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M A Foulkes

Publications and source records attributed to M A Foulkes.

At least 19 recordsLinked to original sources
PubMed1998

Advances in HIV/AIDS statistical methodology over the past decade.

This review provides a synopsis of the developments over the past decade in mathematical and statistical methodology in response to the AIDS epidemic. This review includes highlights of the development of epidemic models, approaches to describing the natural history of HIV infection, and the methods developed for HIV therapeutic or prevention research. A bibliography, which is extensive but purposely not intended to be comprehensive, is included. The intention is to provide a historical perspective on the methodologic developments and a framework for identifying HIV/AIDS-related needs for the future.

Anti-HIV Agents↗
PubMed1998

A phased approach to clinical testing: criteria for progressing from Phase I to Phase II to Phase III studies.

The overall intent of clinical testing is to establish, in a series of phased studies, the clinical tolerance and acceptable "safety" of the candidate vaccine, as well as the type, level and persistence of the immune response after its inoculation, to a representative target population, according to a convenient administration schedule. The final stages involve the direct or indirect demonstration of protective efficacy, if possible in the population(s) for which the vaccine is intended. In addition, consistency of production must be demonstrated. At all these stages, the amount of prior information from preclinical and other studies affects and informs the objectives and design of subsequent studies. Progression from one testing phase to the next is dependent upon attaining the pre-set objectives of each series of studies. The precise objectives to be met will be decided on a case-by-case basis. The earliest assessments in humans (Phase I) involve evaluation of short-term clinical tolerance as measured by local and general reactogenicity, and gross assessments of immunogenicity, in a small number of highly selected individuals in an idealised situation. The selection of "optimal" dose and schedule are the result of further dose-ranging investigations (Phase II), involving more volunteers, with longer, more detailed follow-up assessments. It is at this stage that the accumulated evidence on its immunogenicity profile should be sufficient to assess whether or not the vaccine is worthy of further development. The next level of investigation (Phase III) aims to measure with greater precision the vaccine protective efficacy in the intended target population(s) by comparison of infection and/or disease attack rates in vaccine and placebo recipients. In consistency studies different production lots, manufactured at commercial scale, are tested to demonstrate consistency of manufacture. Additional bridging studies to establish similarity of lots at different production scales, or studies of the duration of the immunity conferred, are conducted in parallel with the progression of the studies in the different phases mentioned above. These latter types of studies are usually carried out concurrently with Phase III studies. This progression continues into the post-marketing period (Phase IV) with surveillance of long term efficacy and observational studies of possible rare adverse events to establish "safety" with more confidence. This paper examines, in general, the aims and designs of studies in each phase as an introduction to the more specific publications that follow.

Clinical Trials as Topic↗
PubMed1994

Parametric modeling of stroke recurrence.

Stroke recurrence has been investigated primarily with respect to prognostic factors predictive of recurrence. Several parametric functions are considered in modeling the distribution of ischemic stroke recurrences recorded within the Stroke Data Bank. A linear hazard function is shown to be the best-fitting function among those considered. This method of parametric modeling may lead to a more informed approach to treatment of ischemic stroke and secondary prevention and may enhance future investigations of prognostic factors as well.

Cerebral Infarction↗
PubMed1994

Issues in analyzing data: experiences with three data bases.

Analytic issues in stroke data base research are reviewed, drawing upon relevant experiences in the analyses of three observational data bases from a variety of clinical fields. The specifics of the data base construct, statistical issues and variations in possible interpretations of results are discussed. Responsible analyses of and conservative inferences from observational data bases are stressed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The role of secondary brain injury in determining outcome from severe head injury.

As triage and resuscitation protocols evolve, it is critical to determine the major extracranial variables influencing outcome in the setting of severe head injury. We prospectively studied the outcome from severe head injury (GCS score < or = 8) in 717 cases in the Traumatic Coma Data Bank. We investigated the impact on outcome of hypotension (SBP < 90 mm Hg) and hypoxia (Pao2 < or = 60 mm Hg or apnea or cyanosis in the field) as secondary brain insults, occurring from injury through resuscitation. Hypoxia and hypotension were independently associated with significant increases in morbidity and mortality from severe head injury. Hypotension was profoundly detrimental, occurring in 34.6% of these patients and associated with a 150% increase in mortality. The increased morbidity and mortality related to severe trauma to an extracranial organ system appeared primarily attributable to associated hypotension. Improvements in trauma care delivery over the past decade have not markedly altered the adverse influence of hypotension. Hypoxia and hypotension are common and detrimental secondary brain insults. Hypotension, particularly, is a major determinant of outcome from severe head injury. Resuscitation protocols for brain injured patients should assiduously avoid hypovolemic shock on an absolute basis.

Abbreviated Injury Scale↗
PubMed1993

Infarct topography and hemiparesis profiles with cerebral convexity infarction: the Stroke Data Bank.

For the 183 of 1276 patients in the NINDS Stroke Data Bank with convexity infarction in the middle cerebral artery territory, the size of the infarct did not differ between the two sides but the location of the main site of the infarct differed: on the left side, it was centred in the inferior parietal region, and was mid-frontal on the right. There was a good correlation between infarct size and weakness severity whether estimated by overall motor function on one side, arm, or hand alone. There was a poor correlation, however, for lesion location (lower third, middle third or upper third on either side of the Rolandic fissure) and any of the specific syndromes of focal weakness, no two cases sharing the same lesion for the same syndrome and several cases sharing the same lesion with a different syndrome. The findings indicated a difference in weakness syndromes between the two hemispheres and great individual variation of the acute syndrome caused by a given site of focal infarction along the Rolandic convexity. These variations may explain some of the difficulties showing effects of a given therapeutic agent in studies of acute ischaemic stroke. Large sample sizes will be required for the reliable assessment of any treatment using currently popular clinical stroke scales.

Brain Mapping↗
PubMed1993

Brain infarction severity differs according to cardiac or arterial embolic source.

We compared clinical and radiologic features between 246 cardiac embolism (EMB) and 66 arterial embolic (tandem arterial pathology [TAP]) patients selected from the 1,273 patients with cerebral infarction in the Stroke Data Bank. Diagnostic definitions accounted for the increased frequency of cardiac disease among patients with EMB compared with TAP (78.4% versus 29.3%), while transient ischemic attacks (32.3% versus 13.1%) and carotid artery bruit (15.1% versus 3.3%) were more prevalent in TAP than in EMB. Multiple logistic regression differentiated TAP and EMB further. The probability of a TAP diagnosis was increased by the CT finding of a superficial infarct alone (odds ratio [OR] = 4.6; 95% CI = 1.5 to 13.7) or by a higher admission hematocrit. The probability of EMB was greater in patients with an initial decreased consciousness (OR = 39.2; 95% CI = 4.0 to 381.3) or with an abnormal first CT (OR = 3.2; 95% CI = 1.2 to 8.6). These findings indicate that the two infarct subtypes differ in the location and extent of the cortical infarction, which argues for a smaller particle size, with smaller and more distal infarction in embolism from an arterial source compared with cardiogenic embolism.

Aged↗
PubMed1993

Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury.

The present study was conducted to further our understanding of the relationship between performance on neuropsychological tests and functional status after head injury and to provide information on the relative usefulness of neuropsychological tests as outcome measures in clinical trials of brain injury. We sought to select the fewest number of 19 neuropsychological tests administered to 110 patients that, in combination, were most closely related to outcome (as measured by the Glasgow Outcome Scale (GOS) and to the remaining neuropsychological measures. The relationship of memory and intellectual deficits to functional status was also considered. To address these questions, we analyzed 19 neuropsychological measures and GOS scores of 110 severely brain injured patients from the Traumatic Coma Data Bank. Of 19 neuropsychological measures compared with GOS at 3 and 6 months, four tests (Controlled Oral Word Association, Grooved Pegboard, Trailmaking Part B, and Rey-Osterrieth Complex Figure Delayed Recall) provided the closest relationship to GOS and to the remaining 15 tests. Similar analyses were performed on 30 moderately injured patients to test the generality of our findings across different levels of patient severity. The same four tests were found to be highly predictive of GOS. Grooved Pegboard, a test of fine motor coordination, accounted for 80% of the variation in GOS. Fifteen percent of 116 patients with severe brain injury could not complete a neuropsychological battery and 39% were excluded because of previous brain injury or known substance abuse.

Adolescent↗
PubMed1992

Thalamic stroke. Presentation and prognosis of infarcts and hemorrhages.

Thalamic strokes in 62 patients selected from the Stroke Data Bank were studied to determine differences among 18 infarctions (INF), 23 localized hemorrhages (ICH), and 21 hematomas with ventricular extension (IVH). Stupor or coma at onset occurred more frequently in the IVH (62%) than in the INF (6%) or ICH (13%) groups and was reflected in significantly lower median Glasgow Coma Scores in the IVH group (7) than in the INF (15) and ICH (14) groups. Although ocular movements were more frequently abnormal in the IVH group compared with the ICH and INF groups, no significant differences were found in the frequency of motor or sensory deficits. Among the 62 strokes, 32 had restricted lesions of the posterolateral (n = 9), anterior (n = 3), paramedian (n = 7), and dorsal (n = 13) portions of the thalamus. Differences in consciousness and in motor, sensory, and oculomotor deficits were found among the topographic subgroups. Stroke-related deaths occurred in 52% of IVH cases, 13% of ICH cases, and no cases of INF. Median lesion volume as detected with computed tomography was greater in hemorrhages (INF, 2 cm3; ICH, 10 cm3; IVH, 16 cm3), with mortality related to increasing hematoma size. Coma, Glasgow Coma Score lower than 9, weakness score greater than 15 of a possible 30, abnormal ocular movements, and fixed pupils were also associated with stroke-related mortality. We conclude that the initial neurologic syndrome does not discriminate infarcts from intrathalamic hemorrhages. Ventricular extension, however, causes significantly more severe deficits and higher mortality.

Cerebral Hemorrhage↗
PubMed1992

Predictors of mortality in severely head-injured patients with civilian gunshot wounds: a report from the NIH Traumatic Coma Data Bank.

Predictors of outcome were examined in this prospective study of 151 patients severely injured by civilian gunshot wounds. Of the 151 patients, 133 (88%) died. Of the 123 patients with an initial Glasgow Coma Scale score of 3-5, 116 (94%) died, whereas of the 20 with an initial Glasgow Coma Scale score of 6-8, 14 (70%) died. There were no good outcomes, and only three moderate recoveries in patients who had initial scores of 8 or less. In those patients who survived long enough for intracranial pressure monitoring, intracranial hypertension predicted a very poor outcome. Computed tomographic scan characteristics such as midline shift, compression or obliteration of the mesencephalic cisterns, the presence of subarachnoid blood, intraventricular hemorrhage, and the presence of hyperdense or mixed-density lesions greater than 15 mL, either bilateral or unilateral, were all associated with a poor outcome. However, neither the caliber of gun nor the distance of the gun from the head significantly affected the risk of dying.

Adolescent↗
PubMed1992

Circadian rhythmicity of stroke onset. Intracerebral and subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Our purpose was to describe and further understand the determinants of the time of onset of parenchymatous intracerebral hemorrhage and subarachnoid hemorrhage in patients enrolled in the Stroke Data Bank. METHODS: We analyzed the observed times of onset of intracerebral hemorrhage (n = 237 patients) and subarachnoid hemorrhage (n = 243 patients) compared with expected times of onset if the probability of onset was constant across all time intervals. We also analyzed the role of clinical features (if any) in explaining the findings. RESULTS: For intracerebral hemorrhage, 52.5% of patients reported onset times between 0600 hours and 1400 hours, with peak onset between 1000 and 1200 hours (chi 2 = 62.94, df = 11, p less than 0.001). Patients with subarachnoid hemorrhage were more likely to lack a history of hypertension compared with patients who had intracerebral hemorrhage (chi 2 = 23.3, df = 1, p less than 0.001). Patients with subarachnoid hemorrhage were more likely to have more uniform onset time throughout the day (chi 2 = 12.92, df = 7, p = 0.074). However, subarachnoid hemorrhage patients with a history of hypertension were more likely to have peak onset times in mid-to-late morning compared with patients without such a history (chi 2 = 35.25, df = 10, p less than 0.001). The nonuniformity of onset times for intracerebral hemorrhage persisted even if patients with unknown onset times were treated as through their onset times were randomly distributed between 0000 and 0800 hours. Seasonal periodicity and the relation between initial systolic or diastolic blood pressure and time of onset for either type of hemorrhage were not observed. CONCLUSIONS: Our data suggest that the time of onset for both intracerebral hemorrhage and subarachnoid hemorrhage patients with a history of hypertension is similar to the diurnal variation in blood pressure.

Adolescent↗
PubMed1992

Early clinical differentiation of cerebral infarction from severe atherosclerotic stenosis and cardioembolism.

BACKGROUND AND PURPOSE: Hyperacute cerebral infarction trials require early differentiation of infarction subtype. Our aim was to determine clinical factors predictive of infarction subtype from data collected in the early hours of admission. METHODS: Using the 1,273 patients enrolled in the Stroke Data Bank, stroke risk factors and demographic, clinical, and radiological features were compared between the 246 cardioembolic and 113 large-vessel atherosclerotic cerebral infarcts. RESULTS: Stroke Data Bank definitions ensured more transient ischemic attacks in atherosclerotic infarcts and more cardiac disease in cardioembolic infarcts, but the diagnosis was distinguished further using a logistic regression model. Fractional arm weakness (shoulder different from hand) (odds ratio 3.1, 95% confidence interval [CI] 1.6-5.8), hypertension (odds ratio 2.8, CI 1.4-5.3), diabetes (odds ratio 2.5, CI 1.2-5.1) and male gender (odds ratio = 2.2, CI 1.2-4.1) occurred more frequently in patients with atherosclerotic than cardioembolic infarcts. Reduced consciousness (odds ratio = 3.2, CI 1.4-7.3) was more frequent in cardioembolism. For a male patient with hypertension, diabetes, and fractional arm weakness, the estimated odds of an atherosclerotic infarction were 47-fold that of a cardioembolic infarction. Patients with atherosclerotic infarcts were more likely to have a fractional arm weakness regardless of infarct size, whereas, for those with cardioembolic infarctions, fractional weakness was more frequent in infarcts less than 20 cc in volume. CONCLUSIONS: Clinical features that are observed at stroke onset can help distinguish cerebral infarction subtypes and may allow for early stratification in therapeutic trials.

Aged↗
PubMed1992

Severe head injury in children: experience of the Traumatic Coma Data Bank.

The outcome at discharge, 6 months, and 1 year after they had sustained severe head injuries was investigated in children (0-15 yr old at injury) who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank. Of 103 eligible children, the quality of recovery was assessed by the Glasgow Outcome Scale (GOS) at 6 months after injury in 92 patients (86% of series) and at 1 year in 82 patients (73% of series). The lowest post-resuscitation Glasgow Coma Scale score and pupillary reactivity were predictive of the 6-month GOS as were their interaction. Analysis of the first computed tomographic scan disclosed that bilateral swelling with/without midline shift was related to a poor outcome as was the presence of mass lesions. Comparison of age-defined subgroups of patients revealed that outcome was poorest in the 0- to 4-year-old patients, as reflected by their mortality, which increased to 62% by 1 year. Distinctive features of the injuries in the 0- to 4-year-olds included evacuated subdural hematomas (20% of patients) and hypotension (32% of patients). The most favorable outcome was attained by 5- to 10-year-olds (2/3 had a good recovery by 1 yr), whereas the GOS distribution of adolescents was intermediate between the children and adults. In summary, the GOS data reflect heterogeneity in the quality of outcome after severe head injury depending on age, neurological indices, and computed tomographic scan diagnostic category.

Adolescent↗
PubMed1992

Diffuse brain swelling in severely head-injured children. A report from the NIH Traumatic Coma Data Bank.

In this study, data were prospectively collected from 753 patients (111 children and 642 adults) with severe head injury and examined for evidence of diffuse brain swelling and its association with outcome. Diffuse brain swelling occurred approximately twice as often in children (aged 16 years or younger) as in adults. A high mortality rate (53%) was found in these children, which was three times that of the children without diffuse brain swelling (16%). Adults with diffuse brain swelling had a mortality rate (46%) similar to that of children, but only slightly higher than that for adults without diffuse brain swelling (39%). When the diagnosis of diffuse brain swelling was expanded to include patients with diffuse brain swelling plus small parenchymal hemorrhages (less than 15 cu cm), these mortality rates were virtually unchanged.

Adolescent↗