Preliminary investigation of Brain Network Activation (BNA) and its clinical utility in sport-related concussion.

BACKGROUND: The clinical diagnosis and management of patients with sport-related concussion is largely dependent on subjectively reported symptoms, clinical examinations, cognitive, balance, vestibular and oculomotor testing. Consequently, there is an unmet need for objective assessment tools that can identify the injury from a physiological perspective and add an important layer of information to the clinician's decision-making process. OBJECTIVE: The goal of the study was to evaluate the clinical utility of the EEG-based tool named Brain Network Activation (BNA) as a longitudinal assessment method of brain function in the management of young athletes with concussion. METHODS: Athletes with concussion (n = 86) and age-matched controls (n = 81) were evaluated at four time points with symptom questionnaires and BNA. BNA scores were calculated by comparing functional networks to a previously defined normative reference brain network model to the same cognitive task. RESULTS: Subjects above 16 years of age exhibited a significant decrease in BNA scores immediately following injury, as well as notable changes in functional network activity, relative to the controls. Three representative case studies of the tested population are discussed in detail, to demonstrate the clinical utility of BNA. CONCLUSION: The data support the utility of BNA to augment clinical examinations, symptoms and additional tests by providing an effective method for evaluating objective electrophysiological changes associated with sport-related concussions.

Prediction of winning amateur boxers using pretournament reaction times.

AIM: Boxing requires agility and manual dexterity, which is associated with fast reflexes and reaction time. This study evaluated the relation between reaction times on cognitive tasks and competition outcomes in boxers. METHODS: The design was a prospective cohort study. Participants were collegiate amateur boxers who won at least one bout in a single elimination tournament. Optimal pre-participation performance using a computerized cognitive assessment tool (CCAT, Axon Sports) and no significant deterioration in cognitive performance within 24 hours post-bout was required to compete in future bouts. Winners were assumed to be motivated to perform optimally on testing. Performance on speed and accuracy measures were compared in winning and non-winning boxers. Pre-competition minutes of sparring and tournament seedings were recorded. RESULTS: There were 96 eligible boxers who won at least one of 160 bouts. The mean age was 21.3 (SD 1.9) years (range 18.5-29.7). A significant improvement in mean reaction times as a function of advancement in the boxing tournament was observed. The 18 winning boxers who advanced to the finals had significantly faster mean reaction times at the baseline assessment before the competition began (speed composite z-score F(1,94)=4.14, P<0.05, effect size 0.54). Winners also had more sparring experience (Mann-Whitney U=302.5, P<0.001) and higher pre-competition rankings (Mann-Whitney U=288.5, P<0.001). CONCLUSION: In highly motivated amateur boxers, finalists performed significantly faster than those who failed to reach the finals on measures of pre-competition reaction time. These findings suggest that winners of boxing tournaments might be predicted using pre-competition measures of processing speed.

Pharmacological studies with vinblastine in the dog.

Tritiated vinblastine was prepared by catalytic exchange and its metabolism was studied in dogs. Plasma levels of drug fell in biphasic mode with initial and secondary phase half-lives of 17 to 38 min and 3 to 5 hr, respectively. Between 28.6 and 79.1% of plasma tritium was precipitable with cold trichloroacetic acid and thus was presumably protein bound. Blood leukocytes had levels of intracellular tritium between 2.4 and 11.8 times those of the coincident plasma samples. Over a 9-day period, urinary excretion accounted for 12.1 to 16.8% and fecal excretion accounted for 30.1 to 36.1% of the administered radioactivity. Ratios of biliary to plasma radioactivity varied between 7.3 and 56.9, with unchanged vinblastine being the mamor component (46.8 to 80.7%) in the bile.

A national study of the quantity and cost of informal caregiving for the elderly with stroke.

BACKGROUND: As the US population ages, increased stroke incidence will result in higher stroke-associated costs. Although estimates of direct costs exist, little information is available regarding informal caregiving costs for stroke patients. OBJECTIVE: To determine a nationally representative estimate of the quantity and cost of informal caregiving for stroke. METHODS: The authors used data from the first wave of the Asset and Health Dynamics (AHEAD) Study, a longitudinal study of people over 70, to determine average weekly hours of informal caregiving. Two-part multivariable regression analyses were used to determine the likelihood of receiving informal care and the quantity of caregiving hours for those with stroke, after adjusting for important covariates. Average annual cost for informal caregiving was calculated. RESULTS: Of 7,443 respondents, 656 (8.8%) reported a history of stroke. Of those, 375 (57%) reported stroke-related health problems (SRHP). After adjusting for cormorbid conditions, potential caregiver networks, and sociodemographics, the proportion of persons receiving informal care increased with stroke severity, and there was an association of weekly caregiving hours with stroke +/- SRHP (p < 0.01). Using the median 1999 home health aide wage (8.20 dollars/hour) as the value for family caregiver time, the expected yearly caregiving cost per stroke ranged from 3,500 dollars to 8,200 dollars. Using conservative prevalence estimates from the AHEAD sample (750,000 US elderly patients with stroke but no SRHP and 1 million with stroke and SRHP), this would result in an annual cost of up to 6.1 billion dollars for stroke-related informal caregiving in the United States. CONCLUSIONS: Informal caregiving-associated costs are substantial and should be considered when estimating the cost of stroke treatment.

Radiation therapy of conjunctival and orbital lymphoid tumors.

Lymphoid tumors of the conjunctiva and orbit are rare and remain localized in the majority of cases. Sometimes it is not possible either clinically or histologically to differentiate between a non-Hodgkin's lymphoma (NHL) and benign lymphoid hyperplasia. A series of 24 patients is reported. Nineteen were classified as having malignant NHL and 5 benign hyperplasia; 1 of these 5 later developed metastases, however. All patients had systemic work-up: 18 had Stage I, 1 had Stage II, and 5 had Stage IV disease. All patients received local radiation therapy with doses of 2400 to 2750 rad in 2-3 weeks for lesions of the eyelid and conjunctiva, and between 3000 and 3750 rad in 3-4 weeks for retrobulbar lesions. The lens was shielded in all patients except in 2 who had NHL of the vitreous body. A method of shielding the lens with a lead block mounted on a "low vac lens" is described, and the dose distribution within the eye and orbit is presented. The dose to the ocular lens is reduced to about 10% of the tumor dose with this technique. Patients who were treated with doses higher than 3000 rad experienced conjunctivitis and skin erythema that resolved completely. No other effects of radiation on normal structures of the ocular adnexa were observed in the 20 patients who are alive and without signs of tumor 10-46 months with a median follow-up time of 22 months.

Three-dimensional photon treatment planning for Hodgkin's disease.

A multi-institutional study was undertaken using computerized planning systems to develop three-dimensional (3-D) radiotherapy plans for Hodgkin's disease (H.D.). Two patients, the first afflicted with bulky stage II disease and another one with early stage I H.D., were studied. Three main categories of plan were produced for each patient: a) a traditional plan which modelled a conventional mantle treatment on the 3-D system, b) a 3-D standard plan where anterior and posterior fields were designed to cover 3-D target volumes, and c) a 3-D unconstrained plan where innovational techniques were employed. Three-dimensional planning provides information about the dose distribution throughout the large volume irradiated in patients with H.D. that is not available with conventional mantle planning. The use of 3-D techniques resulted in improved tumor coverage, but by allowing for uncertainties such as motion, the doses to normal tissues tended to be higher. The use of unorthodox beam arrangements introduced added complexities, and further increased the lung doses. The most even dose distributions were obtained by incorporating compensating filters into anterior fields. Clinicians showed wide variations in their assessment of the plans, possible reasons for which are addressed in this paper. In addition, calculated probabilities from models of tumor control and normal tissue damage are also presented.

The role of uncertainty analysis in treatment planning.

The role of uncertainty analysis in 3-D treatment planning systems was addressed by four institutions which contracted with NCI to evaluate high energy photon external beam treatment planning. Treatment plans were developed at eight disease sites and the effects of uncertainties assessed in a number of experiments. Uncertainties which are patient-site specific included variations in the delineation of target volumes and normal tissues and the effects of positional uncertainties due to physiological motion and setup nonreproducibility. These were found to have a potentially major impact on the doses to the target volumes and to critical normal tissues which could result in significantly altered probabilities of tumor control and normal tissue complications. Other uncertainties, such as the conversion of CT data to electron densities, heterogeneities and dose calculation algorithms' weaknesses, are related to physical processes. The latter was noted to have the greatest potential contribution to uncertainty in some sites. A third category of uncertainty related to the treatment machine, the consequences of compensator misregistration, are exclusive to the site and the treatment portal. Because conventional treatment planning systems have not incorporated uncertainty analysis, tools and techniques had to be devised for this work; further development in this area is needed. Many of the analyses could not have been done without full 3-D capabilities of the planning systems, and it can be anticipated that the availability of uncertainty analysis in these systems which allow nontraditional beam arrangements will be of great value.

Neuroacanthocytosis masquerading as Huntington's disease: CT/MRI findings.

Neuroacanthocytosis (NA) is a rare, degenerative, presumably autosomal-recessive disorder of the nervous system presenting in adulthood and is associated with acanthocytosis of the peripheral blood. The clinical spectrum of NA shares similarities with Huntington's disease (HD), including dyskinetic choreiform movements and degeneration of the caudate nucleus. A woman presented with choreiform movements and was given a presumed diagnosis of HD. Neuroimaging studies were consistent with HD. She lacked the genetic marker for HD, and further evaluation revealed acanthocytosis of the peripheral blood. The case illustrates the similarities and differences in the clinical presentations and neuroimaging studies of these two disease entities, emphasizing the need for a careful clinical evaluation.

Limited small-cell lung cancer: do favorable short-term results predict ultimate outcome?

Advances in the treatment of limited small-cell lung cancer (L-SCLC) have led to improved short-term outcome. However, it is not clear how well this predicts the ultimate fate of the patients. This may be affected by late relapse of SCLC, the development of second malignancies, and the long-term toxicity of therapy. To address this issue we report follow-up in excess of 5 years on a cohort of 36 patients who had high short-term survival resulting from treatment with chemotherapy combined with cranial and thoracic irradiation. All patients were followed until death or the time of analysis. The initially promising result of 31% survival at 3 years, was reflected in survival from SCLC of 27% at 5 years, and 23% at 9 years. However, when death from all causes was analyzed, survival was only 19% at 5 years and 7% at 9 years. There were 2 survivors disease-free at 7 and 8 years; 7 patients died of other causes without any evidence of SCLC. Among those not dying of SCLC, 4 patients developed second malignancies with a risk of 22% at 3.2 years and 50% at 8 years. Clinical neurotoxicity developed in 3 patients. These data suggest that cure of SCLC is possible in a modest proportion of patients with limited disease, but that the survivors are at significant risk of developing second malignancies which emerge as the most common cause of death during prolonged follow-up. Successful outcome of treatment is further hampered by the occurrence of neurotoxicity. Clinical strategies to prevent these sequelae of therapy are discussed.

Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies.

"Bendectin" (Doxylamine/Dicyclomine/Pyridoxine) was widely used for the treatment of nausea and vomiting of pregnancy until 1983, when production was discontinued in the face of lawsuits alleging that the drug caused congenital malformations. We have conducted a meta-analysis of the 16 cohort and 11 case-control studies that report birth defects from Bendectin-exposed pregnancies. This meta-analysis provides an estimate of the relative risk of malformation at birth in association with Bendectin exposure. The pooled estimate of the relative risk of any malformation at birth in association with exposure to Bendectin in the first trimester was 0.95 (95% Cl 0.88 to 1.04). Separate analyses were undertaken for cardiac defects, central nervous system defects, neural tube defects, limb reductions, oral clefts, and genital tract malformations. In these categories, the pooled estimates of relative risk ranged from 0.81 for oral clefts to 1.11 for limb reductions, with all 95% confidence intervals enclosing unity. With the exception of studies for oral clefts and for pyloric stenosis, tests for heterogeneity of association indicated for each table that all studies were estimating the same odds ratio. These studies, as a group, showed no difference in the risk of birth defects between those infants whose mothers had taken Bendectin during the first trimester of pregnancy and those infants whose mothers had not. It is unlikely that Bendectin exposure contributed to the prevalence of congenital malformations in the population.

Mental health concerns of Canadian adolescents: a consumer's perspective.

OBJECTIVE: To evaluate the mental health of adolescent students in Metropolitan Toronto. METHOD: A survey was developed by adolescents for adolescents to evaluate adolescent mental health. The survey was completed by 486 secondary school students in Metropolitan Toronto. RESULTS: The findings of this consumer-directed survey show that the majority of teenagers are not overwhelmed by stress and generally exhibit healthy coping behaviours. Violence is identified as an important concern and help-seeking behaviour for mental health issues, when it occurs, is directed primarily towards the family and teachers rather than physicians. CONCLUSION: A number of important issues regarding mental illness, including its identification and treatment, were not considered by teens to be part of their mental health concerns. The implications of these findings for the development of community-based mental health programs for adolescents are discussed.