RESUMO
Master regulators, such as the hematopoietic transcription factor (TF) GATA1, play an essential role in orchestrating lineage commitment and differentiation. However, the precise mechanisms by which such TFs regulate transcription through interactions with specific cis-regulatory elements remain incompletely understood. Here, we describe a form of congenital hemolytic anemia caused by missense mutations in an intrinsically disordered region of GATA1, with a poorly understood role in transcriptional regulation. Through integrative functional approaches, we demonstrate that these mutations perturb GATA1 transcriptional activity by partially impairing nuclear localization and selectively altering precise chromatin occupancy by GATA1. These alterations in chromatin occupancy and concordant chromatin accessibility changes alter faithful gene expression, with failure to both effectively silence and activate select genes necessary for effective terminal red cell production. We demonstrate how disease-causing mutations can reveal regulatory mechanisms that enable the faithful genomic targeting of master TFs during cellular differentiation.
Assuntos
Anemia , Fator de Transcrição GATA1 , Diferenciação Celular/genética , Cromatina/genética , Imunoprecipitação da Cromatina , Eritropoese/genética , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , HumanosRESUMO
We describe Hb Alcorn County, a heterozygous hemoglobin (Hb) variant, in a 6-month-old Hispanic male and his mother. DNA sequencing demonstrated a mutation on the HBB gene [ß40(C6)ArgâThr; HBB: c.122G>C (p.Arg41Thr)], predictive of a substitution of arginine to threonine at position 40 of the ß-globin protein. This amino acid substitution involves the α1ß2 contact and occurs at the same position as Hb Austin [ß40(C6)ArgâSer; HBB: c.[123G>C or 123G>T] (p.Arg41Ser)] and Hb Athens-GA [ß40(C6)ArgâLys; HBB: c.122G>A (p.Arg41Lys)], both of which show increased oxygen affinity.
Assuntos
Alelos , Substituição de Aminoácidos , Mutação , Oxigênio/metabolismo , Globinas beta/genética , Globinas beta/metabolismo , Cromatografia Líquida de Alta Pressão , Análise Mutacional de DNA , Predisposição Genética para Doença , Genótipo , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinopatias/metabolismo , Humanos , Lactente , Masculino , Fenótipo , Ligação Proteica , Globinas beta/análiseRESUMO
In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Nonrandomized participants from the silent cerebral infarct transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event (stroke, seizure or transient ischemic attack), start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in nontransfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, P = .065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062-0.858; P = .029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification.
Assuntos
Anemia Falciforme/complicações , Infarto Cerebral , Acidente Vascular Cerebral/etiologia , Ultrassonografia Doppler Transcraniana , Adolescente , Criança , Pré-Escolar , Humanos , Incidência , Ataque Isquêmico Transitório , Estudos Prospectivos , ConvulsõesRESUMO
Importance: Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated. Objective: To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Design, Setting, and Participants: Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Interventions: Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks. Main Outcomes and Measures: Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 µg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects. Results: Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P < .001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P < .001) with ferrous sulfate. Mean total iron-binding capacity decreased from 501 to 389 µg/dL (ferrous sulfate) vs 506 to 417 µg/dL (iron complex) (a greater difference of -50 µg/dL [95% CI, -86 to -14 µg/dL] with ferrous sulfate; P < .001). There were more reports of diarrhea in the iron complex group than in the ferrous sulfate group (58% vs 35%, respectively; P = .04). Conclusions and Relevance: Among infants and children aged 9 to 48 months with nutritional iron-deficiency anemia, ferrous sulfate compared with iron polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional iron-deficiency anemia. Trial Registration: clinicaltrials.gov Identifier: NCT01904864.
Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/tratamento farmacológico , Transtornos da Nutrição Infantil/complicações , Compostos Ferrosos/farmacologia , Hemoglobina A/efeitos dos fármacos , Compostos de Ferro/farmacologia , Polissacarídeos/farmacologia , Anemia Ferropriva/etiologia , Pré-Escolar , Método Duplo-Cego , Feminino , Ferritinas/sangue , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/efeitos adversos , Hemoglobina A/metabolismo , Humanos , Lactente , Ferro/metabolismo , Compostos de Ferro/administração & dosagem , Compostos de Ferro/efeitos adversos , Perda de Seguimento , Masculino , Adesão à Medicação/estatística & dados numéricos , Polissacarídeos/administração & dosagem , Polissacarídeos/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the benefits and risks of intravenous (IV) ferric carboxymaltose (FCM) in children with iron deficiency anemia (IDA). STUDY DESIGN: In a retrospective cohort study of patients seen at our center, we identified all FCM infusions in children with IDA over a 12-month period through a query of pharmacy records. Clinical data, including hematologic response and adverse effects, were extracted from the electronic medical record. RESULTS: A total of 116 IV FCM infusions were administered to 72 patients with IDA refractory to oral iron treatment (median age, 13.7 years; range, 9 months to 18 years). Median preinfusion and postinfusion hemoglobin values were 9.1 g/dL and 12.3 g/dL, respectively (at 4-12 weeks after the initial infusion; n = 53). Sixty-five patients (84%) experienced no adverse effects. Minor transient complications were encountered during or immediately after 7 infusions. CONCLUSION: FCM administered as a short IV infusion without a test dose proved to be safe and highly effective in a small yet diverse population of infants, children, and adolescents with IDA refractory to oral iron therapy.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/administração & dosagem , Maltose/análogos & derivados , Administração Oral , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Infusões Intravenosas , Ferro/administração & dosagem , Masculino , Maltose/administração & dosagem , Estudos Retrospectivos , Resultado do TratamentoRESUMO
STUDY OBJECTIVE: To assess the clinical severity and initial treatment of iron deficiency anemia (IDA) in female adolescents with heavy menstrual bleeding (HMB) in our center. DESIGN: Retrospective cohort study of electronic medical records via search of administrative records using International Classification of Diseases Ninth Revision codes for IDA or unspecified anemia and disorders of menstruation. SETTING: Children's Medical Center in Dallas, Texas. PARTICIPANTS: One hundred seven patients with HMB and concomitant IDA (median age, 14.4 years) who presented to the outpatient, emergency department, and/or inpatient settings. RESULTS: The median initial hemoglobin concentration for all patients (n = 107) was 7.4 g/dL, and most (74%, n = 79) presented to the emergency department or via inpatient transfer. Symptomatic IDA was treated with blood transfusion in 46 (43%, n = 46). Ferrous sulfate was the most commonly prescribed oral iron therapy. Seven patients received intravenous iron therapy either initially or after oral iron treatment failure. Combined oral contraceptives were commonly prescribed for abnormal uterine bleeding, yet 10% of patients (n = 11) received no hormonal therapy during their initial management. Evaluation for underlying bleeding disorders was inconsistent. CONCLUSION: Severe anemia because of IDA and HMB resulting in urgent medical care, including hospitalization and blood transfusion, is a common but underemphasized problem in adolescent girls. In addition to prevention and early diagnosis, meaningful efforts to improve initial management of adolescents with severe HMB and IDA are necessary.
Assuntos
Anemia Ferropriva/terapia , Menorragia/terapia , Adolescente , Anemia Ferropriva/sangue , Anemia Ferropriva/etiologia , Transfusão de Sangue/métodos , Transfusão de Sangue/estatística & dados numéricos , Criança , Anticoncepcionais Orais Combinados/uso terapêutico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Compostos Ferrosos/administração & dosagem , Hemoglobinas/análise , Hospitalização , Humanos , Ferro/sangue , Masculino , Menorragia/sangue , Menorragia/complicações , Estudos Retrospectivos , TexasRESUMO
Limited high-quality evidence supports the management of iron deficiency anemia (IDA). To assess our institutional performance in this area, we retrospectively reviewed IDA treatment practices in 195 consecutive children referred to our center from 2006 to mid-2010. The majority of children were ≤4 years old (64%) and had nutritional IDA (74%). In 11- to 18-year-old patients (31%), the primary etiology was menorrhagia (42%). Many were referred directly to the emergency department and/or prescribed iron doses outside the recommended range. Poor medication adherence and being lost-to-follow-up were common. Substantial improvements are required in the management of IDA.
Assuntos
Anemia Ferropriva/diagnóstico , Anemia Ferropriva/tratamento farmacológico , Ferro/administração & dosagem , Adolescente , Anemia Ferropriva/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833.
Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Glicolipídeos/uso terapêutico , Doenças Vasculares/complicações , Doenças Vasculares/tratamento farmacológico , Adolescente , Adulto , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Time to opioid administration (TTO) has been suggested as a quality of care measure for sickle cell disease patients with vaso-occlusive crisis (VOC). We sought to determine whether TTO was associated with outcomes of emergency department (ED) visits for VOC. METHODS: We conducted a single-center retrospective cohort study of ED visits for VOC. The primary outcome was hospital admission, with secondary outcomes of change between the first 2 pain scores, area under the curve (AUC) for pain scores at 4 hours (pain score AUC), total ED length of stay, and total intravenous opioids. In both univariate and multivariate analyses, mixed regression (logistic for admission, linear for secondary outcome variables) was used to evaluate association of TTO with outcome. RESULTS: In 177 subjects, 414 ED visits for VOC were identified. Inpatient admission occurred in 53% of visits. The median TTO for admitted patients was 86 minutes vs 87 minutes for those not admitted. TTO was not associated with inpatient admission in either univariate or multivariate analyses. In multivariate analyses with secondary outcomes, decreased TTO was associated with greater improvement between the first 2 pain scores, decreased pain score AUC, decreased total ED length of stay, and increased total opioids. CONCLUSIONS: Although TTO was not associated with admission, it was independently associated with 4 important secondary outcomes: change in initial pain scores, pain score AUC, total ED length of stay, and total intravenous opioids. The association of a process measure, TTO, with these outcomes encourages the institution of TTO reduction efforts in the ED.
Assuntos
Analgésicos Opioides/administração & dosagem , Anemia Falciforme/complicações , Dor/tratamento farmacológico , Indicadores de Qualidade em Assistência à Saúde , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Masculino , Dor/etiologia , Medição da Dor , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Iron deficiency anemia (IDA) is the most common hematologic condition in children and adolescents in the United States (US). No prior reports have described the management of IDA by a large cohort of pediatric hematology/oncology specialists. PROCEDURE: A 20-question electronic survey that solicited responses to two hypothetical cases of IDA was sent to active members of the American Society of Pediatric Hematology/Oncology (ASPHO) in the US. RESULTS: Of 1,217 recipients, 398 (32.7%) reported regularly treating IDA and completed the survey. In a toddler with nutritional IDA, 15% (N = 61) of respondents reported ordering no diagnostic test beyond a complete blood count. Otherwise, wide variability in laboratory testing was reported. For treatment, most respondents would prescribe ferrous sulfate (N = 335, 84%) dosed at 6 mg/kg/day (N = 248, 62%) divided twice daily (N = 272, 68%). The recommended duration of iron treatment after resolution of anemia and normalized serum ferritin varied widely from 0 to 3 months. For an adolescent with heavy menstrual bleeding and IDA, most respondents recommended ferrous sulfate (N = 327, 83%), with dosing based on the number of tablets daily. For IDA refractory to oral treatment, intravenous iron therapy was recommended most frequently, 48% (N = 188) using iron sucrose, 17% (N = 68) ferric gluconate, and 15% (N = 60) low molecular weight iron dextran. CONCLUSION: The approach to diagnosis and treatment of IDA in childhood was widely variable among responding ASPHO members. Given the lack of an evidence base to guide clinical decision making, further research investigating IDA management is needed.
Assuntos
Anemia Ferropriva/prevenção & controle , Hematologia , Ferro/administração & dosagem , Oncologia , Adolescente , Anemia Ferropriva/sangue , Estudos Transversais , Gerenciamento Clínico , Feminino , Ferritinas/sangue , Seguimentos , Humanos , Lactente , Deficiências de Ferro , Masculino , Prognóstico , Especialização , Inquéritos e QuestionáriosRESUMO
Infantile myofibromatosis (IM) is most commonly limited to cutaneous lesions that resolve spontaneously. However, generalized IM with visceral involvement, which has a reported mortality rate as high as 73%, has been successfully treated with a combination of methotrexate and vinblastine. Here we report the further efficacy of low-dose methotrexate and vinblastine in 2 pediatric patients with IM and visceral involvement and review the literature describing chemotherapy for these patients.
Assuntos
Antineoplásicos/uso terapêutico , Metotrexato/uso terapêutico , Miofibromatose/congênito , Vincristina/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Miofibromatose/tratamento farmacológico , Miofibromatose/patologia , Vísceras/patologiaRESUMO
BACKGROUND: Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care. METHODS: In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS: A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04). CONCLUSIONS: Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).
Assuntos
Anemia Falciforme/terapia , Transfusão de Sangue , Infarto Cerebral/prevenção & controle , Adolescente , Anemia Falciforme/complicações , Infarto Cerebral/etiologia , Criança , Pré-Escolar , Feminino , Ferritinas/sangue , Hemoglobina Falciforme/análise , Humanos , Inteligência , Análise de Intenção de Tratamento , Masculino , Prevenção Secundária , Método Simples-Cego , Reação TransfusionalRESUMO
BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder characterized by a chronic hemolytic anemia that can contribute to fatigue and global cognitive impairment in patients. The study objective was to report on the feasibility, reliability, and validity of the PedsQL™ Multidimensional Fatigue Scale in SCD for pediatric patient self-report ages 5-18 years and parent proxy-report for ages 2-18 years. PROCEDURE: This was a cross-sectional multi-site study whereby 240 pediatric patients with SCD and 303 parents completed the 18-item PedsQL™ Multidimensional Fatigue Scale. Participants also completed the PedsQL™ 4.0 Generic Core Scales. RESULTS: The PedsQL™ Multidimensional Fatigue Scale evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.90; parent proxy-report α = 0.95), and acceptable reliability for the three individual scales (patient self-report α = 0.77-0.84; parent proxy-report α = 0.90-0.97). Intercorrelations of the PedsQL™ Multidimensional Fatigue Scale with the PedsQL™ Generic Core Scales were predominantly in the large (≥0.50) range, supporting construct validity. PedsQL™ Multidimensional Fatigue Scale Scores were significantly worse with large effects sizes (≥0.80) for patients with SCD than for a comparison sample of healthy children, supporting known-groups discriminant validity. Confirmatory factor analysis demonstrated an acceptable to excellent model fit in SCD. CONCLUSIONS: The PedsQL™ Multidimensional Fatigue Scale demonstrated acceptable to excellent measurement properties in SCD. The results demonstrate the relative severity of fatigue symptoms in pediatric patients with SCD, indicating the potential clinical utility of multidimensional assessment of fatigue in patients with SCD in clinical research and practice.
Assuntos
Anemia Falciforme/complicações , Fadiga/diagnóstico , Psicometria/instrumentação , Índice de Gravidade de Doença , Adolescente , Anemia Falciforme/psicologia , Criança , Pré-Escolar , Estudos Transversais , Fadiga/etiologia , Fadiga/psicologia , Estudos de Viabilidade , Humanos , Lactente , Pais , Qualidade de Vida , Reprodutibilidade dos Testes , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Existing therapies for recurrent or refractory histiocytoses, including Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), and Rosai-Dorfman disease (RDD), have limited effectiveness. We report our experience with using clofarabine as therapy in children with recurrent or refractory histiocytic disorders, including LCH (11 patients), systemic JXG (4 patients), and RDD (3 patients). METHODS: Patients treated with clofarabine for LCH, JXG, or RDD by Texas Children's Hospital physicians or collaborators between May 2011 and January 2013 were reviewed for response and toxicity. RESULTS: Patients were treated with a median of three chemotherapeutic regimens prior to clofarabine. Clofarabine was typically administered at 25 mg/m(2) /day for 5 days. Cycles were administered every 28 days for a median of six cycles (range: 2-8 cycles). Seventeen of 18 patients are alive. All surviving patients showed demonstrable improvement after two to four cycles of therapy, with 11 (61%) complete responses, 4 (22%) partial responses, and 2 patients still receiving therapy. Five patients experienced disease recurrence, but three of these subsequently achieved complete remission. All patients with JXG and RDD had complete or partial response at conclusion of therapy. Side effects included neutropenia in all patients. Recurring but sporadic toxicities included prolonged neutropenia, severe vomiting, and bacterial infections. CONCLUSION: Clofarabine has activity against LCH, JXG, and RDD in heavily pretreated patients, but prospective multi-center trials are warranted to determine long-term efficacy, optimal dosing, and late toxicity of clofarabine in this population.
Assuntos
Nucleotídeos de Adenina/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Arabinonucleosídeos/uso terapêutico , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose Sinusal/tratamento farmacológico , Terapia de Salvação , Xantogranuloma Juvenil/tratamento farmacológico , Nucleotídeos de Adenina/administração & dosagem , Nucleotídeos de Adenina/efeitos adversos , Adolescente , Arabinonucleosídeos/administração & dosagem , Arabinonucleosídeos/efeitos adversos , Criança , Pré-Escolar , Clofarabina , Feminino , Humanos , Lactente , Masculino , RecidivaRESUMO
BACKGROUND: Iron deficiency anemia (IDA) in children is usually treated with oral iron, yet many respond poorly. Intravenous low molecular weight iron dextran (LMWID) offers the opportunity of employing a single outpatient infusion to correct the anemia and reduce the overall burden of treatment, but its use in children has been limited due to concerns of serious adverse effects. In this study we report our initial experience using LMWID in children with iron deficiency in whom oral iron was ineffective. METHODS: We performed a case series of LMWID treatment of children with IDA of diverse etiologies who were poorly responsive to oral iron therapy with the aim of measuring its efficacy and adverse effects. LMWID was administered as a total dose infusion over 60 minutes in the outpatient setting. RESULTS: Thirty-one patients age 11 months to 18 years received intravenous LMWID, and 24 were evaluable for hematologic response. Median hemoglobin increments were respectively 3.5, 1.9, and 1.8 g/dl in patients with IDA due to poor nutrition (n = 11), chronic blood loss (n = 13), and miscellaneous causes (n = 7). Two thirds of evaluable patients had a complete hematologic response. Nine of the patients (29%) had mild non-specific adverse effects upon initiation of the LMWID infusion. CONCLUSIONS: LMWID as a total dose infusion was well tolerated and effective in a heterogeneous group of children and adolescents with IDA who were refractory to oral iron therapy. Transient reactions were common but not serious.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Hematínicos/administração & dosagem , Complexo Ferro-Dextran/administração & dosagem , Adolescente , Criança , Pré-Escolar , Feminino , Hematínicos/efeitos adversos , Humanos , Lactente , Infusões Intravenosas , Complexo Ferro-Dextran/efeitos adversos , Masculino , Peso MolecularRESUMO
BACKGROUND: Sickle cell disease (SCD) is an inherited chronic disease that is characterized by complications such as recurrent painful vaso-occlusive events that require frequent hospitalizations and contribute to early mortality. The objective of the study was to report on the initial measurement properties of the new PedsQL™ SCD Module for pediatric patient self-report ages 5-18 years and parent proxy-report for ages 2-18 years. PROCEDURE: The 43-item PedsQL™ SCD Module was completed in a multisite study by 243 pediatric patients with SCD and 313 parents. Participants also completed the PedsQL™ 4.0 Generic Core Scales and PedsQL™ Multidimensional Fatigue Scale. RESULTS: The PedsQL™ SCD Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.95; parent proxy-report α = 0.97), and good reliability for the nine individual scales (patient self-report α = 0.69-0.90; parent proxy-report α = 0.83-0.97). Intercorrelations with the PedsQL™ Generic Core Scales and PedsQL™ Multidimensional Fatigue Scales were medium (0.30) to large (0.50) range, supporting construct validity. PedsQL™ SCD Module Scale Scores were generally worse for patients with severe versus mild disease. Confirmatory factor analysis demonstrated an acceptable to excellent model fit. CONCLUSIONS: The PedsQL™ SCD Module demonstrated acceptable measurement properties. The PedsQL™ SCD Module may be utilized in the evaluation of SCD-specific health-related quality of life in clinical research and practice. In conjunction with the PedsQL™ Generic Core Scales and the PedsQL™ Multidimensional Fatigue Scale, the PedsQL™ SCD Module will facilitate the understanding of the health and well-being of children with SCD.
Assuntos
Anemia Falciforme , Autorrelato , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Time-to-antibiotic (TTA) administration is a widely used quality-of-care measure for children with cancer and febrile neutropenia (FN). We sought to determine whether TTA is associated with outcomes of FN. PROCEDURE: A single-center, retrospective cohort study was conducted of 1,628 FN admissions from 653 patients from 2001 to 2009. Outcome variables included (1) an adverse event (AE) composite of in-hospital mortality, pediatric intensive care unit (PICU) admission within 24 hours of presentation, and/or fluid resuscitation ≥ 40 ml/kg within 24 hours of presentation and (2) length of stay (LOS). TTA was measured as a continuous variable and in 60-minute intervals. Mixed regression models were constructed to evaluate associations of TTA with the outcome variables after adjusting for relevant covariates including cancer diagnosis, degree of myelosuppression, and presence of bacteremia. RESULTS: The composite AE outcome occurred in 11.1% of admissions including 0.7% in-hospital mortality, 4.7% PICU admission, and 10.1% fluid resuscitation. In univariate analysis, TTA was associated with the composite AE outcome (Odds Ratio [OR] 1.29, 95% CI 1.02-1.64) but not LOS. In multivariate analysis, after adjustment for relevant covariates, 60-minute TTA intervals were associated with the composite AE outcome (61-120 minutes vs. ≤ 60 minutes, OR 1.81, 95% CI 1.01-3.26). Unexpectedly, admission from the emergency department (ED) was also independently associated with the composite AE outcome (ED vs. clinic, OR 3.15, 95% CI 1.95-5.09). CONCLUSIONS: TTA and presentation to the ED are independently associated with poor outcomes of FN.
Assuntos
Antibacterianos/administração & dosagem , Mortalidade Hospitalar , Modelos Biológicos , Neoplasias/mortalidade , Neutropenia/tratamento farmacológico , Neutropenia/mortalidade , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Tempo de Internação , Masculino , Neoplasias/complicações , Neoplasias/terapia , Neutropenia/etiologia , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Since the publication of the Prophlyactic Penicillin Study II in 1995, the management of penicillin prophylaxis for children with sickle cell disease (SCD) after 5 years of age has been controversial. In this study, we sought to describe current practice patterns of pediatric hematologists related to cessation of penicillin prophylaxis for children with SCD after 5 years of age. PROCEDURE: We performed a cross-sectional, electronic survey of pediatric hematologists with expertise in SCD to examine practices regarding penicillin prophylaxis in children with SCD after 5 years of age. We also investigated factors potentially associated with continuation of penicillin prophylaxis using the Jonckheere-Terpstra test and Fisher's exact test. RESULTS: Of the 106 physicians surveyed from 76 centers, 84% completed the survey. Among respondents, 76% routinely recommended cessation of penicillin prophylaxis after 5 years of age. The practice of routinely continuing penicillin after 5 years of age was associated with decreased concern about antibiotic resistance in Streptococcus pneumoniae (P = 0.01), with the usage of prophylactic penicillin in mild SCD genotypes (sickle hemoglobin-C disease and sickle ß(+) thalassemia, P = <0.001), and with increasing use of other preventive evaluations (e.g., MRI for silent stroke) in childhood (P = 0.05). CONCLUSION: Most pediatric hematologists with an SCD expertise recommend cessation of prophylactic penicillin after 5 years of age.
Assuntos
Anemia Falciforme/complicações , Antibioticoprofilaxia/estatística & dados numéricos , Penicilinas/uso terapêutico , Infecções Pneumocócicas/prevenção & controle , Padrões de Prática Médica/estatística & dados numéricos , Criança , Pré-Escolar , Estudos Transversais , Humanos , Médicos , Infecções Pneumocócicas/complicaçõesRESUMO
BACKGROUND: The success of primary stroke prevention for children with sickle cell disease (SCD) throughout the United States is unknown. Therefore, we aimed to generate national incidence rates of hospitalization for stroke in children with sickle cell disease (SCD) before and after publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998. PROCEDURE: We performed a retrospective trend analysis of the 1993-2009 Nationwide Inpatient Sample and Kids' Inpatient Databases. Hospitalizations for SCD patients 0-18 years old with stroke were identified by ICD-9CM code. The primary outcome, the trend in annual incidence rate of hospitalization for stroke in children with SCD, was analyzed by linear regression. Incidence rates of hospitalization for stroke before and after 1998 were compared by the Wilcoxon rank-sum test. RESULTS: From 1993 to 2009, 2,024 hospitalizations were identified for stroke. Using the mean annual incidence rate of hospitalization for stroke from 1993 to 1998 as the baseline, the rate decreased from 1993 to 2009 (point estimate = -0.022/100 patient years [95% CI, -0.039, -0.005], P = 0.027). The mean annual incidence rate of hospitalization stroke decreased by 45% from 0.51 per 100 patient years in 1993-1998 to 0.28 per 100 patient years in 1999-2009 (P = 0.008). Total hospital days and charges attributed to stroke also decreased by 45% and 24%, respectively. CONCLUSIONS: After publication of the STOP trial and hydroxyurea licensure in 1998, the incidence of hospitalization for stroke in children with SCD decreased across the United States, suggesting that primary stroke prevention has been effective nationwide, but opportunity for improvement remains.