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Biomedical subjects

Ronald D Barr

Publications and source records attributed to Ronald D Barr.

At least 37 records · Page 2Linked to original sources
PubMed2005

Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute protocols: effect of age and risk stratification of disease.

Children with acute lymphoblastic leukaemia (ALL) are at increased risk for thromboembolism (TE). Identification of a susceptible population is crucial for effective thromboprophylaxis. However, the risk factors for ALL-associated TE are unclear. Concomitant asparaginase (ASP) and steroid therapy has been shown to increase the incidence of TE. Dana-Farber Cancer Institute (DFCI)-ALL protocols use a combination of ASP and steroids during the postinduction intensification phase when high-risk (HR) patients receive thrice the steroid-dose given to standard-risk (SR) patients. We studied prospectively assembled cohorts of children treated on two consecutive DFCI-ALL protocols to define the risk factors for symptomatic TE. Ten (11%) of 91 patients developed symptomatic TE; eight (seven HR) during intensification. Seven (44%) of 16 older patients (>/=10 years) compared with three of 75 (4%) younger patients developed TE (P < 0.0001). Nine of 35 (26%) HR and one of 56 (2%) SR patients developed TE (P = 0.0006). Gender, ALL-immunophenotype, steroid-type or ASP dosing schedule did not alter the risk but older age and HR-disease were factors predisposing to TE associated with DFCI-ALL protocols. Age-related risk may partly reflect the effect of ALL-risk stratification. Higher dose steroids combined with ASP may lead to an increased risk of TE in HR patients.

Adolescent↗
PubMed2005

Proficiency of balance in children and youth who have had acute lymphoblastic leukemia.

BACKGROUND AND PURPOSE: As the survival rate for acute lymphoblastic leukemia (ALL) in childhood increases, long-term sequelae are a growing concern. This cross-sectional, descriptive study compared the balance skills of children and youth who have had ALL with those of comparable subjects and explored associations with demographics, therapy, physical activity, and health-related quality of life (HRQL). SUBJECTS: Ninety-nine subjects treated previously for ALL and 89 comparison subjects were examined. METHODS: Measures included the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) balance subtest, the Children's Self-perceptions of Adequacy in and Predilection for Physical Activity Scale (CSAPPA), and the Health Utilities Index (HUI), a measure of HRQL. RESULTS: The children and youth who had ALL had poorer balance than the comparison subjects (BOTMP = 10.55 and 16.30, respectively) and lower CSAPPA scores (57.72 and 63.72, respectively) and HUI scores (0.86 and 0.97, respectively). Regression analyses identified exposure to cranial irradiation, being overweight, lower CSAPPA scores for adequacy, and lower HUI single-attribute scores for cognition as predictors of lower balance scores in subjects who had ALL. DISCUSSION AND CONCLUSION: Balance abilities in subjects treated for ALL were compromised, and several factors were associated with this deficit.

Adolescent↗
PubMed2004

The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia.

BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter)--the primary end point--or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

Antibiotics, Antineoplastic↗
PubMed2004

Skeletal morbidity in childhood acute lymphoblastic leukemia.

PURPOSE: Treatment for acute lymphoblastic leukemia (ALL) in childhood results in a reduction in bone mineral density (BMD). Whether there is a recovery of this lost bone mass in survivors of ALL is not known. We sought to determine if changes in BMD are common long-term sequelae in children with ALL. METHODS: Bone mineral densitometry of the lumbar spine and femoral neck was performed on 106 patients. The results were compared with those of age-matched normal controls. The effect of treatment was examined in those with low BMD compared with the remainder of the study group. RESULTS: When data were tested with respect to age, sex, and age and sex, no difference was observed in BMD between survivors of childhood ALL and controls. In the subgroup of patients with low BMD, the difference was not related to age, age at diagnosis, or years since diagnosis. Low BMD of the spine was not explained by radiotherapy (RT), methotrexate (MTX) dose, or corticosteroid dose. Low BMD of the femur was not explained by RT. However, those with low femoral BMD were more likely to have received high-dose MTX or higher-dose corticosteroids compared with the remainder of the group. CONCLUSION: It appears that survivors of childhood ALL as a whole recover normal BMD. However, those patients who received a total MTX dose of greater than 40000 mg/m(2) or a total corticosteroid dose of greater than 9000 mg/m(2) may not recover normal BMD and therefore should be screened for decreased BMD of the femoral neck.

Adolescent↗
PubMed2004

Children, cancer, and nutrition--A dynamic triangle in review.

The overall cure rate for cancer in childhood now exceeds 70% and is projected to reach 85% by the year 2010 in industrialized countries. Therefore, major attention is being placed on reducing the side effects of therapy. However, 85% of the world's children live in developing countries, where access to adequate care often is limited and health status frequently is influenced adversely by prevalent infectious diseases and malnutrition. Despite several confounding factors (different definitions of nutritional status, the wide variety of measures used for its assessment, the selection biases by disease and stage, treatment protocols of variable dose intensity and efficacy, small sample sizes of the studies conducted in the last 20 years), it is accepted that the prevalence of malnutrition at diagnosis averages 50% in children with cancer in developing countries; whereas, in industrialized countries, it is related to the type of tumor and the extent of the disease, ranging from < 10% in patients with standard-risk acute lymphoblastic leukemia to 50% in patients with advanced neuroblastoma. The importance of nutritional status in children with cancer is related to its possible influence on the course of the disease and survival. Some authors have described decreased tolerance of chemotherapy associated with altered metabolism of antineoplastic drugs, increased infection rates, and poor clinical outcome in malnourished children. In this article, the authors review methods of nutritional assessment and the pathogenesis of nutritional morbidity in children with cancer as well as correlations of nutritional status with diagnosis, treatment, and outcome.

Child↗
PubMed2004

Challenges to the measurement of health-related quality of life in children receiving cancer therapy.

Measures of health-related quality of life (HRQL) assess those areas of a patient's functioning that are affected by their cancer and its therapy. Although HRQL measures are integrated frequently into studies of survivors of childhood cancer, their use in the assessment of children receiving therapy has been limited by several methodological challenges. These arise from issues specific to measuring HRQL in young children, who comprise a large proportion of the pediatric oncology population, and from issues associated with assessing HRQL during therapy, when the patient's health status is in constant flux. This study summarizes the commonly used HRQL measures, and examines factors that impact their broad application. These include the influence of developmental changes on the content and format of HRQL measures, the role of proxy assessors, the important characteristics of measurement tools used to assess patients receiving active therapy, and the issues related to the ideal timing of serial HRQL assessments in prospective trials.

Child↗
PubMed2004

A survey of resources and activities in the MISPHO family of institutions in Latin America: a comparison of two eras.

BACKGROUND: In developing countries, implementation of effective pediatric cancer programs can reduce the overall rate of childhood mortality. To promote this objective, Monzas International School of Pediatric Hematology-Oncology (MISPHO)--for 14 countries with limited resources in Latin America--was launched in 1996. METHODS: A survey was conducted to evaluate the possible impact of MISPHO on the following areas: research, educational, and clinical activities, diagnostic services, transfusion medicine, supportive care, ancillary staffing complement, and parents' associations--before and after 1996. RESULTS: No institution lost resources or activities after 1996 and there were overall gains, in particular in educational activities, diagnostic capabilities, creation of single and multiple institutional treatment protocols. CONCLUSIONS: Although notable improvements have occurred, there are still important needs that have to be satisfied.

Child↗
PubMed2004

Economic evaluation of treatments for cancer in childhood.

Treatment of cancer in childhood is an expensive undertaking for the health-care system and for the affected families. As there is a substantial burden of treatment-related morbidity, it is important to determine whether the effects of treatment are worth these monetary costs, especially from a societal perspective. Economic evaluation affords a comparison of the costs and consequences (effects) of relevant therapeutic alternatives. Preference-based measures of health-related quality of life are particularly useful for assessing the effects of treatment, for these tools integrate mortality and morbidity. These measures provide utility scores that can be used as weights on survival data to compute quality-adjusted life years (QALYs). Costs are incurred both within and outside of the health-care system. The former should include those in front-line patient care departments (e.g. nursing); the pro-rated share of the expenses of service departments (e.g. materials management) to those in the front line; and the fully allocated costs for capital invested in lands, building and equipment. The latter are costs borne by families that are both out-of-pocket (e.g. for over-the-counter drugs) as well as related to time spent in providing care, which may involve foregone income. Costs and consequences should be subject to discounting; a process for converting those items incurred in the future into contemporary equivalents. Economic evaluation provides estimates of incremental discounted costs per discounted QALY gained. By almost any interpretative standard this appears attractive with respect to cancer in childhood. Examples are provided with the encouragement that economic evaluation be undertaken in more clinical trials in paediatric oncology.

Child↗
PubMed2004

Measurement of balance in survivors of acute lymphoblastic leukemia in childhood.

Survivors of acute lymphoblastic leukemia (ALL) in childhood have been identified with balance problems. The goals of this study were to objectively quantify these observations by measuring the displacement and velocity of the body centre of pressure, a measure of 'sway'. The subjects included 79 ALL survivors who were at least 1 year post-treatment for ALL and 83 age-matched controls. Testing was carried out using various static balance tests designed to challenge central nervous system maintenance of balance and postural control. Patients were different from controls, across all age groups, in the more difficult task in which they were required to balance over a narrow base of support. However this did not reach statistical significance. When they were asked to perform this task with their eyes closed 32% of the patients tested, as opposed to 2% of controls, were unable to complete the task (significant at P<0.01, chi(2)). The youngest group of patients (children aged 5-7 years) presented consistently with lower (or similar) displacement and lower velocity measures. This phenomenon has been observed in healthy children, however, in patients, these trends were magnified and beyond the normal age range in healthy children. The velocity values were significantly different from the other patient groups (normalized values for velocity; P<0.01). These observations then manifested as higher sway values when patients were challenged with a difficult task with their eyes closed. We propose that survivors of childhood ALL have delayed motor development compared to age-matched controls giving rise to impairment in balance and postural control. It is possible that these impairments are a consequence of intensive multi-agent chemotherapy and cranial irradiation.

Adolescent↗
PubMed2004

Hypomagnesemia associated with chemotherapy in patients treated for acute lymphoblastic leukemia: possible mechanisms.

Body weight, height and lumbar spine bone mineral density (BMD) were measured in 40 children (27 male, 13 female, aged 0.3-17.0 years) with acute lymphoblastic leukemia (ALL) at diagnosis and 6 months after initiation of chemotherapy, and in 40 age- and sex-matched local healthy children. Serum and urinary biochemical indices of mineral metabolism were measured in the children with ALL at both time points. From diagnosis to 6 months, a reduction in the fractional excretion of magnesium was found. Serum osteocalcin was low at diagnosis and increased during chemotherapy, whereas 24-h urinary type I collagen cross-linked N-telopeptide was unchanged. The Z-scores for lumbar spine BMD increased and were correlated with the serum osteocalcin at 6 months. The change in serum magnesium was correlated negatively with the change in lumbar spine BMD, and with the lumbar spine BMD Z-score at 6 months. After initiation of treatment for ALL, rapid recovery in bone formation, which results in the movement of extracellular magnesium into the skeleton through bone formation, may be an important contributor to hypomagnesemia.

Adolescent↗
PubMed2003

Height and weight in children treated for acute lymphoblastic leukemia: relationship to CNS treatment.

PURPOSE: We evaluated the long-term effects of treatment on height and weight in children with acute lymphoblastic leukemia (ALL) treated with one of the following three different CNS therapies: intrathecal therapy alone, intrathecal therapy with conventional cranial radiation, or intrathecal therapy with twice-daily radiation. PATIENTS AND METHODS: Between 1987 and 1995, 618 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for ALL were measured for height and weight at diagnosis, and approximately every 6 months thereafter. Patient height, weight, and body mass index (BMI) were converted to z scores for age and sex using the 2000 Centers for Disease Control and Prevention growth charts for the United States. RESULTS: Children younger than 13 years at diagnosis had a statistically significant decrease in their height z scores and an increase in their BMI z scores, regardless of whether they had received cranial radiation. Young age at diagnosis and increased chemotherapy intensity were major risk factors. Unexpectedly, there was no significant difference in long-term height between children who received radiation and those who did not. CONCLUSION: Final height is compromised in survivors of ALL. The detrimental effects on height occur during therapy without the ability for long-term catch-up growth. Although patients became overweight for height, this seemed to be a result of relative height loss with normal weight gain rather than accelerated weight gain. The type of CNS treatment received did not affect changes in height, weight, or BMI.

Adolescent↗
PubMed2003

Childhood cancer registries in Ontario, Canada: lessons learned from a comparison of two registries.

Two childhood cancer registries exist in Ontario. One (POGO) accrues by active registration by pediatric cancer centers, utilizing a histologically based classification system. The other accrues by passive linkage within a larger adult oriented cancer registry (OCR) using a topographically based classification. A reportedly high incidence of childhood cancer based on the latter registry prompted a comparison of the content of the two registries over a 2-year period with the hypothesis that there would be systematic accrual errors. All registrations in both registries for the specified period were reviewed systematically and validated by pathology reports. A small number (2.6%) of registrations in the passive registry were not incident cases, while 2 particular pathologic diagnoses were included in the histologically based registry and not the topographically based registry. These were low grade gliomas and Langerhans cell histiocytosis (LCH). The validated annual incident rate (15.6 per 100000 children 0-14 years of age, excluding LCH) is slightly higher than that reported in other industrialized countries. Ninety-six percent of children aged 0-14 were treated in pediatric oncology centers, while only 46% of adolescents aged 15-17 were treated in such centers. Of the remaining adolescents, more than one-third had lymphomas. This maldistribution of care provided for the young adolescent population may compromise their survival prospects. The results of this study should prompt revision of health care policy and patterns of service delivery.

Adolescent↗
PubMed2003

Health status and health-related quality of life associated with von Willebrand disease.

Von Willebrand disease (VWD) is the commonest inherited disorder of hemostasis and the majority of women with this disorder experience excessive uterine bleeding. Yet very little information is available on the health-related quality of life (HRQL) in individuals with VWD. To test the a priori hypotheses that these individuals will have poorer HRQL than members of the general population, and that this burden of morbidity will correlate with the severity of VWD, a cross-sectional study was undertaken of a population-based cohort in a regional hemophilia program in Ontario, Canada. A survey was made of individuals over 13 years of age with VWD who self-reported their health status using a standard 15 item questionnaire. The responses were converted to levels in the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems to form multi-element vectors from which single attribute morbidity and overall HRQL utility scores were determined. As a group, individuals with VWD were shown to have poorer HRQL than members of the general population and those with Type 2 disease carried a greater burden of overall morbidity than those with Type 1 disorder. Morbidity was evident mainly in the attributes of emotion, cognition with pain. A striking difference was observed between males and females, with the latter having overall HRQL utility scores similar to those reported previously for HIV positive, severe hemophiliacs. It is possible that this remarkable burden of morbidity reflects chronic iron deficiency associated with menorrhagia. A national study has been proposed to address this likelihood as it offers an opportunity for effective therapeutic intervention (iron supplementation) with a concomitant gain in health status and HRQL.

Adolescent↗
PubMed2003

Nutritional support for children with cancer.

Children with cancer are at risk of suffering from under nutrition, which can affect tolerance of therapy and may influence their overall survival. The goals of nutritional support in the cancer patient are to achieve and maintain desirable weight and to prevent or correct nutritional deficiencies. So early identification of patients at high risk for malnutrition is essential. There are different options for nutritional support. Oral feeding, when possible, is the first line. Enteral nutrition should be considered for those patients who cannot consume adequate macronutrients by mouth. Options are nasogastric tube or gastrostomy tube feeding. The advantages of enteral nutrition, when compared with parenteral nutrition, include better maintenance of the structural and functional integrity of the gastrointestinal tract, a decreased risk of bacterial translocation, greater ease and safety of administration, more physiologic and efficient use of nutrient substrates, decreased hepato-biliary complications, improved outcome and cost-effectiveness. Thus, parenteral nutrition should be considered if the gut is not functioning adequately to allow the normal absorption and digestion of nutrients or if enteral nutritional support is not sufficient to meet nutritional needs. Nutritional assessment and support should be integrated into treatment protocols for all children with neoplastic diseases.

Child↗
PubMed2003

Costs and consequences of stem cell transplantation in children.

Economic evaluation is a comparison of the costs and consequences of alternative healthcare interventions. Consequences are best assessed as utilities; quality-adjusted measures of effectiveness. Although few substantive data are available, it appears that hematopoietic stem cell transplantation is even more cost-effective in children than in adults.

Child↗
PubMed2003

Maintenance of ankle range of motion in children treated for acute lymphoblastic leukemia.

PURPOSE: This study documented ankle dorsiflexion range of motion (DF-ROM) in children during treatment for leukemia and studied the effects of preventative education and individualized intervention as a standard of care. METHODS: Active and passive DF-ROM were measured throughout a two-year treatment period and one year after treatment in 40 subjects. Children without health problems and historical controls who had not received therapeutic input were used for comparison. RESULTS: Active DF-ROM showed an average tendency to decline significantly during treatment, whereas passive DF-ROM did not. Both increased significantly following the end of treatment. There were substantial individual differences around these patterns of average change. Gender (female) was a predictor of negative change in DF-ROM during treatment. Average DF-ROM one year after treatment was significantly greater than for the historical controls and not significantly different from the healthy controls. None of the children required surgical intervention, in contrast to the historical controls. CONCLUSIONS: Education and intervention appears to have improved DF-ROM outcome in children treated for leukemia.

Journal Article↗
PubMed2002

Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol.

PURPOSE: Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug, but mechanisms of cardiotoxicity are different in children. We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin. PATIENTS AND METHODS: In a randomized study, children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2) in 30-mg/m(2) doses every 3 weeks either by bolus (within 1 hour, n = 57) or by continuous infusion (over 48 hours, n = 64). Echocardiograms obtained before doxorubicin and at longest follow-up times were centrally remeasured, and z scores of cardiac measurements were calculated based on a healthy population. RESULTS: The groups were similar in age, sex distribution, doxorubicin dose, and duration of follow-up. Before treatment, measures of left ventricular (LV) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups. The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic, but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline. For example, the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms. LV contractility was depressed in both groups (for bolus patients, median z score = -0.70 SD, P =.006; for continuous-infusion patients, median z score = -0.765, P =.005). Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups. Clinical cardiac manifestations and event-free survival did not differ. CONCLUSION: Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion. Both regimens were associated with progressive subclinical cardiotoxicity. Other cardioprotective strategies should be explored.

Adolescent↗