RESUMEN
BACKGROUND: Pediatric arterial ischemic stroke remains incompletely understood. Population-based epidemiological data inform clinical trial design but are scant in this condition. We aimed to determine age-specific epidemiological characteristics of arterial ischemic stroke in neonates (birth to 28 days) and older children (29 days to 18 years). METHODS: We conducted a 16-year, prospective, national population-based study, the Canadian Pediatric Ischemic Stroke Registry, across all 16 Canadian acute care children's hospitals. We prospectively enrolled children with arterial ischemic stroke from January 1992 to December 2001 and documented disease incidence, presentations, risk factors, and treatments. Study outcomes were assessed throughout 2008, including abnormal clinical outcomes (stroke-related death or neurological deficit) and recurrent arterial ischemic stroke or transient ischemic attack. RESULTS: Among 1129 children enrolled with arterial ischemic stroke, stroke incidence was 1.72/100,000/year, (neonates 10.2/100,000 live births). Detailed clinical and radiological information were available for 933 children (232 neonates and 701 older children, 55% male). The predominant clinical presentations were seizures in neonates (88%), focal deficits in older children (77%), and diffuse neurological signs (54%) in both. Among neonates, 44% had no discernible risk factors. In older children, arteriopathy (49% of patients with vascular imaging), cardiac disorders (28%), and prothrombotic disorders (35% of patients tested) predominated. Antithrombotic treatment increased during the study period (P < 0.001). Stroke-specific mortality was 5%. Outcomes included neurological deficits in 60% of neonates and 70% of older children. Among neonates, deficits emerged during follow-up in 39%. Overall, an initially decreased level of consciousness, a nonspecific systemic presentation, and the presence of stroke risk factors predicted abnormal outcomes. For neonates, predictors were decreased level of consciousness, nonspecific systemic presentation, and basal ganglia infarcts. For older children, predictors were initial seizures, nonspecific systemic presentation, risk factors, and lack of antithrombotic treatment. Recurrent arterial ischemic stroke or transient ischemic attack developed in 12% of older children and was predicted by arteriopathy, presentation without seizures, and lack of antithrombotic treatment. Emerging deficit was predicted by neonatal age at stroke and by cardiac disease. CONCLUSIONS: This national data set provides a population-based disease incidence rate and demonstrates the protective effect of antithrombotic treatment in older children, and frequent long-term emerging deficits in neonates and in children with cardiac disorders. Further clinical trials are required to develop effective age-appropriate treatments for children with acute arterial ischemic stroke.
Asunto(s)
Isquemia Encefálica/epidemiología , Isquemia Encefálica/terapia , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Adolescente , Canadá/epidemiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: Hemophilia is an X-chromosome-linked disorder associated with recurrent bleeding into muscles and joints, leading to pain and limitations in physical function that may diminish quality of life. The Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) is a disease-specific measure of quality of life that was recently revised to facilitate cross-cultural adaptation. This study assessed the validity and reliability of version 2.0 of the CHO-KLAT (CHO-KLAT2.0). METHODS: Content validity was assessed via detailed cognitive debriefing to confirm that Canadian boys understood the CHO-KLAT2.0. The measurement properties of the CHO-KLAT2.0 were assessed in comparison to those of the PedsQL, the Haemo-QoL, and two global ratings. Most children completed the CHO-KLAT2.0 a second time to assess test-retest reliability. RESULTS: Cognitive debriefing was completed with 12 boys (age 8.6-17.8 years) and 9 of their parents and resulted in no substantive changes. Sixty boys (mean age 11.8 years) participated in the validation phase, which showed a mean CHO-KLAT2.0 score of 75.4±12.0, strong correlations with the PedsQL (r = 0.62, P<0.001) and Haemo-QoL (r = 0.64, P<0.001), and moderate correlations with global ratings of hemophilia bother (ρ =-0.39, P = 0.002) and health (ρ =-0.47, P = 0.0002). Test-retest concordance was better among parents (0.79) than among boys (0.63). CONCLUSIONS: This study establishes the measurement properties of the CHO-KLAT2.0. The summary scores are very similar to those from the original development study, and thus, these have not been affected by the revisions. These results provide reference standards for comparing data from other countries to the Canadian experience and to estimate sample sizes for future clinical trials.
Asunto(s)
Hemofilia A/psicología , Evaluación de Resultado en la Atención de Salud/métodos , Calidad de Vida , Adolescente , Canadá , Niño , Hemofilia A/terapia , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
The risk of recurrent ischemic stroke after presumed perinatal stroke and the risk factors for such recurrence are rarely reported. Here, we present an adolescent with a history of presumed perinatal stroke who presented with arterial ischemic stroke recurrence at the age of 15 years. Hereditary thrombophilia screening performed at the time of his stroke recurrence demonstrated protein S deficiency. No evidence-based consensus guidelines on thrombophilia screening in children with presumed perinatal stroke exist, nor has the role of secondary prophylaxis been addressed. There is a risk of stroke recurrence after presumed perinatal stroke, and routine thrombophilia screening may identify those children who are at higher risk for recurrence and who might therefore benefit from secondary prophylaxis. Clear guidelines should be developed to standardize investigations and management of children with presumed perinatal ischemic stroke.
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Infarto de la Arteria Cerebral Media/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Adolescente , Angiografía Cerebral , Factor V/genética , Humanos , Infarto de la Arteria Cerebral Media/genética , Masculino , Mutación/genética , Accidente Cerebrovascular/terapia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
INTRODUCTION: Enoxaparin is the current anticoagulant of choice for neonatal thrombosis. Present neonatal treatment guidelines of 1.5 mg/kg every 12 hours (q12 h) are extrapolated primarily from an earlier study with 9 infants less than 2 months of age. More recent studies indicate an increased dose requirement for neonates. MATERIALS AND METHODS: Relevant data from articles and abstracts were identified by searching MEDLINE and pediatric and hematology conference proceedings. RESULTS: Publications between 1996 and 2007 included 8 papers, 4 abstracts and 1 review article with primary research documenting enoxaparin use in 240 neonates. The mean maintenance dose of enoxaparin ranged from 1.48 to 2.27 mg/kg q12 h for all infants, but was higher for preterm neonates at 1.9-2.27 mg/kg q12 h. The efficacy of enoxaparin, causing either complete or partial resolution was between 59 and 100%. Minor side effects were common and adverse events (major bleeding) occurred in 12 patients (0-19%). CONCLUSIONS: Increased experience with enoxaparin use in neonates in the past decade has indicated higher doses to achieve accepted target anti-factor Xa values. The long-term use of indwelling catheters (Insuflon catheter) for enoxaparin administration may need to be reevaluated in ELBW infants. Suggested starting doses of enoxaparin are 1.7 mg/kg q12 h for term neonates and 2.0 mg/kg q12 h for preterm neonates if there is no considerable bleeding risk. However, further prospective studies are needed to validate an increased initial dose of enoxaparin.
Asunto(s)
Anticoagulantes/uso terapéutico , Enoxaparina/uso terapéutico , Trombosis/tratamiento farmacológico , Catéteres de Permanencia , Enoxaparina/administración & dosificación , Enoxaparina/efectos adversos , Humanos , Recién Nacido , Recien Nacido PrematuroRESUMEN
Renal vein thrombosis is a complication that occurs in neonates with various underlying risk factors. It carries a grave prognosis for affected kidneys. Anticoagulant and fibrinolytic therapies have been promoted in the past with anecdotal success in some circumstances. However, prospective controlled trials are still lacking, and to date there have been no evidence-based guidelines available for the treatment of neonates with renal vein thrombosis. We retrospectively reviewed all the available medical literature pertaining to renal vein thrombosis published in English during the past 15 years. A total of 271 patients from 13 case series were identified by using the terms "renal vein thrombosis" and "neonates" via PubMed and Cochrane Library searches. Data then were extracted from each of the studies for analysis. During the past 15 years, a male predominance (67.2%) in neonatal renal vein thrombosis has been reported. More than 70% of patients had unilateral renal vein thrombosis, which was more prevalent on the left side (63.6%). The thrombus involved the inferior vena cava and was associated with adrenal hemorrhage in 43.7% and 14.8% of neonates, respectively. Forty percent of the patients were treated conservatively with supportive care alone. Among those patients who received anticoagulation therapy, unfractionated heparin and low molecular weight heparin were used alone in 21.6% and 20.7% of the patients, respectively. Fibrinolytic treatment alone was used in 11.2% of the patients. Only a minority of patients were treated with antithrombin (1.7%), warfarin alone, (0.9%) or underwent surgical intervention (0.3%). The majority (70.6%) of the involved kidneys became atrophic. A total of 9 neonates died with non-renal vein thrombosis-related conditions during the study period. Evidence-based recommendations on treatment cannot be made at the present time. Cooperative prospective studies that involve multiple centers are needed to elucidate the optimal treatment for neonatal renal vein thrombosis.
Asunto(s)
Venas Renales/patología , Trombosis de la Vena/epidemiología , Trombosis de la Vena/terapia , Humanos , Recién Nacido , Enfermedades Renales/complicaciones , Enfermedades Renales/epidemiología , Enfermedades Renales/terapia , Trombosis de la Vena/complicacionesRESUMEN
Thrombosis occurs in 37% of children with acute lymphoblastic leukaemia (ALL) and is related to an L-asparaginase-induced acquired antithrombin (AT) deficiency. The incidence dictates the need for anticoagulant prophylaxis. Direct thrombin inhibitors (DTI) are independent of AT for effect and may thus have advantages in this population. The objective of this study was to determine the interaction of an AT deficiency with the anticoagulant effects of a DTI and a low molecular weight heparin (LMWH). Plasma samples from children with ALL were pooled (mean AT 0.53 U/ml). LMWH 0.3 and 0.7 U/ml or melagatran 0.3 and 0.5 micromol/l were added to the pools, then divided and AT was added back to one aliquot. In additional experiments, AT was added to AT immuno-depleted plasma. Endogenous thrombin generation capacity (ETGC) was assessed by the continuous method. In plasma with LMWH, there was a 66-88% decrease in ETGC in AT-normalised samples compared with neat. Conversely, no significant difference in ETGC with or without AT added for melagatran was seen. Experiments with AT-depleted plasma showed no effect of AT level on anticoagulant activity of DTI, but a significant relationship for LMWH. By contrast to LMWH, DTI provides a consistent anticoagulant response independent of AT levels in children with AT deficiency.
Asunto(s)
Deficiencia de Antitrombina III/terapia , Antitrombinas/uso terapéutico , Asparaginasa/efectos adversos , Azetidinas/uso terapéutico , Bencilaminas/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Deficiencia de Antitrombina III/sangre , Deficiencia de Antitrombina III/inducido químicamente , Asparaginasa/uso terapéutico , Células Cultivadas , Niño , Preescolar , Humanos , Lactante , Modelos Lineales , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Estadísticas no Paramétricas , Trombina/metabolismoRESUMEN
BACKGROUND: It is important to measure the quality of life (QoL) of boys with haemophilia, because the diagnosis has a significant impact on their lives and this impact fluctuates over time. A disease-specific measure of QoL is required because the aspects of life that are affected by haemophilia may differ from those assessed by generic QoL measures. This paper describes the final phase of development of a disease-specific measure of QoL for boys with haemophilia: the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT). PROCEDURE: A 79-item version of the CHO-KLAT was administered to 52 children. A detailed item analysis was conducted to shorten the CHO-KLAT. The reliability of the revised version was assessed using intraclass correlation coefficients. Validity was assessed by comparing it to the PedsQL and the HaemoQoL. RESULTS: The item analysis resulted in the retention of 35 strongly performing items (CHO-KLAT(35)). These items were aggregated into the CHO-KLAT(35) summary score. Repeated measures reliability of the CHO-KLAT(35) was 0.74 for children and 0.83 for parents, and the child-parent concordance was 0.75. The validity of the CHO-KLAT(35) was confirmed by a correlation of 0.78 with the Haemo-QoL and of 0.59 with the PedsQL. CONCLUSIONS: The CHO-KLAT(35) is a reliable and valid measure of QoL for boys with haemophilia.
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Antibacterianos/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/psicología , Hemofilia B/tratamiento farmacológico , Hemofilia B/psicología , Calidad de Vida , Adolescente , Profilaxis Antibiótica , Canadá , Niño , Preescolar , Estado de Salud , Hemofilia A/diagnóstico , Hemofilia B/diagnóstico , Humanos , Masculino , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
An association has been reported between thrombotic events and the use of L-asparaginase (ASP) in children with acute lymphoblastic leukaemia (ALL). The mechanism for thrombosis is likely related to an acquired antithrombin deficiency. Since a primary prophylaxis using antithrombin concentrates may prevent thrombosis, the PARKAA (Prophylactic Antithrombin replacement in kids with ALL treated with L-asparaginase) study was performed. The objectives of PARKAA were to determine if there was a trend to efficacy and safety of antithrombin treatment as assessed by 1) incidence of thrombosis 2) incidence of bleeding and 3) plasma markers of endogenous thrombin generation as surrogate outcomes for thrombosis. The study was not powered to answer the question of efficacy and safety, but rather to detect a trend. PARKAA was an open, randomised, controlled study in children with ALL being treated with ASP. Children were randomised to receive antithrombin infusions or no antithrombin treatment. All thrombotic events were confirmed using bilateral venography, ultrasound, echocardiography and MRI. The incidence of thrombosis in patients treated with antithrombin was 28% (95% CI 10-46%), compared to 37% (95% CI 24-49%) in the non treated arm. Two minor bleeds occurred in patients in the treated arm, but were not considered to be related to antithrombin. No significant differences were seen in plasma markers by the treatment group. In conclusion, treatment with antithrombin concentrate shows a trend to efficacy and safety. In contrast, there was no difference in surrogate markers for thrombosis. Carefully designed clinical trials are needed to test the efficacy and safety of antithrombin in this population.
Asunto(s)
Antineoplásicos/uso terapéutico , Antitrombinas/uso terapéutico , Asparaginasa/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Trombosis/prevención & control , Adolescente , Antitrombinas/efectos adversos , Antitrombinas/metabolismo , Niño , Preescolar , Trombosis Coronaria/epidemiología , Femenino , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Incidencia , Lactante , Trombosis Intracraneal/epidemiología , Masculino , Método Simple Ciego , Trombosis/epidemiología , Resultado del Tratamiento , Trombosis de la Vena/epidemiologíaRESUMEN
PURPOSE: Immune thrombopenic purpura (ITP) is an important childhood hematologic disorder that is often frightening to patients and their parents because of its acute onset and bleeding symptoms. There is no consensus on the management of ITP in children. Pediatric hematologists have differing management philosophies, yet most, explicitly or implicitly, incorporate into their management approach the potential impact on the child's and family's quality of life. There is no validated ITP-specific health-related quality-of-life instrument for use with children with ITP, nor is there one to evaluate the burden experienced by their parents. ITP is usually a self-limited disorder. With current controversy over management approaches, an evaluation of the disease burden experienced by the child and the family may assist with the assessment of alternative treatment approaches. METHODS: Using standard clinimetric methodology, 88 children with acute or chronic ITP, along with their parents, participated in the development of the instruments. RESULTS: The 26-item ITP-Child Quality-of-Life Questionnaire includes five domains: treatment side effect-related, intervention-related, disease-related, activity-related, and family-related. This instrument can be used as a self-completed instrument for most children older than 7 years or as a proxy-completed instrument by parents of children younger than 7 years. The 26-item ITP-Parental Burden Quality-of-Life Questionnaire includes six domains: concerns related to diagnosis/investigation, treatment/disease monitoring, monitoring of child's activities, interference with daily life, disease outcome, and emotional impacts. CONCLUSIONS: The first steps of the development of these formally developed instruments are complete. The instruments are available for study to validate and test their responsiveness through use in clinical research studies. Such instruments are increasingly recognized as important for comprehensive measurement of patient outcomes in this and other areas of pediatric hematology/oncology practice.
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Indicadores de Salud , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/terapia , Calidad de Vida , Encuestas y Cuestionarios , Adolescente , Canadá , Niño , Preescolar , Estudios de Evaluación como Asunto , Femenino , Estado de Salud , Humanos , Lactante , Masculino , Padres/psicología , Recuento de Plaquetas , Reproducibilidad de los Resultados , Proyectos de Investigación , Estados UnidosRESUMEN
Deep vein thrombosis (DVT) in children occurs primarily in the upper body venous system. This prospective diagnostic study compared bilateral venography and ultrasound for detection of DVT in the upper venous system in 66 children with acute lymphoblastic leukemia. Results were interpreted by central blinded adjudication. Deep venous thrombosis occurred in 29% (19/66) patients. While 15/19 DVT were detected by venography (sensitivity 79%), only 7/19 were detected by ultrasound (sensitivity 37%). The 12 DVT detected by venography but not by ultrasound were located in the subclavian vein or more central veins. Three of 4 DVT detected by ultrasound but not by venography were in the jugular vein. We conclude that ultrasound is insensitive for DVT in the central upper venous system but may be more sensitive than venography in the jugular veins. A combination of both venography and ultrasound is required for screening for DVT in the upper venous system.