS: The overall risk of postoperative stroke or death was nearly twice that reported by Asymptomatic Carotid Atherosclerosis Study (ACAS) investigators in the setting of a clinical trial but was within acceptable guidelines. Women were at higher postoperative risk than men, which supported ACAS findings. Additional high-risk groups were those aged 75 years or older, those with a history of congestive heart failure, and those undergoing prophylactic endarterectomy for asymptomatic stenosis in combination with coronary surgery. Knowledge of these rates may help to better assess an individual's postoperative risk and therefore the anticipated benefit of surgery.
BACKGROUND AND PURPOSE: Discharge ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes have been used to identify patients with acute stroke for epidemiological, quality of care, and cost studies. The aim of this study was to determine if the accuracy of the primary ICD-9-CM codes for ischemic stroke is improved by modifier codes and how specific codes reflect stroke subtype diagnoses. METHODS: Available hospital charts for all patients discharged from a single hospital between May 1995 and June 1997 with ICD-9-CM codes 433 (occlusion and stenosis of precerebral arteries), 434 (occlusion of cerebral arteries), or 436 (acute but ill-defined cerebrovascular disease) listed in the first position were reviewed. The primary discharge diagnosis was verified, and a presumed stroke subtype was assigned on the basis of information provided in the medical record. RESULTS: Charts were available for 175 of the 198 identified patients (88%). Of these, 61% had an acute ischemic stroke (code 433, 4%; 434, 82%; 436, 79%) with the remaining patients having other conditions. Of the 130 patients with a modifier code indicating cerebral infarction, 79% had an acute stroke; of the 45 patients with a modifier code indicating an absence of cerebral infarction, 7% had acute stroke (sensitivity, 0.97; specificity, 0.60). The codes with the highest proportions of ischemic stroke cases were 434.11 (embolic occlusion of cerebral arteries with infarction, 85%), 434.91 (unspecified occlusion of precerebral arteries with infarction, 82%), and 436 (79%), with a combined sensitivity of 0.81 and specificity of 0.90. On review, 73% of patients with code 434.11 had embolic strokes, and 47% of those with code 436 had an identified stroke cause. Of patients with code 434.91, 39% had stroke of uncertain cause, 25% "lacunar," 17% atherothrombosis, and 15% embolism. CONCLUSIONS: Despite the use of modifier codes, 15% to 20% of patients with the indicated primary ICD-9-CM codes have conditions other than acute ischemic stroke. Although the proportion of patients with acute stroke increased from 61% to 79% with the use of modifier codes, the inclusion of modifier codes did not have an appreciable effect on the accuracy of the coding if patients with code 433 are excluded. Assignment of presumed ischemic stroke subtype is particularly inaccurate.
Comprehensive data on the costs of multiple sclerosis is sparse. We conducted a survey of 606 persons with MS who were members of the National Multiple Sclerosis Society to obtain data on their cost of personal health services, other services, equipment, and earnings. Compensation of such cost in the form of health insurance, income support, and other subsidies was measured. Survey data and data from several secondary sources was used to measure costs incurred by comparable persons without MS. Based on the 1994 data, the annual cost of MS was estimated at over $34,000 per person, translating into a conservative estimate of national annual cost of $6.8 billion, and a total lifetime cost per case of $2.2 million. Major components of cost were earnings loss and informal care. Virtually all persons with MS had health insurance, mostly Medicare/Medicaid. Health insurance covered 51 per cent of costs for services, excluding informal care. On average, compensation for earnings loss was 27 per cent. MS is very costly to the individual, health care system, and society. Much of the cost (57 per cent) is in the form of burdens other than personal health care, including earnings loss, equipment and alternations, and formal and informal care. These costs often are not calculated.
Several lines of evidence suggest that the recovery of the ability of rats to traverse a narrow beam after unilateral injury to the sensorimotor cortex is noradrenergically mediated. We tested the hypotheses that the influence of norepinephrine on beam-walking recovery occurs, at least partially, through effects in the contralateral and/or ipsilateral cerebral cortex. Rats had either a selective left or right 6-hydroxydopamine lesion or sham lesion of the dorsal noradrenergic bundle (DNB) 2 weeks before suction-ablation or sham injury of the right sensorimotor cortex. The rats' abilities to perform the beam-walking task were measured over the 10 days following cortex surgery. DNB lesions did not affect the initial severity of the beam-walking deficit and had no effect on the performance of the task in rats with sham cortex injuries. Lesions of the contralateral but not ipsilateral DNB significantly impaired recovery. Further, in cortically lesioned rats with contralateral DNB lesions, norepinephrine content in the cerebral cortex opposite to the sensorimotor cortex lesion was significantly correlated with recovery. These data suggest that the effect of norepinephrine on recovery of beam-walking ability may be partially exerted in the cerebral cortex contralateral to the injury.
Laboratory studies show that recovery after brain injury can be influenced by drugs that affect certain central neurotransmitters. The effects of these drugs may be either beneficial or harmful. Although issues related to drug dose, the timing of interventions relative to the deficit, and the nature of concomitant experience or training may be critical, preliminary clinical studies suggest that similar drug effects may occur in humans recovering from stroke. Recognition of these data is important because many of the drugs that may impair recovery are commonly prescribed to stroke patients for the treatment of coincident medical conditions and should be avoided if possible. Pharmacotherapy to enhance recovery may be possible in the future.
BACKGROUND AND PURPOSE: The reliability of the National Institutes of Health Stroke Scale (NIHSS) has been established through testing its use in live and videotaped patients. This reliability testing has primarily focused on the use of the scale by neurologists. We sought to determine the reliability of the NIHSS as used by non-neurologists in the context of a clinical trial. METHODS: In anticipation of the initiation of a randomized trial of a new therapy for patients with acute ischemic stroke, 30 physician investigators (30% of whom were not neurologists) and 29 non-physician study coordinators were trained in the use of the NIHSS at an informational and training conference using standardized videotaped patient examinations. A series of 4 patients were rated initially. After 3 months, the same 4 patients were rerated, providing a measure of intraobserver reliability. An additional series of 4 new patients were also rated after 3 months and, with the initial 4 ratings, provided data for assessment of interobserver reliability. RESULTS: Overall, 28% of the raters had previous experience with the NIHSS, and 22% had previously used the videotapes as used in the present trial. The coefficients of determination (r2) were each greater than .95 when the means of the two ratings of the same 4 cases were compared between (1) neurologists and other types of physicians, (2) physicians and study coordinators, (3) raters who had prior experience with the NIHSS and those without prior experience, and (4) raters who had used the videotapes in the past and those who had never viewed the tapes. The calculated r2s were greater than .98 for the initial rating of the first 4 cases and for the later rating of the 4 new cases. The slopes of the regression lines were all near 1, indicating that the raters were similarly calibrated. The intraclass correlation coefficients were .93 and .95, reflecting high levels of intraobserver and interobserver reliability. CONCLUSIONS: These data extend the previously demonstrated reliability of the NIHSS to non-neurologists and show that both a variety of physician investigators and nurse study coordinators can be rapidly trained to reliably apply the scale in the context of an actual clinical trial.
BACKGROUND AND PURPOSE: Diminished quality of life and limitations in higher levels of physical functioning are often underestimated in stroke and are not fully captured by measures such as the Barthel Index and the Rankin Outcome Scale. This study used additional measures to assess the health status of 304 persons with mild stroke and to compare these individuals with 184 persons with transient ischemic attack and 654 persons without history of stroke/transient ischemic attack but at elevated risk for stroke (asymptomatic group). METHODS: Subjects were recruited from the Academic Medical Center Consortium (inpatients), the Cardiovascular Health Study (population-based sample of community-dwelling persons 65 years and older), and United HealthCare (inpatients and outpatients typically younger than 65 years). Subjects were interviewed by telephone or in person to assess activities of daily living (Barthel Index), depression (Center for Epidemiological Studies Depression Scale), health status (MOS-36), and utility for current health state. RESULTS: Most respondents were independent on all Barthel items. The stroke group was more impaired on the MOS-36 than the asymptomatic group but similar to the group with transient ischemic attack. Health-related quality of life was lowest for persons with stroke. While symptom status and Barthel Index score were the strongest predictors of health status, the Barthel Index showed a consistent ceiling effect when compared with the physical function subscale of the MOS-36. CONCLUSIONS: The consequences of even mild stroke affect all dimensions of health except pain. Standardized assessment of persons with stroke must evaluate across the entire continuum of health-related functions.
BACKGROUND AND PURPOSE: Stroke is a major healthcare problem in both the United States (US) and the United Kingdom (UK). Little comparative data are available concerning how generalist physicians in the two countries approach the management of patients at high risk of stroke. METHODS: Contemporaneous surveys of random samples of primary care physician-reported stroke prevention practices were performed in the US and UK from 1993 to 1994. The US National Survey of Physician Practices for the Secondary and Tertiary Prevention of Ischemic Stroke included 254 noninternist primary care physicians. The UK Survey of the Care of Patients With Stroke in General Practice obtained responses from 661 general practitioners. The two surveys used many of the same questions, allowing for direct comparisons of reported stroke prevention practices between American and British physicians. RESULTS: More than 80% of American physicians reported a variety of services (24-hour electrocardiography, echocardiography, brain CT scan, brain MR scan, carotid ultrasonography, cerebral angiography) as readily available. These same services were readily available to less than 10% of physicians in the UK (P < .001 for each comparison). Although physicians in the UK reported prescribing lower doses of aspirin for stroke prevention than physicians in the US, the proportions of physicians using aspirin were not different. In contrast, almost 70% of physicians in the US responded that they always or often anticoagulate patients with nonvalvular atrial fibrillation compared with 7% of British physicians (P < .001). Whereas 70% of American versus 14% of British physicians reported obtaining carotid ultrasound studies in patients with asymptomatic bruits (P < .001), physicians in the UK more commonly reported referring this type of patient to neurologists (46% versus 21%, P < .001). For patients with recent carotid-distribution transient ischemic attack or minor stroke, physicians in the US more commonly reported referral to neurologists (55% versus 45%, P = .022), referral to surgeons (39% versus 19%, P < .001), the performance of carotid ultrasonography (80% versus 11%, P < .001), echocardiography (45% versus 5%, P < .001), 24-hour electrocardiography (49% versus 4%, P < .001), brain CT scan (72% versus 3%, P < .001), and the prescription of anticoagulants (53% versus 4%, P < .001). CONCLUSIONS: These data show significant differences in stroke prevention practices as reported by primary care physicians practicing in the US and UK. Some of these differences may be related to the relative availability of specific services in the two countries, potentially leading to overutilization in the US and underutilization in the UK in certain circumstances.
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BACKGROUND AND PURPOSE: Patients who recognize their increased risk for stroke are more likely to engage in (and comply with) stroke prevention practices than those who do not. We describe perceived risk of stroke among a nationally diverse sample of patients at increased risk for stroke and determine whether patients' knowledge of their stroke risk varied according to patients' demographic and clinical characteristics. METHODS: Respondents were recruited from the Academic Medical Center Consortium (n = 621, five academic medical centers, inpatients of varying age); the Cardiovascular Health Study (n = 321, population-based sample of persons aged 65+ years); and United HealthCare (n = 319, five health plans, inpatients and outpatients typically younger than 65 years). The primary outcome was awareness of being at risk for stroke. RESULTS: Only 41% of respondents were aware of their increased risk for stroke (including less than one half of patients with previous minor stroke). Approximately 74% of patients who recalled being told of their increased stroke risk by a physician acknowledged this risk in comparison with 28% of patients who did not recall being informed by a physician. Younger patients, depressed patients, those in poor current health, and those with a history of TIA were most likely to be aware of their stroke risk. CONCLUSIONS: Over one half of patients at increased risk of stroke are unaware of their risk. Healthcare providers play a crucial role in communicating information about risk, and successful communication encourages adoption of stroke prevention practices. Educational messages should be targeted toward patients least likely to be aware of their risk.
BACKGROUND AND PURPOSE: The severity of the initial neurological deficit is a critical determinant of outcome after acute stroke. Retrospective outcome studies are generally limited by a lack of quantitative data relating to this initial stroke severity. We evaluated the validity and reliability of measuring initial stroke severity retrospectively with the Canadian Neurological Scale (CNS). METHODS: The CNS was used to prospectively score the initial neurological deficit in a series of patients with acute ischemic stroke (n = 24). An algorithm was devised for applying the CNS retrospectively on the basis of information in the patient's hospital discharge summary. Those dictating the discharge summaries were not aware of the study, and the retrospective scoring was performed without reference to other scores. The level of agreement between the prospective and retrospective scores (validity) and both intraobserver and interobserver reliability for the retrospective scores were determined. RESULTS: Agreement was high between retrospective and prospective scores (r = .84, R2 = .71, P < .0001), between two sets of retrospective scores obtained by one rater (r = .95, R2 = .91, P < .0001), and between retrospective scores obtained by different raters (r = .91, R2 = .82, P < .0001). Weighted kappa statistics (kappa w) for prospectively versus retrospectively scored items varied from almost perfect (kappa w > 0.81 for level of consciousness and orientation) to substantial (kappa w = 0.68 for speech) and moderate (kappa w = 0.41 to 0.60 for facial weakness, proximal arm, distal arm, proximal leg, and distal leg strength). Using the retrospective algorithm, there was almost perfect intraobserver and interobserver reliability for each of the individual CNS items (kappa w = 0.81 to 1.00). CONCLUSIONS: These data show that retrospective scoring of initial stroke severity using an algorithm based on the CNS is valid and can be reliably performed using information available in hospital discharge summaries.
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