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The efficacy and safety of rivipansel, a predominantly E-selectin antagonist, were studied in a phase 3, randomized, controlled trial for vaso-occlusive crisis (VOC) requiring hospitalization (RESET). A total of 345 subjects (204 adults and 141 children) were randomized and 320 were treated (162 with rivipansel, 158 with placebo) with an IV loading dose, followed by up to 14 additional 12-hourly maintenance doses of rivipansel or placebo, in addition to standard care. Rivipansel was similarly administered during subsequent VOCs in the Open-label Extension (OLE) study. In the full analysis population, the median time to readiness for discharge (TTRFD), the primary end point, was not different between rivipansel and placebo (-5.7 hours, P = .79; hazard ratio, 0.97), nor were differences seen in secondary end points of time to discharge (TTD), time to discontinuation of IV opioids (TTDIVO), and cumulative IV opioid use. Mean soluble E-selectin decreased 61% from baseline after the loading dose in the rivipansel group, while remaining unchanged in the placebo group. In a post hoc analysis, early rivipansel treatment within 26.4 hours of VOC pain onset (earliest quartile of time from VOC onset to treatment) reduced median TTRFD by 56.3 hours, reduced median TTD by 41.5 hours, and reduced median TTDIVO by 50.5 hours, compared with placebo (all P < .05). A similar subgroup analysis comparing OLE early-treatment with early-treatment RESET placebo showed a reduction in TTD of 23.1 hours (P = .062) and in TTDIVO of 30.1 hours (P = .087). Timing of rivipansel administration after pain onset may be critical to achieving accelerated resolution of acute VOC. Trial Registration: Clinicaltrials.gov, NCT02187003 (RESET), NCT02433158 (OLE).
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Anemia Falciforme , Hemoglobinopatias , Compostos Orgânicos Voláteis , Adulto , Criança , Humanos , Selectina E/uso terapêutico , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Compostos Orgânicos Voláteis/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Analgésicos Opioides/uso terapêutico , Método Duplo-CegoRESUMO
BACKGROUND: Red blood cell transfusion is an effective treatment for patients with sickle cell disease (SCD). Alloimmunization can occur after a single transfusion, limiting further usage of blood transfusion. It is recommended to match for the ABO, D, C, E, and K antigens to reduce risks of alloimmunization. However, availability of compatible blood units can be challenging for blood providers with a limited number of Black donors. STUDY DESIGN AND METHODS: A prospective cohort of 205 pediatric patients with SCD was genotyped for the RH and FY genes. Transfusion and alloimmunization history were collected. Our capacity to find RhCE-matched donors was evaluated using a database of genotyped donors. RESULTS: Nearly 9.8% of patients carried a partial D variant and 5.9% were D-. Only 45.9% of RHCE alleles were normal, with the majority of variants affecting the RH5 (e) antigen. We found an alloimmunization prevalence of 20.7% and a Rh alloimmunization prevalence of 7.1%. Since Black donors represented only 1.40% of all blood donors in our province, D- Caucasian donors were mostly used to provide phenotype matched products. Compatible blood for patients with rare Rh variants was found only in Black donors. A donor with compatible RhCE could be identified for all patients. CONCLUSION: Although Rh-compatible donors were identified, blood units might not be available when needed and/or the extended phenotype or ABO group might not match the patient. A greater effort has to be made for the recruitment of Black donors to accommodate patients with SCD.
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Anemia Hemolítica Autoimune , Anemia Falciforme , Humanos , Criança , Genótipo , Estudos Prospectivos , Sistema do Grupo Sanguíneo Rh-Hr/genética , Anemia Falciforme/genética , Anemia Falciforme/terapia , Doadores de Sangue , Sistema ABO de Grupos Sanguíneos/genética , IsoanticorposRESUMO
Classification of inherited bone marrow failure syndromes (IBMFSs) according to clinical and genetic diagnoses enables proper adjustment of treatment. Unfortunately, 30% of patients enrolled in the Canadian Inherited Marrow Failure Registry (CIMFR) with features suggesting hereditability could not be classified with a specific syndromic diagnosis. We analyzed the outcome of hematopoietic stem cell transplantation (HSCT) in unclassified IBMFSs (uIBMFSs) and the factors associated with outcome. Twenty-two patients with uIBMFSs and 70 patients with classified IBMFSs underwent HSCT. Five-year overall survival of uIBMFS patients after HSCT was inferior to that of patients with classified IBMFSs (56% vs 76.5%). The outcome of patients with uIBMFS who received cord blood was significantly lower than that of patients who received other stem cell sources (14.8% vs 90.9%). Engraftment failure was higher among patients with uIBMFS who received cord blood than those who received bone marrow. None of the following factors were significantly associated with poor survival: transfusion load, transplant indication, the intensity of conditioning regimen, human leukocyte antigen-identical sibling/alternative donor. We suggest that identifying the genetic diagnosis is essential to modulate the transplant procedure including conditioning agents and stem cell sources for better outcome and the standard cord blood transplantation (CBT) should be avoided in uIBMFS.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Medula Óssea , Canadá/epidemiologia , Síndrome Congênita de Insuficiência da Medula Óssea , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodosRESUMO
Intima-media thickness is a known subclinical radiologic marker of the early manifestations of atherosclerotic disease. It is the thickness of the vessel wall, most often the carotid artery. Intima-media thickness is measured on conventional US manually or automatically. Other measurement techniques include radiofrequency US. Because there is variation in its measurement, especially in children, several recommendations have been set to increase the measurement's validity and comparability among studies. Despite these recommendations, several pitfalls should be avoided, and quality control should be performed to avoid erroneous interpretation. This article summarizes current literature in relation to the clinical applications for intima-media thickness measurement in children with known risk factors such as obesity, liver steatosis, hypercholesterolemia, diabetes, hypertension, systemic inflammatory diseases, cancer survival, kidney and liver transplant, and sickle cell disease or beta thalassemia major. Most potential indications for intima-media thickness measurement remain in the research domain and should be interpreted combined with other markers. The objective of diagnosing an increased intima-media thickness is to start a multidisciplinary treatment approach to prevent disease progression and its sequelae in adulthood.
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Espessura Intima-Media Carotídea , Hipertensão , Adulto , Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Criança , Humanos , Fatores de RiscoRESUMO
Sickle cell disease (SCD) is a chronic, multi-system disease that requires comprehensive care. The sickling of red blood cells leads to hemolysis and vascular occlusion. Complications include hemolytic anemia, pain syndromes, and organ damage. Patterns of immigration and an increase in newborn screening mean that paediatric health care providers across Canada, in small and large centres alike, need to be knowledgeable about SCD. This statement focuses on principles of prevention, advocacy, and the rapid treatment of common acute complications. Guidance includes the current status of newborn screening, recommendations for immunizations and antibiotic prophylaxis, and an introduction to hydroxyurea, a medication that reduces both morbidity and mortality in children with SCD. Case vignettes demonstrate principles of care for common acute complications of SCD: vaso-occlusive episodes (VOE), acute chest syndrome (ACS), fever, splenic sequestration, aplastic crises, and stroke. Finally, principles of blood transfusion are highlighted, along with indications for both straight and exchange blood transfusions.
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L'anémie falciforme est une maladie multisystémique chronique qui exige des soins globaux. La falciformation des globules rouges entraîne une hémolyse et une occlusion vasculaire. L'anémie hémolytique, les syndromes douloureux et les atteintes organiques en sont des complications. En raison des profils d'immigration et d'une augmentation du dépistage néonatal, les professionnels de la santé pédiatrique du Canada doivent connaître l'anémie falciforme, tant dans les petits que les grands centres. Le présent document de principes porte sur les principes de prévention, de défense d'intérêts et de traitement rapide des complications aiguës courantes de l'anémie falciforme. Les lignes directrices comprennent l'état actuel du dépistage néonatal, les recommandations en matière de vaccination et de prophylaxie antibiotique et une introduction à l'hydroxyurée, un médicament qui réduit à la fois la morbidité et la mortalité chez les enfants atteints d'anémie falciforme. Des scénarios cliniques démontrent les principes de soins en cas de complications aiguës courantes : les épisodes vaso-occlusifs, le syndrome thoracique aigu, la fièvre, la séquestration splénique, les crises aplasiques et les accidents vasculaires cérébraux. Enfin, les principes de transfusion sanguine sont présentés, de même que les indications de transfusion simple ou d'exsanguinotransfusion.
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Previously, we showed that nearly 70% of children followed in our sickle cell disease (SCD) clinic were vitamin D- deficient and had low vitamin intake with poor use of supplements. We compared the change in serum 25-hydroxyvitamin D [25(OH)D], safety and clinical impact of two vitamin D supplementation regimens in children with SCD. Children (5-17 years, all genotypes) were randomized to a single bolus of vitamin D3 (300 000 IU; n = 18) or placebo (n = 20). All children received a prescription for daily 1 000 IU vitamin D3 . Serum 25(OH)D and calcium, urinary calcium/creatinine ratio, musculoskeletal pain, quality of life, haematology and bone markers were assessed at baseline and three months post intervention. Bolus administration led to a greater rise in 25(OH)D levels from baseline compared to placebo (20 ± 16 nmol/l vs. 2 ± 19 nmol/l; P = 0·003) and correction of vitamin D deficiency. No hypercalcaemia nor hypercalciuria occurred during the study, but more children in the bolus group experienced gastrointestinal symptoms within the first month (P = 0·04). There were no differences between groups for other outcomes. The use of a high-dose vitamin D bolus combined with daily 1 000 IU vitamin D3 was more efficient in raising 25(OH)D levels than daily supplementation alone in children with SCD.
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Anemia Falciforme/tratamento farmacológico , Colecalciferol/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Cálcio/sangue , Criança , Pré-Escolar , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Feminino , Humanos , Masculino , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Vitaminas/administração & dosagemRESUMO
Despite recent advances in immunotherapies, cytotoxic chemotherapy continues to be a first-line treatment option for the majority of cancers. Unfortunately, a common side effect in patients undergoing chemotherapy treatment is neutropenia. To mitigate the risk of neutropenia and febrile neutropenia, prophylactic treatment with granulocyte-colony stimulating factor (G-CSF) is administered. Extensive pharmacokinetic/pharmacodynamic modelling of myelosuppression during chemotherapy has suggested avenues for therapy optimization to mitigate this neutropenia. However, the issue of resonance, whereby neutrophil oscillations are induced by the periodic administration of cytotoxic chemotherapy and the coadministration of G-CSF, potentially aggravating a patient's neutropenic/neutrophilic status, is not well-characterized in the clinical literature. Here, through analysis of neutrophil data from young acute lymphoblastic leukaemia patients, we find that resonance is occurring during cyclic chemotherapy treatment in 26% of these patients. Motivated by these data and our previous modelling studies on adult lymphoma patients, we examined resonance during treatment with or without G-CSF. Using our quantitative systems pharmacology model of granulopoiesis, we show that the timing of cyclic chemotherapy can worsen neutropenia or neutrophilia, and suggest clinically-actionable schedules to reduce the resonant effect. We emphasize that delaying supportive G-CSF therapy to 6-7 days after chemotherapy can mitigate myelosuppressive effects. This study therefore highlights the importance of quantitative systems pharmacology for the clinical practice for developing rational therapeutic strategies.
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Neutropenia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fator Estimulador de Colônias de Granulócitos , Humanos , Neutropenia/induzido quimicamente , Neutrófilos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
BACKGROUND: The decision to initiate second-line treatment in children with immune thrombocytopenia (ITP) is complex and involves many different factors. METHODS: In this prospective, observational, longitudinal cohort study of 120 children from 21 centers, the factors contributing to the decision to start second-line treatments for ITP were captured. At study entry, clinicians were given a curated list of 12 potential reasons the patient required a second-line treatment. Clinicians selected all that applied and ranked the top three reasons. RESULTS: Quality of life (QOL) was the most frequently cited reason for starting a second-line therapy. Clinicians chose it as a reason to treat in 88/120 (73%) patients, as among the top three reasons in 68/120 (57%), and as the top reason in 32/120 (27%). Additional factors ranked as the top reason to start second-line treatment included severity of bleeding (22/120, 18%), frequency of bleeding (19/120, 16%), and severity of thrombocytopenia (18/120, 15%). Patients for whom QOL (p = .006) or sports participation (p = .02) were ranked reasons were more likely to have chronic ITP, whereas those for whom severity (p = .003) or frequency (p = .005) of bleeding were ranked reasons were more likely to have newly diagnosed or persistent ITP. Parental anxiety, though rarely the primary impetus for treatment, was frequently cited (70/120, 58%) as a contributing factor. CONCLUSION: Perceived QOL is the most frequently selected reason pediatric patients start second-line therapies for ITP. It is critical that studies of treatments for childhood ITP include assessments of their effects on QOL.
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Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/psicologia , Qualidade de Vida/psicologia , Adolescente , Criança , Pré-Escolar , Fadiga/psicologia , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controle , Humanos , Lactente , Estudos Longitudinais , Masculino , Contagem de Plaquetas , Estudos Prospectivos , Índice de Gravidade de Doença , Falha de TratamentoRESUMO
In busulfan-based conditioning regimen for hematopoietic stem cell transplantation in children, accurate a priori determination of the first dose is important because of its narrow therapeutic window. Sickle cell disease (SCD) influences pharmacokinetics of the commonly used drugs by affecting organs responsible for drug metabolism and elimination. This pharmacokinetics study assesses the influence of SCD on the metabolic pathway of busulfan that is mainly metabolized in the liver. In this retrospective cross-sectional case-control study, 16 patients with SCD were matched to 50 patients without SCD on known busulfan clearance's covariates (glutathione-S-transferase alpha1 polymorphisms, age, weight). Clearance of the first dose of busulfan was not significantly different independently of genetic or anthropometric factors in patients with or without SCD.
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Anemia Falciforme/metabolismo , Bussulfano/farmacocinética , Imunossupressores/farmacocinética , Adolescente , Adulto , Anemia Falciforme/terapia , Bussulfano/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunossupressores/metabolismo , Masculino , Redes e Vias Metabólicas , Estudos Retrospectivos , Condicionamento Pré-Transplante , Adulto JovemRESUMO
Immune thrombocytopenia (ITP), an acquired autoimmune disorder of low platelets and risk of bleeding, has a substantial impact on health-related quality of life (HRQoL). Patients with ITP often report significant fatigue, although the pathophysiology of this is poorly understood. In this observational cohort of 120 children receiving second-line therapies for ITP, we assessed reports of fatigue using the Hockenberry Fatigue Scale. Children and adolescents with ITP reported a similarly high level of fatigue with 54% (29/54) of children and 62% (26/42) of adolescents reporting moderate-to-severe fatigue. There was no correlation between fatigue and age or gender. Adolescents with newly diagnosed and persistent ITP had higher mean fatigue scores than those with chronic ITP (P = 0·03). Fatigue significantly improved in children and adolescents by 1 month after starting second-line treatments, and this improvement continued to be present at 12 months after starting treatment. Fatigue scores at all time-points correlated with general HRQoL using the Kids ITP Tool, but did not correlate with bleeding symptoms, platelet count, or platelet response to treatment. Fatigue is common in children and adolescents with ITP and may benefit from ITP-directed treatment even in the absence of bleeding symptoms.
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Fadiga , Púrpura Trombocitopênica Idiopática , Adolescente , Criança , Pré-Escolar , Fadiga/epidemiologia , Fadiga/etiologia , Fadiga/fisiopatologia , Fadiga/terapia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/fisiopatologia , Púrpura Trombocitopênica Idiopática/terapiaRESUMO
Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.
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Androgênios/uso terapêutico , Transtornos da Insuficiência da Medula Óssea/tratamento farmacológico , Adolescente , Adulto , Androgênios/efeitos adversos , Transtornos da Insuficiência da Medula Óssea/sangue , Transtornos da Insuficiência da Medula Óssea/genética , Transtornos da Insuficiência da Medula Óssea/terapia , Canadá/epidemiologia , Linhagem da Célula , Criança , Pré-Escolar , Terapia Combinada , Danazol/efeitos adversos , Danazol/uso terapêutico , Progressão da Doença , Substituição de Medicamentos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Oximetolona/efeitos adversos , Oximetolona/uso terapêutico , Pancitopenia/tratamento farmacológico , Pancitopenia/etiologia , Sistema de Registros , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Resultado do Tratamento , Virilismo/induzido quimicamenteRESUMO
BACKGROUND: Although erythropoiesis is impaired and anaemia frequent in neonates born preterm, haematopoiesis in adults born preterm has not been previously studied. OBJECTIVE: We, thus, aimed to evaluate haemoglobin and erythropoietin levels in young adults born preterm, to identify neonatal events associated with erythropoiesis in adulthood and to examine the relationships of haemoglobin levels with respiratory function and blood pressure. METHODS: We assessed a cohort of 101 young adults (ages 18-29) born preterm (≤29 weeks of gestation), in comparison to 105 full-term controls. We measured haemoglobin, erythropoietin levels and blood pressure. We also assessed respiratory function using spirometry. RESULTS: Compared with controls, tobacco use and sex-adjusted haemoglobin levels were 5.3 (95% CI 2.9 to 7.7) g/L higher in preterm-born individuals, but erythropoietin levels were similar. Duration of oxygen supplementation in the neonatal period was independently associated with higher haemoglobin levels in the preterm group. In young adults born preterm with bronchopulmonary dysplasia, airflow limitation was associated with higher haemoglobin levels. Both systolic (SBP) and diastolic (DBP) blood pressure were increased in individuals born preterm (p=0.042 and p=0.0008, respectively). Higher haemoglobin levels were associated with higher SBP and DBP, independently of term or preterm status. Mediation analysis suggests that haemoglobin increase contributes to 37% and 32% of the effect of preterm birth on SBP and DBP, respectively. CONCLUSIONS: Haemoglobin levels are higher in young adults born preterm, while erythropoietin levels are similar, especially in case of bronchopulmonary dysplasia and airflow limitation, and haemoglobin increase is associated with elevated blood pressure in this population.
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Eritropoese , Hipertensão/fisiopatologia , Oxigenoterapia , Nascimento Prematuro/fisiopatologia , Adolescente , Adulto , Displasia Broncopulmonar/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Testes de Função Respiratória , Fatores de RiscoRESUMO
An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%), and many were treated with exchange transfusions (46%). Children age 5 years and younger were often transfused until splenectomy. Splenectomy (150 [59%] of 254 patients) was associated with a median increase in hemoglobin of 1.6 g/dL and a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included higher presplenectomy hemoglobin (P = .007), lower indirect bilirubin (P = .005), and missense PKLR mutations (P = .0017). Postsplenectomy thrombosis was reported in 11% of patients. The most frequent complications included iron overload (48%) and gallstones (45%), but other complications such as aplastic crises, osteopenia/bone fragility, extramedullary hematopoiesis, postsplenectomy sepsis, pulmonary hypertension, and leg ulcers were not uncommon. Overall, 87 (34%) of 254 patients had both a splenectomy and cholecystectomy. In those who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. Although the risk of complications increases with severity of anemia and a genotype-phenotype relationship was observed, complications were common in all patients with PK deficiency. Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin. This trial was registered at www.clinicaltrials.gov as #NCT02053480.
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Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Estudos de Associação Genética , Piruvato Quinase/deficiência , Erros Inatos do Metabolismo dos Piruvatos/diagnóstico , Adolescente , Adulto , Anemia Hemolítica Congênita não Esferocítica/etiologia , Anemia Hemolítica Congênita não Esferocítica/metabolismo , Anemia Hemolítica Congênita não Esferocítica/terapia , Transfusão de Sangue , Criança , Pré-Escolar , Colecistectomia/efeitos adversos , Colecistectomia/métodos , Terapia Combinada , Ativação Enzimática , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Piruvato Quinase/metabolismo , Erros Inatos do Metabolismo dos Piruvatos/etiologia , Erros Inatos do Metabolismo dos Piruvatos/metabolismo , Erros Inatos do Metabolismo dos Piruvatos/terapia , Esplenectomia/efeitos adversos , Esplenectomia/métodos , Avaliação de Sintomas , Resultado do Tratamento , Adulto JovemRESUMO
Liver abscesses are poorly known in sickle cell disease. We report here multiple liver abscesses occurring in a 17-year-old patient with hemoglobin SC disease. A Fusobacterium nucleatum was identified on cyst puncture. Such complications have been described in only 11 children and young adults with hemoglobin SS/Sß-thalassemia diseases. Fusobacterium species are the most frequent pathogens reported and require anaerobic culture to be identified.
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Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/isolamento & purificação , Doença da Hemoglobina SC/microbiologia , Abscesso Hepático/complicações , Adolescente , Antibacterianos/uso terapêutico , Infecções por Fusobacterium/microbiologia , Doença da Hemoglobina SC/patologia , Humanos , Abscesso Hepático/microbiologia , Masculino , PrognósticoRESUMO
BACKGROUND: Vaso-occlusive crisis (VOC) is one of the most frequent causes of emergency visits and admission in children with sickle cell disease (SCD). OBJECTIVES: This study aims to evaluate whether the use of a new pain management pathway using intranasal (IN) fentanyl from triage leads to improved care, translated by a decrease in time to first opiate dose. METHODS: We performed a retrospective chart review of patients with SCD who presented to the emergency department (ED) with VOC, in the period pre- (52 patients) and post- (44 patients) implementation period of the protocol. Time to first opiate was the primary outcome and was evaluated pre- and postimplementation. Patients received a first opiate dose within 52.3 minutes of registration (interquantile range [IQR] 30.6, 74.6), corresponding to a 41.4-minute reduction in the opiate administration time (95% confidence interval [CI] -56.1, -27.9). There was also a 43% increase in the number of patients treated with a nonintravenous (IV) opiate as first opiate dose (95% CI 26, 57). In patients who were discharged from the ED, there was a 49% decrease in the number of IV line insertions (95% CI -67, -22). There was no difference in the hospitalization rates (difference of 6 [95% CI -13, 25]). CONCLUSIONS: This study validates the use of our protocol using IN fentanyl as first treatment of VOC in the ED by significantly reducing the time to first opiate dose and the number of IVs.
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Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and hemorrhagic risk. While many children with ITP can be safely observed, treatments are often needed for various reasons, including to decrease bleeding, or to improve health related quality of life (HRQoL). There are a number of available second-line treatments, including rituximab, thrombopoietin-receptor agonists, oral immunosuppressive agents, and splenectomy, but data comparing treatment outcomes are lacking. ICON1 is a prospective, multi-center, observational study of 120 children starting second-line treatments for ITP designed to compare treatment outcomes including platelet count, bleeding, and HRQoL utilizing the Kids ITP Tool (KIT). While all treatments resulted in increased platelet counts, romiplostim had the most pronounced effect at 6 months (P = .04). Only patients on romiplostim and rituximab had a significant reduction in both skin-related (84% to 48%, P = .01 and 81% to 43%, P = .004) and non-skin-related bleeding symptoms (58% to 14%, P = .0001 and 54% to 17%, P = .0006) after 1 month of treatment. HRQoL significantly improved on all treatments. However, only patients treated with eltrombopag had a median improvement in KIT scores at 1 month that met the minimal important difference (MID). Bleeding, platelet count, and HRQoL improved in each treatment group, but the extent and timing of the effect varied among treatments. These results are hypothesis generating and help to improve our understanding of the effect of each treatment on specific patient outcomes. Combined with future randomized trials, these findings will help clinicians select the optimal second-line treatment for an individual child with ITP.
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Púrpura Trombocitopênica Idiopática , Qualidade de Vida , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Rituximab/administração & dosagem , Trombopoetina/administração & dosagem , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Contagem de Plaquetas , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: Vaso-occlusive crisis (VOC) is one of the most frequent causes of emergency visit and admission in children with sickle cell disease (SCD). OBJECTIVES: This study aimed to evaluate whether the implementation of a protocol promoting the use of oral morphine as a primary intervention has led to improved care of SCD. METHODS: We performed a retrospective chart review of patients with SCD who presented to the emergency department (ED) and hematology outpatient clinic (HOC) with VOC, in the year pre and postimplementation of the protocol. The primary outcome was the hospitalization rate. RESULTS: The protocol resulted in a significant 43% reduction of hospitalization rate (95% confidence interval [CI] -53.0, 26.5). Results also showed a 35% increase in the use of oral morphine as first-line opiate treatment (95% CI 17.9, 45.2), a 28% increase in the use of pain scales (95% CI 17.3, 43.2) and a 30% net increase in patients eventually not requiring intravenous (IV) line placement (95% CI 16.0, 39.9). While we did observe an overall decrease in length of stay in ED of -55 min (95% CI -100.6, -12.0), there was a nonsignificant decrease of 7 minutes (95% CI -26, 3) in the opiate administration time. CONCLUSIONS: This study validates the use of our oral morphine protocol for the treatment of VOC by significantly reducing the admission rate and decreasing the number of IVs.
RESUMO
Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians.
Assuntos
Tomada de Decisão Clínica , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Criança , Tomada de Decisões , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Médicos/psicologia , Rituximab/uso terapêutico , EsplenectomiaRESUMO
Sickle cell disease (SCD) and vitamin D deficiency share manifestations such as bone complications and bony pains. Canadian SCD children are characterized by compromised sun exposure all year long and potential dietary deficiency, which combined to SCD-causing high nutritional demands, may lead to impaired vitamin D status. The objectives of this study were to document vitamin D status and intake and assess the relationship between vitamin D status and SCD-related outcomes in Canadian children with SCD followed in a tertiary pediatric center. Our study population included 119 children (47% males, median age [interquartile range]: 11.1 [9.2-14.8]) mainly of Haitian and Sub-Saharan African origin who had at least one measure of serum 25-hydroxyvitamin D (25OHD) performed between June 2015 and February 2017. Predominant genotypes were homozygous hemoglobin S (60%) and sickle hemoglobin-C (32%). Vitamin D deficiency (25OHD<30 nmol/L) and insufficiency (30 to 49 nmol/L) were present in 31% and 37% of children, respectively. Vitamin D-sufficient children (25OHD>50 nmol/L) had higher hemoglobin levels, lower leukocyte, reticulocyte, and neutrophil counts, compared with vitamin D-deficient and insufficient children. Vitamin D intake was low and modestly correlated to serum 25OHD levels. Acute SCD complications in the preceding 2 years were not associated with vitamin D status in these children.